atrial-natriuretic-factor and Chronic-Disease

To assess the diagnostic accuracy of point-of-care natriuretic peptide tests in patients with chronic heart failure, with a focus on the ambulatory care setting.. Systematic review and meta-analysis.. Ovid Medline, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Embase, Health Technology Assessment Database, Science Citation Index, and Conference Proceedings Citation Index until 31 March 2017.. Eligible studies evaluated point-of-care natriuretic peptide testing (B-type natriuretic peptide (BNP) or N terminal fragment pro B-type natriuretic peptide (NTproBNP)) against any relevant reference standard, including echocardiography, clinical examination, or combinations of these, in humans. Studies were excluded if reported data were insufficient to construct 2×2 tables. No language restrictions were applied.. 42 publications of 39 individual studies met the inclusion criteria and 40 publications of 37 studies were included in the analysis. Of the 37 studies, 30 evaluated BNP point-of-care testing and seven evaluated NTproBNP testing. 15 studies were done in ambulatory care settings in populations with a low prevalence of chronic heart failure. Five studies were done in primary care. At thresholds >100 pg/mL, the sensitivity of BNP, measured with the point-of-care index device Triage, was generally high and was 0.95 (95% confidence interval 0.90 to 0.98) at 100 pg/mL. At thresholds <100 pg/mL, sensitivity ranged from 0.46 to 0.97 and specificity from 0.31 to 0.98. Primary care studies that used NTproBNP testing reported a sensitivity of 0.99 (0.57 to 1.00) and specificity of 0.60 (0.44 to 0.74) at 135 pg/mL. No statistically significant difference in diagnostic accuracy was found between point-of-care BNP and NTproBNP tests.. Given the lack of studies in primary care, the paucity of NTproBNP data, and potential methodological limitations in these studies, large scale trials in primary care are needed to assess the role of point-of-care natriuretic peptide testing and clarify appropriate thresholds to improve care of patients with suspected or chronic heart failure.

Topics: Ambulatory Care; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Heart Failure; Humans; Peptide Fragments; Point-of-Care Testing; Reproducibility of Results; Sensitivity and Specificity; Technology Assessment, Biomedical

Natriuretic peptides (NPs) promote diuresis, natriuresis and vasodilation in early chronic heart failure (CHF), countering renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS) overstimulation. Despite dramatic increases in circulating NP concentrations as CHF progresses, their effects become blunted. Increases in diuresis, natriuresis, and vasodilation after administration of exogenous atrial (ANP) or brain (BNP) natriuretic peptides are attenuated in patients with advanced CHF compared with controls. Several major factors may account for the reduced effectiveness of the natriuretic peptide system (NPS) in CHF. First, there is reduced availability of active forms of NPs, namely BNP. Second, target organ responsiveness becomes diminished. Third, the counter-regulatory hormones of the RAAS and SNS, and endothelin-1 become over-activated. Therefore, pharmacological approaches to enhance the functional effectiveness of the NPS in CHF have been explored in recent years. In terms of clinical outcomes, studies of synthetic BNP, or of neprilysin inhibitors alone or associated with an angiotensin converting enzyme inhibitor, have been controversial for several reasons. Recently, however, encouraging results have been obtained with the angiotensin receptor neprilysin inhibitor sacubitril/valsartan. The available data show that treatment with sacubitril/valsartan is associated with increased levels of NPs and their intracellular mediator cyclic guanosine monophosphate, suggesting improved functional effectiveness of the NPS, in addition to beneficial effects on mortality and morbidity outcomes. Therefore, combined targeting of the NPS and RAAS with sacubitril/valsartan emerges as the current optimal approach for redressing the neurohormonal imbalance in CHF.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Atrial Natriuretic Factor; Biphenyl Compounds; Chronic Disease; Drug Combinations; Endothelin-1; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Neprilysin; Receptors, Atrial Natriuretic Factor; Renin-Angiotensin System; Sympathetic Nervous System; Tetrazoles; Valsartan

Heart failure (HF) is a fatal complication in many muscular dystrophy cases and has become the most common cause of death in Duchenne muscular dystrophy (DMD) since 2001. HF deaths in DMD occur in young patients and increase, along with respiratory failure, in older patients. Managing HF, therefore, is the most important component of DMD treatment. Management of HF is necessary in DMD patients of all ages because myocardial damage progresses regardless of age and disability. Electrocardiography, echocardiography, myocardial single-photon emission computed tomography (SPECT), and natriuretic peptides are used for the diagnosis of myocardial damage and chronic HF. Tissue Doppler echocardiography is in particularly useful for early detection of minute myocardial damage and dysfunction in DMD. The first-line drugs for chronic HF are angiotensin-converting enzyme inhibitors, and the prognosis of DMD patients has been improved using these drugs and beta-blockers. Diuretics are added in the presence of pulmonary congestion. Digoxin is most effective at a blood level of 0.5-0.8 ng/mL because of its pharmacokinetics in DMD. Surgical treatment may be necessary in cases of intractable HF. Cardiac resynchronization therapy (biventricular pacing), a treatment with an artificial pacemaker, is indicated for cases that meet specific criteria, including HF with ventricular dyssynchrony. Applications of partial left ventriculectomy (Batista procedure) and left ventricular assist devices in muscular dystrophy are likely in the near future.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Cardiac Resynchronization Therapy; Cardiomyopathies; Chronic Disease; Diagnostic Imaging; Heart Failure; Humans; Muscular Dystrophy, Duchenne; Natriuretic Peptide, Brain

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Cardiopulmonary Bypass; Chronic Disease; Cyclic GMP; Glomerular Filtration Rate; Heart Failure; Humans; Intraoperative Care; Myocardial Infarction; Natriuresis; Renin-Angiotensin System; Urination; Vasodilation

B-type natriuretic peptide (BNP) is a neurohormone synthesized in the cardiac ventricles, which is released as N-terminal pro-brain natriuretic peptide (NT-proBNP) and then enzymatically cleaved in to the NT fragment and the immunoreactive BNP. Both tests have been used to identify patients with congestive heart failure (CHF). Important considerations for these tests include their half-lives in plasma, dependence on renal function for clearance, and the interpretation of their units of measure. In general, a BNP level below 100 pg/mL has strong negative predictive value in the assessment of patients with dyspnea caused by a disorder other than CHF. In addition, BNP levels can be used to gauge the effect of short-term treatment of acutely decompensated heart failure, and the peptide has been shown to be a reliable independent predictor of sudden cardiac death. In the absence of renal dysfunction NT-proBNP has also been shown to be an independent predictor of sudden death in CHF patients. Because both a large area of myonecrosis or concomitant left ventricular failure are related to prognosis in acute coronary syndromes, B-type natriuretic peptides have also been linked to outcomes in this condition. This article describes the physiology and timing of release of B-type natriuretic peptides and the rationale for their use in the following settings: 1) evaluation of decompensated CHF, 2) screening for chronic CHF, 3) prognosis of CHF and sudden death, and 4) prognosis in acute coronary syndromes with inferred left ventricular dysfunction.

Topics: Atrial Natriuretic Factor; Brain; Chronic Disease; Dyspnea; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Sensitivity and Specificity

The atrial natriuretic peptide (ANP) plays an important role in chronic heart failure (CHF), delaying the progression of the disease. However, despite high ANP levels, natriuresis falls when CHF progresses from a compensated to a decompensated state, suggesting emergence of renal resistance to ANP. Several mechanisms have been proposed to explain renal hyporesponsiveness, including decreased renal ANP availability, down-regulation of natriuretic peptide receptors and altered ANP intracellular transduction signal. It has been demonstrated that the activity of neutral endopeptidase (NEP) is increased in CHF, and that its inhibition enhances renal cGMP production and renal sodium excretion. In vitro as well as in vivo studies have provided strong evidence of an increased degradation of intracellular cGMP by phosphodiesterase in CHF. In experimental models, ANP-dependent natriuresis is improved by phosphodiesterase inhibitors, which may arise as new therapeutic agents in CHF. Sodium-retaining systems likely contribute to renal hyporesponsiveness to ANP through different mechanisms. Among these systems, the renin-angiotensin-aldosterone system has received particular attention, as angiotensin II and ANP have renal actions at the same sites and inhibition of angiotensin-converting enzyme and angiotensin-receptor blockade improve ANP hyporesponsiveness. Less is known about the interactions between the sympathetic nervous system, endothelin or vasopressin and ANP, which may also blunt ANP-induced natriuresis. To summarize, renal hyporesponsiveness to ANP is probably multifactorial. New treatments designed to restore renal ANP efficiency should limit sodium retention in CHF patients and thus delay the progression to overt heart failure.

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Biological Availability; Cardiac Output, Low; Chronic Disease; Guanylate Cyclase; Humans; Kidney; Renin-Angiotensin System; Signal Transduction; Sympathetic Nervous System; Vasoconstriction

This literature review presents current information on mechanisms of realization and action of natriuretic peptides in heart failure and hypertension. Significant role in degradation of natriuretic peptides belongs to neutral endopeptidase. Basing on theoretical and experimental data novel class of drugs - inhibitors of neutral endopeptidase - has been developed. The paper contains discussion of first results of the use of drugs from this class for the treatment of chronic heart failure.

Topics: Atrial Natriuretic Factor; Chronic Disease; Heart Failure; Humans; Hypertension; Neprilysin

Chronic heart failure (CHF) is a complex syndrome involving activation of multiple cellular, metabolic, and neurohumoral pathways following the initial myocardial insult. Recently, there have been considerable advances in the pharmacologic management of CHF. The current approach to treatment recognizes the need to target neurohormonal activation, and the use of angiotensin-converting enzyme (ACE) inhibitors and beta blockers should now be regarded as part of standard therapy in many patients with CHF. However, because of the complexity of the disease, blockade of additional pathways is likely to be required to maximize the therapeutic benefit of intervention. To this end, there are several agents under active late-phase clinical evaluation. The most advanced of these new strategies (beyond renin-angiotensin-aldosterone blockade) is inhibition of the endothelin system. There is a substantial body of evidence that this system is intimately involved in CHF disease progression. Early-phase clinical data are very encouraging and support the potential utility of long-term endothelin inhibition. Other novel approaches involve the use of cytokine antagonists (e.g., agents that block tumor necrosis factor-alpha activity) and the augmentation of natriuretic peptides. If all these potential agents prove to be of benefit in CHF, the question of which agent or combination of agents to use in which patients will arise. There is therefore a need to develop scientific approaches in order to be able to identify more accurately patients who will obtain benefit from specific classes or combinations of drugs.

Topics: Atrial Natriuretic Factor; Cardiovascular Agents; Chronic Disease; Clinical Trials as Topic; Cytokines; Endothelins; Heart Failure; Humans; Renin-Angiotensin System

Digitalis works not only as a positive agent in congestive heart but as a modulator of neurosecretion as well. Opposite to its positive inotropic activity the latter refers to small doses. It leads to restoring of the autonomic balance. Its effect is resulted from the increased vagal activity that suppresses the adrenergic tone. Disregulating of the neurosecreting system may occur in patients with left ventricular impairment even without symptoms of left ventricular failure. Digitalis then besides stimulating contractility stops the neurosecretion and may be used not only to improve hemodynamics but also to slow the process of progressive deterioration of cardiac function.

Topics: Atrial Natriuretic Factor; Chronic Disease; Digitalis Glycosides; Heart Failure; Hemodynamics; Humans; Neurosecretion; Renin-Angiotensin System

Patients with chronic liver disease (Läennec's cirrhosis) present sodium chloride retention, leading to fluid accumulation within the extracellular space (edema) and specially in the abdomen (ascites). This article reviews the pathogenesis of the hemodynamic abnormalities observed in these patients, particularly the hypothesis of "primary arterial vasodilation", with an increased nitric oxide production by endothelial cells playing a major role in the pathogenesis of vasodilation. Since excessive renal sodium reabsorption precedes ascites formation, two hypotheses are analyzed with respect to the handling of renal sodium in chronic liver disease: the underfilling and overflow theories. Furthermore, the role of natriuretic peptides is reviewed, the increment in atrial natriuretic peptide observed in well compensated cirrhotic patients being considered as a compensatory response to volume expansion, although with renal resistance to this peptide in early stages of the disease. This review ends with an integrated explanation of the circulatory disturbances, renal sodium retention and renal resistance to atrial natriuretic peptide resulting in the sodium and water abnormalities observed in chronic liver disease.

Topics: Animals; Ascites; Atrial Natriuretic Factor; Calcitonin Gene-Related Peptide; Chronic Disease; Humans; Kidney; Liver Cirrhosis; Liver Diseases; Natriuretic Agents; Nitric Oxide; Sodium; Vasodilation

Numerous hormonal and neuroendocrine changes have been described in patients with chronic cardiac failure. These affect the balance of vasodilator and vasoconstrictor factors in favour of the latter, to the detriment of the circulation. Whether this is a reaction to central cardiac (haemodynamic) abnormalities, or is an integral part of the syndrome of heart failure, remains to be determined. Catecholamine levels are increased, especially in severe heart failure, and contribute to the vasoconstriction and probably also to lethal ventricular arrhythmias. The renin-angiotensin-aldosterone system (RAAS) is also activated, causing fluid retention and further vasoconstriction. In the earlier stages, some of this increase may be iatrogenic due to the use of loop diuretics or inhibitors of angiotensin converting enzyme, but there is evidence for independent RAAS activation in more severe grades of heart failure. The role of vasoconstrictor peptides such as neuropeptide Y and endothelin is briefly considered. Counterbalancing these are vasodilator peptides, in particular atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP). The possibility of therapeutic interventions to increase circulating natriuretic hormone levels is discussed.

Topics: Atrial Natriuretic Factor; Bombesin; Chronic Disease; Glucagon; Heart Failure; Humans; Insulin; Neuropeptide Y; Neurosecretory Systems; Neurotensin; Renin-Angiotensin System

The role of atrial natriuretic peptide (ANP) and potential defects of ANP in liver disease are reviewed. Patients with cirrhosis of the liver show no decrease of ANP plasma concentrations nor changes in the pattern of ANP immunoreactivity nor changes of splanchnic ANP clearance. The renal effects of exogenously administered as well as endogenously released ANP are blunted in cirrhosis, in particular in patients with ascites. This seems due to increased activity of sodium-retaining hormonal systems and changes of the renal ANP receptor status. Pharmacological inhibition of ANP-degradation or clearance may yield therapeutic potential.

Topics: Animals; Atrial Natriuretic Factor; Chronic Disease; Hemodynamics; Humans; Kidney; Liver Circulation; Liver Diseases

One important indicator of increased activity of the neurohormonal vasoconstrictor systems is the finding that the average plasma level of each neurohormone is frequently increased in patients with congestive heart failure. There is general agreement that these levels do reflect increased activity of the renin angiotensin system, the sympathetic nervous system, and the arginine vasopressin pathway. Plasma renin activity is influenced by many factors that can stimulate or suppress its release into the circulation. Several important areas are being investigated that may provide insight into the mechanisms by which neurohormonal vasoconstrictor systems regulate tone.

Topics: Atrial Natriuretic Factor; Chronic Disease; Heart Failure; Hemodynamics; Humans; Renin-Angiotensin System; Sodium; Vasodilation

Reports that sodium glucose cotransporter 2 inhibitors decrease cardiovascular death and events in patients with diabetes have attracted attention in the cardiology field. We conducted a study of canagliflozin in patients with chronic heart failure and type II diabetes.. Thirty-five Japanese patients with chronic heart failure and type II diabetes were treated with canagliflozin for 12 months. The primary endpoints were the changes of subcutaneous, visceral, and total fat areas at 12 months determined by computed tomography. Secondary endpoints included markers of glycemic control, renal function, and oxidative stress, as well as lipid parameters, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), flow-mediated dilation (FMD), and echocardiographic left ventricular function.. All fat areas (subcutaneous, visceral, and total) showed a significant decrease at 12 months. ANP and BNP also decreased significantly, along with improvement of renal function, oxidized LDL, and E/e', FMD increased significantly after canagliflozin treatment.. Canagliflozin demonstrated cardiac and renal protective effects as well as improving oxidative stress, diastolic function, and endothelial function. This drug was effective in patients who had heart failure with preserved ejection fraction and could become first-line therapy for such patients with diabetes. Trial registration UMIN ( http://www.umin.ac.jp/ ), Study ID: UMIN000021239.

Topics: Adiposity; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Blood Glucose; Canagliflozin; Chronic Disease; Diabetes Mellitus, Type 2; Female; Heart; Heart Failure; Humans; Japan; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome; Weight Loss

To investigate the effects of catheter ablation and rate control strategies on cardiac and inflammatory biomarkers in patients with heart failure and persistent atrial fibrillation (AF).. Patients were recruited from the ARC-HF trial (catheter Ablation vs Rate Control for management of persistent AF in Heart Failure, NCT00878384), which compared ablation with rate control for persistent AF in heart failure. B-type natriuretic peptide (BNP), midregional proatrial natriuretic peptide (MR-proANP), apelin, and interleukin-6 (IL-6) were assayed at baseline, 3 months, 6 months, and 12 months. The primary end point, analyzed per-protocol, was changed from baseline at 12 months.. Of 52 recruited patients, 24 ablation and 25 rate control subjects were followed to 12 months. After 1.2 ± 0.5 procedures, sinus rhythm was present in 22 (92%) ablation patients; under rate control, rate criteria were achieved in 23 (96%) of 24 patients remaining in AF. At 12 months, MR-proANP fell significantly in the ablation arm (-106.0 pmol/L, interquartile range [IQR] -228.2 to -60.6) compared with rate control (-28.7 pmol/L, IQR -69 to +9.5, P = 0.028). BNP showed a similar trend toward reduction (P = 0.051), with no significant difference in apelin (P = 0.13) or IL-6 (P = 0.68). Changes in MR-proANP and BNP correlated with peak VO2 and ejection fraction, and MR-proANP additionally with quality-of-life score.. Catheter ablation, compared with rate control, in patients with heart failure and persistent AF was associated with significant reduction in MR-proANP, which correlated with physiological and symptomatic improvement. Ablation-based rhythm control may induce beneficial cardiac remodeling, unrelated to changes in inflammatory state. This may have prognostic implications, which require confirmation by event end point studies.

Topics: Anti-Arrhythmia Agents; Apelin; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Cardiac Pacing, Artificial; Catheter Ablation; Chronic Disease; Female; Heart Failure; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome

Renal handling of sodium and water is abnormal in chronic kidney diseases. To study the function and regulation of the aquaporin-2 water channel (AQP2) and the epithelial sodium channel (ENaC) in autosomal dominant polycystic kidney disease (ADPKD), we measured urinary excretion of AQP2 (u-AQP2), the β-subunit of ENaC (u-ENaC(β)), cAMP (u-cAMP), and prostaglandin E(2) (u-PGE(2)); free water clearance (C(H2O)); fractional sodium excretion (FE(Na)); and plasma vasopressin (p-AVP), renin (p-Renin), angiotensin II (p-ANG II), aldosterone (p-Aldo), and atrial and brain natriuretic peptide (p-ANP, p-BNP) in patients with ADPKD and healthy controls during 24-h urine collection and after hypertonic saline infusion during high sodium intake (HS; 300 mmol sodium/day) and low sodium intake (LS; 30 mmol sodium/day). No difference in u-AQP2, u-ENaC(β), u-cAMP, u-PGE(2), C(H2O), and vasoactive hormones was found between patients and controls at baseline, but during HS the patients had higher FE(Na). The saline caused higher increases in FE(Na) in patients than controls during LS, but the changes in u-ENaC(β), p-Aldo, p-ANP, p-BNP, p-Renin, and p-ANG II were similar. Higher increases in u-AQP2 and p-AVP were seen in patients during both diets. In conclusion, u-AQP2 and u-ENaC(β) were comparable in patients with ADPKD and controls at baseline. In ADPKD, the larger increase in u-AQP2 and p-AVP in response to saline could reflect an abnormal water absorption in the distal nephron. During LS, the larger increase in FE(Na) in response to saline could reflect a defective renal sodium retaining capacity in ADPKD, unrelated to changes in u-ENaC(β).

Topics: Adolescent; Adult; Aged; Aldosterone; Angiotensin II; Aquaporin 2; Atrial Natriuretic Factor; Chronic Disease; Cross-Over Studies; Cyclic AMP; Dinoprostone; Epithelial Sodium Channels; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Polycystic Kidney, Autosomal Dominant; Renin; Saline Solution, Hypertonic; Sodium; Vasopressins; Young Adult

Loop diuretics have two different classes with different duration of activity: short-acting such as furosemide (duration of activity, 6h) and long-acting such as azosemide (duration of activity, 10-12h). We conducted a multicenter, randomized, controlled trial in order to compare the therapeutic effects of azosemide, a long-acting loop diuretic, and furosemide, a short-acting one, on neurohumoral factors and cardiac function in outpatients with chronic heart failure (CHF).. We enrolled 98 patients with CHF who were receiving furosemide and an angiotensin-converting enzyme inhibitor, and they were randomly divided into furosemide (n=49) and azosemide (n=49) groups. The furosemide group continued furosemide at the same dosage, and the azosemide group switched from furosemide to azosemide. At baseline and after 3 months, we measured body weight, and levels of brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), norepinephrine, active renin, creatinine, blood urea nitrogen, sodium, potassium, and hematocrit. Chest X-ray and echocardiography were also performed.. Body weight and plasma levels of BNP and ANP significantly decreased after 3 months in the azosemide group compared to the furosemide group. There were no significant differences in changes of levels of creatinine, blood urea nitrogen, sodium, potassium, hematocrit, norepinephrine, and active renin after 3 months between the furosemide and azosemide groups. Echocardiography and chest X-ray did not demonstrate significant differences between the two groups.. Long-acting azosemide is suggested to be useful for the improvement of neurohumoral factors compared with short-acting furosemide in patients with CHF.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Delayed-Action Preparations; Echocardiography; Female; Furosemide; Heart Failure; Heart Function Tests; Humans; Male; Natriuretic Peptide, Brain; Outpatients; Sodium Potassium Chloride Symporter Inhibitors; Sulfanilamides

Sleep-disordered breathing (SDB), including Cheyne-Stokes respiration with central sleep apnea (CSR-CSA), causes a deterioration in the prognosis of patients with chronic heart failure (CHF). Adaptive servo-ventilation (ASV) and oxygen therapy (O(2)) are useful for improving the CSR-CSA of CHF. The purpose of the present study was to examine the short-term effects of ASV and O(2) on suppressing SDB (CSR-CSA dominant) in CHF, and the accompanying neurohumoral abnormalities (cardiac overload, sympathetic nervous activation, and myocardial damage).. FORTY-two patients with CHF and SDB (mean LVEF 34.6%, apnea hypopnea index (AHI) 39.0/h, central apnea index (CAI) 17.6/h, obstructive apnea index (OAI) 2.6/h) were enrolled. We performed polysomnography (baseline, O(2), and ASV) for 3 consecutive days, and we measured levels of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), noradrenalin, urinary catecholamines, and high-sensitivity troponin T. Both O(2) and ASV reduced the AHI, CAI, arousal index, mean heart rate during sleep, and the levels of noradrenalin, urinary catecholamines, and high-sensitivity troponin T. However, only ASV, not O(2), decreased the levels of ANP and BNP.. ASV reduces cardiac overload, attenuates sympathetic nervous activity and ongoing myocardial damage effectively in CHF patients with SDB, and for patients who cannot use ASV, O(2) is an alternative therapy.

Topics: Aged; Atrial Natriuretic Factor; Chronic Disease; Cross-Over Studies; Female; Heart Failure; Humans; Male; Middle Aged; Myocardium; Oxygen; Sleep Apnea, Obstructive; Sympathetic Nervous System; Troponin T

Carperitide is used to treat acute decompensated heart failure (ADHF), but its effects on long-term prognosis have not been studied.. A multicenter randomized controlled study of 49 patients with ADHF was performed to clarify the drug's effects on long-term prognosis. Low-dose carperitide (0.01-0.05 microg x kg(-1 ) x min(-1)) was infused for 72 h as the initial treatment (n=26), whereas in the control group (n=23), standard medical treatment other than carperitide was given without limitation. Anti-aldosterone drugs were prohibited in both groups. During carperitide infusion, significant increases of the atrial natriuretic peptide and cyclic GMP levels and a significant decrease in the heart-type fatty acid-binding protein/serum creatinine ratio were observed, suggesting inhibition of myocyte cell membrane damage. On the other hand, no significant differences in the plasma brain natriuretic peptide, troponin T, and creatinine levels were noted in either group. During 18-month follow-up, significant reductions of death and rehospitalization occurred in the carperitide vs control group (11.5% vs 34.8%; p=0.0359). Cox regression analysis revealed that randomization to carperitide (p=0.020), pretreatment systolic blood pressure >or=140 mmHg (p=0.043), and beta-blocker therapy (p=0.016) were independent predictors for freedom from cardiac events.. Acute-phase low-dose carperitide infusion improved the long-term prognosis of patients with ADHF.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Creatinine; Cyclic GMP; Fatty Acid-Binding Proteins; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Remission Induction; Troponin T

Patients with chronic heart failure (CHF) have decreased ability to excrete water and increased urinary excretion of aquaporin-2 (U-AQP2). The natriuretic and diuretic effects of furosemide are antagonized by an increased reabsorption of sodium and water in the collecting ducts. It is unknown whether aquaporin-2 (AQP2) renal water channels are involved in this compensatory reabsorption. We tested the hypothesis that U-AQP2 increases after a single intravenous dose of furosemide in CHF patients.. In a randomized, single-blind, placebo-controlled, crossover study, we measured the effect of furosemide (80 mg) on U-AQP2, urine volume, free water clearance (C(H2O)) and fractional excretion of sodium (FE(Na)) in 12 CHF patients. Plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), atrial (ANP) and brain natriuretic peptides (BNP) were measured during the study. U-AQP2 and hormones were determined by radioimmunoassays.. Furosemide increased U-AQP2 (140 %), urine volume (280 %), C(H2O) (95 %) and FE(Na) by a factor of 15 (p<0.008 for all), and also AVP (51 %), PRC, Ang II (86 %) and Aldo (59 %) (p<0.021 for all). ANP and BNP did not change.. In CHF, furosemide increased the vasopressin level, which stimulated water reabsorption via the APQ2 water channels. This is most likely a compensatory phenomenon in addition to the increase in the renin-angiotensin system to prevent excess loss of sodium and water. However, both these effects were overridden by the effect of furosemide, as shown by increased free water clearance and sodium excretion.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin II; Aquaporin 2; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Cross-Over Studies; Female; Furosemide; Glomerular Filtration Rate; Heart Failure; Humans; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Renin

Short-term infusion of carperitide (atrial natriuretic peptide) has beneficial effects on neurohumoral factors; however, it remains unclear whether the effects are sustained for long-term infusion. To evaluate the effects of long-term infusion of carperitide on neurohumoral factors in patients with chronic congestive heart failure (CHF), we measured neurohumoral factors before and 1 hour after stopping carperitide infusion in 42 CHF patients. Carperitide infusion was continued for more than 2 days until there was symptomatic improvement of CHF. Patients were divided into 2 groups by the median value of infusion duration: group 1 (less than 7 days, n=21) and group 2 (more than 7 days, n=21). In group 1, aldosterone (ALD) and endothelin-1 (ET-1) were significantly increased after stopping carperitide. In contrast, ALD and ET-1 did not change after stopping carperitide in group 2. The molar ratio of cyclic guanosine monophosphate/atrial natriuretic peptide before stopping carperitide was significantly lower in group 2 than in group 1. Suppression of ALD and ET-1 was maintained for 7 days of carperitide infusion, but the beneficial effect on neurohumoral factors was attenuated after more than 7 days, probably through down-regulation of biologic receptors coupled with guanylate cyclase in CHF patients.

Topics: Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Cardiomyopathy, Dilated; Chronic Disease; Cyclic GMP; Endothelin-1; Female; Heart Failure; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Stroke Volume; Time Factors; Treatment Outcome

Urodilatin (ularitide), a natriuretic peptide, is produced within the kidneys. The aim of this study was to define the role of 24-hour intravenous infusions of urodilatin in the treatment of decompensated chronic heart failure (DHF).. In this randomized, double-blind, ascending-dose safety study, 24 patients with DHF (cardiac index 1.91 +/- 0.34 L/min per square meter, pulmonary capillary wedge pressure 26 +/- 6 mm Hg, right atrial pressure 11 +/- 4 mm Hg) received urodilatin (7.5, 15, or 30 ng/(kg.min)) or placebo infusions over 24 hours.. Compared with baseline, urodilatin decreased pulmonary capillary wedge pressure by 10 mm Hg in the 15 ng/(kg.min) group (P < .05) and by 15 mm Hg in the 30 ng/(kg.min) group (P < .05) at 6 hours. In the same dose groups, right atrial pressure decreased, and dyspnea as reported by patients tended to improve. At 24 hours, 15 and 30 ng/(kg.min) urodilatin infusions decreased N-terminal-pro-brain natriuretic peptide levels by 40% and 45%, respectively, compared with baseline. Between 1 to 12 hours, plasma cyclic guanosine monophosphate levels at 15 and 30 ng/(kg.min) urodilatin were significantly higher than both placebo and the respective baseline after infusion start (P < .05 and .01). Among the different groups, there was no obvious difference regarding total number of patients with adverse events and total number of adverse events. During infusion, 3 transient asymptomatic hypotensions occurred in the urodilatin groups.. Our findings show that urodilatin may be a new agent for the therapy for DHF.

Topics: Aged; Atrial Natriuretic Factor; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heart Failure; Heart Function Tests; Humans; Kidney; Male; Middle Aged; Patient Selection; Peptide Fragments; Placebos; Respiratory Function Tests

The prevalence of chronic heart failure (CHF) with systolic dysfunction is increasing. Plasma natriuretic peptides have been envisaged as diagnostic and predictive markers.. To investigate the relationship between the levels of B-type natriuretic peptide (BNP) and A-type natriuretic peptide (ANP) and the clinical and functional parameters of CHF in outpatients with CHF at baseline, compared with normal healthy controls; to find out the differences in a randomised controlled trial between patients treated with an angiotensin-converting enzyme (ACE) inhibitor, captopril, or an angiotensin receptor blocker (ARB), irbesartan. These differences were assessed throughout the six-month treatment period and at the sixth month.. Plasma BNP (pmol/L) and ANP (pmol/L) were determined in 68 hypertensive patients with dilated cardiomyopathy, NYHA class III-IV and ejection fraction (EF) < or = 40%, and in 26 normal controls. Statistical analysis for BNP and ANP was done by Students t-test. The patient group was randomly subdivided into two subgroups of 34 patients, each treated with either an ARB, irbesartan, or an ACE inhibitor (ACE-I), captopril. BNP and ANP were measured in both subsamples and correlated with clinical, functional and neurohormonal parameters throughout a follow-up period of six months and at the sixth month.. The mean EF in the patient sample was 33.43+/-6.52% and in the controls was 61.96 +/-3.53% (p=0.000). The mean BNP (pmol/L) in patients was 44.78+/-54.36 and in the controls was 7.12+/-8.28 (p=0.000) and the mean ANP (pmol/L) was 30.32+/-25.97 in patients and 11.18+/-7.92 in controls (p=0.000). A statistically significant difference was found between patients and healthy controls. Significant correlations were found between natriuretic peptides and EF. Between the baseline phase and the sixth month, BNP and ANP decreased significantly in the ARB group. At the sixth month, both BNP and ANP were lower in the ARB group. Evidence of clinical benefit was found with both ARB or ACE-I treatment throughout the six months, with patients moving from classes III and IV to class II NYHA. Improvement of EF was also found, with transition of patients with lower EF (even <30%) to higher values. EF was higher in the ARB group at the sixth month.. BNP and ANP can be useful diagnostic tools in hypertensive CHF patients with moderate-to-severe LV dysfunction. The decrease in BNP and ANP in the ARB group throughout six months, as well as the lower value at the sixth month, suggest a prognostic value of these parameters.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Biphenyl Compounds; Captopril; Cardiac Output, Low; Chronic Disease; Echocardiography; Electrocardiography, Ambulatory; Female; Follow-Up Studies; Humans; Irbesartan; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Radiography, Thoracic; Radionuclide Ventriculography; Tetrazoles; Ventricular Dysfunction, Left

C-type natriuretic peptide (CNP) is a vasodilator produced by the vascular endothelium. It shares structural and physiological properties with the cardiac hormones atrial natriuretic peptide and brain natriuretic peptide (BNP), but little is known about its pathophysiological role in chronic heart failure (CHF). We assessed the hypothesis that CNP is produced by the heart in patients with CHF.. Myocardial CNP production was determined (difference in plasma levels between the aortic root and coronary sinus [CS]) in 9 patients undergoing right and left heart catheterization as part of their CHF assessment (all male, age 59+/-9 years; New York Heart Association class 2.2+/-0.1; left ventricular ejection fraction 29+/-5%; creatinine 105+/-8 micro mol/L [all values mean+/-SEM]). BNP, established as originating from myocardium, was assessed from the same samples as a positive control. Analyses were performed by a blinded operator using a standard competitive radioimmunoassay kit (Peninsula Laboratories, Bachem Ltd UK). A step-up (29%) in plasma CNP concentration was found from the aorta to the CS (3.55+/-1.53 versus 4.59+/-1.54 pg/mL, respectively; P=0.035). The mean increase in CNP was 0.90+/-0.35 pg/mL (range 0.05 to 2.80 pg/mL). BNP levels increased by 57% from aorta to CS (86.0+/-20.5 versus 135.0+/-42.2 pg/mL; P=0.01). CS CNP levels correlated with mean pulmonary capillary wedge pressure (r=0.82, P=0.007).. We have shown that CNP is produced by the heart in patients with CHF. Although further evaluation is required to define its full pathophysiological role in this condition, CNP may represent an important new local mediator in the heart.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Cardiac Catheterization; Chronic Disease; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Pulmonary Wedge Pressure; Stroke Volume; Ventricular Dysfunction, Left

To determine whether the plasma concentration of the putative new cardiac hormone relaxin is predictive of clinical outcome in patients with chronic heart failure (CHF).. Plasma relaxin and N-terminal pro B type natriuretic peptide (NT pro BNP) concentrations were measured in 87 patients admitted in an emergency with CHF caused by left ventricular systolic dysfunction. These were related to death and death or readmission with CHF over the following year.. Western Infirmary, Glasgow, UK.. Plasma concentrations of relaxin and NT pro BNP; time to death or hospitalisation caused by heart failure.. Plasma concentrations of both relaxin and NT pro BNP were greatly increased. Of the 43 patients with NT pro BNP above the group median concentration, 23 (53%) died and 30 (70%) died or were hospitalised with CHF. Among the 44 with concentrations below the median, these numbers were 5 (11%) and 12 (27%), respectively (p < 0.0001 and p < 0.0001, respectively). Plasma NT pro BNP concentration remained an independent predictor of an adverse clinical outcome in a multivariate analysis. Of the 42 patients with a relaxin concentration above the median, 13 (31%) died and 20 (48%) died or were hospitalised. Below the median, these numbers were 15 of 45 (33%) and 22 of 45 (49%) (p = 0.76 and p = 0.84, respectively).. NT pro BNP is a powerful and independent predictor of outcome in CHF, whereas relaxin, also secreted by the heart in increased amounts in CHF, is not.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Cardiac Output, Low; Chronic Disease; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Relaxin; Survival Analysis

Adrenergic receptor blockers used in the treatment of heart failure have distinct receptor affinity profiles. We hypothesized that alpha-adrenergic-blocking effects of carvedilol would limit vasoconstriction in response to adrenergic stimuli when compared with metoprolol.. Forearm vascular resistance responses to isometric handgrip and cold pressor test were determined by plethysmography before and during adrenergic receptor blockade in prospective randomized trials. Acute effects were assessed in a crossover trial in normal subjects (single dose of 25 mg carvedilol, 100 mg metoprolol tartrate, and placebo). Chronic effects (25 mg carvedilol BID versus 200 mg extended-release metoprolol succinate daily for 6 months) were assessed in a parallel group trial of chronic heart failure subjects. In normal subjects, carvedilol decreased forearm vascular resistance responses to adrenergic stimuli when compared with metoprolol and placebo (isometric handgrip -3.5 U for carvedilol versus -1.2 U for metoprolol and -2.2 U for placebo, P=0.15; cold pressor test 3.1+/-8.9 U for carvedilol versus 9.0+/-2.7 U for metoprolol and 8.2+/-5.8 U for placebo, P<0.05). In heart failure subjects, vasomotor responses to isometric handgrip and cold pressor test did not differ between treatment groups.. Acute administration of carvedilol attenuates the vasoconstriction response to adrenergic stimuli when compared with placebo and metoprolol in normal subjects, whereas chronic administration of carvedilol does not attenuate the vasoconstrictor response to adrenergic stimuli when compared with metoprolol in heart failure subjects. These data suggest that long-term benefits of carvedilol in heart failure are not mediated by alpha-adrenergic blockade.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Adult; Atrial Natriuretic Factor; Carbazoles; Carvedilol; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Exercise; Female; Forearm; Heart Failure; Humans; Male; Metoprolol; Middle Aged; Muscle, Skeletal; Natriuretic Peptide, Brain; Norepinephrine; Propanolamines; Prospective Studies; Reference Values; Regional Blood Flow; Vascular Resistance; Vasodilator Agents; Vasomotor System

The purpose of this study was to evaluate whether or not cardiac sympathetic nerve activity, using (123)I-meta-iodobenzylguanidine ((123)I-MIBG) imaging, and cardiac natriuretic peptides (atrial and brain, ANP and BNP) were independent predictors of cardiac events, and, if so, which was the stronger predictor. Planar (123)I-MIBG images were obtained from 62 patients with heart disease. Plasma ANP and BNP levels, left ventricular ejection fraction (LVEF) by echocardiography, serum total cholesterol and triglyceride were measured. (123)I-MIBG was assessed as the heart-to-mediastinum (H/M) ratio of the delayed image and the washout rate (WoR) from the early to the delayed image. Patients were followed up for an average of 16.2 months, and 12 of 62 patients had cardiac events. Patients with events had significantly lower LVEF and H/M ratio compared with those without events. They had significantly higher WoR, ANP and BNP. By multivariate Cox proportional hazard analysis, (123)I-MIBG (H/M or WoR), ANP and BNP were independent predictors for cardiac events. Event-free survival using a Kaplan-Meier model, with a threshold value of 2.0 for H/M and 45% for WoR, showed that patients with H/M<2.0 and/or WoR>45% had a significantly poorer prognosis. These results suggest that (123)I-MIBG imaging and cardiac natriuretic peptides are useful tools for the evaluation of patients with heart disease, and that cardiac sympathetic nerve activity is a stronger predictor of cardiac events.

Topics: 3-Iodobenzylguanidine; Angina Pectoris; Atrial Natriuretic Factor; Cardiomyopathies; Chronic Disease; Female; Follow-Up Studies; Heart Diseases; Heart Valve Diseases; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Predictive Value of Tests; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Statistics as Topic

Angiotensin-converting enzyme (ACE) inhibitors exert their effects by modulating the neurohumoral milieu. Vasopeptidase inhibitors (VPI) are ACE and neutral endopeptidase inhibitors and may increase natriuretic peptides, bradykinin, and perhaps endothelin-1 in patients with congestive heart failure. Patients (n = 107) with ischemic or dilated cardiomyopathy, New York Heart Association functional class II to III, with left ventricular ejection fraction <40%, and on ACE inhibitor therapy were randomized to either the VPI omapatrilat 40 mg/day or the ACE inhibitor lisinopril 20 mg/day. Trough levels of neurohormones (24 hours after dosing) were assessed at baseline, and at 12 and 24 weeks of follow-up. C-terminal atrial natriuretic peptide (C-ANP) levels decreased with lisinopril (p = 0.035), but not with omapatrilat. In contrast, N-terminal ANP levels did not change, and brain natriuretic peptide (BNP) levels tended to decrease similarly in both groups. Endothelin-1 levels increased in both groups, the increase reaching statistical significance with omapatrilat (p = 0.008). Levels of the proinflammatory cytokine interleukin-6 tended to decrease, and the anti-inflammatory cytokine interleukin-10 increased in both groups, with statistical significance only for interleukin-10 with omapatrilat therapy. Neither agent changed catecholamines or angiotensin II. Thus, even at trough levels, omapatrilat potentiates C-ANP more than lisinopril. Potentially important effects of omapatrilat on endothelin-1 and anti-inflammatory cytokines were identified, providing potential explanations for differences in clinical outcome.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Cytokines; Double-Blind Method; Endothelin-1; Female; Follow-Up Studies; Heart Failure; Humans; Lisinopril; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Predictive Value of Tests; Prospective Studies; Pyridines; Stroke Volume; Thiazepines; Treatment Outcome

Although Doppler echocardiography has been used to identify abnormal left ventricular (LV) diastolic filling dynamics, inherent limitations suggest the need for additional measures of diastolic dysfunction. Because data suggest that B-natriuretic peptide (BNP) partially reflects ventricular pressure, we hypothesized that BNP levels could predict diastolic abnormalities in patients with normal systolic function.. We studied 294 patients referred for echocardiography to evaluate ventricular function. Patients with abnormal systolic function were excluded. Cardiologists making the assessment of LV function were blinded to BNP levels. Patients were classified as normal, impaired relaxation, pseudonormal, and restrictivelike filling patterns. Patients diagnosed with evidence of abnormal LV diastolic function (n=119) had a mean BNP concentration of 286 +/- 31 pg/mL; those in the normal LV group (n=175) had a mean BNP concentration of 33 +/- 3 pg/mL. Patients with restrictive like filling patterns on echocardiography had the highest BNP levels (408 +/- 66 pg/mL), and patients with symptoms had higher BNP levels in all diastolic filling patterns. The area under the receiver-operating characteristic curve for BNP to detect any diastolic dysfunction was 0.92 (95% CI, 0.87 to 0.95; P<0.001). A BNP value of 62 pg/mL had a sensitivity of 85%, a specificity of 83%, and an accuracy of 84% for detecting diastolic dysfunction.. A rapid assay for BNP can reliably detect the presence of diastolic abnormalities on echocardiography. In patients with normal systolic function, elevated BNP levels and diastolic filling abnormalities might help to reinforce the diagnosis diastolic dysfunction.

Topics: Aged; Area Under Curve; Atrial Function, Left; Atrial Natriuretic Factor; Chronic Disease; Diastole; Echocardiography; Electrocardiography; Female; Heart Failure; Heart Ventricles; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction, Left

Assessment of left atrial appendage (LAA) function with transesophageal echocardiography is useful for detecting patients at high risk for thromboembolism as a result of atrial fibrillation (AF). A recent study reported that the atrium is the main source of brain natriuretic polypeptide (BNP) in AF patients without overt heart failure. The purpose of this study was to assess a possible relationship between LAA function and plasma BNP levels in nonvalvular AF.. Thirty-four consecutive patients with chronic nonvalvular AF (age, 69+/-9 years) underwent transesophageal echocardiography and plasma BNP measurement. Thirteen patients with a history of thromboembolism or echocardiographic evidence of thrombus (E + group) were compared with 21 AF patients without complications (E- group).. The E+ group patients demonstrated greater impairment of LAA velocity and higher plasma BNP levels than the E- group patients (LAA velocity: 12+/-6 versus 31+/-17 cm/s, P<0.05; plasma BNP: 126+/-53 versus 86+/-45 ng/L, P<0.05). Overall analysis of the continuous variables with multiple logistic regression analysis revealed that BNP was a significant predictor of thromboembolism. There was a weak but significant negative correlation between plasma BNP levels and LAA flow velocity (r=0.38, P<0.05). No intergroup difference in plasma atrial natriuretic polypeptide levels was found.. The present data suggest the usefulness of measuring plasma BNP levels, which may reflect augmented atrial secretion of BNP from the impaired atrial myocardium, in detecting patients at high risk for thromboembolic complications in nonvalvular AF.

Topics: Adult; Aged; Aged, 80 and over; Atrial Appendage; Atrial Fibrillation; Atrial Function, Left; Atrial Natriuretic Factor; Biomarkers; Blood Flow Velocity; Chronic Disease; Echocardiography, Transesophageal; Electrocardiography; Female; Humans; Logistic Models; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Assessment; Thromboembolism

We studied the effects of a short-term hypertonic stimulus on plasma levels of the stress hormones adrenocorticotropin (ACTH), cortisol, prolactin, and the blood volume- and electrolyte-controlling hormones arginine vasopressin (AVP) and atrial natriuretic peptide (ANP). Seven patients suffering from chronic schizophrenia with negative symptoms and ten healthy control subjects were investigated by a 20-minute infusion of 10 ml/kg body weight of hypertonic (2.5%) versus isotonic (0.9%) saline. All patients, who were medication-free for at least one week prior to the study, and all control subjects participated in two investigations in randomized order according to a single-blind cross-over design. During hypertonic infusion, plasma osmolarity and sodium levels were increased similarly in both groups and significantly more than during isotonic saline. Hypertonic saline caused a significant increase of plasma ACTH, cortisol and prolactin in patients in contrast to controls. AVP and ANP plasma concentrations were elevated after infusion of hypertonic saline, however, only patients showed a significant rise in plasma ANP. These results show that a dysregulation of the hypothalamic-pituitary-adrenal (HPA) system in a subset of patients with chronic schizophrenia may become overt during an osmotic stimulation, indicating an increased sensitivity of patients with schizophrenia to osmotic stress.

Topics: Adrenocorticotropic Hormone; Adult; Arginine Vasopressin; Atrial Natriuretic Factor; Chronic Disease; Cross-Over Studies; Female; Humans; Hydrocortisone; Infusions, Intravenous; Isotonic Solutions; Male; Osmotic Pressure; Prolactin; Saline Solution, Hypertonic; Schizophrenia; Single-Blind Method; Time Factors

The mechanisms of action of omapatrilat, an agent that inhibits both neutral endopeptidase 24.11 and angiotensin-converting enzyme, on arterial function in patients with heart failure have not been previously reported. Forty-eight patients in New York Heart Association functional class II to III, left ventricular ejection fraction < or = 40%, and in sinus rhythm were randomized to a dose-ranging (2.5, 5, 10, 20, or 40 mg) study of omapatrilat for 12 weeks. Measurements were obtained at baseline and 12 weeks. Decreases in systolic (25.0 +/- 4.5 vs 2.8 +/- 5.0 mm Hg, p < 0.05) and mean arterial (13.9 +/- 3.0 vs 0.3 +/- 3.3 mm Hg, p < 0.05) pressure were seen after 12 weeks of therapy with higher doses. Ventricular-arterial coupling was improved with a dose-related decrease in augmentation index (-13.8 +/- 1.7% vs +6.1 +/- 2.1%, p < 0.01). There was no change in resting forearm blood flow between groups; however, maximum forearm vasodilator response during reactive hyperemia increased in the high-dose groups compared with the control group (+266 +/- 43% vs - 14 +/- 92%, p < 0.05). Omapatrilat induced an increase in postdose plasma atrial natriuretic peptide levels (30 +/- 11 vs -2 +/- 7 pmol/L, p < 0.01) in high-dose groups consistent with endopeptidase 24.11 inhibition. Omapatrilat shows beneficial changes in ventricular-vascular coupling and arterial function in heart failure.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Dose-Response Relationship, Drug; Female; Heart Failure; Humans; Male; Middle Aged; Pyridines; Stroke Volume; Thiazepines; Vasodilation; Ventricular Function, Left

Topics: Adrenergic beta-Antagonists; Atrial Natriuretic Factor; Blood Pressure; Carbazoles; Carvedilol; Chronic Disease; Double-Blind Method; Endothelial Growth Factors; Female; Heart Failure; Heart Rate; Humans; Lymphokines; Male; Middle Aged; Propanolamines; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Three specific receptors for the cardiac natriuretic peptide system have been identified to date. Down-regulation of the biologically active binding sites (i.e. NPR-A and NPR-B) could explain the blunted response to cardiac natriuretic hormones observed in heart failure (HF), but not the increased metabolic clearance rate. Variations in the ratio between biological and clearance (NPR-C) receptors in target tissue may explain this increase.. The aim of this study was to investigate the regulation of NPR-C receptors on platelets, in patients with HF.. Eighteen patients with HF (NYHA class: I-II, n=8; III-IV, n=10) and 18 age-matched healthy subjects were studied. The affinity constant (K(d)) and density (B(max)) of binding sites were derived by saturation assays on platelet suspensions using 125I-ANP as radioligand.. B(max) increased as a function of the severity of disease: 21.3+/-3.3 fmol/10(9) cells in class III-IV, 11.7+/-2.2 in class I-II, and 11.6+/-1.1 in controls, respectively (P=0.0179 for class III-IV vs. controls and P=0.0451 vs. NYHA I-II).. The increase in density of 'clearance' receptors in severe HF is theoretically consistent with the reduction in cardiac natriuretic peptide biological activity, as well as the increase in metabolic clearance rate. This suggests that clearance receptor blockade may be of potential therapeutic value in HF.

Topics: Adult; Aged; Analysis of Variance; Atrial Natriuretic Factor; Biomarkers; Blood Platelets; Chronic Disease; Cyclic GMP; Female; Heart Failure; Humans; Male; Middle Aged; Receptors, Atrial Natriuretic Factor; Reference Values; Sensitivity and Specificity; Severity of Illness Index; Up-Regulation

The study tested the hypothesis that left atrial appendage (LAA) dysfunction in nonvalvular atrial fibrillation (NVAF) correlates with a prothrombotic state, and investigated whether the plasma natriuretic peptides are marker of LAA dysfunction in NVAF. Sixty-seven patients underwent transthoracic and transesophageal echocardiography. The left ventricular fractional shortening, left atrial diameter (LAD), LAA flow velocity and the grade of spontaneous echo contrast (SEC) were determined. The plasma concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), D-dimer, and thrombin-antithrombin III complex (TAT) were measured. The patients were divided into 2 groups according to LAA flow velocity: group I (LAA velocity <20 cm/s) and group II (LAA velocity > or = 20cm/s). The SEC score, D-dimer, TAT, BNP and LAD were significantly increased in group I. Based on simple linear regression analysis, SEC score (r=-0.638), LAD (r=-0.493), D-dimer (r = -0.485), BNP (r = -0.463), TAT (r = -0.455) and age (r = -0.314) were inversely correlated with LAA flow velocity. Multivariate analysis showed that SEC score (p = 0.0014) and plasma BNP level (p=0.0075) were independent negative predictors for LAA flow velocity. In conclusion, LAA dysfunction is associated with a prothrombotic state, and the plasma BNP concentration may serve as a determinant of LAA function in NVAF.

Topics: Aged; Atrial Appendage; Atrial Fibrillation; Atrial Function, Left; Atrial Natriuretic Factor; Biomarkers; Blood Flow Velocity; Chronic Disease; Echocardiography, Transesophageal; Humans; Middle Aged; Natriuretic Peptide, Brain; Thrombophilia

The efficacy of treating dilated cardiomyopathy with metoprolol was compared with that of carvedilol. Metoprolol was administered to 29 patients, and carvedilol to 62. Patients who could not be dosed with up to 40 mg daily of metoprolol or 20 mg daily of carvedilol were defined as intolerant. As well as the tolerability of these beta-blockers, the effects on left ventricular end-diastolic dimension (LVDd), fractional shortening (FS), plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations, the delayed heart and mediastinum (H/M) ratio determined from metaiodobenzylguanidine imaging were compared. Drug intolerance occurred in 24% of patients in the metoprolol group and 19% in the carvedilol group. Among the drug-tolerant patients, LVDd, FS and plasma BNP concentration improved in both groups and to the same degree. Only 25% of drug-tolerant patients in the metoprolol group had a delayed H/M ratio below 1.9 compared with 57% in the carvedilol group. Both metoprolol and carvedilol, when tolerated, improve cardiac function and neurohumoral factors to the same degree. However, carvedilol is preferable to metoprolol for patients with a low delayed H/M ratio.

Topics: 3-Iodobenzylguanidine; Adrenergic beta-Antagonists; Adult; Atrial Natriuretic Factor; Carbazoles; Cardiomyopathy, Dilated; Carvedilol; Chronic Disease; Female; Hemodynamics; Humans; Male; Metoprolol; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Norepinephrine; Propanolamines; Therapeutic Equivalency; Tomography, Emission-Computed, Single-Photon; Ventricular Function, Left

Although transient atrial dysfunction has been reported after electrical cardioversion of atrial fibrillation (AF), the difference in the time to recover from the atrial hormonal, mechanical, and electrical dysfunction has not been described. Thus, we evaluated the time course of recovery from atrial hormonal, mechanical, and electrical dysfunction after cardioversion in patients with nonvalvular AF. We attempted electrical cardioversion in 87 consecutive patients with nonvalvular AF that had persisted for > or =6 months, and in 24 patients (28%) with maintained sinus rhythm for > or =6 months. To evaluate atrial hormonal, mechanical, and electrical dysfunction in these 24 patients, we measured plasma concentration of atrial natriuretic peptide, the atrial peak velocity in transmitral flow, and the ratio of peak systolic-to-diastolic pulmonary venous flow (S/D ratio) using echocardiography, and the duration and the root mean voltage for the terminal 20 ms (LP20) of the filtered P wave using P-wave signal-averaged electrocardiography. Atrial natriuretic peptide rapidly returned to baseline within 1 day after cardioversion, and maintained these levels for 6 months. Atrial peak velocity in transmitral flow and S/D ratio were significantly increased at 2 weeks, and continued to increase until 1 month, and then reached a plateau. The duration and LP20 began to recover only 6 months after cardioversion. One to 3 years after conversion, the duration and LP20 had nearly reached a plateau, but the latter value remained below normal. In patients with nonvalvular AF of prolonged duration, recovery from atrial electrical dysfunction after sinus conversion took much longer than that from either atrial hormonal or mechanical dysfunction.

Topics: Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Blood Flow Velocity; Chronic Disease; Electric Countershock; Electrocardiography; Female; Follow-Up Studies; Heart Atria; Humans; Male; Middle Aged; Mitral Valve; Time Factors

Because renal function is affected by chronic heart failure (CHF) and it relates to both cardiovascular and hemodynamic properties, it should have additional prognostic value. We studied whether renal function is a predictor for mortality in advanced CHF, and we assessed its relative contribution compared with other established risk factors. In addition, we studied the relation between renal function and neurohormonal activation.. The study population consisted of 1906 patients with CHF who were enrolled in a recent survival trial (Second Prospective Randomized study of Ibopamine on Mortality and Efficacy). In a subgroup of 372 patients, plasma neurohormones were determined. The baseline glomerular filtration rate (GFR(c)) was calculated using the Cockroft Gault equation. GFR(c) was the most powerful predictor of mortality; it was followed by New York Heart Association functional class and the use of angiotensin-converting enzyme inhibitors. Patients in the lowest quartile of GFR(c) values (<44 mL/min) had almost 3 times the risk of mortality (relative risk, 2. 85; P<0.001) of patients in the highest quartile (>76 mL/min). Impaired left ventricular ejection fraction (LVEF) was only modestly predictive (P=0.053). GFR(c) was inversely related with N-terminal atrial natriuretic peptide (ANP; r=-0.53) and, to a lesser extent, with ANP itself (r=-0.35; both P<0.001).. Impaired renal function (GFR(c)) is a stronger predictor of mortality than impaired cardiac function (LVEF and New York Heart Association class) in advanced CHF, and it is associated with increased levels of N-terminal ANP. Moreover, impaired renal function was not related to LVEF, which suggests that factors other than reduced cardiac output are causally involved.

Topics: Aged; Aldosterone; Atrial Natriuretic Factor; Cardiac Output; Cardiotonic Agents; Catecholamines; Chronic Disease; Deoxyepinephrine; Dopamine; Epinephrine; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Male; Middle Aged; New York; Norepinephrine; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Renin; Renin-Angiotensin System; Survival Analysis; Ventricular Dysfunction, Left; Ventricular Function, Left

The aim of this study was to determine the value of an increase in plasma atrial natriuretic peptide (ANP) concentrations during submaximal exercise as a predictor of return of sinus rhythm (SR), and of its maintenance over a period of 6 months after cardioversion (CV) of chronic atrial fibrillation (AF). The study group included 42 patients with AF (mean duration 7 +/- 7 months) and a controlled ventricular rate. They underwent submaximal exercise testing 24 hours before CV. Blood samples were collected at rest and at peak of exercise for measurement of plasma ANP concentrations. Thirty-five of 42 patients were successfully cardioverted to SR. At 6 months, 23 patients remained in SR, while 12 had recurrence of AF. The plasma ANP concentrations before CV increased insignificantly during exercise in patients with unsuccessful CV or with recurrence of AF (60.8 +/- 17.3 pg/mL to 64 +/- 13.5 pg/mL, NS). The mean increase in plasma ANP concentration during exercise was significantly greater in the 23 patients who remained in SR than in the 19 patients unsuccessfully cardioverted or with recurrence of AF (17.5 +/- 7.6 pg/mL vs 5.8 +/- 4.5 pg/mL, P < 0.01). In multivariate logistic regression analysis, an increase in ANP plasma concentration was independently associated with successful CV and maintenance of SR up to 6 months of observation. In patients with chronic AF an exercise-induced increase in ANP concentration predicts successful CV and maintenance of SR.

Topics: Adult; Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Electric Countershock; Electrocardiography; Exercise Test; Female; Heart Rate; Humans; Logistic Models; Male; Middle Aged; Oxygen Consumption; Predictive Value of Tests; Recurrence

We investigated whether levels of N-terminal proatrial natriuretic peptide (N-terminal proANP) reflect the severity of coronary artery disease in chronic, stable angina pectoris. Furthermore, we investigated if revascularization by percutaneous transluminal coronary angioplasty (PTCA) affected the N-terminal proANP level and, finally, whether restenosis could be predicted by changes in N-terminal proANP after PTCA.. N-terminal proANP was measured in 286 patients before and after PTCA. The patients' baseline level of N-terminal proANP (787+/-403 pmol/l) correlated significantly with left ventricular end diastolic pressure, age and serum creatinine, but not with the number of stenotic vessels. Twenty-four hours post-PTCA N-terminal proANP decreased significantly, and completely revascularized patients demonstrated a decline two-fold larger than those incompletely revascularized (deltaN-terminal proANP -114+/-178 vs. -53+/-231 pmol/l, P<0.05). After 14 days N-terminal proANP had returned to baseline in both groups. Changes in N-terminal proANP from post-PTCA to the final follow-up was not predictive of angiographic restenosis.. The significant decrease in N-terminal proANP observed after angioplasty, most pronounced in patients completely revascularized, is thought to reflect a transient improvement in resting left ventricular function.

Topics: Adult; Age Factors; Aged; Amlodipine; Angina Pectoris; Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Calcium Channel Blockers; Chronic Disease; Coronary Disease; Creatinine; Double-Blind Method; Female; Humans; Linear Models; Male; Middle Aged; Myocardial Revascularization; Prospective Studies; Protein Precursors; Radioimmunoassay; Statistics, Nonparametric

Candoxatril is a novel neutral endopeptidase inhibitor that increases plasma concentrations of atrial natriuretic factor and thereby produces natriuresis, diuresis, and vasorelaxation. This profile of action offers theoretical advantages over standard diuretic therapy in the treatment of patients with heart failure. The aims of the study were to compare the effects of candoxatril with those of frusemide in the treatment of patients with mild heart failure.. Male patients with mild heart failure were randomly assigned to 9 days of therapy with 20 mg frusemide twice a day, 200 mg candoxatril twice a day, or 400 mg candoxatril twice a day (n = 10 per group) after a 14-day placebo washout phase. Systemic hemodynamic measurements, exercise tolerance, and urinary and plasma hormone concentrations were assessed during the placebo run-in and at the beginning and end of the double-blind therapy.. Frusemide and candoxatril caused similar diuresis and natriuresis. Candoxatril caused a slight decrease in systolic blood pressure and a dose-dependent increase in plasma and urinary concentrations of atrial natriuretic factor without elevating plasma renin activity. Frusemide reduced plasma concentrations of atrial natriuretic factor and increased plasma renin activity. Treadmill exercise capacity decreased 30 +/- 26 seconds after use of frusemide, compared with increases of 12 +/- 35 seconds after use of 200 mg candoxatril twice a day and 35 +/- 31 seconds after use of 400 mg candoxatril twice a day (P =.13; frusemide versus 400 mg candoxatril twice a day).. In the treatment of patients with mild heart failure, candoxatril has diuretic effects equivalent to those of 20 mg frusemide twice a day without the associated and potentially detrimental activation of the renin-angiotensin-aldosterone system. The trend for improved exercise capacity with candoxatril warrants further investigation.

Topics: Atrial Natriuretic Factor; Chronic Disease; Diuretics; Double-Blind Method; Exercise Test; Furosemide; Heart Failure; Humans; Indans; Male; Middle Aged; Propionates; Protease Inhibitors; Renin; Severity of Illness Index; Time Factors

The AT1 receptor antagonists differ from the angiotensin converting enzyme inhibitors by achieving a more complete blockade of angiotensin II's actions and by not affecting bradykinin metabolism. There is little information on whether this causes clinically significant differences in haemodynamics, neurohormones and exercise tolerance in heart failure.. To compare the effects of losartan and captopril upon central and regional haemodynamics, neurohormones and exercise capacity in heart failure.. In a double-blind, randomised trial 18 patients aged > or =65 years with symptomatic heart failure were allocated to treatment with losartan (10 patients) or captopril (eight patients). Patients underwent assessment at baseline, after the first dose, at 12 weeks and at 24 weeks.. Systolic blood pressure fell by - 10.7% 1 h after captopril 6.25 mg (P = 0.007) and by - 4.8% 3 h after losartan 12.5 mg (P = 0.02). The blood pressure reduction was sustained with losartan at 12 and 24 weeks. Systemic vascular resistance fell acutely after captopril (-16.4%, P = 0.01). Captopril caused an acute and sustained rise in superior mesenteric artery blood flow (+ 22.9%, P = 0.04), and a slower rise in renal artery blood flow (+31.7%, P = 0.01). Losartan had no acute effects on regional haemodynamics but had increased superior mesenteric artery blood flow by 38.1% at 12 weeks (P = 0.02). There were no substantial differences between losartan and captopril, and no changes occurred in neurohormones or exercise capacity.. No substantial differences were observed between losartan and captopril on central or regional haemodynamics, neurohormones or exercise capacity in elderly patients with stable symptomatic heart failure.

Topics: Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Captopril; Chronic Disease; Double-Blind Method; Exercise Test; Exercise Tolerance; Female; Heart Failure; Hemodynamics; Humans; Losartan; Male; Neurotransmitter Agents; Norepinephrine; Renin

B-type natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) are secreted from the heart and are thought to be equally important factors in the regulation of vascular tone in health and in congestive heart failure (CHF). However, no studies directly compare vasodilator effects of these peptides in healthy subjects and in patients with CHF.. Plethysmography was used to determine the vasodilatory effects of BNP and to compare these to the effects of ANP in patients with CHF (n = 15) and age-matched healthy subjects (n = 16). Graded doses of ANP and BNP (8, 16, 32, and 48 pmol/min per 100 ml of tissue volume for both) were administered randomly into the brachial artery. Forearm blood flow (FBF) was measured, and cyclic GMP (cGMP) spillover was calculated.. Responses in FBF to both peptides in CHF were significantly lower than those of healthy subjects (BNP p < 0.05; ANP p < 0.01). Similarly, forearm spillover of cGMP was significantly lower in CHF than in healthy subjects (BNP p < 0.05; ANP p < 0.01). When vascular responses in healthy subjects were compared between BNP and ANP, BNP-induced changes in FBF (p < 0.05) and forearm cGMP spillover (p < 0.01) were significantly less than changes induced by ANP. In CHF, though, FBF change and cGMP spillover induced by the two peptides were not significantly different.. These results suggest that the metabolism and action of these natriuretic peptides in CHF may differ from the healthy state.

Topics: Aged; Atrial Natriuretic Factor; Chronic Disease; Cyclic GMP; Female; Forearm; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Plethysmography; Regional Blood Flow; Vasodilation

This study was designed to investigate the effect of angiotensin-converting enzyme (ACE) inhibitors with and without a sulfhydryl group on intracellular production of cGMP, forearm blood flow, and neurohormonal factors during continuous transdermal application of nitroglycerin in patients with chronic heart failure. Platelet cGMP level and forearm blood flow were measured before and 5 min after sublingual administration of nitroglycerin (NTG) in 20 patients with chronic heart failure during the following 4 phases: (1) baseline phase; (2) NTG phase (1 week after NTG tape 10 mg/day); (3) CPT phase (1 week after both captopril 37.5 mg/day and NTG tape 10 mg/day); and (4) ENL phase (1 week after both enalapril 5 mg/day and NTG tape 10 mg/day). The platelet GMP level before sublingual NTG and forearm blood flow were significantly higher during the 3 phases with NTG tape than during the control phase. The percent increases in platelet cGMP level and forearm blood flow after sublingual NTG were significantly lower during the NTG phase than during the baseline phase. In contrast, concomitant application of ACE inhibitors maintained the percent increase in platelet cGMP level and forearm blood flow. These results indicate that concomitant therapy with ACE inhibitors may be helpful in preventing the attenuation of intracellular cGMP production in patients with chronic heart failure during continuous transdermal application of NTG.

Topics: Administration, Cutaneous; Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Blood Platelets; Blood Pressure; Body Weight; Chronic Disease; Cyclic GMP; Drug Tolerance; Female; Forearm; Heart Failure; Heart Rate; Hematocrit; Humans; Male; Middle Aged; Nitrates; Nitroglycerin; Norepinephrine; Regional Blood Flow; Renin; Systole; Vasodilator Agents

It is generally accepted that plasma atrial natriuretic peptide release occurs secondary to atrial stretch. The influence of coordinated atrial contraction (AC) upon this process is not fully appreciated. The aim of the study was to determine the importance of coordinated AC upon peripheral atrial natriuretic peptide levels (alpha-hANP) during exercise. Peripheral alpha-hANP levels were measured at rest and during exercise in 12 patients with complete heart block (CHB) and permanent rate responsive pacemakers. Seven patients had coordinated AC and five had chronic atrial fibrillation (AF). Each patient performed three treadmill exercise tests. Maximal inspired oxygen volume (VO2 max) was determined during test 1. Tests 2 and 3 were performed to 70% VO2 max, the pacemaker being programmed to either VVI or VVIR mode. Plasma alpha-hANP was measured using a two-site immunoradiometric assay. At rest there was a small but significant difference between the two patient groups: AF 60.2 pg/mL versus AC97.6 pg/mL; P = 0.03. During exercise in the AC patients, there was a significant increase in alpha-hANP levels, in VVIR mode, to 238.4 pg/mL, and in VVI mode, to 207.9 pg/mL, P = 0.002 and 0.003, respectively. In those patients with chronic AF, there was no significant rise or fall in alpha-hANP levels in either pacing mode, VVIR 65.2 pg/mL, VVI 46.6 pg/mL. Previous workers have suggested that alpha-hANP release by nonfunctioning atria is normal. We have shown that the presence of coordinated AC is required for the release of alpha-hANP during exercise in patients with CHB, and that this appears to be independent of ventricular rate.

Topics: Adult; Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Chronic Disease; Cross-Over Studies; Echocardiography; Electrocardiography; Exercise Test; Female; Heart Atria; Heart Block; Heart Rate; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Contraction; Oxygen Consumption; Physical Exertion; Rest; Single-Blind Method

C-type natriuretic peptide (CNP) is a newly identified peptide that is structurally related to atrial natriuretic peptide (ANP). Although it has been suggested that CNP is released from the endothelium for the regulation of local vascular tone, no data are available concerning the vasodilatory response to CNP in humans.. Strain-gauge plethysmography was used to determine the vasodilatory effects of intra-arterially infused CNP compared with the effects of ANP infusion in 11 patients with chronic heart failure (CHF) and 11 age-matched healthy controls. Graded doses of CNP and ANP (8, 16, 32, and 48 pmol.min-1.dL-1 tissue volume) were administered randomly into the nondominant brachial artery, and forearm blood flow (FBF) was measured. No significant changes in systemic blood pressure and heart rate were found during the study. Both the absolute and percent FBF responses to ANP relative to the baseline value were significantly lower in CHF patients than in healthy controls (P < .01), whereas the responses to CNP were similar. The calculated forearm spillover of cyclic GMP (cGMP) was significantly lower in CHF patients receiving the highest dose of ANP (P < .02), whereas changes in cGMP spillover after the equimolar dose of CNP were significantly higher (P < .02), despite the lesser potency of CNP.. In patients with CHF the peripheral vasodilatory effect of ANP is attenuated, but CNP-induced peripheral vasorelaxation is preserved, with CNP being less potent for equimolar doses.

Topics: Atrial Natriuretic Factor; Blood Vessels; Cardiac Output, Low; Chronic Disease; Cyclic GMP; Female; Forearm; Humans; Injections, Intra-Arterial; Male; Middle Aged; Natriuretic Peptide, C-Type; Plethysmography; Proteins; Regional Blood Flow; Vascular Resistance; Vasodilation

To determine whether renal reserve capacity was preserved in patients with chronic glomerulonephritis with well-preserved kidney function, and how sodium was handled in proximal and distal tubules, 13 healthy control subjects and 13 patients with biopsy-verified chronic glomerulonephritis were studied before and during a continuous 120-min amino-acid infusion. Glomerular filtration rate (GFR), renal plasma flow (RPF), and tubular function evaluated by the lithium clearance method, were determined during six clearance periods of 30 min each. Plasma concentrations of angiotensin II, atrial natriuretic peptide (ANP), aldosterone, arginine vasopressin (AVP), glucagon, amino acid and serum osmolality were determined before, 60, and 120 min after infusion. GFR and RPF increased about 10% in both groups; filtration fraction (FF) was unchanged. Proximal tubular reabsorption of sodium and water decreased, and distal tubular reabsorption of sodium and water increased, and thus the net excretion of sodium and water was unchanged. Angiotensin II and aldosterone were reduced in control subjects, but not in the patients. ANP and glucagon increased equally in both groups. Most amino acids increased two- or threefold. It is concluded that renal reserve capacity and glomerulotubular balance are intact in patients with chronic glomerulonephritis with well-preserved renal function, but there is an abnormal lack of suppression of the renin-angiotensin-aldosterone system in response to an amino acid infusion in these patients.

Topics: Adult; Aldosterone; Amino Acids; Atrial Natriuretic Factor; Chronic Disease; Female; Glomerular Filtration Rate; Glomerulonephritis; Hemodynamics; Humans; Infusions, Intravenous; Kidney Tubules; Male; Middle Aged; Neuropeptides; Renal Circulation; Renin-Angiotensin System; Sodium; Water-Electrolyte Balance

Supply of sulfhydryl groups with the administration of N-acetylcysteine (NAC) has been reported to reverse tolerance to nitroglycerin but not to isosorbide dinitrate (ISDN). Lack of interaction between NAC and ISDN was suggested as an explanation for these findings. The present study was therefore designed to further evaluate this hypothesis. For this purpose, we compared the hemodynamic and hormonal effects of ISDN when given alone and in combination with NAC.. We performed a randomized, cross-over design evaluation of the hemodynamic and hormonal effects of ISDN and ISDN + NAC in 14 patients with chronic congestive heart failure due to left ventricular systolic dysfunction. The findings of this study demonstrated a substantial NAC-mediated potentiation of ISDN effect on mean right atrial pressure (-11 +/- 21% versus -38 +/- 27%, -17 +/- 20% versus -34 +/- 27%, and -7 +/- 20% versus -25 +/- 26% at 2, 3, and 4 hours, respectively; all P < .05), mean pulmonary artery wedge pressure (-18 +/- 16% versus -33 +/- 14%, -15 +/- 25% versus -33 +/- 19%, -14 +/- 22% versus -25 +/- 22%, and -16 +/- 16% versus -26 +/- 16% at 2, 3, 4, and 5 hours, respectively; all P < .05), mean pulmonary artery pressure (-8 +/- 11% versus -20 +/- 15% at 3 hours, P < .05), and cardiac output (an increase of 2 +/- 16% versus 25 +/- 20% at 4 hours, P < .05). Although there were no significant changes in serum catecholamine levels and plasma renin concentration with both regimens, ISDN + NAC resulted in a greater fall in plasma levels of atrial natriuretic peptide (296 +/- 251 pg/mL after ISDN versus 202 +/- 118 pg/mL after ISDN + NAC, P < .05).. The results of this study provide strong evidence for the existence of an interaction between thiols and ISDN and further support the role of sulfhydryl groups in the activation and therapeutic action of organic nitrates. The discrepancy between the results of this study demonstrating NAC-induced potentiation of ISDN effects and a previous study showing failure to reverse ISDN tolerance with NAC may suggest that ISDN-NAC interaction requires normal intracellular levels of sulfhydryl groups and does not occur after intracellular sulfhydryl group depletion.

Topics: Acetylcysteine; Adult; Aged; Atrial Natriuretic Factor; Catecholamines; Chronic Disease; Drug Synergism; Drug Therapy, Combination; Female; Heart Failure; Humans; Isosorbide Dinitrate; Male; Middle Aged; Renin

1. To examine whether or not atrial natriuretic peptide-induced proteinuria simply results from increases in urine flow or glomerular filtration rate, we infused dopamine (1 microgram min-1 kg-1) and alpha-human atrial natriuretic peptide (0.025 microgram min-1 kg-1) into nine patients with chronic glomerulonephritis and nine essential hypertensive patients without renal damage, and compared the effects of the two agents on renal function and urinary protein excretion. 2. In patients with chronic glomerulonephritis, dopamine infusion significantly increased urinary sodium excretion (+59%), renal blood flow (+20%) and creatinine clearance (+14%). However, urinary protein excretion was not changed. Addition of atrial natriuretic peptide to the dopamine infusion further increased urinary sodium excretion and maintained creatinine clearance at the same level. In contrast to the infusion of dopamine alone, atrial natriuretic peptide markedly increased urinary protein excretion (77 versus 229 mg min-1 m2, P less than 0.02). Furthermore, the addition of atrial natriuretic peptide elevated the urinary protein/creatinine ratio (1.55 versus 5.35, P less than 0.05), while dopamine alone did not (1.55 versus 1.45, not significant). 3. In essential hypertensive patients, dopamine and dopamine plus ANP showed renal effects similar to those of chronic glomerulonephritis; however, the urinary excretion of protein was not changed significantly. 4. These results suggest that atrial natriuretic peptide may increase urinary protein excretion mainly by increasing the permeability of the damaged glomeruli to protein rather than by simply increasing urine flow or glomerular filtration. Possible mechanisms underlying the proteinuria-increasing effects of atrial natriuretic peptide are discussed.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Cyclic GMP; Dopamine; Glomerular Filtration Rate; Glomerulonephritis; Heart Rate; Humans; Hypertension; Kidney; Middle Aged; Proteinuria; Urination

Atrial natriuretic factor (ANF) is a peptide hormone secreted by the heart that is degraded in vivo by endopeptidase 24:11 (atriopeptidase). UK 69,578 is a novel atriopeptidase inhibitor that raises plasma levels of ANF in animals and normal volunteers, with associated diuresis and natriuresis. This study examines the effects of UK 69,578 in patients with mild heart failure. UK 69,578 was administered as an intravenous infusion over 20 min in a placebo-controlled, cross-over study to six patients with stable (NYHA Class 2) chronic heart failure. The atriopeptidase inhibitor was well tolerated and no side effects were encountered. Mean baseline plasma ANF was elevated at 88 pg/mL (normal less than 50), and increased 2- to 5-fold after UK 69,578 administration. Plasma ANF did not change significantly following placebo. There was a marked diuresis after UK 69,578 compared to placebo. Urinary sodium excretion doubled for 4 to 6 h, but there was no significant rise in potassium excretion. There was no increase in plasma active renin concentration during the study period. Noninvasive hemodynamic monitoring revealed no significant changes in heart rate, systemic arterial blood pressure, or echocardiographic left ventricular dimensions. However, invasive measurements using a Swan-Ganz catheter demonstrated falls in mean right atrial and pulmonary artery wedge pressures after UK 69,578. There was no change in cardiac output. Thus, inhibition of endopeptidase 24:11 by UK 69,578 results in significant elevation of plasma ANF, with associated diuresis, natriuresis and venodilatation. The compound was well tolerated in these patients with mild chronic heart failure.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Carbamates; Cardiac Output, Low; Chronic Disease; Cyclohexanecarboxylic Acids; Diuresis; Dose-Response Relationship, Drug; Hemodynamics; Humans; Kidney; Male; Middle Aged; Natriuresis; Neprilysin; Propionates; Pulmonary Wedge Pressure; Renin; Sodium

This study aimed at evaluating the effects of sacubitril/valsartan on neprilysin (NEP), and the metabolism of natriuretic peptides in heart failure (HF) and providing additional mechanistic information on the mode of action of the drug.. We enrolled 73 chronic HF patients who were switched from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to sacubitril/valsartan. In addition to clinical and echocardiographic assessment, plasma biomarkers were measured at baseline, day 30 and day 90 after initiation of treatment. Sacubitril/valsartan led to decrease in New York Heart Association class and improvement of echocardiographic parameters, as well as a dose-dependent decrease in soluble NEP (sNEP) activity, while sNEP concentration remained unchanged. Neprilysin inhibition translated into an increase in its substrates such as atrial natriuretic peptide (ANP), substance P, and glucagon-like peptide 1, the latter translating into a decrease in fructosamine. Cardiac troponin and soluble ST2 levels, biomarkers of HF severity unrelated to NEP metabolism also decreased. While there was a ∼4-fold increase in ANP, we observed no change in plasma brain natriuretic peptide (BNP) and plasma BNP activity, and a mild decrease in N-terminal proBNP (NT-proBNP) concentrations. Finally, we found a progressive increase in the relationship between BNP and NT-proBNP, which strongly correlated with an increase in T71 proBNP glycosylation (R. Sacubitril/valsartan rapidly and strongly reduced sNEP activity, leading to an increase in levels of NEP substrates. These data suggest a pleiotropic favourable impact of sacubitril/valsartan on the metabolism of HF patients with ANP rather than BNP as major effectors amongst natriuretic peptides.

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Atrial Natriuretic Factor; Biphenyl Compounds; CD146 Antigen; Chronic Disease; Dose-Response Relationship, Drug; Drug Combinations; Echocardiography; Female; Fructosamine; Glucagon-Like Peptide 1; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Substance P; Tetrazoles; Treatment Outcome; Troponin I; Valsartan

Secondary mitral regurgitation (sMR) drives adverse cardiac remodelling in patients with heart failure with reduced ejection fraction (HFrEF). Progression in severity over time contributes to a transition towards more advanced HF stages. Early identification of patients at risk for sMR progression remains challenging. We therefore sought to assess a broad spectrum of neurohumoral biomarkers in patients with HFrEF to explore their ability to predict progression of sMR.. A total of 249 HFrEF patients were enrolled. Biomarkers encompassing key neurohumoral pathways in heart failure were sampled at baseline, and sMR progression was assessed over 3 years of follow-up.. Of 191 patients with nonsevere sMR at baseline, 18% showed progressive sMR within three years after study enrolment. Progression of sMR was associated with higher levels of MR-proADM (adj.OR 2.25, 95% CI 1.29-3.93; P = .004), MR-proANP (adj.OR 1.84, 95% CI 1.14-3.00; P = .012), copeptin (adj.OR 1.66, 95% CI 1.04-2.67; P = .035) and CT-pro-ET1 (adj.OR 1.68, 95% CI 1.06-2.68; P = .027) but not with NT-proBNP (P = .54).. Increased plasma levels of neurohumoral cardiac biomarkers are predictors of sMR progression in patients with HFrEF and add easily available incremental prognostic information for risk stratification. Importantly, NT-proBNP was not useful to predict progressive sMR in the present analysis. On the contrary, MR-proANP, primarily produced in the atria, copeptin partly triggered by intra-cardiac and intra-arterial pressures and MR-proADM, a marker of forward failure and peripheral released vasoactive CT-proET1, increase based on a progressive loading burden by sMR and may thus serve as better predictors of sMR progression.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Disease Progression; Echocardiography; Endothelin-1; Female; Glycopeptides; Heart Failure, Systolic; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Peptide Fragments; Phenotype; Prognosis; Protein Precursors; Risk Assessment; Stroke Volume

BACKGROUND The aim of this study was to investigate the effects of sulforaphane (SFN), a natural isothiocyanate compound, in a rabbit ascending aortic cerclage model of chronic heart failure (CHF). MATERIAL AND METHODS Thirty New Zealand White rabbits were divided into the sham operation group (n=10), the CHF group (n=10), and the CHF + SFN group (n=10) treated with subcutaneous SFN (0.5 mg/kg) for five days per week for 12 weeks. After 12 weeks, echocardiography and biometric analysis were performed, followed by the examination of the rabbit hearts. Enzyme-linked immunosorbent assay (ELISA) and Western blot were used to detect levels of inflammatory cytokines, superoxide dismutase (SOD), and malondialdehyde (MDA). RESULTS In the CHF group, compared with the sham operation group, there was an increase in the heart weight to body weight ratio (HW/BW), the left ventricular weight to body weight ratio (LVW/BW), the left ventricular end diastolic diameter (LVEDD), the left ventricular end systolic diameter (LVESD), plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) levels, the cardiac collagen volume fraction (CVF), apoptotic index, expression levels of collagen I, collagen III, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and malondialdehyde (MDA) in the myocardial tissue, and a decrease in the left ventricular shortening fraction (LVFS) and left ventricular ejection fraction (LVEF), and cardiac superoxide dismutase (SOD) activity. These changes were corrected in the SFN-treated group. CONCLUSIONS In a rabbit model of CHF, treatment with SFN improved cardiac function and remodeling by inhibiting oxidative stress and inflammation.

Topics: Animals; Apoptosis; Atrial Natriuretic Factor; Chronic Disease; Collagen; Cytokines; Female; Fibrosis; Heart Failure; Heart Function Tests; Hemodynamics; Inflammation; Isothiocyanates; Male; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oxidative Stress; Rabbits; RNA, Messenger; Sulfoxides

Functional imaging studies have argued that interactions between cortical motor areas and the cerebellum are relevant for motor output and recovery processes after stroke. However, the impact of the underlying structural connections is poorly understood. To investigate this, diffusion-weighted brain imaging was conducted in 26 well-characterized chronic stroke patients (aged 63 ± 1.9 years, 18 males) with supratentorial ischemic lesions and 26 healthy participants. Probabilistic tractography was used to reconstruct reciprocal cortico-cerebellar tracts and to relate their microstructural integrity to residual motor functioning applying linear regression modeling. The main finding was a significant association between cortico-cerebellar structural connectivity and residual motor function, independent from the level of damage to the cortico-spinal tract. Specifically, white matter integrity of the cerebellar outflow tract, the dentato-thalamo-cortical tract, was positively related to both general motor output and fine motor skills. Additionally, the integrity of the descending cortico-ponto-cerebellar tract contributed to rather fine motor skills. A comparable structure-function relationship was not evident in the controls. The present study provides first tract-related structural data demonstrating a critical importance of distinct cortico-cerebellar connections for motor output after stroke.

Topics: Aged; Atrial Natriuretic Factor; Brain Ischemia; Cerebellum; Cerebral Cortex; Chronic Disease; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Female; Humans; Linear Models; Male; Middle Aged; Motor Activity; Neural Pathways; Stroke; White Matter

Natriuretic peptides play an important role in the diagnosis and risk stratification of patients with acute and chronic heart failure. Multiple studies have shown that these peptides are liable to the influence of individual factors. For N-terminal-pro-B-type natriuretic peptide (NT-proBNP) some of these confounding factors have been evaluated over the years such as age, gender, New York Heart Association (NYHA) class and body mass index (BMI). The aim of this study was to establish confounding factors of mid-regional pro-atrial natriuretic peptide (MR-proANP) assessment.. We studied 684 patients (94% male, age 61.2±11.2, left ventricular ejection fraction [LVEF]<35%-45%, NYHA class (I/II/III/IV: 8.4/45.8/39.5/6.3%), ischaemic aetiology 71%, body mass index [BMI] 26.5±4.3kg/m(2), mean MR-proANP 296.0±281.0pmol/L, mean NT-proBNP 2792.0±5328.6pg/mL, mean creatinine level 110.2±38.0μmol/L and mean haemoglobin 13.9±1.5g/dL) with clinically stable chronic heart failure. MR-proANP levels increased with increasing NYHA class (p<0.0001) and an increasing BMI category was associated with decreasing values of MR-proANP (p<0.0001). We found MR-proANP to be independently associated with BMI, creatinine, ischaemic aetiology, LVEF and NYHA class. Meanwhile, NT-proBNP was independently associated with BMI, creatinine, haemoglobin, LVEF and NYHA class.. MR-proANP is subject to the almost identical influencing factors like NT-proBNP. The effects of anaemia warrant further study.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Cohort Studies; Confounding Factors, Epidemiologic; Female; Heart Failure; Humans; Internationality; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

Besides the established biomarker NT-proBNP, the new cardiovascular biomarkers MR-proANP, MR-proADM, Copeptin, and CT-proET-1 are promising to evaluate hemodynamics, exercise parameters, and prognosis in patients with pulmonary hypertension (PH).. 125 consecutive patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) were prospectively enrolled at five German PH centers. Blood samples were taken during right heart catheterization. The primary study endpoint was the correlation between biomarkers and hemodynamic and exercise parameters. As secondary endpoint, prediction of 1-year mortality was evaluated.. MR-proADM showed the strongest correlations with 6MWD and VO2peak, whereas NT-proBNP showed the strongest correlations with PVR, PAPm, and CI. In multivariate analysis, only MR-proADM was independently associated with exercise variables, whereas only NT-proBNP independently predicted hemodynamic parameters. All biomarkers were associated with 1-year survival, with MR-proADM showing the highest C index of 0.78. In multivariate analysis, MR-proADM predicted survival independent of age, 6-MWD, CI, RAP, and NT-proBNP. The cut-off of 1.08 nmol/l provided a sensitivity of 83 % and specificity of 66 %.. Different biomarkers reflect distinctive disease aspects in PH. NT-proBNP best predicts hemodynamic impairment while MR-proADM strongly correlates with exercise capacity. Additionally, MR-proADM represents a promising new marker to evaluate prognosis in patients with PAH and CTEPH. Multi-marker strategies should further be evaluated.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Chronic Disease; Endothelin-1; Exercise Tolerance; Female; Germany; Glycopeptides; Heart Atria; Humans; Hypertension, Pulmonary; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors; Pulmonary Embolism; Pulmonary Wedge Pressure; Vascular Resistance

Timely diagnosis, early introduction of appropriate treatment, accurate risk stratification, and optimal titration of therapy are all key to the management of acute and chronic heart failure (HF). Plasma concentrations of the cardiac natriuretic peptides (NPs) are valuable aids in each of these elements of care. However, most data are derived from cohorts with undifferentiated HF or HF with reduced ejection fraction (HFREF), and the performance and best application of NPs in HF with preserved ejection fraction (HFPEF) is less certain. This review outlines the evidence for use of NPs in the evaluation and management of HFPEF.

Topics: Acute Disease; Aged; Atrial Natriuretic Factor; Biomarkers; Cardiac Output, Low; Case-Control Studies; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Prognosis; Reference Values; Sensitivity and Specificity; Stroke Volume; Syndrome

There is no agreement in current publications regarding the reliability of serum concentrations of natriuretic peptides (NPs) to detect dogs with subclinical myxomatous mitral valve disease (MMVD) and to differentiate between asymptomatic stages.. We sought to compare N-terminal pro-B-type natriuretic peptide (NT-proBNP) and pro-atrial natriuretic peptide 31-67 (proANP) concentrations between various stages of canine MMVD and to investigate the influence of age, weight, and sex.. In this prospective study, dogs were classified in different disease stages using the modified Canine Heart failure International Expert Forum (CHIEF) system. Serum NP concentrations were compared between groups.. A total of 559 samples from 116 healthy dogs and 236 dogs with MMVD were analyzed. Using cut-off values (1207 pmol/L for NT-proBNP, 1578 fmol/mL for proANP), dogs with MMVD with and without congestive heart failure (CHF) could be differentiated with a sensitivity of 83% for both and specificities of 85% and 86%, respectively. Dogs staged in CHIEF B1 and B2 could not be distinguished based on NP concentrations due to wide variation within the groups. Intact females (means 598 pmol/L and 1036 fmol/mL, respectively) had significantly higher values of both NPs than intact males (315 pmol/L and 836 fmol/mL).. NPs in canine MMVD are useful to discriminate between asymptomatic dogs and dogs with CHF. Due to a large overlap of NP-concentrations between the groups, NPs do not seem to be useful to differentiate between dogs in stages B1 and B2. Interpretation of NT-proBNP and proANP values should include consideration of sex-specific differences.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Chronic Disease; Dog Diseases; Dogs; Female; Heart Failure; Heart Valve Diseases; Male; Mitral Valve; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Reproducibility of Results; Sensitivity and Specificity; Sex Factors

Patients with chronic heart failure (CHF) have an increased catabolic state that affects both muscle and adipose tissue (AT), and may ultimately result in cardiac cachexia. Increased plasma levels of ANP might contribute to increased lipid mobilization and oxidation in CHF. We tested the hypothesis that increased plasma ANP levels are associated with an increased catabolic (lipolytic) state of white AT in patients with CHF.. After an overnight fast, AT metabolism was studied by microdialysis in patients with CHF and healthy controls of a similar age and body composition (both n = 8). AT glycolytic and lipolytic activities were assessed at rest (fasting) and after an oral glucose load (oGL). Fasting and post-prandial profiles of serum glucose, insulin, and free fatty acids and of dialysate glucose did not differ significantly between patients and controls. In contrast, fasting dialysate lactate and glycerol levels were two-fold higher in patients vs. controls (lactate, 0.51 ± 0.10 and 0.26 ± 0.06 mmol/L, P < 0.01; glycerol, 116 ± 18 and 50 ± 8 µmol/L, P < 0.001), indicating increased AT glycolytic and lipolytic rates in patients. After an oGL, dialysate lactate increased ∼2- and 2.5-fold, whereas dialysate glycerol decreased by ∼60% and 50% in patients vs. controls, but metabolite levels were always significantly higher in patients vs. controls (all P < 0.05). Plasma ANP levels were increased in patients and significantly correlated with adipose tissue dialysate glycerol.. In patients wiuth CHF, there is a direct correlation between plasma ANP levels and increased AT catabolic (lipolytic) state. This might contribute to AT wasting and the development of cardiac cachexia in patients with CHF.

Topics: Adipose Tissue; Adult; Aged; Atrial Natriuretic Factor; Blood Glucose; Cachexia; Case-Control Studies; Chronic Disease; Fatty Acids, Nonesterified; Female; Glycerol; Glycolysis; Heart Failure; Humans; Insulin; Lactic Acid; Lipolysis; Male; Microdialysis; Middle Aged; Oxidation-Reduction

Despite the evidence that the hyperpolarization-activated current (If) is highly modulated in human cardiomyopathies, no definite data exist in chronic atrial fibrillation (cAF). We investigated the expression, function, and modulation of If in human cAF.. Right atrial samples were obtained from sinus rhythm (SR, n = 49) or cAF (duration >1 year, n = 31) patients undergoing corrective cardiac surgery. Among f-channel isoforms expressed in the human atrium (HCN1, 2 and 4), HCN4 mRNA levels measured by RT-PCR were significantly reduced. However, protein expression was preserved in cAF compared to SR (+85% for HCN4); concurrently, miR-1 expression was significantly reduced. In patch-clamped atrial myocytes, current-specific conductance (gf) was significantly increased in cAF at voltages around the threshold for If activation (-60 to -80 mV); accordingly, a 10-mV rightward shift of the activation curve occurred (P < 0.01). β-Adrenergic and 5-HT4 receptor stimulation exerted similar effects on If in cAF and SR cells, while the ANP-mediated effect was significantly reduced (P < 0.02), suggesting downregulation of natriuretic peptide signaling.. In human cAF modifications in transcriptional and posttranscriptional mechanisms of HCN channels occur, associated with a slight yet significant gain-of-function of If , which may contribute to enhanced atrial ectopy.

Topics: Action Potentials; Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Atrial Natriuretic Factor; Chronic Disease; Female; Heart Atria; Humans; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Male; MicroRNAs; Middle Aged; Muscle Proteins; Potassium Channels; RNA Processing, Post-Transcriptional; RNA, Messenger; Serotonin 5-HT4 Receptor Agonists; Transcription, Genetic

The development of left ventricular hypertrophy and dysfunction in aortic regurgitation (AR) has only been sparsely studied experimentally. In a new model of chronic AR in rats, we examined activation of molecular pathways involved in myocardial hypertrophy. Chronic AR was produced by damaging one or two valve cusps, resulting in eccentric remodeling and left ventricular dysfunction, with no increase in overall fibrosis. Western blotting showed increased activation of Akt and p38 at 12 weeks and of c-Jun amino-terminal kinase at 2 weeks, decreased activation of extracellular regulated kinase 5 at both 2 and 12 weeks, while activation of calcium/calmodulin-dependent protein kinase II and extracellular regulated kinase 1/2 was unchanged. Expression of calcineurin and ANF was also unchanged. Eccentric hypertrophy and early cardiac dysfunction in experimental AR are associated with a pattern of activation of intracellular pathways different from that seen with pathological hypertrophy in pressure overload, and more similar to that associated with benign physiological hypertrophy.

Topics: Animals; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Calcineurin; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Chronic Disease; Disease Models, Animal; Echocardiography, Doppler, Color; Extracellular Signal-Regulated MAP Kinases; Hypertrophy, Left Ventricular; JNK Mitogen-Activated Protein Kinases; Male; Myocardium; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

Dilated cardiomyopathy (DCM) is a leading cause of chronic morbidity and mortality in muscular dystrophy (MD) patients. Current pharmacological treatments are not yet able to counteract chronic myocardial wastage, thus novel therapies are being intensely explored. MicroRNAs have been implicated as fine regulators of cardiomyopathic progression. Previously, miR-669a downregulation has been linked to the severe DCM progression displayed by Sgcb-null dystrophic mice. However, the impact of long-term overexpression of miR-669a on muscle structure and functionality of the dystrophic heart is yet unknown.. Here, we demonstrate that intraventricular delivery of adeno-associated viral (AAV) vectors induces long-term (18 months) miR-669a overexpression and improves survival of Sgcb-null mice. Treated hearts display significant decrease in hypertrophic remodeling, fibrosis, and cardiomyocyte apoptosis. Moreover, miR-669a treatment increases sarcomere organization, reduces ventricular atrial natriuretic peptide (ANP) levels, and ameliorates gene/miRNA profile of DCM markers. Furthermore, long-term miR-669a overexpression significantly reduces adverse remodeling and enhances systolic fractional shortening of the left ventricle in treated dystrophic mice, without significant detrimental consequences on skeletal muscle wastage.. Our findings provide the first evidence of long-term beneficial impact of AAV-mediated miRNA therapy in a transgenic model of severe, chronic MD-associated DCM.

Topics: Animals; Apoptosis; Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Chronic Disease; Dependovirus; Disease Models, Animal; Fibrosis; Gene Expression Regulation; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Hypertrophy, Left Ventricular; Mice; Mice, Knockout; MicroRNAs; Muscular Dystrophies; Myocardial Contraction; Myocardium; Recovery of Function; Sarcoglycans; Sarcomeres; Severity of Illness Index; Time Factors; Ventricular Function, Left; Ventricular Remodeling

A method for the estimation of severity of chronic cardiac failure (CCF) based on the quantitative evaluation of the regulatory and adaptive status (RAS) of the organism. Patients with FC I-III HCF concomitant with grade I-III hypertensive disease and/or coronary heart disease underwent cardiorespiratory synchronism test for the quantitative estimation of RAS (6 min walk), echocardiography, treadmill measuring maximum oxygen consumption (VO2max), measurement of plasma N-terminal precursor of brain natriuretic peptide. The lowering of RAS was especially pronounced when HCF FC changed from I to III, in agreement with results of traditional instrumental and laboratory tests. Specifically, left ventricle systolic and diastolic function was impaired, tolerance of physical exercise decreased while neurohumoral regulation was activated. There was positive correlation between RAS indices at HCF CF I and II for left ventricular ejection fraction, maximum physical load, VO2max and negative correlation for N-terminal precursor of brain natriuretic hormone. At HCF FC II and III, positive correlation was documented for left ventricular ejection fraction, maximum physical load, VO2max and negative correlation for the N-terminal precursor of brain natriuretic hormone. It means that the qualitative estimate of RAS obtained in the cardiorespiratory synchronism test can be used to assess severity of HCF in patients with hypertensive disease and/or coronary heart disease.

Topics: Atrial Natriuretic Factor; Chronic Disease; Coronary Disease; Dimensional Measurement Accuracy; Female; Heart Failure; Heart Function Tests; Humans; Hypertension; Male; Middle Aged; Oxygen Consumption; Predictive Value of Tests; Severity of Illness Index; Ventricular Dysfunction, Left

There are few experimental models of heart failure (HF) in large animals, despite structural and functional similarities to human myocardium. We have developed a porcine model of chronic tachycardia-induced cardiomyopathy.. Homogenous siblings of White Large breed swine (n=6) underwent continuous right ventricular (RV) pacing at 170 bpm; 2 subjects served as controls. In the course of RV pacing, animals developed a clinical picture of HF and were presented for euthanasia at subsequent stages: mild, moderate and end-stage HF. Left ventricle (LV) sections were analyzed histologically and relative ANP, BNP, phospholamban and sarcoplasmic reticulum calcium ATPase 2a transcript levels in LV were quantified by real time RT-PCR.. In the course of RV pacing, animals demonstrated reduced exercise capacity (time of running until being dyspnoeic: 6.6 ± 0.5 vs. 2.4 ± 1.4 min), LV dilatation (LVEDD: 4.9 ± 0.4 vs. 6.7 ± 0.4 cm), impaired LV systolic function (LVEF: 69 ± 8 vs. 32 ± 7 %), (all baseline vs. before euthanasia, all p<0.001). LV tissues from animals with moderate and end-stage HF demonstrated local foci of interstitial fibrosis, congestion, cardiomyocyte hypertrophy and atrophy, which was not detected in controls and mild HF animals. The up-regulation of ANP and BNP and a reduction in a ratio of sarcoplasmic reticulum calcium ATPase 2a and phospholamban in failing myocardium were observed as compared to controls.. In pigs, chronic RV pacing at relatively low rate can be used as an experimental model of HF, as it results in a gradual deterioration of exercise tolerance accompanied by myocardial remodeling confirmed at subcellular level.

Topics: Animals; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Cardiomyopathies; Chronic Disease; Disease Models, Animal; Exercise Test; Female; Natriuretic Peptide, Brain; Random Allocation; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Swine; Tachycardia

Aortic regurgitation (AR) is a chronic disease for which there is currently no approved medical treatment. We previously reported in an animal model that β-blockade with metoprolol exerted beneficial effects on left ventricular remodeling and survival. Despite the recent publication of promising human data, β-blockade in chronic AR remains controversial. More data are needed to support this potentially new treatment strategy. We hypothesized that carvedilol might be another safe treatment option in chronic AR, considering its combined β-blocking and α-blocking effects and proven efficacy in patients with established heart failure.. The effects of a 6-month treatment with carvedilol 30 mg/kg/d orally were evaluated in adult Wistar rats with severe AR. Sham-operated and untreated AR animals were used as controls. Carvedilol treatment resulted in less left ventricular hypertrophy and dilatation. Ejection fraction was improved and filling pressures were reduced by carvedilol. β1-Receptor expression was also improved as well as myocardial capillary density. Those beneficial effects were noted despite the presence of drug-induced bradycardia.. Carvedilol exerted protective effects against volume-overload cardiomyopathy in this model of aortic valve regurgitation with preserved ejection fraction. These results suggest a protective class effect of β-blockers. Combined with the recent publication of promising human data, our findings support the need to carefully design a prospective study in humans to evaluate the effects of β-blockers in chronic aortic valve regurgitation.

Topics: Administration, Oral; Adrenergic beta-Antagonists; Animals; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Bradycardia; Capillaries; Carbazoles; Carvedilol; Chronic Disease; Disease Models, Animal; Extracellular Matrix Proteins; Follistatin-Related Proteins; Gene Expression Regulation; Heart Rate; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Propanolamines; Rats; Rats, Wistar; Receptors, Adrenergic; RNA, Messenger; Stroke Volume; Time Factors; Ultrasonography; Ventricular Function, Left; Ventricular Pressure

Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease. We investigated the effectiveness of human atrial natriuretic peptide (hANP) infusion in CKD patients undergoing coronary artery bypass grafting (CABG).. We analyzed 134 consecutive cases in which CABG had been performed in our hospital from 2002 to 2005. They were divided into four groups: Group A (n = 19) was CKD + placebo, Group B (n = 30) was non-CKD + placebo, Group C (n = 22) was CKD + hANP, and Group D (n = 63) was non-CKD + hANP). The serum creatinine (mg/dl) and estimated glomerular filtration rate (ml/min/1.73 m²) were measured as evaluation values.. The value of sCr changed preoperatively and at 1 year postoperatively from 1.09 ± 0.09, 51.3 ± 4.4 to 1.26 ± 0.42, 49.4 ± 14.4 in Group A, from 0.77 ± 0.14, 75.5 ± 12.1 to 0.91 ± 0.40, 72.3 ± 19.5 in Group B, from 0.99 ± 0.12, 54.8 ± 3.0 to 0.93 ± 0.16, 64.2 ± 12.3 in Group C and from 0.77 ± 0.13, 77.7 ± 13.4 to 0.83 ± 0.17, 75.9 ± 16.2 in Group D, respectively. There was a significant difference between Group A and Group C regarding the change of creatinine (p =0.0022).. Our study has confirmed that an infusion of hANP during CABG in patients with CKD not only improves perioperative renal function, but also prevents the progression of CKD.

Topics: Aged; Analysis of Variance; Atrial Natriuretic Factor; Biomarkers; Chi-Square Distribution; Chronic Disease; Coronary Artery Bypass; Coronary Artery Disease; Creatinine; Female; Glomerular Filtration Rate; Humans; Infusions, Parenteral; Japan; Kidney; Kidney Diseases; Male; Middle Aged; Randomized Controlled Trials as Topic; Retrospective Studies; Time Factors; Treatment Outcome

Serial measurements of neurohormones have been shown to improve prognostication in the setting of acute heart failure (HF) or chronic HF without therapeutic intervention. We investigated the prognostic role of serial measurements of emerging neurohormones and BNP in a cohort of chronic HF patients undergoing increases in HF-specific therapy.. In this prospective study we included 181 patients with chronic systolic HF after an episode of hospitalization for worsening HF. Subsequently, HF therapy was gradually increased in the outpatient setting until optimized. We measured copeptin, midregional proadrenomedullin, C-terminal endothelin-1 precursor fragment, midregional proatrial natriuretic peptide, and B-type natriuretic peptide before and after optimization of HF therapy. The primary endpoint was all-cause mortality at 24 months.. Angiotensin-converting enzyme/angiotensin receptor blocker and beta-blockers were increased significantly during the 3-month titration period (P < 0.0001 for both). In a stepwise Cox regression analysis adjusted for age, sex, glomerular filtration rate, diabetes mellitus, and ischemic HF, baseline and follow-up neurohormone concentrations were predictors of the primary endpoint as follows (baseline hazard ratios): copeptin 1.92, 95% CI 1.233-3.007, P = 0.004; midregional proadrenomedullin 2.79, 95% CI 1.297-5.995, P = 0.009; midregional proatrial natriuretic peptide 2.05, 95% CI 1.136-3.686, P = 0.017; C-terminal endothelin-1 precursor fragment 2.24, 95% CI 1.133-4.425, P = 0.025; B-type natriuretic peptide 1.46, 95% CI 1.039-2.050, P = 0.029.. In pharmacologically unstable chronic HF patients, baseline values and follow-up measures of copeptin, midregional proadrenomedullin, C-terminal endothelin-1 precursor fragment, midregional proatrial natriuretic peptide, and B-type natriuretic peptide were equally predictive of all-cause mortality. Relative change of neurohormone values was noncontributory.

Topics: Adrenomedullin; Adult; Aged; Atrial Natriuretic Factor; Chronic Disease; Endothelin-1; Female; Glycopeptides; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Prognosis; Protein Precursors

Measurement of natriuretic peptide's (NP) release in response to hemodynamic stress may be complementary to its baseline assessment in individuals. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) increase in patients with atrial fibrillation (AF) and decrease after successful cardioversion, suggesting that AF may stimulate secretion of NPs. However, there are conflicting data on the predictive value of NPs on the cardioversion outcome.. The purpose of this study was to investigate whether baseline and exercise-induced NP plasma levels can be useful in predicting successful cardioversion of persistent AF and maintenance of sinus rhythm during 6-month follow-up.. A prospective study enrolled 77 consecutive subjects with persistent AF with normal left ventricular function, referred for elective cardioversion. Patients underwent a modified Bruce protocol treadmill exercise test 24 hours before cardioversion. Blood samples for ANP and BNP analyses were obtained at rest and 5 minutes after exercise peak.. The group of successful cardioversion and stable sinus rhythm presented higher exercise ANP (110.6 ± 41.2 pg/mL vs 43.8 ± 36.1; pg/mL, P < 0.0001) and lower BNP increase (5.2 ± 5.2 pg/mL vs 40.5 ± 34.2 pg/mL, P < 0.0001) than the group of unsuccessful cardioversion or AF recurrence. Using an optimized cutoff level of ≤12% of relative exercise-induced increase in BNP concentration, and of >50 pg/mL of ANP increase, successful cardioversion can be predicted with high accuracy.. An increase in ANP and stability of BNP plasma concentration during exercise testing are independently associated with successful cardioversion and maintenance of sinus rhythm during 6-month follow-up. (PACE 2010; 33:1203-1209).

Topics: Adult; Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Chronic Disease; Coronary Sinus; Electric Countershock; Exercise Test; Humans; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Treatment Outcome

In chronic heart failure (CHF), several plasma biomarkers identify subjects at risk of death over the midterm. However, their long-term predictive value in the context of other candidate predictors has never been assessed. This information may prove valuable in the management of a chronic disease with a long natural history, as CHF is today.. We aimed to assess the very-long-term prognostic power of a set of biomarkers to identify CHF patients at highest risk for all-cause mortality.. A group of 106 consecutive outpatients with CHF (85 male and 21 female, median age 56 y) was followed for 15 years. Echocardiographic tracings and blood samples were collected at study entry to evaluate cardiac function, plasma atrial natriuretic peptide (ANP), aldosterone, and erythropoietin, and plasma renin activity. The relationships between biomarkers, clinical and echocardiographic variables, and mortality were assessed.. After 15 years, 86 of the 106 patients (81%) had died. Multivariate analysis showed that ANP was the best independent predictor of survival over several clinical, echocardiographic, and humoral variables (hazard ratio: 5.62, 95% confidence interval: 3.37-9.39, P < 0.001 for plasma levels < median value of 71 pg/mL). Plasma renin activity and erythropoietin provided prognostic information in univariate analysis, but lost their predictive power when adjusted for covariates.. The present study represents the longest available follow-up of patients with CHF evaluating the prognostic power of multiple biomarkers. It shows that a simple assessment of plasma ANP levels is the strongest long-term predictor of death in all stages of heart failure.

Topics: Aldosterone; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Erythropoietin; Female; Follow-Up Studies; Heart Failure; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Prognosis; Proportional Hazards Models; Prospective Studies; Renin; Risk Assessment; Risk Factors; Survival Rate; Time Factors; Ultrasonography

Biovariability, reference change values (RCV), and index of individuality (IOI) have not been previously described for NT-proANP or GDF15. Also, the relation of changes of these markers to other clinical variables or biomarkers is unknown. In 41 patients with stable chronic systolic dysfunction, NT-proANP and GDF15 were measured alongside with clinical variables/markers comprising NT-proBNP, hsTnT, and hsCRP at four sampling intervals (2 weeks, 1-, 2-, 3-month intervals). At 2 weeks, 1-, 2-, and 3-month-follow-up, individual NT-proANP variations were 27.1, 22.5, 28.9, 15.6%, respectively, corresponding to RCVs of 53.2, 62.4, 80.2, and 43.2%, respectively. For GDF15, the respective individual variations were 6.8, 4.1, 5.5, 6.8%, corresponding to RCVs of 18.8, 11.5, 15.3 and 18.8%. Neither changes of NT-proANP or GDF15 correlated with changes in any of the clinical variables or biomarkers examined except for GDF15 with renal function. Baseline hormonal levels and clinical variables did not consistently influence the extent of change. The IOI was 0.19-0.35 according to interval for NT-proANP and 0.06-0.09 for GDF 15. In patients with CHF preselected for clinical stability changes of NT-proANP at intermediate follow-up do not correlate with changes in other variables; changes of GDF15 inversely correlate with renal function. The extent of change in both markers is not related to baseline hormonal levels or other baseline variables. RCVs are high for NT-proANP and low for GDF15, while inter-individual variation is high in GDF15 and intermediate in NT-proANP.

Topics: Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Growth Differentiation Factor 15; Heart Failure; Humans; Male; Middle Aged; Reference Values; Risk Factors

Because both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) competitively bind to natriuretic peptide receptors but not N-terminal proBNP (NT-proBNP), the diagnostic value of BNP as a marker of the severity of heart failure in comparison with NT-proBNP during exogenous ANP (carperitide) infusion remains unclear. Forty-two patients with CHF (NYHA class III or IV) treated with the infusion of carperitide were included in the present study. We measured plasma levels of BNP and NT-proBNP at baseline and after the improvement of symptoms. We also measured these parameters before and 1 hour after stopping the infusion of carperitide. After stopping the infusion of carperitide, the plasma BNP level was significantly decreased by about 20% (394 +/- 53.8 versus 312.8 +/- 46 pg/mL, P < 0.0001) but plasma NT-proBNP did not change (1674.5 +/- 282.1 versus 1777.5 +/- 300.3 pg/mL, P = 0.259). The molar ratio of plasma BNP/NT-proBNP was significantly higher during carperitide infusion (0.74 +/- 0.08) than those at baseline (0.63 +/- 0.06) and after stopping carperitide (0.59 +/- 0.07). During carperitide infusion, plasma NT-proBNP may be a more reliable marker of endogenous cardiac natriuretic peptides than plasmaBNP, which may be increased by carperitide infusion.

Topics: Algorithms; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Diagnosis, Differential; Female; Heart Failure; Humans; Infusion Pumps; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Severity of Illness Index; Treatment Outcome

In this study, circulating levels of proinflammatory and anti-inflammatory mediators are studied in patients with chronic heart failure (CHF) in China. Sixty-five patients with CHF and 32 control subjects are studied. The proinflammatory and anti-inflammatory cytokines interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) in plasma are determined by immunoradiometric assay kits. Catecholamine (CA) in plasma is evaluated by high-performance liquid chromatography. Plasma levels of IL-6, IL-10, TNF-alpha, ANP, BNP, and CA in CHF patients are significantly higher than those in control subjects. Patients in a higher New York Heart Association (NYHA) class show higher concentrations of inflammatory mediators than those in a lower NYHA class, although the ratio of plasma IL-10 to TNF-alpha in patients with CHF is significantly lower than in the control group. It is concluded that proinflammatory and anti-inflammatory cytokine levels are increased and IL-10/TNF-alpha is decreased in Chinese patients with CHF.

Topics: Atrial Natriuretic Factor; Catecholamines; China; Chromatography, High Pressure Liquid; Chronic Disease; Cytokines; Female; Heart Failure; Humans; Immunoradiometric Assay; Inflammation Mediators; Interleukin-10; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Tumor Necrosis Factor-alpha

Atrial natriuretic peptide (ANP) is a key regulator in the homeostasis of water excretion and has emerged as an important prognostic marker for symptomatic chronic heart failure (CHF). The stability of ANP represents a crucial factor in assessing its use as a cardiac biomarker. Accordingly, we assessed the stability of ANP in blood samples collected from healthy controls and CHF subjects for a 12 month period.. Blood samples from 10 healthy controls and 12 symptomatic CHF subjects with left ventricular systolic dysfunction were drawn. Determination of plasma ANP was performed by a standardized radioimmunoassay protocol.. The ANP levels of healthy subjects were 68.5+/-11.6 pg/mL at baseline and 69.9+/-17.2 pg/mL at 12 months (p=0.71). The ANP concentrations of CHF subjects were 199.25+/-44.8 pg/mL at baseline and 197.83+/-47.4 pg/mL at 12 months (p=0.70) respectively.. ANP is a stable molecule with no evidence of degradation when stored at -80 degrees C.

Topics: Adult; Atrial Natriuretic Factor; Case-Control Studies; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Protein Stability; Thermodynamics

To investigate the diagnostic and prognostic value of N-terminal probrain natriuretic peptide(NT-proBNP)and atrium natriuretic peptide(ANP)in chronic congestive heart failure.. One hundred and eighteen coronary heart disease patients were enrolled in the study. Among them 78 patients were accompanied by heart failure and 40 with no heart failure. Plasma NT-proBNP was determined with Elecsys Chemiluminescence Immunoassay method, and plasma ANP was determined with radioimmunoassay method.The results were compared with those of 40 healthy individuals. All patients were followed up accordingly.. Compared with patients with no heart failure and healthy individuals, the patients with heart failure had a higher plasma NT-proBNP and ANP contents(P<0.05). Cardiac function grade IV patients had a significantly higher plasma NT-proBNP than cardiac function grade II and III patients, and their plasma ANP level was significanthy higher than that of cardiac function grade III patients, but there was no significantly difference in ANP content between cardiac function grade IV and II.The diagnostic sensitivity of NT-proBNP and ANP was 91.25% and 73.46%, respectively. The diagnostic specificity of NT-proBNP and ANP was 90.25%, 80.33%, respectively. In the heart failure group, it was found that there was no significant difference in the plasma NT-proBNP and ANP between the deaths and surviving patients.. The diagnostic value of NT-proBNP in chronic heart failure is higher than that of ANP. According to our follow- up result, the plasma NT-proBNP and ANP can not be relied up on to predict short -term cardiogenic death in heart failure.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Chronic Disease; Coronary Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Radioimmunoassay

Exercise training improves functional parameters in patients with congestive heart failure (CHF). The aim of this study was to establish whether exercise training influence the elevated CgA levels in CHF patients. Plasma CgA was determined at baseline and at peak exercise before and after 12 weeks of training in 25 men (mean age 67+/-8 years) with CHF (NYHA functional class II and III). Plasma Chromogranin A (CgA) was significantly elevated in CHF, however without change after the 12 week exercise period. A positive correlation was obtained for CgA versus N-ANP and CgA versus TNFalpha for the patients with poor survival, indicating that in these patients the elevated plasma CgA was more closely connected to the myocardial release of natriuretic peptides and the inflammatory response than to activation of the sympathoadrenergic system.

Topics: Aged; Atrial Natriuretic Factor; Chromogranin A; Chronic Disease; Cytokines; Exercise Therapy; Heart Failure; Humans; Male; Prognosis

Obstructive sleep apnea (OSA) increases cardiovascular morbidity and mortality. We have reported that chronic intermittent hypoxia (CIH), a direct consequence during OSA, leads to left ventricular (LV) remodeling and dysfunction in rats. The present study is to determine LV myocardial cellular injury that is possibly associated with LV global dysfunction. Fifty-six rats were exposed either to CIH (nadir O(2) 4-5%) or sham (handled normoxic controls, HC), 8 h/day for 6 wk. At the end of the exposure, we studied LV global function by cardiac catheterization, and LV myocardial cellular injury by in vitro analyses. Compared with HC, CIH animals demonstrated elevations in mean arterial pressure and LV end-diastolic pressure, but reductions in cardiac output (CIH 141.3 +/- 33.1 vs. HC 184.4 +/- 21.2 ml x min(-1) x kg(-1), P < 0.01), maximal rate of LV pressure rise in systole (+dP/dt), and maximal rate of LV pressure fall in diastole (-dP/dt). CIH led to significant cell injury in the left myocardium, including elevated LV myocyte size, measured by cell surface area (CIH 3,564 +/- 354 vs. HC 2,628 +/- 242 microm(2), P < 0.05) and cell length (CIH 148 +/- 23 vs. HC 115 +/- 16 microm, P < 0.05), elevated terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-stained positive cell number (CIH 98 +/- 45 vs. HC 15 +/- 13, P < 0.01), elevated caspase-3 activity (906 +/- 249 vs. 2,275 +/- 1,169 pmol x min(-1) x mg(-1), P < 0.05), and elevated expression of several remodeling gene markers, including c-fos, atrial natriuretic peptide, beta-myosin heavy chain, and myosin light chain-2. However, there was no difference between groups in sarcomere contractility of isolated LV myocytes, or in LV collagen deposition on trichrome-stained slices. In conclusion, CIH-mediated LV global dysfunction is associated with myocyte hypertrophy and apoptosis at the cellular level.

Topics: Animals; Apoptosis; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Cardiac Myosins; Cardiac Output; Cardiomegaly; Caspase 3; Cell Size; Chronic Disease; Collagen; Disease Models, Animal; Hypertrophy; Hypoxia; Male; Myocardial Contraction; Myocardium; Myocytes, Cardiac; Myosin Heavy Chains; Myosin Light Chains; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Research Design; RNA, Messenger; Ventricular Dysfunction, Left; Ventricular Pressure; Ventricular Remodeling

Circulating levels of atrial natriuretic peptide and brain natriuretic peptide (BNP) are elevated in patients with cyanotic congenital heart disease and associated with the severity of ventricular dysfunction. We evaluated the effect of chronic hypoxemia on left ventricle pro-atrial natriuretic peptide and pro-BNP, the cytoplasmic precursors of the plasma hormones.. Forty newborn piglets were randomized to placement of a pulmonary artery to left atrium shunt to create hypoxemia or sham thoracotomy. Animals were studied at 1 or 2 weeks after the procedure (four groups, n = 10 per group). Arterial oxygen tension and hematocrit were obtained. Left ventricular shortening fraction was measured by echocardiography. Left ventricular tissue was harvested and cytoplasm was extracted. Pro-BNP levels were determined by Western blot analysis. Pro-atrial natriuretic peptide levels were determined using enzyme-linked immunosorbent assay.. Significant differences among treatment groups were observed for arterial oxygen tension (p < 0.001) and hematocrit (p < 0.001). Pairwise comparisons indicated lower arterial oxygen tension and higher hematocrit for hypoxemic piglets compared with control piglets at 1 and 2 weeks. Left ventricular shortening fraction was not decreased in the hypoxemic animals at any time (p = 0.638). Left ventricular pro-atrial natriuretic peptide decreased in hypoxemic piglets (p = 0.029), whereas left ventricular pro-BNP increased in hypoxemic piglets at 2 weeks (p = 0.002).. Chronic hypoxemia alone, even in the absence of cardiac dysfunction, is sufficient to increase ventricular levels of pro-BNP. This finding may have implications for the interpretation of BNP levels in the clinical management of patients with cyanotic congenital heart disease.

Topics: Animals; Animals, Newborn; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Heart Defects, Congenital; Hypoxia; Natriuretic Peptide, Brain; Probability; Prognosis; Protein Precursors; Random Allocation; Sensitivity and Specificity; Swine

Inducible nitric oxide synthase (iNOS) protein is expressed in cardiac myocytes of patients and experimental animals with congestive heart failure (CHF). Here we show that iNOS expression plays a role in pressure overload-induced myocardial chamber dilation and hypertrophy. In wild-type mice, chronic transverse aortic constriction (TAC) resulted in myocardial iNOS expression, cardiac hypertrophy, ventricular dilation and dysfunction, and fibrosis, whereas iNOS-deficient mice displayed much less hypertrophy, dilation, fibrosis, and dysfunction. Consistent with these findings, TAC resulted in marked increases of myocardial atrial natriuretic peptide 4-hydroxy-2-nonenal (a marker of lipid peroxidation) and nitrotyrosine (a marker for peroxynitrite) in wild-type mice but not in iNOS-deficient mice. In response to TAC, myocardial endothelial NO synthase and iNOS was expressed as both monomer and dimer in wild-type mice, and this was associated with increased reactive oxygen species production, suggesting that iNOS monomer was a source for the increased oxidative stress. Moreover, systolic overload-induced Akt, mammalian target of rapamycin, and ribosomal protein S6 activation was significantly attenuated in iNOS-deficient mice. Furthermore, selective iNOS inhibition with 1400W (6 mg/kg per hour) significantly attenuated TAC induced myocardial hypertrophy and pulmonary congestion. These data implicate iNOS in the maladaptative response to systolic overload and suggest that selective iNOS inhibition or attenuation of iNOS monomer content might be effective for treatment of systolic overload-induced cardiac dysfunction.

Topics: Amidines; Animals; Aortic Diseases; Atrial Natriuretic Factor; Benzylamines; Cardiomegaly; Chronic Disease; Enzyme Inhibitors; Fibrosis; Heart Failure; Hypertension; Matrix Metalloproteinase 2; Mice; Mice, Knockout; Myocardium; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Protein Kinases; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Ribosomal Protein S6; Systole; TOR Serine-Threonine Kinases; Vasoconstriction

Although intracoronary administration of bone marrow-derived mononuclear progenitor cells (BMCs) may be associated with improved cardiac function in patients with chronic postinfarction heart failure, the impact on prognosis and clinical outcome of these patients is unknown. To identify potential predictors for a favorable clinical outcome, we assessed natriuretic peptide serum levels as objective markers of heart failure and the occurrence of cardiac death in relation to functional capacity of the infused cells in a consecutive series of 121 patients with chronic ischemic heart disease treated with intracoronary infusion of BMCs. Our analyses show that both N-terminal pro-brain natriuretic peptide (NT-proBNP) and N-terminal pro-atrial natriuretic peptide (NT-proANP) serum levels were significantly reduced in patients with established postinfarction heart failure 3 months after transcoronary progenitor cell administration. NT-proBNP serum levels greater than or equal to median (735 pg/mL) at baseline and a high number of infused progenitor cells with colony-forming capacity were the only independent predictors of a favorable response 3 months after intracoronary administration of BMCs. During extended clinical follow-up (577+/-442 days), a total of 14 deaths occurred in the overall patient population. Kaplan-Meier curves for both all cause and cardiac mortality showed that patients receiving a higher number of colony-forming cells were significantly less likely to die than those patients receiving low numbers of colony-forming cells (P=0.01). Most importantly, infusion of a high number of cells with colony-forming capacity was associated with a complete abrogation of increased mortality in patients with elevated NT-proBNP serum levels (> or =735 pg/mL; median) at baseline (P<0.001). Taken together, our results show that patients with objective evidence of postinfarction heart failure demonstrate a significant reduction of both NT-proBNP and NT-proANP serum levels within 3 months following intracoronary infusion of BMCs. Importantly, infusion of progenitor cells with a high functional capacity is associated with a significantly lower mortality during further follow-up.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Bone Marrow Transplantation; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Registries; Survival Rate

The purpose of this study was to evaluate the relationship between natriuretic peptides (NT-proANP and NT-proBNP) and hemodynamic parameters in preeclampsia.. This was a cross-sectional study of 19 preeclamptic, 15 chronic hypertensive, and 26 normotensive women in the third trimester of pregnancy. Stroke index (SI), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI), and left cardiac work index (LCWI) were derived by whole-body impedance cardiography. Systolic blood pressure (SAP), diastolic blood pressure (DAP), and mean arterial pressure (MAP) were measured. The plasma levels of NT-proANP and NT-proBNP were determined with radioimmunoassays.. NT-proANP and NT-proBNP concentrations were significantly higher in preeclamptic women compared to chronic hypertensive and normotensive pregnancies. Preeclamptic women had lower CI and HR and higher SAP, MAP, and SVRI than the control groups. In preeclampsia NT-proANP correlated significantly with SAP and SVRI; meanwhile, NT-proBNP correlated significantly with SVRI and CI. These correlations persisted in the subgroup of nonmedicated preeclamptic women, except in the case of NT-proBNP and CI.. High NT-proANP and NT-proBNP concentrations in preeclampsia reflect the strain on the heart caused by high afterload, rather than the function of the heart expressed as SI or CI.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Cross-Sectional Studies; Female; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Placental Circulation; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, Third; Probability; Reference Values; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index

Cardiovascular complications are a major problem in chronic renal failure. We examined the effects of plasma calcium, phosphate, parathyroid hormone (PTH), and calcitriol on cardiac morphology in 5/6 nephrectomized rats. Fifteen weeks after nephrectomy rats were given a control diet, high-calcium or -phosphorus diet, or given paricalcitol treatment for 12 weeks. Sham-operated rats were on a control diet. Blood pressure, plasma phosphate, and PTH were increased, while the creatinine clearance was reduced in remnant kidney rats. Phosphate and PTH were further elevated by the high-phosphate diet but suppressed by the high-calcium diet, while paricalcitol reduced PTH without influencing phosphate or calcium. The high-calcium diet increased, while the high-phosphate diet reduced plasma calcium. Plasma calcitriol was significantly reduced in other remnant kidney groups, but further decreased after paricalcitol. Cardiac perivascular fibrosis and connective tissue growth factor were significantly increased in the remnant kidney groups, and further increased in paricalcitol-treated rats. Hence, regardless of the calcium, phosphate, or PTH levels, cardiac perivascular fibrosis and connective tissue growth factor increase in rats with renal insufficiency in association with low calcitriol. Possible explanations are that aggravated perivascular fibrosis after paricalcitol in renal insufficiency may be due to further suppression of calcitriol, or to a direct effect of the vitamin D analog.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Calcitriol; Calcium; Cardiovascular System; Chronic Disease; Creatinine; Ergocalciferols; Fibrosis; Male; Nephrectomy; Parathyroid Hormone; Peptidyl-Dipeptidase A; Phosphorus; Rats; Rats, Sprague-Dawley; Renal Insufficiency; Renin

Our aim was assess the prognostic value of midregional pro-atrial natriuretic peptide (MR-proANP) using a new immunoassay in patients with chronic heart failure (HF).. Assessment of natriuretic peptides represents a useful addition in establishing the diagnosis of chronic HF. Their plasma values are powerful predictors of survival in chronic HF.. We assessed MR-proANP in 525 chronic HF patients (derivation study: age 61 +/- 12 years, New York Heart Association (NYHA) functional class I/II/III/IV 6%/44%/41%/9%, N-terminal pro-B-type natriuretic peptide (NT-proBNP) 3,637 +/- 6,362 pg/ml) and validated our findings in 249 additional chronic HF patients (age 63 +/- 9 years, NYHA functional class I/II/III/IV 14%/50%/33%/3%, NT-proBNP 1,116 +/- 1,991 pg/ml).. The MR-proANP levels (mean 339 +/- 306 pmol/l, range 24.5 to 2,280 pmol/l) increased with NYHA functional class (p < 0.0001). During follow-up (>6 months in survivors), 171 patients (33%) died. Increasing MR-proANP was a predictor of poor survival (risk ratio 1.35 per increase in standard deviation, 95% confidence interval 1.17 to 1.57; p = 0.0061), adjusted for NT-proBNP, age, left ventricular ejection fraction, NYHA functional class, creatinine, and body mass index (BMI). In receiver operating characteristic curve analysis of 12-month survival, the area under the curve for MR-proANP was 0.74 and that of NT-proBNP was 0.75 (p = 0.7). In a validation study, MR-proANP levels above the optimal prognostic cutoff value from the validation cohort remained a significant independent predictor of death. In chronic HF patients in NYHA functional class II to III and all subgroups of BMI and kidney function, MR-proANP added prognostic value to NT-proBNP. In patients with BMI > or =30 kg/m2, MR-proANP had higher prognostic power than NT-proBNP.. Midregional proANP is an independent predictor of mortality in patients with chronic HF. Midregional proANP adds prognostic information to NT-proBNP.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Cohort Studies; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Survival Rate

Left ventricular hypertrophy (LVH), which is a strong predictor of mortality in patients with endstage renal disease, is present in over 70% of patients commencing dialysis. However, only a few studies on LVH are available in patients before the start of dialysis treatment. The purpose of this study was to evaluate the prevalence and clinical correlates of LVH in patients with advanced stages of chronic kidney disease(CKD). We performed a cross sectional study of 90 patients who had renal diseases but no history of either cardiovascular diseases or arrhythmia. Circulating levels of human atrial natriuretic peptide (hANP) were also measured. LVH was present in 40.0% of the study population. The prevalence of LVH tended to increase with progression of renal decline: 22.7% in stage 3, 43.6% in stage 4, and 48.3% in stage 5 (creatinine clearance >10 mL/min) (p = 0.15). Univariate analyses revealed that hANP and albumin were significantly different between the groups with and without LVH. Stepwise logistic regression analysis showed that hANP and albumin were selected as the independent risk factors. These findings suggest that strict control of body fluid and nutrition could prevent the progression of LVH, and as a result, could attenuate the risk of cardiovascular events in CKD.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Cross-Sectional Studies; Dialysis; Female; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Male; Middle Aged; Regression Analysis; Risk Factors; Serum Albumin

Measurement of natriuretic peptides, particularly brain natriuretic peptide (BNP) is an established method for the diagnosis of cardiovascular disorders, chiefly left ventricular (LV) dysfunction. The influence of renal function on the diagnostic utility of natriuretic peptides is unclear.. We performed a cross-sectional study of 296 patients with renal disease but no history of cardiac disease using echocardiography to assess LV mass and function. Circulating levels of atrial natriuretic peptide (ANP) and BNP were also measured.. The incidence of LV hypertrophy increased with progressive renal dysfunction; from 39% in patients with near-normal renal function, to 80% in renal transplant patients. There was a negative correlation between both ANP and BNP, and glomerular filtration rate (GFR) (ANP: r = -0.28, P<0.001; BNP: r = -0.40, P<0.001). Serum ANP and BNP had sensitivity and specificity for LV hypertrophy of 39.9%, 87.4% (ANP) and 61.4%, 67.6% (BNP) respectively. Sensitivity and specificity for LV dysfunction was 77.2%, 32.4% (ANP) and 71.8%, 40.0% (BNP). Significant confounders in determining serum ANP were haemoglobin, beta blockade and albumin, while serum BNP levels were significantly confounded by GFR, albumin, haemoglobin, beta blockade and age.. Across a spectrum of renal dysfunction, GFR is a more important determinant of serum BNP than ventricular function, and several factors are predictors of natriuretic peptide levels. In chronic kidney disease, the use of natriuretic peptides to diagnose LV hypertrophy must be interpreted in light of these other factors. The use of these peptides in renal dysfunction to diagnose LV dysfunction may be of limited value.

Topics: Adult; Atrial Natriuretic Factor; Cardiomyopathies; Chronic Disease; Cross-Sectional Studies; Female; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain

Hypoxic stress upsets the balance in the normal relationships between mitogenic and growth inhibiting pathways in lung, resulting in pulmonary vascular remodeling characterized by hyperplasia of pulmonary arterial smooth muscle cells (PASMCs) and fibroblasts and enhanced deposition of extracellular matrix. Atrial natriuretic peptide (ANP) reduces pulmonary vascular resistance and attenuates hypoxia-induced pulmonary hypertension in vivo and PASMC proliferation and collagen synthesis in vitro. The current study utilized an ANP null mouse model (Nppa-/-) to test the hypothesis that ANP modulates the pulmonary vascular and alveolar remodeling response to normobaric hypoxic stress. Nine-10 wk old male ANP null (Nppa-/-) and wild type nontransgenic (NTG) mice were exposed to chronic hypoxia (10% O(2), 1 atm) or air for 6 wks.. pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial and alveolar remodeling were assessed. Hypoxia-induced pulmonary arterial hypertrophy and muscularization were significantly increased in Nppa-/- mice compared to NTG controls. Furthermore, the stimulatory effects of hypoxia on alveolar myofibroblast transformation (8.2 and 5.4 fold increases in Nppa-/- and NTG mice, respectively) and expression of extracellular matrix molecule (including osteopontin [OPN] and periostin [PN]) mRNA in whole lung were exaggerated in Nppa-/- mice compared to NTG controls. Combined with our previous finding that ANP signaling attenuates transforming growth factor (TGF)-beta-induced expression of OPN and PN in isolated PASMCs, the current study supports the hypothesis that endogenous ANP plays an important anti-fibrogenic role in the pulmonary vascular adaptation to chronic hypoxia.

Topics: Actins; Animals; Atrial Natriuretic Factor; Blotting, Northern; Chronic Disease; Collagen; Hemodynamics; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Immunohistochemistry; Lung; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Smooth, Vascular; Pulmonary Alveoli; Pulmonary Artery; Pulmonary Circulation; RNA, Messenger

The objective of the present study was to investigate whether InBody 2.0 might be useful in measuring the dry weight of chronic hemodialysis (HD) patients. Thirty-five HD patients (22 males and 13 females; mean age 62.6 +/- 14.0 years; mean HD duration 101.0 +/- 118.06 months) were examined. Multifrequency bioelectric impedance analysis was used to estimate the ratio of extracellular water (ECW) to total body water (TBW). The body resistance was measured at frequencies ranging from 1 kHz to 1 MHz. The impedance index was determined at a low frequency (5 kHz) and correlated closely with ECW, using sodium bromide dilution as standard comparison. The levels of serum albumin, prealbumin, total cholesterol (TC), triglycerides (TG), transferrin, and human atrial natriuretic peptide (hANP) were measured by routine methods in our hospital. The ECW/TBW ratio was significantly associated with the levels of hANP (p < 0.05). However, no associations between the levels of serum albumin, TC, TG, or transferrin and the ECW/TBW were observed. It appears that the body composition analyzer, InBody 2.0, may be useful for estimating the dry weight in chronic HD patients.

Topics: Adult; Aged; Atrial Natriuretic Factor; Body Composition; Chronic Disease; Electric Impedance; Female; Humans; Male; Middle Aged; Renal Dialysis

Inhibition of established left ventricular hypertrophy (LVH) and fibrosis may bring clinical benefits by reducing cardiac morbidity and mortality. The mammalian target of rapamycin, mTOR, is known to play a critical role in determining cell and organ size. We investigated whether mTOR inhibition can inhibit the chronic pressure-overload-induced LVH and fibrosis.. Male FVB/N mice underwent transverse aortic constriction (TAC) for 5 weeks to allow for establishment of LVH, followed by treatment with the mTOR inhibitor, Rapamune (2 mg/kg per day, gavage), for 4 weeks. Echocardiography was used to monitor changes in LVH and function. Haemodynamic, morphometric, histological and molecular analyses were conducted.. Inhibition of mTOR by Rapamune was confirmed by a suppression of activated phosphorylation of ribosomal S6 protein and eukaryotic translation initiation factor-4E due to pressure overload. Despite a comparable degree of pressure overload between the vehicle- or Rapamune-treated TAC groups, Rapamune treatment for 4 weeks attenuated TAC-induced LVH by 46%, estimated by LV weight or myocyte size, and LV fractional shortening was also preserved versus vehicle-treated control (39 +/- 1 versus 32 +/- 2%, P < 0.05). Inhibition of established LVH by Rapamune was associated with a 38% reduction in collagen content. Moreover, altered gene expression due to pressure overload was largely restored.. Despite sustained pressure overload, inhibition of mTOR by a 4-week period of Rapamune treatment attenuates chronically established LVH and cardiac fibrosis with preserved contractile function.

Topics: Analysis of Variance; Animals; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Disease Models, Animal; Down-Regulation; Eukaryotic Initiation Factor-4E; Fibrosis; Heart Rate; Hypertrophy, Left Ventricular; Immunosuppressive Agents; Male; Mice; Mitogen-Activated Protein Kinase 3; Myosin Heavy Chains; Phosphatidylinositol 3-Kinases; Phosphorylation; Protein Kinases; Ribosomal Protein S6; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Signal Transduction; Sirolimus; STAT3 Transcription Factor; Stroke Volume; TOR Serine-Threonine Kinases

To analyse the mid region of plasma N-terminal pro-atrial natriuretic peptide (MR-proANP) levels in patients with lower respiratory tract infections to evaluate its prognostic use for the severity of disease and outcome.. Prospective observational study. Setting. Emergency department of a university hospital.. A total of 545 consecutive patients with lower respiratory tract infections and 50 healthy controls. Interventions. MR-proANP was measured in serum from all patients using a new sandwich immunoassay.. MR-proANP levels (median [IQR], in pmol L(-1)) were significantly higher in patients with lower respiratory tract infections when compared with controls (138.0 [74.1-279.0] vs. 72.7 [62.5-89.5], P < 0.001), with highest levels in patients with community-acquired pneumonia (CAP). MR-proANP, but not C-reactive protein (CRP) levels, gradually increased with increasing severity of CAP, classified according to the pneumonia severity index (PSI) score (P < 0.001). On admission, MR-proANP levels were significantly higher in nonsurvivors when compared with survivors (293.0 [154.0-633.0] vs. 129.0 [71.4-255.0], P < 0.001). In a receiver operating characteristic (ROC) analysis for the prediction of survival of patients with CAP the area under the ROC curve (AUC) for MR-proANP was 0.69, similar when compared with the PSI (AUC 0.74, P = 0.31), and better when compared with other biomarkers, i.e. procalcitonin (AUC 0.57, P = 0.08), CRP (AUC 0.52, P = 0.02), and leucocyte count (AUC 0.56, P = 0.07).. MR-proANP levels are increased in lower respiratory tract infections, especially in CAP. Together with other clinical, radiographic and laboratory findings, MR-proANP levels might be helpful for the risk stratification in CAP.

Topics: Acute Disease; Aged; Atrial Natriuretic Factor; Biomarkers; Bronchitis; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Chronic Disease; Community-Acquired Infections; Female; Humans; Leukocyte Count; Male; Pneumonia; Prognosis; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; ROC Curve; Severity of Illness Index

Atrial dilatation is an important risk factor for atrial fibrillation (AF). In the present study, we monitored the electrophysiological changes during progressive atrial dilatation in chronically instrumented goats.. In 8 goats, 2 screw-in leads with piezoelectric crystals were implanted transvenously in the right atrium. After 2 weeks, atrial diameter and effective refractory period were measured. AF paroxysms were induced by burst pacing to determine the baseline AF cycle length and stability of AF. After His-bundle ablation, the above measurements were repeated once a week. After 4 weeks of complete AV block, the free wall of the right atrium was mapped and the atrium was fixed in formalin for histological analysis. After His-bundle ablation, the ventricular rate decreased from 113.8+/-4.8 to 44.6+/-2.5 bpm. Right atrial diameter increased gradually by 13.5+/-3.9% during 4 weeks of AV block (P<0.01). The duration of induced AF paroxysms increased from 4.6 seconds to 6.4 minutes (P<0.05). Atrial effective refractory period and AF cycle length remained constant. Spontaneous paroxysms of AF were not observed. Atrial mapping during rapid pacing revealed that slow conduction (<30 cm/s) was present in 3.7+/-1.0% of the mapped area (control, 0.9+/-0.5%, P<0.05). Histological analysis showed hypertrophy without atrial fibrosis. Connexin40 and connexin43 expression was unchanged.. Chronic AV block in the goat leads to progressive atrial dilatation, prolongation of induced AF paroxysms, and local conduction delays. The increase in AF stability was not a result of a shortening of atrial refractoriness or atrial fibrosis.

Topics: Aldosterone; Angiotensin II; Animals; Atrial Fibrillation; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Cardiomegaly; Cell Size; Chronic Disease; Connexin 43; Connexins; Female; Gap Junction alpha-5 Protein; Goats; Heart Block; Heart Conduction System; Hemodynamics; Hypertrophy; Myocytes, Cardiac; Neural Conduction; Norepinephrine; Refractory Period, Electrophysiological

The prognostic value of cardiac troponin T (cTn-T) in a mixture of patients with both acute and chronic congestive heart failure (CHF), simultaneously assessed and compared with neurohormonal factors, has not yet been thoroughly evaluated. Thus, we focused on the prognostic value of cTn-T in comparison with atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and plasma norepinephrine (PNE) in this population.. Prognostic correlates of elevation of cTn-T, ANP, BNP, PNE were analyzed in 63 acute and chronic CHF patients followed up to record worsening CHF and cardiac death.. cTn-T (> or =0.03 microg/L) was found in 17.4% (11 of 63) of patients. cTn-T correlated with ANP, BNP, PNE. Acute CHF patients were more positive for cTn-T and BNP. In our cohort, neither cTn-T (> or =0.03 microg/L) nor PNE were associated with increased mortality and worsening HF in CHF patients. After adjustment, BNP was the only independent predictor of cardiac events (RR, 3.23; p=0.01).. BNP emerged as the only independent predictor of cardiac events in a mixture of patients with both acute and chronic CHF, suggesting that it is the analyte that best reflects long-term prognosis in a diverse population enrolled to mirror the "real world" situation.

Topics: Acute Disease; Adult; Aged; Atrial Natriuretic Factor; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Predictive Value of Tests; Prognosis; Troponin T

Topics: Atrial Natriuretic Factor; Cardiovascular Diseases; Chronic Disease; Circadian Rhythm; Comorbidity; Continuous Positive Airway Pressure; Heart Failure; Humans; Natriuretic Peptide, Brain; Oxygen; Polysomnography; Sleep Apnea Syndromes; Wakefulness

We prospectively determined the time course of recovery of atrial mechanical and endocrine function in patients following DC cardioversion for persistent atrial fibrillation (AF). Twenty-three consecutive patients underwent successful DC cardioversion (mean age 64 years, 20 male). By 28 days, nine had reverted to atrial fibrillation. Recovery of atrial mechanical (peak A wave velocity) and endocrine function (atrial natriuretic peptide, ANP) were assessed at four time points: immediately pre-cardioversion, and then 4 h, 7 and 28 days post. The 14 patients maintaining sinus rhythm formed the success group. In this group, peak A wave velocity increased significantly over time from 0.28+/-0.03 m/s (mean+/-S.E.M.) at 4 h to 0.50+/-0.03 m/s at day 7 and 0.67+/-0.05 m/s at day 28 (p<0.001). Plasma ANP was 150+/-34 pg/ml immediately prior to DC cardioversion in the success group. This showed an initial dip at 4 h to 44+/-9 pg/ml (p<0.001). By day 7, plasma ANP had increased to 105+/-21 pg/ml (p<0.05 vs. baseline and 4 h) and then appeared to remain constant, being 102+/-19 pg/ml at day 28 (p=0.06 vs. baseline). A similar early reduction in ANP levels was seen in the group who subsequently reverted to atrial fibrillation. Baseline ANP levels did not predict subsequent successful maintenance of sinus rhythm. Initial "stunning" in both atrial mechanical and endocrine function occurs in patients following DC cardioversion for atrial fibrillation. Whilst endocrine function appears to fully recover by day 7, mechanical function continues to improve beyond day 7.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Atrial Natriuretic Factor; Chronic Disease; Electric Countershock; Endocrine System; Female; Heart Atria; Humans; Male; Middle Aged; Prospective Studies; Recovery of Function; Time Factors

To investigate the diagnostic and prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and atrium natriuretic peptide (ANP) in chronic congestive heart failure.. Seventy-one coronary heart disease patients were enrolled in the study. Among them 58 patients were accompanied by heart failure and 13 with no heart failure. Plasma NT-ProBNP was determined with enzyme linked immunoadsorbent assay method, and plasma ANP was determined with radioimmunoassay method. The results were compared with those of 30 healthy individuals. All patients were followed up accordingly.. Compared with patients with no heart failure and healthy individuals, the patients with heart failure had a higher plasma NT-proBNP and ANP contents. Cardiac function grade IV patients had a significantly higher plasma NT-ProBNP than cardiac function grade II and III patients, and their plasma ANP level was significantly higher than that of cardiac function grade III patients, but there was no significantly difference in ANP content between cardiac function grade IV and II. The diagnostic sensitivity of NT-proBNP and ANP was 94.38% and 75.86%, respectively. The diagnostic specificity of NT-proBNP and ANP was 96.67%, 83.33%, respectively. In the heart failure group, after being followed up for (11.35+/-1.69) months, it was found that there was no significant difference in the plasma NT-proBNP and ANP between the deaths and surviving patients.. The diagnostic value of NT-proBNP in chronic heart failure is higher than that of ANP. According to our follow-up result, the plasma NT-proBNP and ANP can not be relied upon to predict short-term cardiogenic death in heart failure.

Topics: Atrial Natriuretic Factor; Chronic Disease; Coronary Disease; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

We investigated the correlations between exercise intolerance and the plasma levels of neurohormonal factors and proinflammatory cytokines in chronic heart failure (CHF) patients. Sixty-two CHF patients who underwent cardiopulmonary exercise testing (CPX) were enrolled in this study. Peak oxygen uptake (peak VO2) and the plasma concentrations of noradrenaline (NA), brain natriuretic peptide (BNP), and soluble tumor necrosis factor receptors I and II (TNFR-I and -II) were all measured during the CPX. The patients were divided into three groups according to their peak VO2; a severe exercise intolerance group (severe group; peak VO2 < 18 mL/min/kg), moderate exercise intolerance group (moderate group; 18 24). There were no significant differences in left ventricular ejection fraction (EF) among the three groups. NA and BNP both increased gradually in parallel with the worsening of exercise intolerance (NA, 211.5 +/- 75.7 pg/mL, 331.8 +/- 163.7, 441.9 +/- 202.9, respectively; BNP, 37.9 +/- 25.4 pg/mL, 148.9 +/- 117.1, 247.9 +/- 150.0, respectively). TNFR-I and II were significantly higher in the severe group than in the moderate group (1746.1 +/- 950.7 versus 1085.2 +/- 370.5 pg/mL and 2855.3 +/- 1550.9 versus 2047.7 +/- 648.7 pg/mL, respectively), while the values in the moderate group were not significantly different from those in the mild group. EF showed no significant correlations with NA, BNP, TNFR-I, or TNFR-II, whereas peak VO2 exhibited significant negative correlations with NA (r = -0.50, P < 0.0001), BNP (r = -0.53, P < 0.0001), TNFR-I (r = -0.50, P < 0.0001), and TNFR-II (r = -0.45, P < 0.0001). It is concluded that NA and BNP rise in parallel with the degree of exercise intolerance, while TNFR-I and -II rise only when exercise intolerance reaches severe levels.

Topics: Aged; Atrial Natriuretic Factor; Chronic Disease; Exercise Test; Exercise Tolerance; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Oxygen Consumption; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Tumor Necrosis Factor-alpha

The mandatory use of pharmacotherapy in human heart failure (HF) impedes further study of natural history and remodeling mechanisms. We created a sheep model of chronic, severe, ischemic HF [left ventricular (LV) ejection fraction (LVEF) <35% stable over 4 wk] by selective coronary microembolization under general anesthesia and followed hemodynamic, energetic, neurohumoral, structural, and cellular responses over 6 mo. Thirty-eight sheep were induced into HF (58% success), with 23 sheep followed for 6 mo (21 sheep with sufficient data for analysis) after the LVEF stabilized (median of 3 embolizations). Early doubling of LV end-diastolic pressure persisted, as did increases in LV end-diastolic volume, LV wall stress, and LV wall thinning. Contractile impairment (LV end-systolic elastance, LV preload recruitable stroke work, and dobutamine-responsive contractile reserve) and diastolic dysfunction also remained stable. Cardiac mechanical energy efficiency did not recover. Plasma atrial natriuretic peptide levels remained elevated, but rises in plasma aldosterone and renin activity were transient. Collagen content increased 170%, the type I-to-III phenotype ratio doubled in the LV, but right ventricular collagen remained unaltered. Fas ligand cytokine levels correlated with expression of both caspase-3 and -2, suggesting a link in the apoptotic "death cascade." Caspase-3 activity also bore a close relationship to LV meridional wall stress calculated from echocardiographic and intraventricular pressure measurements. We concluded that the stability of chronic untreated severe ischemic HF depends on the recruitment of myocardial remodeling mechanisms that involve an interaction among hemodynamic load, contractile efficiency/energetics, neurohumoral activation, response of the extracellular matrix, wall stress, and the myocyte apoptotic pathway.

Topics: Aldosterone; Angiotensin II; Animals; Atrial Natriuretic Factor; Caspase 2; Caspase 3; Caspase 8; Caspases; Chronic Disease; Collagen; Coronary Vessels; Embolism; Extracellular Matrix; Fas Ligand Protein; Female; Heart Failure; Male; Membrane Glycoproteins; Microcirculation; Microspheres; Myocardial Contraction; Myocardial Ischemia; Myocardium; Severity of Illness Index; Sheep; Stroke Volume; Ventricular Remodeling

The hemodynamic consequences of atrial fibrillation (AF) may lead to impairment of the left ventricular function and a reduction in exercise capacity. Studies on mechanical and neurohormonal remodelling in patients with AF are becoming increasingly important. The results could possibly enhance treatment strategies of these patients. The aim of this study was to assess changes in exercise capacity, echocardiographic findings and plasma atrial natriuretic peptide (ANP) concentrations in patients with non-rheumatic persistent AF, before and 30 days after successful cardioversion.. We attempted cardioversion in 42 consecutive patients, aged 58 +/- 8 years, with persistent non-valvular AF of duration 7.1 +/- 7.1 months. They underwent echocardiography examination and submaximal exercise testing 24 h before and 30 days after cardioversion. Exercise capacity was determined during symptom-limited exercise testing, according to a modified Bruce protocol with peak VO2 analysis. Plasma samples of ANP were obtained at rest: before, the day after, and 30 days after cardioversion therapy, and were prepared by refrigerated centrifugation and stored until radioimmunoassay. The control study group, without AF, comprised of 11 subjects.. Cardioversion was successful in 35 patients. However, in six of the 35 patients, AF reappeared within 1 month. There were no statistical differences before cardioversion in exercise tolerance and ejection fraction of left ventricle between the group with successful cardioversion and the group with unsuccessful cardioversion or with recurrence of AF. On the 30th day after cardioversion we recorded a significant increase in exercise tolerance: duration of exercise 13.7 +/- 3.2 versus 9.5 +/- 3.4 min, (P < 0.05); peak oxygen consumption 32.2 +/- 3.6 versus 19.85 +/- 3.5 ml/min per kg, (P < 0.05); and ejection fraction of left ventricle 58.6 +/- 9.4 versus 52.7 +/- 10.2% (P < 0.05); in the sinus rhythm group. There was no significant improvement observed in the AF group. The mean baseline ANP level was 58.5 +/- 15.7 pg/ml in the study group and 34.3 +/- 10.2 pg/ml in the control group (P < 0.01). The successful therapy reduced significantly the pretreatment mean plasma ANP concentration from 58.5 +/- 15.7 to 31.4 +/- 15.0 pg/ml, (P < 0.01); the day after cardioversion, in the group of 35 patients. It remained stable for the next 30 days (36.9 +/- 15.2 pg/ml) in the group of 29 patients who remained in sinus rhythm, and increased to 53.4 +/- 16.4 pg/ml in the group of six patients who had recurrence of AF. Plasma ANP did not change in the group of seven patients with unsuccessful cardioversion.. The restoration of sinus rhythm in patients with persistent AF was associated with a significant improvement in cardiac performance and exercise tolerance 1 month after cardioversion. Such improvement was not observed in the group with unsuccessful cardioversion or with AF recurrence. The plasma ANP concentration in patients with AF was significantly reduced after successful cardioversion and remained stable for a period of 30 days.

Topics: Aged; Analysis of Variance; Atrial Fibrillation; Atrial Function, Left; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Chronic Disease; Echocardiography, Doppler; Electric Countershock; Exercise Tolerance; Female; Humans; Male; Middle Aged; Probability; Prognosis; Reference Values; Sensitivity and Specificity; Treatment Outcome

We compared brain natriuretic peptide (BNP) levels in patients with obstructive sleep apnea (OSA) with and without cardiovascular disease to BNP in healthy control subjects. OSA was not associated with increased plasma BNP or atrial natriuretic peptide (ANP) in otherwise healthy subjects during wakefulness. Untreated OSA increased ANP overnight, and ANP levels decreased with treatment of OSA. However, OSA did not elicit acute overnight changes in BNP, either in normal subjects or in patients with coexisting cardiovascular disease (including chronic heart failure).

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiovascular Diseases; Chronic Disease; Circadian Rhythm; Comorbidity; Continuous Positive Airway Pressure; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen; Polysomnography; Reference Values; Sleep Apnea Syndromes; Wakefulness

Heart failure is a major and escalating public health problem. Recent studies have demonstrated that statins prevented chronic heart failure (CHF) in animal studies. However, it is unknown whether statins therapy initiated after left ventricular (LV) hypertrophy is evident can still effectively prevent CHF. This study tested the hypothesis that statins can prevent the transition of hypertrophy to heart failure.. The rats were studied at 6, 12, and 20 weeks after aortic stenosis (AS) operation. Some rats were given simvastatin (2.0 mg kg(-1) per day) from 13 weeks after AS operation for 8 weeks. Coarctation of aorta in rats resulted in compensatory LV hypertrophy (LVH), concomitant with an increase of superoxide levels and cardiomyocyte apoptosis in LV tissues at 12 weeks after AS operation. This was followed by CHF with a progressive increase in superoxide levels and cardiomyocyte apoptosis in LV tissues at 20 weeks after AS operation. Simvastatin treatment initiated from 13 weeks after AS operation significantly improved LV function and reduced superoxide levels and cardiomyocyte apoptosis in LV tissues. Pretreatment of simvastatin suppressed the hydrogen peroxide-induced apoptosis of cultured cardiomyocytes from neonatal rats.. These data indicate that long-term administration of simvastatin improved LV function and prevented the transition of hypertrophy to CHF. Inhibition of oxidative stress and cardiomyocyte apoptosis may contribute to the benefits of simvastatin treatment on heart of rats with AS.

Topics: Animals; Aortic Coarctation; Aortic Valve Stenosis; Apoptosis; Atrial Natriuretic Factor; Cardiac Output, Low; Caspase 3; Caspases; Chronic Disease; Heart Ventricles; Hydrogen Peroxide; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertrophy, Left Ventricular; Male; Myocytes, Cardiac; Oxidative Stress; Rats; RNA, Messenger; Simvastatin; Superoxides

Chronic heart failure (CHF) is characterized by the activation of neurohormones and cytokines. Strenuous exercise causes activation of both systems but the effect of acute bouts of exercise on cytokines is not known in patients with CHF. This study determined whether maximal exercise induces activation of cytokines in CHF. Plasma interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, epinephrine, norepinephrine, and atrial and brain natriuretic peptides (ANP and BNP) were determined before and after symptom-limited cardiopulmonary exercise testing in 80 patients with CHF (LVEF=38+/-1%, peak VO(2)=18.8+/-0.5 ml/min/kg) and age-matched 33 controls. Resting IL-6 (Controls vs. CHF: 1.3+/-0.2 vs. 2.5+/-0.3 pg/ml, P<0.001) and TNF-alpha (2.7+/-0.2 vs. 3.8+/-0.2 pg/ml, P<0.01) were elevated in CHF. LogIL-6 and logTNF-alpha were positively correlated (r=0.34 and r=0.35, respectively) with logplasma norepinephrine, and were negatively correlated (r=-0.39 and r=-0.32, respectively) with peak VO(2). Maximal exercise increased IL-6 and TNF-alpha both in controls and CHF (all P<0.01). Changes in IL-6 (DeltaIL-6) correlated with Deltaepinephrine (r=0.63, P<0.0001) and Deltanorepinephrine (r=0.57, P=0.0006) in controls, but not in CHF. DeltaTNF-alpha correlated with DeltaANP (r=0.28, P=0.01) only in CHF. In summary, cytokine activation at rest was associated with high plasma norepinephrine and exercise intolerance. Maximal exercise caused increases in IL-6 and TNF-alpha concentrations. Sympathetic activation seems to be important for the IL-6 increase during exercise in controls. In CHF, changes in ANP during exercise were associated with the exercise-induced increase in TNF-alpha, but still unknown mechanisms are involved for the cytokine activation during exercise.

Topics: Atrial Natriuretic Factor; Case-Control Studies; Chronic Disease; Epinephrine; Exercise Test; Female; Heart Failure; Humans; Interleukin-6; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Statistics, Nonparametric; Tumor Necrosis Factor-alpha

Topics: Atrial Natriuretic Factor; Chronic Disease; Death, Sudden, Cardiac; Heart Failure; Humans; Natriuretic Peptide, Brain; ROC Curve; Sensitivity and Specificity

Patients with liver cirrhosis and chronic heart failure (CHF) have a reduced capacity to excrete water. Studies in healthy humans have shown that an acute water load reduces the excretion of aquaporin-2 in urine (u-AQP-2). We wanted to test the hypothesis that an acute water load reduces u-AQP-2 less in patients with liver cirrhosis or CHF than in healthy humans.. Fourteen healthy subjects, 14 patients with liver cirrhosis, and 14 patients with CHF were given an oral water load of 20 mL/kg. Urine was collected every 30 minutes for 4 hours for analysis of u-AQP-2. Blood samples were drawn at the beginning and at the end of the study for analysis of arginine vasopressin (AVP). u-AQP-2 was determined by radioimmunoassay.. During the study period, urinary output was 22.8% higher than water intake in the healthy controls and increased 14-fold from baseline, but in patients with liver cirrhosis and CHF urinary output was 14% and 24% less than the intake, while urinary output increased 7- and 19-fold from baseline, respectively. u-AQP2 decreased significantly more in patients with CHF (39%) than in healthy controls (17%) but it was unchanged in those with liver cirrhosis. AVP decreased 46% in patients with CHF, but was unchanged in healthy controls and those with liver cirrhosis. A 24-hour urinary excretion of AQP-2 was significantly elevated in patients with CHF (median, 25.7 nmol/mol creatinine) compared to healthy controls (15.7 nmol/mol creatinine) and those with liver cirrhosis (17 nmol/mol creatinine).. The excretion of AQP-2 in urine is abnormal both in liver cirrhosis in which we find less suppression of u-AQP2 by an acute water load and in CHF in which we find a high baseline level and an exaggerated suppression of u-AQP2 by an acute water load.

Topics: Adult; Aldosterone; Angiotensin II; Aquaporin 2; Aquaporin 6; Aquaporins; Arginine Vasopressin; Atrial Natriuretic Factor; Chronic Disease; Drinking; Female; Heart Failure; Humans; Liver Cirrhosis; Male; Middle Aged; Natriuretic Peptide, Brain; Osmolar Concentration; Renin; Urine; Water-Electrolyte Balance

To determine if B-type natriuretic peptide (BNP) measurement could be useful in determination of functional capacity in patients suffering from chronic heart failure.. Evaluating functional capacity is a crucial factor in the follow-up of patients with chronic heart failure. There are numerous methods for measuring functional capacity and their relative merits remain under discussion. Clinical classifications are very subjective and other methods are difficult to use in clinical practice.. We evaluated functional capacity in 151 consecutive patients using the 6-min walk test. All patients were clinically classified using the New York Heart Association (NYHA) classification. We measured BNP plasma levels using a bedside BNP test.. Six minute walk test performance decreased through NYHA classes 1 to 4 (469+/-87, 411+/-82, 325+/-83 and 196+/-63 m, respectively, P<0.01) and BNP levels increased through NYHA classes 1 to 4 (26.3+/-7.2, 73+/-13, 401+/-74 and 924+/-84 pg/ml, respectively, P<0.001). There was a significant correlation between 6-min walk test performance and BNP plasma levels (R=0.69 P<0.001) and a weaker correlation between BNP and left ventricular ejection fraction (R=0.45 P<0.04). In some patients there was a mismatch between NYHA classification and 6-min walk test performance. In all cases BNP could correct the clinical estimation of functional capacity. When we divided the patients into three sub-groups within each NYHA class, we showed that using BNP could better define functional capacity in patients suffering from chronic heart failure in NYHA classes I to III.. The measurement of BNP levels thus usefully supplements the clinical examination. The existence of bedside BNP testing methods facilitates its use in routine clinical practice. It also permits easier follow-up of patients with chronic heart failure.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Carbazoles; Carvedilol; Chronic Disease; Diuretics; Dose-Response Relationship, Drug; Follow-Up Studies; France; Furosemide; Heart Failure; Humans; Incidence; Lisinopril; Middle Aged; Natriuretic Peptide, Brain; Propanolamines; Severity of Illness Index; Spironolactone; Stroke Volume; Treatment Outcome

Clinical results of the Maze procedure for treatment of atrial fibrillation (AF) are excellent, suggesting improved ventricular function after restoring sinus rhythm. However, long-term corresponding effects on the release of cardiac natriuretic peptides and other vasoactive hormones are incompletely investigated after isolated Maze surgery.. Plasma levels of brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), antidiuretic hormone, aldosterone, and angiotensin II were measured in 15 patients (mean age, 52 +/- 11 years) undergoing isolated surgical Maze (III) procedures for medically refractory AF, preoperatively and 6 months postoperatively. At the time of blood sampling, hemodynamic correlates were obtained at baseline and after 6 and 12 minutes of rapid ventricular pacing at 150 stimulations/minute.. All patients were free of AF at 6-month follow-up. The measured plasma levels of BNP, ANP, and angiotensin II were all significantly lower (p = 0.03) late after the isolated Maze procedure. Cardiac output was significantly higher postoperatively (p < 0.01). Other hemodynamic values and left atrial size were unchanged after surgery. Ventricular pacing caused almost identical hemodynamic changes in atrial pressures before and late after surgery, but the associated plasma ANP response was significantly attenuated postoperatively (p < 0.001).. Levels of cardiac natriuretic peptides and angiotensin II as markers of ventricular function are improved in the long term after clinically successful isolated Maze procedures. ANP response to hemodynamic challenge by ventricular pacing was attenuated postoperatively, possibly due to atrial scarring.

Topics: Adult; Aged; Aldosterone; Angiotensin II; Atrial Fibrillation; Atrial Natriuretic Factor; Chronic Disease; Cryosurgery; Female; Follow-Up Studies; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Postoperative Complications; Vasopressins; Ventricular Dysfunction, Left; Ventricular Function, Left

The ventricles of the normal heart are virtually devoid of atrial natriuretic peptide (ANP). Although ANP occurs in ventricles submitted to elevated wall stress, it is not clear whether ANP expression is affected by myocarditis. We investigated the immunohistochemical expression of ANP in chronic chagasic cardiomyopathy, an inflammatory cardiomyopathy caused by infection with the protozoan Trypanosoma cruzi.. Necropsy samples from the left and right ventricles of 16 patients exhibiting chronic chagasic cardiomyopathy were evaluated for myocarditis, fibrosis, T. cruzi parasites and ANP immunoreactivity. The diameters of 50 myocytes per sample were measured.. ANP was present in myocytes of the subendocardial region in 13/16 (81.3%) left and 10/16 (62.5%) right ventricular samples (P=0.25). Myocytes present in the inflammatory foci, near the infiltrating inflammatory cells but distant from the subendocardial region, did not express ANP. Trypanosoma cruzi parasites exhibited intense immunoreactivity for ANP. The mean myocyte diameter and the incidence of myocarditis, fibrosis, and T. cruzi parasites was similar between the left and right ventricular samples. No statistical differences were found between the ANP-positive and ANP-negative cases.. In chronic chagasic cardiomyopathy, both ventricles exhibit hypertrophy, fibrosis and ANP in the subendocardial region. The inflammatory infiltrate does not induce ANP expression in the myocytes. Regional stress but not myocarditis itself, is probably responsible for ventricular ANP expression in myocarditis.

Topics: Adolescent; Adult; Aged; Animals; Atrial Natriuretic Factor; Chagas Cardiomyopathy; Child; Chronic Disease; Female; Fibrosis; Heart Ventricles; Humans; Male; Middle Aged; Muscle Fibers, Skeletal; Myocarditis; Trypanosoma cruzi

By virtue of no identifiable causes in the majority of children with habitual epistaxis, it continues to be problematic in pediatric clinical practice. The purpose of this study is to explore the possible change of atrial natriuretic peptide (ANP) levels in the children with epistaxis.. Both the plasma and nasal mucus ANP levels have been determined in 30 sick children by a sensitive radioimmunoassay (RIA) technique.. Our results revealed that the plasma and nasal mucus ANP levels were considerably decreased in 24 children with habitual epistaxis when compared with control group (P<0.05), making up 80%, and amongst the interest of these are the nasal mucus ANP levels changing inversely as the times bled from the nose.. Although the plasma and nasal mucus ANP levels will not establish the diagnosis of its etiology, it is helpful for us to know the cardiovascular status compensating for chronic blood loss in the children with habitual epistaxis.

Topics: Adolescent; Atrial Natriuretic Factor; Case-Control Studies; Chronic Disease; Epistaxis; Female; Habituation, Psychophysiologic; Humans; Male; Nasal Mucosa; Radioimmunoassay

Previous reports indicate that plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) increase in atrial fibrillation (AF), but decrease after successful direct current (DC) cardioversion. Although the maze procedure is the only curative therapy for AF, the effects on atrial and left ventricular function remain unclear. The study aim was to determine whether plasma ANP and BNP levels decrease after the maze procedure in patients with mitral valve disease.. Twenty-seven patients either with (n = 23) or without (n = 4) AF underwent mitral valve surgery; of these patients, 13 underwent a maze procedure for chronic AF. Blood samples and echocardiographic data were obtained before and at one year after surgery.. Ten patients with AF achieved sinus rhythm (SR) or junctional rhythm after the maze procedure. In patients subjected to mitral valve surgery, mean plasma levels of ANP and BNP were 59.8 +/- 11.9 and 139.2 +/- 53.7 pg/ml, respectively. ANP and BNP plasma levels fell significantly after surgery (to 32.1 +/- 4.1 and 46.7 +/- 10.2 pg/ml, respectively; p = 0.04 and p = 0.004). In patients with successful maze procedure, plasma levels of BNP and left ventricular end-diastolic dimension (LVDd) were significantly decreased by 35.7% and 82.7% compared with preoperative values (BNP, 35.7 +/- 4.9% for SR versus 83.4 +/- 9.6% for AF, p = 0.008; LVDd, 82.7 +/- 3.7% for SR versus 97.0 +/- 3.2% for AF, p = 0.0159).. A successful maze procedure significantly decreased LVDd and plasma levels of BNP after surgery. These results show that the maze procedure is effective in improving left ventricular diastolic dysfunction for a mid-term period in patients with mitral valve disease.

Topics: Adult; Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Cohort Studies; Electric Countershock; Female; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Mitral Valve Stenosis; Natriuretic Peptide, Brain; Probability; Prognosis; Regression Analysis; Retrospective Studies; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome

Cardiac troponin I (cTnI), a sensitive and specific marker of myocardial cell injury, is useful in diagnosing and assessing prognosis in acute coronary syndromes. Small studies report that cTnI is elevated in severe heart failure (HF) and may predict adverse outcomes.. The present study evaluated 238 patients with advanced HF referred for cardiac transplantation evaluation who had cTnI assay drawn at the time of initial presentation. Patients with acute myocardial infarction or myocarditis were excluded from analysis. cTnI was detectable (cTnI > or =0.04 ng/mL) in serum of 117 patients (49.1%). Patients with detectable cTnI levels had significantly higher B-type natriuretic peptide (BNP) levels (P<0.001) and more impaired hemodynamic profiles, including higher pulmonary wedge pressures (P=0.002) and lower cardiac indexes (P<0.0001). A significant correlation was found between detectable cTnI and progressive decline in ejection fraction over time. Furthermore, detectable cTnI was associated with increased mortality risk (RR, 2.05; 95% CI, 1.22 to 3.43). After adjustment for other factors associated with adverse prognosis including age, sex, ejection fraction, and coronary artery disease, cTnI remained a significant predictor of death. cTnI used in conjunction with BNP further improved prognostic value.. cTnI is associated with impaired hemodynamics, elevated BNP levels, and progressive left ventricular dysfunction in patients with HF. cTnI may be a novel, useful tool in identifying patients with HF who are at increased risk for progressive ventricular dysfunction and death.

Topics: Academic Medical Centers; Atrial Natriuretic Factor; California; Chronic Disease; Cohort Studies; Comorbidity; Disease Progression; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Risk Assessment; Survival Rate; Troponin I; Ventricular Dysfunction

Stimulation of cardiomyocyte guanosine 3',5'-cyclic monophosphate (cyclic GMP) via endothelial-derived nitric oxide (NO) is an important mechanism by which bradykinin and ACE inhibitors prevent hypertrophy. Endothelial NO dysfunction and cardiac hypertrophy are morbid features of diabetes not entirely prevented by ACE inhibitors. In cardiomyocyte/endothelial cell cocultures, bradykinin efficacy is abolished by high-glucose-induced endothelial NO dysfunction. We now demonstrate that antihypertrophic actions of natriuretic peptides, which stimulate cyclic GMP independently of NO, are preserved in cardiomyocytes despite high-glucose-induced endothelial dysfunction. Further, streptozotocin-induced diabetes significantly impairs the effectiveness of acute antihypertrophic strategies in isolated rat hearts. In hearts from citrate-treated control rats, angiotensin II-stimulated [(3)H]phenylalanine incorporation and atrial natriuretic peptide and beta-myosin heavy chain mRNA expression were prevented by B-type natriuretic peptide (BNP), bradykinin, the ACE inhibitor ramiprilat, and the neutral endopeptidase inhibitor candoxatrilat. These antihypertrophic effects were accompanied by increased left ventricular cyclic GMP. In age-matched diabetic hearts, the antihypertrophic and cyclic GMP stimulatory actions of bradykinin, ramiprilat, and candoxatrilat were absent. However, the blunting of hypertrophic markers and accompanying increases in cyclic GMP stimulated by BNP were preserved in diabetes. Thus BNP, which increases cyclic GMP independently of NO, is an important approach to prevent growth in the diabetic myocardium, where endothelium-dependent mechanisms are compromised.

Topics: Acute Disease; Animals; Atrial Natriuretic Factor; Cardiomegaly; Cells, Cultured; Chronic Disease; Cyclic GMP; Diabetes Mellitus, Experimental; Gene Expression; Heart Ventricles; Male; Myocytes, Cardiac; Natriuretic Peptide, Brain; Phenylalanine; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tritium

In 40 patients with chronic moderate to severe aortic regurgitation, brain natriuretic peptide, N-brain natriuretic peptide, and atrial natriuretic peptide were higher in symptomatic patients compared with asymptomatic patients after adjustment for age, gender, and ejection fraction, but each natriuretic peptide correlated weakly with echocardiographic measures of left ventricular size and function. In patients with chronic aortic regurgitation, measurement of natriuretic peptide levels may provide information on left ventricular function in addition to echocardiography.

Topics: Adult; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Chronic Disease; Echocardiography; Female; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Sensitivity and Specificity; Severity of Illness Index; Stroke Volume; Ventricular Dysfunction, Left

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, and patients with chronic heart failure (CHF) are reported to have high plasma ET-1 levels. The aim of this study was to investigate the relation between plasma ET-1 levels and clinical correlates in patients with CHF. The effects of maximal exercise on plasma ET-1 levels were also investigated.. Plasma concentrations of ET-1, norepinephrine, and atrial and brain natriuretic peptide (ANP and BNP) both at rest and after maximal cardiopulmonary exercise test were determined in 100 patients with CHF (60 +/- 12 years, New York Heart Association [NYHA] class I-III, left ventricular ejection fraction [LVEF]=36 +/- 8%, peak oxygen uptake [VO2] = 18.2 +/- 5.0 mL/min/kg) and 27 controls.. Patients with NYHA class II and III CHF had higher ET-1 levels (controls, NYHA class I, II, III: 2.1 +/- 0.6, 2.1 +/- 1.0, 2.6 +/- 0.9, 3.4 +/- 0.8 pg/mL, analysis of variance P <.0001). Maximal exercise did not alter ET-1 levels in controls or in each CHF subgroup. When all CHF patients were analyzed together, cardiothoracic ratio (P<.01), peak VO2 (P<.001), plasma norepinephrine (P<.01), plasma ANP (P<.01), and plasma BNP (P<.001) were significantly related with resting ET-1 levels on univariate analysis. Multivariate analysis revealed peak VO2 and plasma BNP levels showed an independent and significant relationship with the resting plasma ET-1 levels.. Resting ET-1 levels were increased in symptomatic patients with CHF, and maximal exercise did not increase ET-1 levels. Peak VO2 and plasma BNP levels were independently associated with resting plasma ET-1 levels in patients with CHF.

Topics: Aged; Anaerobic Threshold; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Endothelin-1; Exercise; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Norepinephrine; Severity of Illness Index; Statistics as Topic; Systole; Ventricular Dysfunction, Left

The selection of patients for cardiac transplantation (CTx) is notoriously difficult and traditionally involves clinical assessment and an assimilation of markers of the severity of CHF such as the left ventricular ejection fraction (LVEF), maximum oxygen uptake (peak VO2) and more recently, composite scoring systems e.g. the heart failure survival score (HFSS). Brain natriuretic peptide (BNP) is well established as an independent predictor of prognosis in mild to moderate chronic heart failure (CHF). However, the prognostic ability of NT-proBNP in advanced heart failure is unknown and no studies have compared NT-proBNP to standard clinical markers used in the selection of patients for transplantation. The purpose of this study was to examine the prognostic ability of NT-proBNP in advanced heart failure and compare it to that of the LVEF, peak VO2 and the HFSS.. We prospectively studied 142 consecutive patients with advanced CHF referred for consideration of CTx. Plasma for NT-proBNP analysis was sampled and patients followed up for a median of 374 days. The primary endpoint of all-cause mortality was reached in 20 (14.1%) patients and the combined secondary endpoint of all-cause mortality or urgent CTx was reached in 24 (16.9%) patients. An NT-proBNP concentration above the median was the only independent predictor of all cause mortality (chi2=6.03, P=0.01) and the combined endpoint of all cause mortality or urgent CTx (chi2 =12.68, P=0.0004). LVEF, VO2 and HFSS were not independently predictive of mortality or need for urgent cardiac transplantation in this study.. A single measurement of NT-proBNP in patients with advanced CHF, can help to identify patients at highest risk of death, and is a better prognostic marker than the LVEF, VO2 or HFSS.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Oxygen Consumption; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Regression Analysis; ROC Curve; Sensitivity and Specificity; Survival Rate; Ventricular Dysfunction, Left

Cyclic GMP (cGMP) serves as an intracellular second messenger of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and nitric oxide (NO) and its peripheral blood concentration is an index of its biological activity. It has been reported that the plasma concentration of cGMP is correlated with the concentrations of ANP and BNP and is related to the prognosis of chronic heart failure patients, but the relation with NO has not been studied. Therefore, we investigated the roles of ANP, BNP, and NO in relation to cGMP in the blood during worsening and improvement of chronic heart failure. The subjects were 25 patients who were hospitalized in our hospital for acute worsening of chronic heart failure. Plasma concentrations of NO, norepinephrine (NE), ANP, BNP, and cGMP were measured on acute worsening (admission) and improvement (discharge) of heart failure. The cGMP concentration on worsening showed a positive correlation with the NO concentration (r = (0.57, P < 0.01), but no correlations with ANP or BNP were observed. The cGMP concentration on improvement showed no correlation with the NO concentration, but a positive correlation with ANP (r = 0.69, P < 0.001) and BNP (r = 0.67, P < 0.001). No correlation was observed between the NO and NE concentrations. We also studied serious cases of NYHA IV and mild cases of NYHA II to III. The cGMP concentration in the serious group showed a positive correlation with the NO concentration but no correlations with ANP or BNP concentrations on worsening. However, in the mild group, the cGMP concentration during worsening showed positive correlations with both the NO and BNP concentrations. On improvement, the cGMP concentration showed no correlation with the NO concentration but positive correlations with both the ANP and BNP concentrations in both the severe and mild groups. The results suggest the possibility that cGMP is produced mainly by NO during worsening, and by ANP and BNP rather than NO during improvement of chronic heart failure.

Topics: Aged; Analysis of Variance; Atrial Natriuretic Factor; Chronic Disease; Cyclic GMP; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Nitric Oxide; Norepinephrine; Tropanes

Chronic heart failure (CHF) is characterized by the activation of neurohormones and cytokines. This study determined whether peak oxygen uptake (VO2) can be predicted by the degree of neurohormonal and cytokine activations in CHF. Plasma norepinephrine. epinephrine, renin-angiotensin system activity, ANP, BNP, and serum interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha were measured in 84 CHF patients (age, 59 +/- 1 years, LVEF, 36 +/- 1%) and 34 controls. Maximal cardiopulmonary exercise testing was performed. Peak VO2 (Controls vs CHF: 27.8 +/- 1.3 vs 18.2 +/- 0.5 mL/min/kg, P < 0.0001) was lower in CHF. Patients with CHF had increased plasma norepinephrine (211 +/- 11 vs 315 +/- 24 pg/mL), renin activity (1.2 +/- 0.2 vs 6.2 +/- 1.1 ng/mL/hr), ANP (22 +/- 3 vs 72 +/- 7 pg/mL), and BNP levels (18 +/- 3 vs 200 +/- 25 pg/mL) (all P < 0.01). Serum IL-6 (1.1 0.1 vs 2.4 +/- 0.3 pg/mL) and TNF-alpha (2.7 +/- 0.2 vs 4.0 +/- 0.3 pg/mL) levels were higher in CHF (both P < 0.001). Univariate analysis revealed that age (P < 0.001), cardiothoracic ratio (P < 0.001), norepinephrine (P < 0.0001), ANP (P < 0.001), BNP (P < 0.01), and log IL-6 (P < 0.05) were significantly related with peak VO2. Stepwise regression analysis indicated that plasma norepinephrine and ANP emerged as significant determinants of peak VO2, independent of patient age (overall R = 0.61, P < 0.0001). In summary, patients with CHF exhibited activation of neurohormones and proinflammatory cytokines. Among the elevated hormonal and cytokine markers, plasma norepinephrine and ANP levels were independent predictors of exercise capacity.

Topics: Atrial Natriuretic Factor; Chronic Disease; Cytokines; Exercise Test; Female; Heart Failure; Humans; Interleukin-6; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Neurotransmitter Agents; Norepinephrine; Oxygen Consumption; Renin-Angiotensin System; Tumor Necrosis Factor-alpha

Several reports have documented the potential benefits of cell transplantation as an alternative to cardiac transplantation. This study was designed to investigate whether cardiomyocyte transplantation is effective in rats with chronic myocardial infarction.. Syngeneic Lewis rats were used in this study. Chronic myocardial infarction was induced in rats by ligating the left anterior descending artery. Four weeks later, after left ventricular (LV) dysfunction with akinetic regions was confirmed by echocardiography, the rats were randomized into two groups: a group that received fetal cardiomyocyte transplantation (TX group; n = 11); and a group that received an intramyocardial injection of culture medium only (control group; n = 12).. Four weeks after treatment, the TX group had smaller end-systolic dimension (LVDs) (7.5 +/- 0.9 vs 8.9 +/- 0.8 mm, p < 0.01) and better fractional shortening (FS) (26.2 +/- 5.9 vs 17.7% +/- 5.1%, p < 0.01) than the control group. However, there were no differences in LV end-diastolic dimension, LVDs, and FS between baseline and post-treatment values in the TX group. In addition, plasma levels of atrial natriuretic peptide were not significantly different between the two groups 4 weeks after treatment. In microscopic examination, small amounts of transplanted cardiomyocytes were found only in the periinfarct area, not in the center of scar area, and a thicker ventricular wall in the infarct area was detected in the TX group.. Fetal cardiomyocyte transplantation prevented, but did not reverse, cardiac remodeling that was accompanied with heart failure in myocardial infarction rats. Further investigation is warranted for optimal clinical application to the failing heart.

Topics: Animals; Atrial Natriuretic Factor; Cell Transplantation; Chronic Disease; Disease Models, Animal; Fetal Heart; Male; Myocardial Infarction; Myocardium; Random Allocation; Rats; Rats, Inbred Lew; Ventricular Dysfunction, Left

Topics: Aged; Analysis of Variance; Atrial Natriuretic Factor; Chronic Disease; Female; Heart Failure; Hemodynamics; Humans; Male; Norepinephrine; Posture

Heart endocrine studies concerning patients with chronic atrial fibrillation (AF) have become increasingly important. Atrial natriuretic peptide (ANP) is released from atrial myocytes. The increased level of ANP in patients with AF is probably caused by the hemodynamic effect of the arrhythmia. The aim of this study was to explore plasma ANP levels in patients with chronic AF and to describe plasma ANP concentration changes following sinus rhythm (SR) restoration. The study group was comprised of 42 patients, aged between 43 and 76 years with chronic AF (more than 1 month) and a relatively controlled ventricular response (85.8+/-11.3 beats/min). Plasma ANP levels were measured before and 24 h after AF cardioversion. The control group comprised of 11 subjects. All had normal SR without history of AF and were compatible in age, sex and concomitant diseases with the examined group. ANP level values were expressed as mean+/-standard deviation. The mean plasma ANP level in the AF group was significantly higher than in the control group (59.5+/-15.6 vs. 34.3+/-10.2 pg/ml, P<0,001). Electrical or pharmacological cardioversion was performed in 42 patients. SR was successfully restored in 35 patients. Plasma ANP concentrations decreased significantly from baseline values (from 59.4+/-16.6 to 31.4+/-15.0 pg/ml, P<0.001) 24 h after cardioversion in the successful group, while they remained unchanged (60.2+/-10.7 to 59.4+/-10.4 pg/ml, NS) in patients with an unsuccessful cardioversion.. The mean concentration of ANP in patients with chronic AF was nearly two-times higher than in the control group with sinus rhythm. Conversion to SR was associated with a significant decrease and normalization in plasma ANP concentrations.

Topics: Adult; Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Echocardiography; Electric Countershock; Female; Follow-Up Studies; Heart Rate; Humans; Linear Models; Male; Middle Aged; Monitoring, Physiologic; Probability; Prognosis; Prospective Studies; Reference Values; Sensitivity and Specificity; Treatment Outcome

Given the high incidence of sudden death in patients with chronic heart failure (CHF) and the efficacy of implantable cardioverter-defibrillators, an appropriate tool for the prediction of sudden death is desirable. B-type natriuretic peptide (BNP) has prognostic significance in CHF, and the stimuli for its production cause electrophysiological abnormalities. This study tests BNP levels as a predictor of sudden death.. BNP levels, in addition to other neurohormonal, clinical, and hemodynamic variables, were obtained from 452 patients with a left ventricular ejection fraction (LVEF) < or =35%. For prediction of sudden death, only survivors without heart transplantation (HTx) or a mechanical assist device and patients who died suddenly were analyzed. Up to 3 years, 293 patients survived without HTx or a mechanical assist device, 89 patients died, and 65 patients underwent HTx. Mode of death was sudden in 44 patients (49%), whereas 31 patients (35%) had pump failure and 14 patients (16%) died from other causes. Univariate risk factors of sudden death were log BNP (P=0.0006), log N-terminal atrial natriuretic peptide (P=0.003), LVEF (P=0.005), log N-terminal BNP (P=0.006), systolic blood pressure (P=0.01), big endothelin (P=0.03), and NYHA class (P=0.04). In the multivariate model, log BNP level was the only independent predictor of sudden death (P=0.0006). Using a cutoff point of log BNP <2.11 (130 pg/mL), Kaplan-Meier sudden death-free survival rates were significantly higher in patients below (99%) compared with patients above (81%) this cutoff point (P=0.0001).. BNP levels are a strong, independent predictor of sudden death in patients with CHF.

Topics: Adrenergic beta-Antagonists; Alprostadil; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cardiotonic Agents; Chronic Disease; Comorbidity; Death, Sudden, Cardiac; Endothelin-1; Endothelins; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Protein Precursors; Risk Factors; Stroke Volume; Survival Analysis; Treatment Outcome

Congestive heart failure (CHF) is a disease that is characterized by progressive left ventricular (LV) dysfunction and dilatation. Oxidative stress is thought to contribute to the progression of CHF, and antioxidants have been shown to have beneficial effects when started early after myocardial infarction (MI). In this study, we tested whether the powerful antioxidant probucol would attenuate progression of CHF once it was established after MI in the rat.. Ligation of a coronary artery was used to create an MI in rats (n=266). Survivors were then randomized 20 days after MI to either probucol 61 mg. kg(-1). d(-1) or vehicle and followed up for a total of 100 days after MI. Studies of cardiac hemodynamics, LV remodeling, cardiac apoptosis and morphology, systemic neurohumoral activation, oxidative stress, and renal function were then evaluated. Probucol improved LV function (LV maximum rate of pressure rise from 3103 to 4250 mm Hg/s, P<0.05, and LV end-diastolic pressure decrease from 28 to 24 mm Hg, P<0.05), reduced pulmonary weights, prevented right ventricular systolic hypertension, and preserved renal function compared with vehicle. Probucol also prevented LV dilatation, prevented wall thinning (1.70 versus 1.42 mm, P<0.05), reduced cardiac fibrosis and cardiac apoptosis, attenuated increased myocardial cell cross-sectional area, and increased scar thickness.. In chronic CHF, probucol exerts multiple beneficial morphological effects that result in better LV remodeling and function, reduced neurohumoral activation, and preserved renal function.

Topics: Animals; Antioxidants; Apoptosis; Atrial Natriuretic Factor; Chronic Disease; Disease Models, Animal; Heart Failure; Heart Ventricles; Hemodynamics; Kidney Failure, Chronic; Kidney Function Tests; Male; Myocardial Infarction; Myocardium; Norepinephrine; Oxidative Stress; Probucol; Rats; Rats, Wistar; Survival Rate; Time; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling

In chronic heart failure, several hormonal systems are activated with diagnostic and prognostic implications. We tested the hypotheses that serum Chromogranin-A (CgA) -- a 49 kDa acid protein present in the secretor granules of neuroendocrine cells -- is increased in chronic heart failure and that CgA levels are a predictive factor for mortality.. In 160 patients with chronic heart failure, we measured serum CgA and other neuroendocrine hormones. The results showed that CgA is increased in chronic heart failure and the increase is related to the clinical severity of the syndrome: CgA levels in New York Heart Failure (NYHA) class II (median 146.9 ng x ml(-1), inter-quartiles 108.3-265.5) were significantly higher (P<0.05) than in class I (median 109.7 ng x ml(-1), inter-quartiles 96.7-137.6), and significantly lower (P<0.05) than in class III (median 279.0 ng x ml(-1), inter-quartiles 203.6-516.1). Class IV patients showed the highest serum levels of CgA (median 545.0 ng. ml(-1), inter-quartiles 231.8-1068.3), being statistically significantly different from class III patients (P<0.001). The association between survival and some recognized variables of prognostic significance, including CgA was also studied. The results showed that ejection fraction, noradrenaline, atrial natriuretic peptide, NYHA class and CgA were significant univariate prognosticators; however, in the multivariate analysis by the Cox proportional-hazard model, CgA and NYHA class were the only independent predictive factors for mortality (P<0.005, RR=1.22, 95% CI=1.06-1.41 and P=0.04, RR=1.58, 95% CI=1.02-2.46, respectively).. CgA is a pro-hormone, precursor of several active fragments likely to exert biological effects in chronic heart failure. CgA serum levels are increased in patients with chronic heart failure and are a predictive factor for mortality.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Chromogranin A; Chromogranins; Chronic Disease; Female; Follow-Up Studies; Heart Failure; Humans; Italy; Male; Middle Aged; Predictive Value of Tests; Prognosis; Renin; Severity of Illness Index; Stroke Volume; Survival Analysis

Individuals with chronic mountain sickness (CMS) show severe hypoxemia, excessive polycythemia, and marked pulmonary hypertension. The pathophysiologic mechanisms of CMS are still not completely understood.. We determined plasma atrial natriuretic peptide (ANP), red cell 2,3-diphosphoglycerate (2,3-DPG), hematocrit, hemoglobin, and arterialized ear lobe blood gas values in 13 patients with CMS (9 Hans, 4 Tibetans) and 18 control Han Chinese men of similar age, height, and weight who had been living at 4300 m on the Tibetan plateau of Qinghai Province, China, for approximately 14 years.. A significantly higher level of ANP was found in the CMS patients compared to the non-CMS patients (113.4+/-5.5 pg/mL vs 87.6+/-4.7 pg/mL, P < .01), and the levels of ANP correlated positively with the hemoglobin concentration (r = 0.8282, P < .01). The 2,3-DPG levels in the CMS patients were significantly increased compared to the non-CMS subjects (5.23+/-0.16 mmol/L vs 4.40+/-0.12 mmol/L, P < .01), and the 2,3-DPG concentrations in the CMS patients were negatively correlated with their PaO2 values (r = -0.7898, P < .01). The CMS patients had significantly higher PaCO2 levels, lower pH values, lower PaO2 levels, and greater alveolar-arterial oxygen differences (PAO2 - PaO2) compared to the non-CMS subjects.. These findings suggest that overproduction of ANP and 2,3-DPG at high altitudes may play an important role in the pathophysiology of chronic mountain sickness.

Topics: 2,3-Diphosphoglycerate; Adult; Altitude Sickness; Atrial Natriuretic Factor; Blood Gas Analysis; Case-Control Studies; Chronic Disease; Erythrocytes; Humans; Male; Respiratory Function Tests

Enhanced atrial natriuretic factor (ANF) production by the heart is related to hemodynamic overload, cardiac growth, and hypertrophy. The heart is one of the most affected organs during Trypanosoma cruzi infection. We tested the hypothesis that myocarditis produced by parasite infection alters the natriuretic peptide system by investigating the behavior of plasma ANF during the acute and chronic stages of T. cruzi infection in rats. Sprague-Dawley rats were infected with T. cruzi clone Sylvio-X10/7. Cardiac morphology showed damage to myocardial cells and lymphocyte infiltration in the acute phase; and fibrosis and cell atrophy in the chronic period. Plasma ANF levels (radioimmunoassay) were significantly higher in acute (348 +/- 40 vs. 195 +/- 36 pg/ml, P < 0.05, n = 17) and chronic T. cruzi myocarditis (545 +/- 81 vs. 229 +/- 38 pg/ml, P < 0.001, n = 11) than in their respective controls (n = 10 and 14). Rats in the chronic phase also showed higher levels than rats in the acute phase (P < 0.01). The damage of myocardial cells produced by the parasite and the subsequent inflammatory response could be responsible for the elevation of plasma ANF during the acute period of T. cruzi infection. The highest plasma ANF levels found in chronically infected rats could be derived from the progressive failure of cardiac function.

Topics: Acute Disease; Animals; Atrial Natriuretic Factor; Body Weight; Chagas Cardiomyopathy; Chronic Disease; Disease Models, Animal; Heart; Male; Myocardium; Rats; Rats, Sprague-Dawley

The purpose of this study was to assess whether transthoracic Doppler echocardiography and serum natriuretic peptide levels could predict mean pulmonary capillary wedge pressure (PCWP) in patients with chronic atrial fibrillation. We examined mitral flow velocity and pulmonary venous flow (PVF) velocity patterns in 32 patients with chronic atrial fibrillation. Plasma A-type and B-type natriuretic peptide (ANP, BNP, respectively) levels in the peripheral vein were measured. Significant correlations were observed between mean PCWP and the following: peak velocity (r = 0.51) and deceleration time (r = -0.65) of the mitral flow; peak velocity (r = 0.64) and deceleration time (r = -0.80) of the PVF; BNP (r = 0.60); and ANP (r = 0.36). Stepwise multiple linear regression analysis selected PVF deceleration time and mitral flow deceleration time as independent predictors of PCWP. A cutoff value of PVF deceleration time of < or =150 ms and a mitral flow deceleration time of < or =100 ms predicted a mean PCWP of > or =18 mm Hg, with a sensitivity of 100% and 80% and a specificity of 96% and 85%, respectively. In conclusion, PVF deceleration time and mitral flow deceleration time obtained from transthoracic Doppler echocardiography are more accurate predictors of mean PCWP than values obtained with natriuretic peptides in patients with chronic atrial fibrillation.

Topics: Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Chronic Disease; Echocardiography, Doppler; Female; Humans; Male; Middle Aged; Mitral Valve; Pulmonary Valve; Pulmonary Wedge Pressure; Regional Blood Flow; Regression Analysis

Atrial transport and atrial natriuretic peptide secretion is severely reduced from normal after the maze III procedure. To improve these factors, we developed a bilateral appendage-preserving maze procedure (BAP-maze).. Forty-six patients with chronic atrial fibrillation who underwent the BAP-maze procedure were compared with 40 patients who underwent the maze III procedure. The ratio of the peak velocity of the A and E waves of transmitral flow (transthoracic pulsed Doppler echocardiography), the left atrial appendage ejection fraction (transesophageal echocardiography), and the atrial natriuretic peptide secretory reserve during treadmill exercise test were measured at 6 months postoperatively.. Sinus rhythm was restored in 44 patients (95.7%) by the BAP-maze procedure and in 39 patients (97.5%) by the maze III procedure. The ratio of the peak velocity of the A and E waves was 0.52 +/- 0.22 in the BAP-maze group and 0.25 +/- 0.19 in the maze III group (p < 0.0001). The left atrial appendage ejection fraction was 44.7% +/- 11.5%, and the atrial natriuretic peptide secretory reserve was greater in the BAP maze group (p = 0.037).. The BAP-maze procedure improved atrial transport and atrial natriuretic peptide secretion as well as simplifying the maze operation, without decreasing its effectiveness against atrial fibrillation.

Topics: Aged; Atrial Fibrillation; Atrial Function; Atrial Natriuretic Factor; Cardiac Surgical Procedures; Chronic Disease; Female; Follow-Up Studies; Humans; Male; Middle Aged; Postoperative Complications

The objective was to determine the independent association between atrial fibrillation (A-Fib) and activation of natriuretic peptides.. The association of A-Fib with activation of N-terminal atrial and brain natriuretic peptides (N-ANPs and BNPs, respectively) is uncertain but of great importance for the diagnostic utilization of natriuretic peptides. This uncertainty is related to the lack of appropriate controls, with left ventricular (LV) and atrial overload similar to A-Fib.. We prospectively measured N-terminal atrial and BNPs and endothelin-1 levels in 100 patients and 14 age- and gender-matched control subjects. The 32 patients with A-Fib were compared with 68 patients in sinus rhythm and similar LV and atrial overload (due to mitral regurgitation or LV dysfunction) measured simultaneously with hormonal levels with comprehensive Doppler echocardiography.. Patients with A-Fib compared with those in sinus rhythm had similar symptoms, comorbid conditions, cardioactive medications, pulmonary pressure, left atrial volume, and LV ejection fraction and filling characteristics but demonstrated higher N-ANP levels (2,613 +/- 1,681 vs. 1,654 +/- 1,323 pg/ml, p = 0.007) even after adjustment for the underlying cardiac disease (p < 0.0001). Conversely, BNP levels were similar in both groups (165 +/- 163 vs. 160 +/- 269 pg/ml, p = 0.9). In multivariate analysis, a higher N-ANP level was associated with A-Fib (p = 0.0003), symptom class (p < 0.0001) and endothelin-1 level (p = 0.032) independently of left atrial volume and LV ejection fraction. Conversely, BNP showed no independent association with and was most strongly associated with LV ejection fraction (p < 0.0001).. Atrial fibrillation is an independent determinant of higher N-ANP levels and blurs its association with LV dysfunction. Conversely, the BNP is not independently associated with A-Fib and is strongly determined by LV dysfunction, for which it is an independent marker.

Topics: Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Chronic Disease; Echocardiography, Doppler; Endothelin-1; Female; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Prospective Studies; Protein Precursors; Reproducibility of Results; Severity of Illness Index; Stroke Volume; Ventricular Dysfunction, Left

Endothelin-converting enzyme-1 (ECE-1) processes big endothelin-1 (ET-1) to ET-1, a peptide implicated in atheroma formation. ECE-1 exists in 2 isoforms (ECE-1alpha and ECE-1beta), the result of alternative splicing of a common gene. Neutral endopeptidase (NEP) is a genetically distinct metallopeptidase that degrades the natriuretic peptides. These peptides mediate antiproliferative and vasodilating actions. We sought to demonstrate the distribution of the 2 ECE-1 isoforms in experimental atherosclerosis, to determine the effects of chronic NEP-I on plasma cGMP concentrations, vascular wall ECE-1 activity, and ET-1 concentration, and to correlate these actions with atheroma formation. Our hypothesis was that chronic NEP-I, in association with augmented cGMP, would inhibit ECE-1 conversion of big ET-1 to active ET-1, thus reducing tissue ET-1 concentrations and associated atheroma formation.. Cholesterol-fed New Zealand White rabbits (n=8, 1% cholesterol diet) and NEP-I-treated cholesterol-fed New Zealand White rabbits (n=8; candoxatril, 30 mg/kg per day, Pfizer) were euthanized after 8 weeks of feeding. ECE-1alpha and ECE-1beta immunoreactivity was present in the aortas of both groups. Compared with control values, plasma cGMP concentrations were increased (2.8+/-0.6 versus 8.4+/-1.2 pmol/mL, P<0.05), ECE-1 activity was attenuated (68+/-3% versus 32+/-8%, P<0. 05), aortic tissue ET-1 concentrations were reduced (4.6+/-0.5 versus 3.2+/-0.3 pg/mg protein, P<0.05), and atheroma formation was attenuated (62+/-6% versus 34+/-5%, P<0.01) by NEP-I.. These studies suggest that ECE-1 is present and functionally active in the vascular wall in atherosclerosis. Inhibition of ECE-1 by NEP-I represents a novel approach to interruption of the endothelin system in this cardiovascular disease state.

Topics: Animals; Aorta; Arteriosclerosis; Aspartic Acid Endopeptidases; Atrial Natriuretic Factor; Chronic Disease; Cyclic GMP; Diet, Atherogenic; Disease Models, Animal; Endothelin-1; Endothelin-Converting Enzymes; Endothelins; In Vitro Techniques; Isoenzymes; Male; Metalloendopeptidases; Neprilysin; Protein Precursors; Rabbits; Time Factors; Vasoconstriction

We compared the value of plasma neurohormones and cardiopulmonary exercise testing for predicting long-term prognosis in patients with moderate congestive heart failure (CHF). We studied 264 consecutive patients with CHF due to left ventricular systolic dysfunction. Plasma atrial natriuretic peptide (ANP), norepinephrine, and endothelin-1 were measured at rest in all patients, who also underwent a symptom-limited maximal exercise with oxygen consumption (VO(2)) determination. After a median follow-up of 789 days, 52 deaths and 31 heart transplantations occurred, of which 4 were urgent. In an univariate analysis, New York Heart Association functional class, systolic blood pressure at rest, left ventricular end-diastolic diameter, left ventricular ejection fraction, peak VO(2), percent of predicted peak VO(2), plasma ANP, plasma norepinephrine, and plasma endothelin-1 were associated with survival without urgent heart transplantation. In a multivariate stepwise regression analysis, only plasma ANP (p = 0.0001), left ventricular ejection fraction (p = 0.007), and plasma norepinephrine (p = 0.035), but neither peak VO(2) nor percentage of predicted peak VO(2), were independent predictors of death or urgent heart transplantation. Determination of plasma ANP and norepinephrine provides additional independent information for long-term prognostic determination compared with exercise testing alone. Measurement of plasma neurohormones should therefore be considered routinely as a complementary or alternative tool for identifying high-risk patients with moderate CHF.

Topics: Atrial Natriuretic Factor; Chronic Disease; Disease-Free Survival; Endothelin-1; Exercise Test; Female; Heart Failure; Heart Transplantation; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Oxygen Consumption; Prognosis; Stroke Volume

Chronic atrial fibrillation (AF) is one of the main complications of sick sinus syndrome (SSS). As previously reported, plasma brain natriuretic peptide (BNP), reflects hemodynamic changes in different pacing modes, as does plasma atrial natriuretic peptide (ANP), so the present study investigated whether plasma BNP or ANP can predict chronic AF after single-chamber ventricular (VVI) pacemaker implantation in patients with SSS. Plasma ANP and BNP levels were measured before and 1-3 months after implantation in 99 SSS patients. Long-term follow-up was conducted with chronic AF as an endpoint. Chronic AF occurred in 19 patients during a mean follow-up of 5.1 years. Plasma ANP and BNP were significantly higher in the patients who developed chronic AF after implantation than in those who did not, despite similar ANP and BNP levels between the 2 groups before implantation. Post-implant high BNP and a history of paroxysmal AF were independent predictors of chronic AF by a multivariate Cox proportional hazards analysis. Plasma BNP can predict the development of chronic AF after VVI pacemaker implantation in patients with SSS because increased levels may reflect latent hemodynamic abnormalities, which may contribute to the development of AF after VVI pacemaker implantation.

Topics: Actuarial Analysis; Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Cardiac Pacing, Artificial; Chronic Disease; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Proportional Hazards Models; Sick Sinus Syndrome; Survival Rate

This study was designed to determine whether the restrictive filling transmitral flow velocity pattern is associated with increased plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). It was also designed to evaluate the prognostic value of these parameters from patients with chronic congestive heart failure (CHF) admitted for episodes of acute decompensation. We performed Doppler echocardiography, measured plasma levels of ANP and BNP in 33 patients at the time of admission, and assessed the subsequent cardiac mortality for 3 months. Eleven patients (33%) had a restrictive filling pattern of deceleration time (DcT) < 120ms. Plasma ANP and BNP levels were markedly increased in all patients to 189 +/- 145 pg/ml and 865 +/- 559 pg/ml, respectively. Seventeen patients (52%) showed more than 700 pg/ml of plasma levels of BNP. There was a significant correlation of DcT with the plasma ANP level (r = -0.41, P = 0.017), and a better correlation of DcT with the plasma BNP level (r =-0.50, P = 0.003). The combined index of both shorter DcT (< 120 ms) and higher plasma BNP levels (>700 pg/ml) was the best predictor of cardiac mortality by Cox univariate analysis (chi2 = 5.87, P = 0.015). Furthermore, the sensitivity and specificity of this index for the detection of cardiac mortality were 80% and 86%, respectively. In conclusion, the combined analysis of the Doppler transmitral flow velocity pattern and measurement of the plasma BNP level is noteworthy since it is noninvasive and convenient. Moreover, it is extremely useful in predicting the prognosis for patients with chronic CHF admitted for episodes of acute decompensation.

Topics: Acute Disease; Aged; Atrial Natriuretic Factor; Blood Flow Velocity; Chronic Disease; Echocardiography, Doppler; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Prognosis

Atrial Natriuretic Peptide (ANP) exerts a chronic hypotensive effect which is mediated by a reduction in total peripheral resistance (TPR). Mice with a homozygous disruption of the pro-ANP gene (-/-) fail to synthesize ANP and develop chronic hypertension in comparison to their normotensive wild-type (+/+) siblings. In order to determine whether alterations in basal hemodynamics underlie the hypertension associated with lack of endogenous ANP activity, we used anesthetized mice to measure arterial blood pressure (ABP) and heart rate (HR), as well as cardiac output (CO) by thermodilution technique. -/- (n = 7) and +/+ (n = 10) mice of comparable weight and age were used. Stroke volume (SV) and TPR were derived from CO, HR, and ABP by a standard formula. ABP (mm Hg) was significantly higher in -/- (132+/-4) (P < 0.0001) than in +/+ mice (95+/-2). CO (ml min(-1)), HR(beats min(-1))and SV (microl beat(-1)) did not differ significantly between -/- and +/+ mice (CO -/- = 7.3+/-0.5, +/+ = 8.3+/-0.6; HR -/- = 407+/-22, +/+ = 462+/-21; SV -/- = 17.6+/-1.1, +/+ = 17.6+/-1.7). However, TPR (mm Hg ml(-1) min(-1)) was significantly elevated in -/- mice (18.4+/-0.7) compared to +/+ mice (12.3+/-1) (P = 0.0003). Autonomic ganglion blockade with a mixture of hexamethonium and pentolinium was followed by comparable percent reductions in CO (-/- = 28+/-4, +/+ = 29+/-3), HR (-/- = 9+/-4, +/+ = 16+/-4) and SV(-/- = 21+/-4, +/+ = 15+/-6) in both genotypes. However, the concomitant decrease in ABP (%) in -/- (41+/-2) was significantly greater than in +/+ (23+/-4) mice (P = 0.0009) and was accompanied by a significant reduction in TPR. We conclude that the hypertension associated with lack of endogenous ANP is due to elevated TPR, which is determined by an increase in cardiovascular autonomic tone.

Topics: Animals; Atrial Natriuretic Factor; Cardiac Output; Chronic Disease; Hemodynamics; Hypertension; Mice; Mice, Knockout; Vascular Resistance

In the present study, the relationship between the blood erythropoietin level and cardiac function was investigated in 15 patients on chronic hemodialysis who developed chronic heart failure. Another 45 patients without cardiac dysfunction were selected as a control group that was matched for gender, age, and the duration of dialysis. The erythropoietin level was 256.3 +/- 481.8 mU/ml in the heart failure group, which was significantly higher than that in the control group (17.0 +/- 10.0 mU/ml, P < 0.01). Eight of the 15 patients in the heart failure group maintained a hematocrit of more than 30% without receiving recombinant human erythropoietin therapy, whereas 29 of the 45 patients in the control group required erythropoietin. In the heart failure group, the erythropoietin level was significantly correlated with the levels of atrial natriuretic peptide and brain natriuretic peptide (P < 0.01). These results suggest that heart failure can increase the erythropoietin level in proportion to the severity of cardiac dysfunction, even in patients on long-term dialysis.

Topics: Adult; Aged; Atrial Natriuretic Factor; Chronic Disease; Erythropoietin; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis

We investigated whether the effect of long-term intermittent hypoxia (LTIH) on cardiovascular function may be modified by preexisting genetic traits. To induce LTIH experimentally, cycles of 90-s hypoxia (nadir 6%) followed by 90-s normoxia were applied to six Wistar-Kyoto and six spontaneously hypertensive rats during 8 h daily. Comparison with the same number of control animals after 70 days revealed no alteration of intra-arterial blood pressure or heart rate. Blood pressure responsiveness to a brief hypoxic stimulus was enhanced in the LTIH animals, regardless of strain, whereas the hypoxia-induced increase in heart rate was abolished. In the spontaneously hypertensive but not the Wistar-Kyoto rats, LTIH increased left ventricular weight-to-body weight ratio and content of atrial natriuretic peptide mRNA. Expression of B-type natriuretic peptide was unchanged (Northern blot). Slightly increased right ventricular weight-to-body weight ratios in the LTIH animals were associated with higher right ventricular atrial natriuretic peptide and B-type natriuretic peptide mRNA amounts. Consequently, the effects of LTIH on different components of cardiovascular function appear incompletely related to each other and differentially influenced by constitutional traits.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Heart Ventricles; Hemodynamics; Hypoxia; Myocardium; Natriuretic Peptide, Brain; Organ Size; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger

The mechanism of atrial natriuretic peptide (ANP) release has been difficult to demonstrate in patient studies because of inaccuracies in measuring atrial volumes using conventional techniques.. Magnetic resonance imaging was performed in 28 clinically stable patients (New York Heart Association class 3) with chronic heart failure to determine right atrial (RA), left atrial (LA), and ventricular volumes. In addition, right heart catheterization was serially performed and plasma ANP levels (in picograms per milliliter) were drawn from the right atrium.. Five patients had to be excluded from data analysis for technical reasons. The remaining 23 patients had the following hemodynamic measurements (mean +/- SD): RA mean pressure 7+/-5 mm Hg, pulmonary artery mean pressure 28+/-10, pulmonary capillary wedge pressure 21+/-8 mm Hg, and cardiac index 2.9+/-1.4 (L/min/m2), respectively. Plasma ANP levels were significantly elevated at 162+/-117 (normal range 20 to 65 pg/ml, p < 0.05), as were LA and RA volumes compared with healthy controls (RA volume 128+/-64 ml vs 82+/-25 ml, p < 0.05; LA volume 157+/-54 ml vs 71+/-24 ml, p < 0.01, respectively). ANP showed a stronger relation with atrial volumes (RA volume, r = 0.91, p = 0.0001; LA volume, r = 0.80, p = 0.001) than with atrial pressures (RA mean pressure, r = 0.45, p = 0.03; pulmonary capillary wedge pressure, r = 0.67, p = 0.001). A subgroup analysis of patients with increased RA or LA volumes (>1 SD of mean of controls) revealed a stronger relation between ANP and RA volumes than between ANP and LA volumes.. These data suggest that increased right heart volume with subsequent increased atrial stretch is the major determinant for ANP release in patients with stable CHF.

Topics: Adult; Aged; Atrial Function; Atrial Natriuretic Factor; Blood Pressure; Cardiac Catheterization; Chronic Disease; Female; Heart Atria; Heart Failure; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myocardial Contraction; Prospective Studies; Pulmonary Wedge Pressure; Radioimmunoassay; Radionuclide Ventriculography; Regression Analysis

To determine if atrial natriuretic peptide (ANP) level is associated with mortality in the oldest old and to develop a comprehensive model of mortality in the oldest old using clinical and laboratory parameters.. Prospective cohort study with 7 years of follow-up.. A 725-bed life care facility.. 282 frail older individuals (mean age 88, range 70-102).. Variables measured included age, gender, Charlson Comorbidity Index, functional measurements, weight, blood pressure, and multiple laboratory variables, including ANP. Main outcome measurement was death.. Eighty-four percent (237/282) of subjects died during the 7-year follow-up period. On univariate analysis, the risk ratio (RR) for ANP tertile was 1.28. On bivariate analysis, adjusting for the development of congestive heart failure, the RR was 1.22. On multivariate analysis, the following variables were associated with mortality: ANP tertile (RR 1.24), age (RR 1.04), female gender (RR 0.43), Charlson Comorbidity Index score (RR 1.13), mentation score (RR 1.27), BUN/Cr ratio (RR 1.04), albumin level (RR 0.63), and hemoglobin level (RR 0.84).. ANP level and other variables are independent risk factors for mortality in frail individuals. ANP level may indicate homeostatic failure to adapt to fluid volume changes or may reflect subclinical heart disease. ANP level contributes to a multivariate model of mortality in frail older individuals.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Blood Pressure; Blood Urea Nitrogen; Chronic Disease; Comorbidity; Confidence Intervals; Creatinine; Female; Frail Elderly; Geriatric Assessment; Heart Rate; Hemoglobinometry; Humans; Male; Mental Status Schedule; Models, Statistical; Risk; Serum Albumin; Survival Analysis

Chronic schizophrenic patients are reported to develop imbalanced water homeostasis by the pathological secretion of vasopressin and aldosterone. We measured plasma vasopressin, aldosterone and atrial natriuretic peptide in schizophrenic patients to elucidate the role of these hormones during a perioperative period. Eighteen schizophrenic patients with chronic antipsychotic drugs over 10 years and 22 as a control group who underwent elective lower abdominal surgery were the subjects of this study. In the schizophrenic patients, plasma aldosterone secretion was significantly inhibited, while plasma vasopressin and atrial natriuretic peptide were significantly increased during surgery. A good relationship (r = 0.69, p < 0.01) between plasma atrial natriuretic peptide and plasma osmolality was obtained 60 min after skin incision, but not before the induction of anesthesia. The findings suggest that chronic schizophrenic patients may develop an abnormal secretion of vasopressin, aldosterone and atrial natriuretic peptide during anesthesia.

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Case-Control Studies; Chronic Disease; Dopamine; Female; Humans; Intraoperative Period; Linear Models; Male; Middle Aged; Osmolar Concentration; Prospective Studies; Schizophrenia; Time Factors; Vasopressins; Water-Electrolyte Imbalance

Topics: Animals; Atrial Natriuretic Factor; Chronic Disease; Hypertension, Pulmonary; Hypoxia; Mice

One of the earliest recognized postoperative complications of the maze procedure was the fluid retention in the immediate postoperative period. Routine postoperative administration of diuretics markedly reduces the frequency and severity of the fluid retention. However, the cause of the abnormal fluid balance is still uncertain.. We evaluated 24 patients: 15 patients underwent the maze procedure (maze group) and 9 patients did not (nonmaze group). Blood samples were obtained before and in the time course after operation for atrial natriuretic peptide measurement. To evaluate the influence of atrial natriuretic peptide on the body fluid balance, we also measured the amount of body fluid balance and the total doses of furosemide and dopamine administered after operation. To examine the effect of the maze procedure on atrial natriuretic peptide secretion in chronic phase, we measured plasma atrial natriuretic peptide levels during dynamic exercise in 21 patients who had undergone cardiac operations 2 years before.. Plasma atrial natriuretic peptide levels in the nonmaze group significantly increased after operation. In contrast, plasma atrial natriuretic peptide levels in the maze group did not increase, and these levels were significantly lower than in the nonmaze group. Although significantly greater doses of furosemide and dopamine were administered to the maze group than to the nonmaze group, the body fluid balance in the maze group was comparable with that in the nonmaze group in the early postoperative period. The response of atrial natriuretic peptide secretion by exercise was significantly attenuated in the maze group (n = 12) compared with the nonmaze group (n = 9) even 2 years after surgery, although there were no significant differences in heart rate or blood pressure during exercise between two groups.. These results suggest that the maze procedure attenuates atrial natriuretic peptide secretion in the early postoperative period and persists in chronic phase. This attenuated atrial natriuretic peptide secretion may reduce the ability of the kidneys to handle fluid load early after surgery.

Topics: Atrial Fibrillation; Atrial Natriuretic Factor; Body Fluids; Cardiac Surgical Procedures; Chronic Disease; Diuretics; Dopamine; Exercise; Female; Follow-Up Studies; Furosemide; Heart Atria; Heart Rate; Humans; Male; Middle Aged; Postoperative Complications

Chronic, complete AV block (CAVB) in the dog leads to ventricular hypertrophy, which has been described as an independent risk factor for arrhythmias. In this model, we examined (1) whether the short- and long-term electrical adaptations predispose to acquired torsade de pointes arrhythmias (TdP) and (2) the nature of the structural and functional adaptations involved.. We determined (1) endocardial right (RV) and left (LV) ventricular APD, DeltaAPD (LV APD-RV APD), presence of EADs at 0 weeks (acute: AAVB), and CAVB (6 weeks) and inducibility of TdP by pacing and d-sotalol (n=10); (2) steady-state and dynamic LV hemodynamics at 0 and 6 weeks (n=6); (3) plasma neurohumoral levels in time (n=7); (4) structural parameters of the LV and RV of CAVB dogs (n=6) compared with sinus rhythm (SR) dogs (n=6); and (5) expression of ventricular mRNA atrial natriuretic factor (ANF) in CAVB (n=4) and SR (n=4) dogs. Compared with AAVB, CAVB led to nonhomogeneous prolongation of LV and RV APD and different sensitivity for d-sotalol, leading to EADs (4 of 14 versus 9 of 18, P<0.05), increased DeltaAPD (45+/-30 versus 125+/-60 ms, P<0.05), and induction of TdP in most dogs (0% versus 60%, P<0.05). CAVB led to biventricular hypertrophy, whereas LV function was similar in AAVB and CAVB. The neurohumoral levels were transiently elevated. The LV and RV collagen and the capillary/fiber ratio remained normal, whereas ventricular ANF mRNA was not detectable.. The electrical remodeling occurring after CAVB predisposes the heart to acquired TdP, whereas the structural changes (hypertrophy) are successfully aimed at maintaining cardiac function.

Topics: Action Potentials; Adaptation, Physiological; Animals; Atrial Natriuretic Factor; Cardiomegaly; Chronic Disease; Coronary Vessels; Disease Models, Animal; Dogs; Electrocardiography; Electrophysiology; Female; Fibrosis; Gene Expression; Heart Block; Heart Ventricles; Hemodynamics; Male; Norepinephrine; Organ Size; RNA, Messenger; Torsades de Pointes

Cardiac natriuretic peptides are activated in heart failure. However, their diagnostic and prognostic values have not been compared under the routine conditions of an outpatient practice.. We studied the diagnostic and prognostic value of plasma N- and C-terminal peptides of the atrial natriuretic factor prohormone (N-proANF and ANF respectively) and brain natriuretic peptide (BNP) to evaluate the severity of congestive heart failure (CHF) as reflected by the New York Heart Association (NYHA) classification and to predict its 2-year mortality. Peripheral plasma concentrations of the three natriuretic peptides were measured in 27 normal subjects (CTR), in 32 patients with coronary artery disease (CAD) and normal left ventricular ejection fraction and in 101 patients with chronic CHF in functional classes I and II (n = 61) or III and IV (n = 40).. Plasma concentrations of the three peptides increased in the presence of CHF in relation to its severity (P < 0.01). BNP was unable to distinguish CTR from CAD, just as ANF could not differentiate CAD from CHF I-II; only N-proANF displayed a significant and continuous increase from CTR to CAD, CHF I-II and III-IV. Receiver-operating characteristic curves showed better evaluation of the degree of CHF by BNP than by ANF or ejection fraction (P < 0.05). Assessment of the 2-year prognosis revealed that N-proANF and BNP were the best independent predictors of outcome after the NYHA classification. These peptides identify a very high-mortality group.. Plasma N-proANF and BNP concentrations are good indicators of the severity and prognosis of CHF in an outpatient practice. CAD does not stimulate BNP as long as ventricular dysfunction is not present, although increased N-proANF levels in this setting suggest an early humoral activation.

Topics: Aged; Atrial Natriuretic Factor; Chronic Disease; Coronary Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Outpatients; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Survival Analysis; Ventricular Dysfunction, Left

We studied the changes in pulmonary hemodynamics induced by arm-stretching exercise in 12 patients with chronic pulmonary emphysema (CPE) and 9 control subjects (Controls). Both patients and control subjects underwent right heart catheterization with inspired gas analysis at rest and during exercise for the 6 minute-exercise test. Mean pulmonary arterial pressure (mPAP) in patients with CPE significantly increased from 18.5 +/- 3.9 mmHg at rest to 25.7 +/- 5.1 mmHg during exercise without decreased oxygen tension of the arterial blood. Both mPAP and total pulmonary resistance increased in proportion to the increases in cardiac output. Mixed venous plasma atrial natriuretic peptide (ANP) was significantly evaluated during exercise in patients with CPE, but did not in Controls. There were a significantly positive relationships between ANP and mPAP, and a significantly negative relationships between ANP and PvO2 during exercise. These results suggest that pulmonary hypertension during light exercise in cases of CPE may be caused by deterioration of the pulmonary capillary bed, and that ANP may be a useful indicator for evaluating pulmonary hypertension in patients with CPE.

Topics: Atrial Natriuretic Factor; Chronic Disease; Exercise; Hemodynamics; Humans; Male; Middle Aged; Pulmonary Circulation; Pulmonary Emphysema

Neurohormonal activation and elevated ventricular filling pressures are prominent features in heart failure. Carmoxirole is a DA2 receptor agonist with limited central activity that modulates sympathetic activation and subsequently reduces pre-load and afterload in animals. The effect of carmoxirole on neurohormones and hemodynamics in humans was evaluated in 12 normotensive patients with NYHA class III-IV heart failure on stable ACE 1 and diuretic therapy. Carmoxirole (0.25-1.00 mg) was administered on 2 consecutive days, and hemodynamic and neurohormonal measurements were carried out. Values given are maximal percent changes from prestudy baseline (significance level P < 0.05). The lower dose on day 1 (0.25-0.50 mg) reduced circulating norepinephrine, vasopressin, and ANP by 40%, 19%, and 25%, respectively. In addition, on day 2, at a dose level of 0.75-1.00 mg, plasma renin activity decreased by 30%. Mean arterial pressure and systemic vascular resistance were reduced by 10% and 18%, and pulmonary wedge and right atrial pressure by 38% and 39%, respectively. Cardiac index improved by 20%. Despite a concomitant 12% reduction in heart rate, both stroke volume and stroke work index increased by 32% and 31%, respectively. Mean pulmonary artery pressure decreased by 21%, whereas pulmonary resistance was not affected. Thus, carmoxirole modulates sympathetic activation, accompanied by changes in vasopressin and ANP, and the renin-angiotensin system at higher dosages. These effects lead to a reduction in systemic resistance and heart rate, and an improvement in cardiac pump function and left and right ventricular filling pressures. It is concluded that carmoxirole induces beneficial effects on hemodynamic and neurohumoral parameters in heart failure.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Chronic Disease; Dopamine Agonists; Electrocardiography; Female; Heart Failure; Heart Rate; Humans; Indoles; Male; Neurotransmitter Agents; Norepinephrine; Pulmonary Wedge Pressure; Pyridines; Receptors, Dopamine D2; Vasopressins

The concentrations of adrenaline, noradrenaline, dopamine, aldosterone, the atrial natriuretic hormone, and plasma renin activity were investigated in 50 patients with mild chronic heart failure. The patients received oral digoxin chronically in a daily dose of 0.125 mg. On the basis of the estimate of the dosing of digoxin these patients were divided into two groups: the first with therapeutic and the second with subtherapeutic concentrations of digoxin in serum. The therapeutic concentration of digoxin in serum was found in 23 patients (46%), while subtherapeutic levels were found in 27 patients (54%). The concentrations of noradrenaline, dopamine, the renin activity of plasma, aldosterone and the atrial natriuretic hormone in the blood serum in the group of patients in whom the presence of subtherapeutic concentrations of digoxin was found, did not differ essentially from the concentration that was observed in the group with therapeutic concentrations. Only the concentration of adrenaline was higher (p < 0.05) in the group of patients with therapeutic concentrations of digoxin. The above results reveal that the neuroendocrine activity of plasma (except for the concentration of adrenaline) is alike in both ranges of digoxin concentrations in serum.

Topics: Aged; Aged, 80 and over; Aldosterone; Atrial Natriuretic Factor; Catecholamines; Chronic Disease; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Renin

Endothelin-1 is a potent vasoconstrictive and multifunctional peptide. Elevated concentrations have been reported in congestive heart failure. We hypothesized that the level of endothelin-1 in plasma is a prognostic marker in congestive heart failure.. Plasma levels of endothelin-1 were measured by radioimmunoassay in 120 congestive heart failure patients with ischaemic or non-ischaemic cardiomyopathy (mean ejection fraction 28 +/- 11%, in New York Heart Association (NYHA) functional class I:21, class II 35, class III: 61, class IV: 3). During a median follow-up of 361 +/- 338 days, 14 cardiac deaths occurred. In the univariate Cox model, endothelin-1 was the most powerful prognostic marker among the variables tested (P = 0.0001). A multivariate model, including plasma atrial natriuretic peptide and noradrenaline, NYHA class, age, and echocardiographic left ventricular end-diastolic diameter index was highly predictive of mortality (P = 0.00008), but only endothelin-1 remained significantly associated with outcome (P = 0.02). Patients with plasma endothelin-1 > or = 5 pg. ml-1 had a higher mortality rate than those with endothelin-1 < 5 pg. ml-1 (21% vs 4%, P = 0.001).. Our results suggest that elevated endothelin-1 plasma levels are associated with a poor prognosis and routine plasma endothelin-1 determination provides important prognostic information in mild to moderate heart failure.

Topics: Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Death; Echocardiography; Endothelin-1; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Norepinephrine; Prognosis; Radioimmunoassay; Survival Rate

It has been suggested that renal disease is characterized by the presence of resistance to the natriuretic effects of atrial peptide (ANP). In this study, plasma ANP (pANP) and renal function were evaluated during stepwise infusion of low ANP doses (2, 4, 8, and 16 ng/kg per min) in glomerulonephritic patients with (CRF) or without (GN) moderate renal failure, and in normal subjects (NOR), kept at low-sodium diet (LSD; 35 mEq NaCl/day). To assess the physiological ANP levels, pANP was also measured in the three groups after normal-sodium diet (NSD; 235 mEq NaCl/day). ANP did not affect systemic and renal perfusion at any of the doses tested; a significant increment of GFR was observed only in NOR and GN. The 2-, 4-, and 8-ng/kg doses increased pANP to values overlapping the physiological concentrations measured at NSD; this was associated with a dose-dependent increment of urinary excretion of sodium (UNaV) that reached analogous levels in the three groups. ANP accounted for approximately 40% of the UNaV increment evoked by NSD in patients and in normal subjects. The 16-ng/kg dose led to supraphysiological levels that induced a similar marked enhancement of UNaV (from the basal value of 0.12 +/- 0.02 to 0.42 +/- 0.08 mEq/min in CRF, from 0.13 +/- 0.02 to 0.73 +/- 0.08 in GN, and from 0.09 +/- 0.02 to 0.49 +/- 0.11 in NOR). In CRF, the normal natriuretic response to the highest dose was caused by a larger increase of fractional UNaV that was strictly dependent on the greater pANP increment, as demonstrated by similar changes in the fractional excretion of cGMP, and, in part, on the greater aldosterone decrease. In all groups, ANP also induced a dose-dependent urinary loss of phosphate, potassium, and urea, resulting in a significant 15 to 25% decrease in the plasma levels. Thus, in GN and CRF patients, ANP plays a significant role in the renal handling of sodium; moreover, the achievement of low supraphysiological pANP levels leads to a conspicuous natriuresis associated with unique extranatriuretic effects.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Chronic Disease; Cyclic GMP; Diet, Sodium-Restricted; Diuresis; Dose-Response Relationship, Drug; Glomerulonephritis; Hemodynamics; Humans; Kidney Failure, Chronic; Male; Natriuresis; Reference Values; Renal Circulation

We evaluated the possible role of an imbalance between vasoconstrictor and vasodilator hormones in the pathophysiology of chronic hypotension in uraemia.. Fourteen hypotensive haemodialysed patients, 14 normotensive haemodialysed patients, and 17 control subjects were included in this study. Plasma renin activity (PRA) and plasma levels of catecholamines, angiotensin II (AII), atrial natriuretic peptide (ANP), and arginine vasopressin (AVP) were measured.. The mean time on haemodialysis (HD) was longer in hypotensive patients than in normotensive patients (P < 0.01). Catecholamine levels were higher in the whole group of HD patients than in controls (P < 0.01). Catecholamine levels were higher in hypotensive patients than in normotensive patients, but the differences reached significance only for adrenaline (P < 0.05). PRA and plasma AII levels were higher in hypotensive patients than in the other two groups (P < 0.05), while no differences were observed between normotensive patients and controls. Plasma ANP and AVP levels were higher in HD patients than in controls (P < 0.01), but there were no differences between hypotensive and normotensive patients. In HD patients, mean blood pressure inversely correlated with PRA (r = -0.59, P < 0.01) and plasma AII levels (r = -0.80, P < 0.01).. Our results indicate that in HD patients with chronic hypotension there is an activation of the sympathetic and the renin-angiotensin systems. This activation is probably secondary in an attempt to compensate the vascular resistance to pressor stimuli reported in these patients.

Topics: Adult; Aged; Angiotensin II; Arginine Vasopressin; Atrial Natriuretic Factor; Catecholamines; Chronic Disease; Female; Humans; Hypotension; Male; Middle Aged; Parathyroid Hormone; Renin; Uremia

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are known to be elevated in patients with chronic heart failure at rest. While it is known that during exercise the circulating level of ANP increases in patients with heart failure, the response of BNP to exercise in these patients relative to control subjects is unclear. Ten patients with stable chronic heart failure and 10 normal control subjects performed symptom-limited exercise with respired gas analysis. All patients had depressed left ventricular ejection fractions (LVEF). Patients had lower peak oxygen consumption PVo2) than the control group [median (range) 1.18 (0.98-1.76) vs. 1.94 (1.53-2.31) L min-1; P < 0.001]. Circulating plasma levels of ANP and BNP were higher at rest in patients than in control subjects [ANP 335 (140-700) vs. 90 (25-500) pg mL-1; BNP 42 (25-50) vs. 20 (10-20) pg mL-1], and at peak exercise [ANP 400 (200-1000) vs. 130 (10-590); BNP 46 (40-51) vs. 20 (10-30)]. The rise in ANP at peak exercise was significant in patients compared with the resting level, but not in control subjects. For BNP, there was a significant rise in patients but no change in control subjects. The circulating plasma levels of both peptides showed a strong negative correlation with LVEF (ANP, P < 0.005; BNP, P < 0.0001) and, to a less extent, with RVEF. It is possible that BNP may give a better indication of cardiac function.

Topics: Adult; Aged; Atrial Natriuretic Factor; Chronic Disease; Exercise; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Stroke Volume; Ventricular Function, Left

The interaction between renal prostaglandins and atrial natriuretic factor (ANF) for the regulation of renal hemodynamic and excretory function was examined in conscious dogs with arteriovenous fistula and chronic compensated high-output heart failure (n = 6). After two control clearance periods, 100 ng/kg/min ANF was administered for the duration of the study. After two clearance periods with ANF infusions, 10 mg/kg indomethacin intravenous bolus was given, and three additional clearance periods were obtained. Atrial natriuretic factor alone increased sodium excretion from a baseline of 25 +/- 7 microEq/min to 158 +/- 24 microEq/min (P < 0.05), whereas creatinine clearance was elevated by 9 mL/min (P < 0.05). Indomethacin reduced ANF-induced sodium excretion and creatinine clearance by 75% (P < 0.05) and 35% (P < 0.05), respectively. In a time control series in dogs with arteriovenous fistula (n = 4), indomethacin vehicle did not alter ANF-induced natriuresis or renal hemodynamic function. These results suggest a modulatory role of the prostaglandins on the renal response to ANF infusions in this canine model of compensated heart failure.

Topics: Aldosterone; Animals; Arteriovenous Fistula; Atrial Natriuretic Factor; Chronic Disease; Creatinine; Cyclooxygenase Inhibitors; Disease Models, Animal; Dogs; Female; Heart Failure; Indomethacin; Kidney; Natriuresis; Prostaglandin Antagonists; Renin

In order to develop and validate an ovine model of myocardial infarction with subsequent impairement of left ventricular function, 15 instrumented sheep underwent selective microembolization of the left coronary arteries with 0.5 mL 90 microns polystyrene beads. Hemodynamics and plasma hormones were measured preembolization (baseline) and then at hours 2, 4, 6, and 12 and days 1, 2, 3, 5 and 7 postembolization. Of the 15 sheep studied, 2 (13%) died on the day of embolization from arrhythmias. In the remaining sheep, left ventricular systolic pressure and stroke work (both P < 0.001) were reduced promptly and remained below basal levels. Mean arterial pressure (P < 0.001) increased initially, then decreased to below basal levels by hour 6. Heart rate (P < 0.001) and left atrial pressure (P < 0.05) were increased while cardiac output was decreased (P < 0.05). Left ventricular ejection fraction at day 7 was reduced (38.8 +/- 3.5 vs 46.0 +/- 3.9% preembolization; P < 0.05). The cardiac enzymes creatine kinase (P < 0.001) and troponin-T (P < 0.001) were increased following microembolization and returned to basal levels by days 2 and 5 respectively. Plasma atrial and brain natriuretic peptides (both P < 0.001) and plasma renin activity (P < 0.005) were all increased following embolization. This ovine model mimics the hemodynamic and neurohumoral features of acute myocardial infarction, resulting in left ventricular dysfunction, and should prove suitable for the study of interventions in a number of these conditions.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Chronic Disease; Creatine Kinase; Disease Models, Animal; Female; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Renin; Sheep; Stroke Volume; Ventricular Dysfunction, Left

Administration of angiotensin converting enzyme (ACE) inhibitors to patients with congestive heart failure (CHF) is associated to a decrease in the abnormal vasoconstrictor neurohormonal activity. This contributes to the sustained benefits of these drugs on symptoms and survival of patients with CHF. There is little information, however, regarding the effects of ACE inhibition on vasodilator and natriuretic hormones.. To evaluate the chronic effects of enalapril, in addition to digitalis and diuretics in patients with chronic cardiac failure.. Nine patients with an idiopathic dilated cardiomyopathy (8 male, aged 48 to 76 years old) under treatment with digitalis and diuretics, received enalapril 20 mg bid during eight weeks. Before and after this treatment period resting left ventricular ejection fraction, functional class, plasma levels of atrial natriuretic factor and bradykinins (BK) and urinary excretion of kalikreins (BK) and prostaglandin E2 (PGE2) were measured.. After enalapril therapy, there was a significant increase in maximal O2 consumption (14.8 +/- 1.2 to 18.6 +/- 1.5 ml/kg/min, p < 0.05) and radionuclide LV ejection fraction (27.4 +/- 1.1 to 31.4 +/- 0.9% p < 0.05). This was associated with a significant decrease in plasma ANP levels (559 +/- 158 to 178 +/- 54.8 pg/ml) and UK (391 +/- 112 to 243 +/- 92 Cu/24 h).. The decrease in ANP levels, which is a well known marker of prognosis in CHF, could contribute to explain the sustained clinical benefits observed with ACE inhibitors in patients with CHF.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Bradykinin; Cardiac Output, Low; Cardiomyopathy, Dilated; Chronic Disease; Dinoprostone; Enalapril; Female; Humans; Kallikreins; Male; Middle Aged; Oxygen Consumption; Stroke Volume; Vasodilator Agents

Cultured vascular endothelial and smooth muscle cells actively produce adrenomedullin, a novel vasodilator peptide discovered in human pheochromocytoma tissue. This present study was designed to determine whether the plasma level of adrenomedullin is a useful indicator for estimating the degree of endothelial injury in patients with atherosclerotic disease.. We used a radioimmunoassay to measure plasma adrenomedullin concentrations in 51 patients with chronic cerebrovascular disease (34 infarctions and 17 haemorrhages) and in 10 subjects without symptomatic cerebrovascular disease. We also measured the plasma concentrations of thrombomodulin and endothelin as markers of endothelial injury. The patients were divided into three groups (A, B, and C) on the basis of the number of risk factors for atherosclerosis: hypertension, hyperlipidemia, smoking, low HDL-cholesterol, diabetes mellitus, and hyperuricaemia. Group A (68.7+/-2.7 years) consisted of patients with 0 or 1 risk factors; B (68.3+/-4.2 years) those with 2 risk factors; and C (69.2+/-3.6 years) those with 3 or more risk factors.. The plasma concentration of adrenomedullin in these patients showed a significant positive correlation with age (r=0.33, p<0.05), as well as with the plasma concentrations of thrombomodulin (r=0.54, p<0.001) and endothelin (r=0.53, p<0.001). Moreover, the plasma concentrations of adrenomedullin and thrombomodulin (p<0.005 and p<0.02, respectively) tended to be higher in Group B and to be significantly higher in Group C as compared to Group A. Plasma adrenomedullin concentrations did not, however, significantly differ between the infarction and haemorrhage patients.. These findings suggest that the plasma adrenomedullin concentrations reflect the degree of endothelial injury in patients with atherosclerotic disease.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Blood Urea Nitrogen; Brain Ischemia; Cerebral Angiography; Cerebral Hemorrhage; Cholesterol; Chronic Disease; Endothelins; Female; Humans; Intracranial Arteriosclerosis; Magnetic Resonance Imaging; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptides; Risk Factors; Thrombomodulin; Tomography, X-Ray Computed; Vasodilator Agents

This study evaluated the role of changes in heart rate, cardiac filling pressures and cardiac tissue atrial and brain natriuretic peptides in the modulation of their plasma levels in a model of heart failure.. Atrial and brain natriuretic peptides constitute a dual natriuretic peptide system that regulates circulatory homeostasis.. The effects of 1) acute ventricular pacing, 2) acute volume expansion, and 3) volume expansion after 1 week of continuous pacing on plasma atrial and brain natriuretic peptide levels were compared in eight dogs. Atrial and ventricular tissue levels of the peptides were examined in 5 normal dogs (control group), 21 dogs paced for 1 week (group 1) and 10 dogs paced for 3 weeks (group 2).. Both acute pacing and volume expansion increased plasma atrial natriuretic peptide levels (from 53 +/- 41 to 263 +/- 143 pg/ml [mean +/- SD], p < 0.01, and from 38 +/- 23 to 405 +/- 221 pg/ml, p < 0.001, respectively). After 1 week, there was a marked increase in plasma levels of atrial natriuretic peptide, but the level did not increase further with volume expansion (from 535 +/- 144 to 448 +/- 140 pg/ml, p = 0.72). By contrast, plasma brain natriuretic peptide levels increased only modestly with acute pacing (from 12 +/- 4 to 20 +/- 8 pg/ml, p < 0.05) and after pacing for 1 week (from 13 +/- 4 to 48 +/- 20 pg/ml, p < 0.05) but did not change with acute or repeat volume expansion. In groups 1 and 2, atrial tissue levels of atrial natriuretic peptide (1.9 +/- 1.3 and 2.0 +/- 0.9 ng/mg, respectively) were lower than those in the control group (11.7 +/- 6.8 ng/mg, both p < 0.001), whereas ventricular levels were similar to those in the control group. Atrial tissue brain natriuretic peptide levels in groups 1 and 2 were similar to those in the control group. However, ventricular levels in group 2 (0.018 +/- 0.006 ng/mg) were increased compared with those in the control group (0.013 +/- 0.006 ng/mg, p < 0.05) and in group 1 (0.011 +/- 0.006 ng/mg, p < 0.05).. Atrial and brain natriuretic peptides respond differently to changes in heart rate and atrial pressures. Reduced atrial tissue atrial natriuretic peptide levels in heart failure may indicate reduced storage after enhanced cardiac release. However, the relatively modest change in cardiac tissue brain natriuretic peptide levels suggests that the elevated plasma levels may be mediated by mechanisms other than increased atrial pressures.

Topics: Acute Disease; Animals; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Chronic Disease; Dextrans; Disease Models, Animal; Dogs; Heart Failure; Hemodynamics; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Plasma Substitutes

1. The effects of prolonged chlorothiazide treatment of left ventricular failure on cardiac hypertrophy, circulating vasoactive hormones and exchangeable body sodium were examined in rats with chronic myocardial infarction induced by left coronary artery ligation. Chlorothiazide therapy commenced either immediately or 2 weeks after infarction. For 4 weeks, the rats were given either chlorothiazide (50 mg day-1 kg-1) in their drinking water or drinking water alone. 2. Cardiac weight increased in untreated rats with infarction in comparison with sham-operated controls, indicating the presence of chronic left ventricular dysfunction, although exchangeable body sodium, plasma renin activity, plasma vasopressin and plasma osmolality remained unchanged. 3. Chlorothiazide raised haematocrit and plasma renin activity equally in rats with and without infarction, although exchangeable body sodium, plasma vasopressin and plasma osmolality were not changed by the treatment. Plasma atrial natriuretic peptide was 2-fold higher in rats with infarction and this response was not affected by chlorothiazide treatment. Chlorothiazide therapy did not prevent or reverse cardiac hypertrophy. 4. Chronic diuretic therapy in this experimental model of heart failure did not reduce extracellular sodium, plasma vasopressin or the extent of ventricular hypertrophy, possibly because the condition was associated with activation of the renin-angiotensin system.

Topics: Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Cardiomegaly; Chlorothiazide; Chronic Disease; Diuretics; Female; Myocardial Infarction; Myocardium; Organ Size; Rats; Rats, Wistar; Sulfonamides; Time Factors; Ventricular Dysfunction, Left

We measured plasma concentrations of atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP, respectively) and endothelin-1 in 20 patients with chronic respiratory diseases (CRD) to establish whether these peptides are increased in patient groups with CRD (group A, PaO2 > or = 60 mm Hg; group B, PaO2 < 60 mm Hg) and whether a correlation exists between the levels of natriuretic peptides or endothelin-1, and blood gas variables. In patients receiving long-term oxygen therapy (LTOT), plasma ANP, BNP, and endothelin-1 were compared before and after LTOT. We compared the levels of plasma ANP, BNP, and endothelin-1 in the presence or absence of right heart overloading (RHO) found in the ECG. Plasma ANP and BNP levels in group B patients were higher than those in group A and control subjects, and endothelin-1 in group B patients was higher than in control subjects. Inverse correlations were found between PaO2 and levels of plasma ANP, BNP, and endothelin-1. Plasma ANP, BNP, and endothelin-1 decreased significantly 25.4 days after LTOT. In 10 patients with RHO findings in the ECG, plasma ANP and BNP levels were significantly elevated compared with those in patients without RHO. These findings show that plasma ANP, BNP, and endothelin-1 are elevated according to the degree of hypoxemia, and they suggest that decreases in plasma ANP, BNP, and endothelin-1 may be used as indexes of the improvement by LTOT, and that plasma ANP and BNP may represent markers of RHO.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Chronic Disease; Electrocardiography; Endothelins; Female; Heart; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Oxygen; Oxygen Inhalation Therapy; Proteins; Respiratory Tract Diseases

The aim of this study was to evaluate clinical, adrenergic and endocrine factors that could predict sinus rhythm maintenance after direct current cardioversion in chronic atrial fibrillation. Nineteen patients with chronic non-rheumatic atrial fibrillation (mean duration 6 +/- 5 months) were studied. They were exercised 24 h before cardioversion at maximum effort with the Naughton protocol. Heart rate and blood pressure at rest and exercise were recorded and blood samples were taken for the assessment of adrenergic activity, by measuring cyclic adenosine monophosphate, heart endocrine function, atrial natriuretic peptide and its second messenger, cyclic guanosine monophosphate. Fifteen of the 19 patients were initially converted to sinus rhythm (eight patients with external and seven patients with internal DC shocks). After 3 months eight patients remained in sinus rhythm and 11 had relapsed, most of them within the first month. On exercise the chronotropic response was lower in the group who remained in sinus rhythm than in the group in atrial fibrillation (peak heart rate 147 +/- 11 beats.min-1 vs 165 +/- 24 beats.min-1 P = 0.02). During exercise, the systolic blood pressure in the sinus group reached higher values than in the group who relapsed (192 +/- 17 mmHg vs 176 +/- 18 mmHg, P = 0.03). Cyclic adenosine monophosphate increased significantly from rest to peak exercise in the sinus rhythm group (from 23 +/- 9 pmol.ml-1 to 31 +/- 15 mol.ml-1, P = 0.02) while it remained unchanged in the atrial fibrillation group (25 +/- 10 pmol.ml-1 to 24 +/- 8 pmol.ml-1, P = 0.02). For all 19 patients the difference in cyclic adenosine monophosphate between rest and exercise was negatively correlated with maximum heart rate (r = 0.58, P = 0.009). Atrial natriuretic peptide increased from rest to peak exercise in the sinus rhythm group (from 129 +/- 58 fmol.ml-1 to 140 +/- 66 fmol.ml-1) while it remained unchanged in the group in which atrial fibrillation persisted or recurred (from 112 +/- 58 fmol.ml-1 to 111 +/- 53 fmol.ml-1, P = 0.002). A significant correlation between atrial natriuretic peptide and cyclic guanosine monophosphate levels at exercise before cardioversion was found for the sinus rhythm group only (r = 0.76, P = 0.02). In patients with non-rheumatic chronic atrial fibrillation evaluation of clinical parameters such as heart rate and blood pressure changes during maximal exercise can be useful in the choice of suitable therapy. An inadequate increase

Topics: Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Chronic Disease; Cyclic AMP; Cyclic GMP; Discriminant Analysis; Electric Countershock; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Prognosis; Treatment Outcome

To elucidate the predictors of the mortality rate in the elderly with chronic heart failure (HF), 120 consecutive patients (mean age, 75.2 +/- 7.8 years) with heart failure (NYHA I-II) were analyzed prospectively for 5 years. [Methods] Left ventricular ejection fraction (EF), left ventricular diastolic and systolic dimension (LVDD and LVDS) and wall thickness (WT) were measured by echocardiogram. Venipuncture for measurement of ANP and norepinephrine (NE) was done in supine position after 30 minute rest. [Results] 1) HF was associated with hypertension (47.5%), ischemic heart disease (34%), valvular disease (15%) and atrial fibrillation (AF, 23%). 2) 15 and 11 patients died for cardiac and non-cardiac events, respectively. 3) There was no difference in mean ages, gender, blood pressure, plasma-NE, EF, LVDD, LVDS, WT and AF between cardiac death and control groups. However, plasma ANP was higher in cardiac death group (173 pg/ml) than in control group (76 pg/ml) (p < 0.01). 4) Cox proportional hazard regression model revealed that ANP was an independent predictor for cardiac death (p < 0.005). We conclude that only plasma ANP level predicts long-term prognosis of chronic heart failure in the elderly.

Topics: Aged; Atrial Natriuretic Factor; Chronic Disease; Female; Heart Failure; Humans; Male; Prognosis; Proportional Hazards Models; Prospective Studies; Survival Rate

We have considered the behaviour of the atrial natriuretic factor (ANF) in eight patients suffering from chronic obstructive pulmonary disease (COPD), who have been treated with aminophylline for 24 hours. The mean of ANF concentration decreased from a basic value of 171.31 pg/ml to a value of 128.83 pg/ml (p: n.s.) after treatment. With the exception of patient n. 5 and 7, in the remaining group a significant inverse correlation between ANF and aldosterone was found in accordance with the powerful inhibitory action exerted by the ANF on the secretion of the mineralocorticoid hormone. The changes of the ANF, after a treatment with aminophylline, are characterized by considerable differences among the several patients. In all patients who had a very high basic value, we generally assist to a plasmatic concentration reduction of the hormone after methylxantine. It can be assumed that the reduction of the pulmonary arterial pressure owing to the direct vessel-dilating action of the methylxantine as well as to the effect of vein-dilating and diuretic action reduce the stimulus to the secretion of ANF.

Topics: Adult; Aged; Atrial Natriuretic Factor; Bronchodilator Agents; Bronchopneumonia; Chronic Disease; Female; Humans; Male; Middle Aged; Remission Induction; Theophylline

We measured immunoreactive atrial natriuretic peptide (ANP) in 18 selected, microdissected brain areas. Rats were studied 8 wk after coronary ligation or sham operation or as nonoperated control animals. In separate animals, hemodynamic and plasma parameters were measured. Rats with myocardial infarction had marked elevated right atrial and left ventricular end-diastolic pressure (2.6 +/- 0.6 and 16.2 +/- 3.1 mmHg, respectively; n = 15) vs. sham-operated rats (1.3 +/- 1.0 and 5.5 +/- 1.2 mmHg, n = 14; P < 0.05) and depressed maximal rate of pressure development (9,613 +/- 980 vs. 15,600 +/- 2,027 mmHg/s; P < 0.05) but similar arterial pressure (126 +/- 4 vs. 124 +/- 3 mmHg; P > 0.05). After myocardial infarction (n = 10), plasma ANP, renin activity, and angiotensin (ANG) II were elevated (53.1 +/- 16.2 pg/ml, 10.7 +/- 2.5 ng ANG I ml-1 h-1, and 219.6 +/- 11.0 fmol/ml, respectively) vs. sham rats (12.0 +/- 2.2 pg/ml, 5.7 +/- 0.7 ng ANG I ml-1, h-1, and 142.9 +/- 9.4 fmol/ml; n = 10; P < 0.05), whereas vasopressin and aldosterone levels remained unchanged among groups. In rats with myocardial infarction, a substantial decrease of ANP was found in the medial preoptic nucleus, the supraoptic nucleus, the subfornical organ, the paraventricular nucleus, and the locus ceruleus. These nuclei are involved in electrolyte, and fluid homeostasis, blood pressure regulation, and modulation of neuroendocrine systems. The mechanism of this reduction and the consequences for systemic adaption or decompensation remain unclear. However, the data suggest that myocardial infarction and chronic left ventricular dysfunction may induce changes of a neurotransmitter in brain.

Topics: Animals; Atrial Natriuretic Factor; Brain; Chronic Disease; Hemodynamics; Male; Myocardial Infarction; Osmolar Concentration; Radioimmunoassay; Rats; Rats, Wistar; Tissue Distribution

Experiments were performed to test the postulate that neural influences underlie the suppressed excretory response to acute volume expansion (VE) typically observed 3-4 wk after myocardial infarction to induce chronic heart failure (CHF). Responses to VE were assessed in innervated (intact) and denervated (DNX) kidneys of anesthetized CHF rats and sham-operated controls. CHF rats exhibited blunted natriuretic responses to VE in both intact kidneys (35% of sham response) and DNX kidneys (55% of sham DNX response). CHF rats also displayed suppressed excretory responses to atrial natriuretic factor (0.25 microgram.kg-1.min-1 iv) in both intact kidneys (74% of sham response) and DNX kidneys (63% of sham DNX response). Additional experiments confirmed that the compliance of the venoatrial junction did not differ between sham rats (52 +/- 2 mmHg/microliter) and CHF rats (54-2 mmHg/microliter). The observations support the contention that both tonic renal sympathetic renal nerve activity and suppressed renal atrial natriuretic factor responsiveness likely contribute to the blunted excretory response to VE during CHF.

Topics: Animals; Atrial Function; Atrial Natriuretic Factor; Blood Volume; Cardiac Output, Low; Chronic Disease; Hemodynamics; Kidney; Male; Myocardium; Nervous System; Plasma Substitutes; Pressure; Rats; Rats, Sprague-Dawley; Venae Cavae

The kidney damage in chronic glomerulonephritis develops not only as a result of causal immunopathological evens, but also due to chronic adaptation changes. The study was aimed at identification of active agents, which can serve as markers of proceeding adaptation changes and to determine, if these changes may be determined in patients undergoing the stage of remission of chronic glomerulonephritis.. The authors determined renin activity, concentration of atrium natriuretic peptide and endothelin in plasma and elimination of some prostanoids in urine in 33 patients with chronic stabilized glomerulonephritis with normal glomerular filtration and with normal blood pressure and in 21 healthy subjects. Seventeen patients without proteinuria did not receive therapy, 16 patients with minute proteinuria received 100 mg of acetylosalicylic acid daily. In the untreated patients without proteinuria, the elimination of thromboxane in urine was significantly higher than in both other groups. The plasma level of atrium natriuretic peptide in all 33 patients was significantly lower than in the healthy persons.. Based on this study the authors believe that adaptation changes proceed even in patients with chronic glomerulonephritis in clinical remission. The increased production of renal thromboxane, which can be successfully blocked by acetylosalicylic acid may be the marker of glomerular changes. A decreased level of atrium natriuretic peptide could reflect tubulointerstitial changes.

Topics: Adaptation, Physiological; Adult; Atrial Natriuretic Factor; Chronic Disease; Endothelins; Glomerular Filtration Rate; Glomerulonephritis; Humans; Middle Aged; Prostaglandins; Proteinuria; Renal Circulation; Renin; Vasomotor System

Topics: Atrial Natriuretic Factor; Chronic Disease; Heart Failure; Hemodynamics; Humans; Radioimmunoassay; Reference Values

The aim of our study was to evaluate the effects of endogenous opioids on the secretion of atrial natriuretic factor (ANF) in moderate chronic heart failure (HF).. We evaluated the effects of i.v. volume load (NaCl 0.9% at 0.25 ml/Kg/min for 60 minutes) on heart rate (HR), on mean arterial pressure (MAP) and on the plasma levels of beta-endorphin (beta-end), met-enkephalin (Met-enk), dynorphin (Dyn), atrial natriuretic factor (ANF) and noradrenaline (NA) in 10 patients (age 58 +/- 9) with HF in NYHA class II (group I) and in 8 healthy control subjects (age 54 +/- 10) group II). The volume load was repeated after at least three days during infusion of naloxone (2 micrograms/Kg/min), evaluating the above mentioned hemodynamic and hormonal parameters.. The acute volume expansion caused an increase in ANF concentration (from 51.7 +/- 19.7 to 67.4 +/- 36.9 pg/ml; p < 0.05) and in beta-end (from 11.9 +/- 5.3 to 16.6 +/- 7.5 fmol/ml; p < 0.05), In group I. In group II an isolated increase in ANF was observed (from 14.1 +/- 7.8 to 21.9 +/- 7.9 pg/ml; p < 0.02). No significant changes were detected for HR, MAP, Dyn, Met-enk and NA. In group I the percent increase of ANF is less than in group II (30 vs 55%; p < 0.05). The volume load infused during naloxone infusion caused a significant increase in HR (from 73 +/- 6 to 78 +/- 9 bpm; p < 0.05) and in NA (from 311 +/- 123 to 415 +/- 142 pg/ml; p < 0.05) In group I. In group II, an increase in ANF was detected (from 13.8 +/- 6.0 to 23.6 +/- 5.0 pg/ml; p < 0.01).. Our data suggest that in moderate HF beta-end stimulates the secretion of ANF and inhibits the activity of the sympatho-adrenergic system during acute volume expansion.

Topics: Adult; Aged; Analysis of Variance; Atrial Natriuretic Factor; beta-Endorphin; Chronic Disease; Data Interpretation, Statistical; Dynorphins; Enkephalin, Methionine; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Norepinephrine; Plasma Volume; Receptors, Adrenergic; Sodium Chloride; Sympathetic Nervous System

We investigated the relationship between exercise capacity and the level of neurohormonal activation at rest and during exercise in patients with various degrees of severity of chronic heart failure. We performed exercise testing with measurements of peak oxygen consumption (pVo2) and blood sampling at rest and at peak exercise in eight patients with moderate heart failure (pVo2 = 17 +/- 0.4 ml/kg/min) (mean +/- S.E.M.) and eight patients with severe CHF (pVo2 = 9 +/- 1 ml/kg/min). None of the patients was taking angiotensin converting enzyme inhibitors or beta-blockers. Plasma levels of atrial natriuretic peptide, cGMP, arginine-vasopressin, renin, angiotensin II, epinephrine and norepinephrine increased significantly (P < 0.01), from rest to peak exercise, in all patients. Among all the studied neurohormonal factors, only atrial natriuretic peptide levels at rest as well as at peak exercise, in patients with severe heart failure were correlated significantly to pVo2 (r = -0.77, P = 0.04; r = -0.85, P = 0.01, respectively) and to exercise duration (r = -0.72, P = 0.05; r = -0.79; P = 0.03, respectively). The relationship between plasma levels of atrial natriuretic peptide and of cGMP was shifted downward in the more severe patients suggesting the loss of biological activity of atrial natriuretic peptide.

Topics: Adult; Aged; Angiotensin II; Atrial Natriuretic Factor; Chronic Disease; Epinephrine; Exercise Test; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Norepinephrine; Oxygen Consumption; Prognosis; Radioimmunoassay; Renin; Sensitivity and Specificity; Severity of Illness Index; Vasoconstrictor Agents; Vasopressins

The response of atrial natriuretic peptide (ANP) release to haemodynamic influences after cardioversion of atrial fibrillation has not been fully examined. We measured plasma concentrations of ANP and assessed haemodynamic changes 60-120 min after DC cardioversion in 22 patients with non-valvular chronic atrial fibrillation. Passive leg elevation to enhance volume expansion was performed 60 min after DC cardioversion. Sinus rhythm was restored in 18 of the 22 patients (successful DC cardioversion group). The control group consisted of seven patients with non-valvular chronic atrial fibrillation who did not undergo DC cardioversion (atrial fibrillation control group). In the successful DC cardioversion group, the mean pulmonary artery wedge pressure decreased significantly 15 min after cardioversion (P < 0.05) and then remained unchanged. Plasma concentrations of ANP also decreased significantly 15 min after cardioversion (P < 0.05). Furthermore, there was an additional significant decrease in ANP levels for up to 60 min after cardioversion (P < 0.05 from 15 min). Passive leg elevation for 15 min led to an increase in the mean pulmonary artery wedge pressure (P < 0.01) and right atrial pressure (P < 0.05), but did not result in increased plasma concentrations of ANP (47.1 +/- 27.6 vs 43.9 +/- 34.4 pg.ml-1, mean +/- SD, P = ns). In the atrial fibrillation control group, passive leg elevation increased the mean pulmonary artery wedge pressure (P < 0.01), the mean right atrial pressure (P < 0.05) and plasma concentrations of ANP (139.9 +/- 85.8 vs 168.1 +/- 108.2, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Cardiac Output; Chronic Disease; Cyclic GMP; Electric Countershock; Female; Hemodynamics; Humans; Male; Middle Aged; Pulmonary Wedge Pressure; Treatment Outcome

We determined the renal and depressor activities of 10, 50, and 100 pmol/kg per minute i.v. of human atrial natriuretic peptide-(99-126) in conscious one-kidney, one clip dogs with chronic hypertension and modest renal dysfunction, as indicated by mild proteinuria. Atrial natriuretic peptide increased fractional sodium excretion by 0.009 +/- 0.002, 0.042 +/- 0.005, and 0.049 +/- 0.007, respectively; urinary excretion of atrial natriuretic peptide by -0.4 +/- 0.8, 3.3 +/- 1.4, and 15.8 +/- 7.4 fmol/min; and cGMP excretion by 0.65 +/- 0.06, 1.65 +/- 0.08, and 4.88 +/- 0.85 nmol/min in one-kidney shams. The changes in fractional sodium excretion were significantly attenuated in the hypertensive dogs (0.005 +/- 0.002, 0.018 +/- 0.003, and 0.022 +/- 0.004, respectively) despite exaggerated increases in atrial natriuretic peptide excretion (3.3 +/- 1.6, 22.0 +/- 5.0, and 46.6 +/- 10.8 fmol/min) and cGMP excretion (0.96 +/- 0.47, 4.51 +/- 1.27, and 7.06 +/- 1.38 nmol/min). The slope of the line relating urinary atrial natriuretic peptide to cGMP was significantly suppressed in the hypertensive dogs, suggesting a downregulation of the guanylate cyclase-linked receptors. The slope of the relationship between cGMP excretion and the natriuretic response was also depressed in the hypertensive dogs, indicating possible impairment of cGMP signal transduction. The differences between sham and hypertensive dogs were diminished when urinary levels of atrial natriuretic peptide were maximized by prior treatment with SQ 28603, an inhibitor of neutral endopeptidase EC 3.4.24.11. Atrial natriuretic peptide caused comparable decreases in mean arterial pressure and increases in glomerular filtration rate in sham and hypertensive dogs, suggesting similar vascular reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Alanine; Animals; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Diuretics; Dogs; Female; Humans; Hypertension, Renovascular; Injections, Intravenous; Kidney; Male; Neprilysin; Peptide Fragments

The present study was to investigate a role for endothelium-derived nitric oxide (EDNO) system in the development and maintenance of 2-kidney, 1 clip (2K1C) hypertension. Effects of blocking the synthesis or supplementing the precursor of EDNO on the developmental phase of hypertension were examined in 2K1C rats. Responses of the isolated vasculature to phenylephrine, acetylcholine, sodium nitroprusside, and atrial natriuretic peptide were also examined in chronic 2K1C rats. Ingestion of NG-nitro-L-arginine methyl ester or L-arginine did not affect the development of hypertension in 2K1C rats. Contraction response to phenylephrine was enhanced and relaxation response to acetylcholine was attenuated in the thoracic aortic ring isolated from chronic hypertensive rats, both being more marked in the 12-week hypertensive than in the 7-week hypertensive. Indomethacin did not significantly affect the degree of the attenuated vasorelaxation response to acetylcholine. The vasorelaxation response to sodium nitroprusside and atrial natriuretic peptide remained unaltered in the hypertensives. These results indicate that EDNO does not affect the developmental phase of 2K1C hypertension, whereas an impaired endothelium-dependent vasorelaxation is associated with chronic 2K1C hypertension.

Topics: Acetylcholine; Animals; Arginine; Atrial Natriuretic Factor; Chronic Disease; Disease Models, Animal; Hypertension, Renal; Indomethacin; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Nitroprusside; Phenylephrine; Rats; Rats, Sprague-Dawley; Vasodilation

Little is known about the effect of posture on the circulatory abnormalities of advanced cirrhosis. We evaluated the systemic hemodynamics, measured by Doppler-echocardiography, atrial natriuretic factor, plasma renin activity and plasma norepinephrine, in 10 patients with cirrhosis and ascites and 10 healthy controls, after 2 h of standing and during lying down for a further 2 h. Standing hemodynamic patterns of controls and patients with cirrhosis did not differ significantly. The latter, however, showed higher plasma renin activity, norepinephrine and atrial natriuretic factor. The assumption of the supine position led to greater increases in cardiac index and atrial natriuretic factor, and reduction in systemic vascular resistance in patients with cirrhosis. Norepinephrine and plasma renin activity declined in both groups to a similar extent, while heart rate only slowed in controls. Thus, after 2 h in the supine position, patients with cirrhosis showed hyperdynamic circulation with increased cardiac index and heart rate and reduced systemic vascular resistance. Norepinephrine, plasma renin activity and atrial natriuretic factor were also elevated. The hyperdynamic circulation in advanced cirrhosis appears during or is enhanced by lying down. This finding suggests that this syndrome is, at least in part, attributable to excessive blood volume translocation towards the central area. However, the persistent activation of renin-angiotensin and sympathoadrenergic systems suggests that a concomitant reduced vascular sensitivity to vasoconstrictors concurs in its development.

Topics: Adult; Aged; Ascites; Atrial Natriuretic Factor; Chronic Disease; Echocardiography, Doppler; Hemodynamics; Humans; Liver Cirrhosis; Male; Middle Aged; Norepinephrine; Posture; Renin

The decreased volume of maternal extracellular fluid in preeclamptics may result in a different rate of atrial natriuretic peptide secretion and thus affect its plasma levels. Our objectives were to determine whether there was a difference in plasma levels of atrial natriuretic peptide in the various hypertensive disorders of pregnancy. Forty-nine pregnant women in the third trimester of pregnancy were evaluated: 21 with preeclampsia, 17 with chronic hypertension during pregnancy and 11 normotensives. The atrial natriuretic peptide concentration was 13.9 +/- 5.9 pg/ml, 17.8 +/- 13.5 pg/ml and 16.7 +/- 7.4 pg/ml in the preeclamptics, chronic hypertensives and normotensives, respectively. The differences between the three groups were not statistically significant. Atrial natriuretic peptide plasma levels remained stable in the various hypertensive disorders of pregnancy.

Topics: Adult; Atrial Natriuretic Factor; Chronic Disease; Female; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, Third

The effects of cilazapril on exercise tolerance and neurohumoral factors were investigated in old myocardial infarction (OMI) patients with asymptomatic heart failure and reduced left ventricular ejection fraction. Cilazapril (0.5 mg) was administered once daily to OMI patients (n = 20) [NYHA class I, sinus rhythm, ejection fraction by radionuclide scanning < 50% (36.8 +/- 9.1%, mean +/- SD)]. Two weeks later, five patients were excluded from the study because of cough or hypotension, and 15 patients received 1.0 mg cilazapril once daily for the next 6 weeks. Exercise tolerance, neurohumoral factors and ejection fraction were measured in OMI patients before and after administration of cilazapril. Seven age-matched healthy adults served as the controls. OMI patients had latent heart failure because their exercise tolerance values and aldosterone levels were lower and alpha-atrial natriuretic polypeptide levels were higher than those in healthy subjects. In OMI patients, 8 weeks after cilazapril administration, exercise duration increased from 545 +/- 59 to 590 +/- 74 sec (p < 0.05), anaerobic threshold from 17.5 +/- 3.2 to 20.1 +/- 2.8 ml/min/kg (p < 0.05), peak-VO2 from 23.5 +/- 4.7 to 27.1 +/- 4.4 ml/min/kg (p < 0.05), plasma renin activity from 1.34 +/- 1.13 to 5.82 +/- 5.47 ng/ml/hr (p < 0.01) and alpha-atrial natriuretic polypeptide decreased from 100.7 +/- 44.3 to 80.5 +/- 28.0 pg/ml (p < 0.05). In patients with asymptomatic left ventricular dysfunction after myocardial infarction, 8 week's cilazapril administration improved exercise tolerance and neurohumoral conditions.

Topics: Aged; Aldosterone; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Chronic Disease; Cilazapril; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Neurotransmitter Agents; Norepinephrine; Renin; Stroke Volume

Chronic fetal anemia causes polyhydramnios and fetal hydrops and is associated with increased fetal diuresis and natriuresis. To determine the role of atrial natriuretic peptide (ANP) in the renal adaptation to chronic fetal anemia we studied the effects of HS-142-1 (HS), a specific inhibitor of the guanylate cyclase-linked ANP receptor (ANP-GC), in two groups of chronically instrumented unanesthetized sheep fetuses. Seven fetuses were made anemic by serial isovolemic hemorrhage over 1 wk, and five fetuses served as nonanemic controls. Over the 7 d of hemorrhage ANP concentrations increased (45 +/- 7 to 234 +/- 15 fmol/mL). Hematocrit and arterial blood oxygen content were significantly lower in the anemic compared with the nonanemic fetuses (13.8 +/- 0.7 versus 34.6 +/- 2.3% and 0.7 +/- 0.1 versus 2.6 +/- 0.2 mmol/L). Before HS urine flow rate, urinary sodium excretion, fractional excretion of sodium, and renal blood flow were increased in the anemic fetuses, and the extracellular fluid volume (inulin space) was increased (674 +/- 94 versus 497 +/- 71 mL/kg). However, GFR was not different between the groups. HS caused a significant increase in the central venous pressure of the anemic fetuses (0.49 +/- 0.03 to 0.70 +/- 0.05 kPa). Urinary excretion of cGMP was considered to be a marker of endogenous ANP renal effect and was measured before and after a single bolus of HS (5.2 +/- 0.30 mg/kg). HS decreased urinary cGMP excretion to 50 and 37% of baseline levels in anemic and nonanemic fetuses, respectively. Urine flow decreased in both nonanemic and anemic fetuses (0.48 +/- 0.13 to 0.25 +/- 0.06 and 1.30 +/- 0.66 +/- 0.06 mL/min). Sodium excretion decreased in both groups after HS (19 +/- 5 to 9 +/- 2 and 83 +/- 16 to 39 +/- 5 mumol/min). GFR decreased after HS (3.0 +/- 0.8 to 2.4 +/- 0.5 and 3.6 +/- 0.3 to 2.6 +/- 0.2 mL/min. Fraction excretion of sodium also decreased in both groups after HS (4.6 +/- 2.7 to 2.7 +/- 0.5 and 16.1 +/- 2.4 to 11 +/- 1.6). Percent decreases in urine flow, sodium excretion, GFR, and fractional excretion of sodium observed in the anemic fetuses were not statistically different from the nonanemic fetuses. Urine flow and sodium excretion did not decrease to control levels after HS, suggesting that factors in addition to ANP contribute to the natriuresis seen with chronic anemia. After HS a transient increase in renal blood flow was observed in the nonanemic fetuses. An immediate and sustained further increase in renal blood flow

Topics: Anemia; Animals; Atrial Natriuretic Factor; Carbon Dioxide; Cattle; Chronic Disease; Cyclic GMP; Disease Models, Animal; Fetal Diseases; Hemodynamics; Oxygen; Polysaccharides; Receptors, Atrial Natriuretic Factor; Sheep; Sodium

Studies in patients with moderate heart failure have shown a positive relation between atrial size and plasma atrial natriuretic peptide (ANP)(99-126) concentrations; however, the relation of the hormone level and left atrial size and left ventricular function in patients with severe chronic heart failure has not been determined. Fifty-three patients from the Cooperative North Scandinavian Enalapril Survival Study with severe chronic heart failure were evaluated with M-mode echocardiography and determination of plasma concentrations of ANP(99-126). In 35 patients, the plasma level of N-terminal ANP(1-98) was also measured. A significant negative relation was found between ANP(1-98), ANP(99-126), and left atrial diameter (r = -.28, P = .05 and r = -.41, P < .005, respectively). Plasma concentrations of both ANP(1-98) and ANP(99-126) were related to left ventricular systolic function as determined by the systolic time interval index (r = .4, P < .05 and r = .29, P < .05, respectively). A significant improvement of left ventricular systolic function was found in the enalapril group but not in the placebo group. After 6 weeks of therapy, no correlation was found between changes in left atrial size or systolic function or changes in either the ANP(1-98) or ANP(99-126) concentration. The results indicate that high ANP(1-98) or ANP(99-126) plasma concentration is determined by the depressed left ventricular function rather than increased left atrial size in patients with chronic severe heart failure. The findings suggest that the ANP release relation to atrial pressure/atrial size is distorted in severe heart failure.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Chronic Disease; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Peptide Fragments; Protein Precursors; Ultrasonography; Ventricular Function, Left

The influence of 1000 ml of 0.9% NaCl infusion induced hypervolemia on the water-electrolyte and hormonal balance was investigated in HBV-infected patients with chronic persistent hepatitis, chronic active hepatitis and compensated cirrhosis. All examined patients showed higher concentrations of vasopressin and atrial natriuretic peptide and the increased activity of RAA system before the trial. The induced hypervolemia caused the decrease of RAA system's activity and vasopressin concentration and increase of atrial natriuretic peptide's secretion, different in every group of patients. The latent deficiency of calcium and magnesium was found, too. The results showed that all determined patients had water-electrolyte and hormonal disorders, significantly increased in patients with chronic active hepatitis.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Calcitonin; Chronic Disease; Hepatitis B; Humans; Middle Aged; Parathyroid Hormone; Renin-Angiotensin System; Sodium Chloride; Vasopressins; Water-Electrolyte Balance

We hypothesized that a downregulation in pulmonary atrial natriuretic peptide (ANP) receptors helps raise plasma ANP levels during chronic hypoxia. We measured in vivo pulmonary uptake and plasma clearance of 125I-ANP and in vitro pulmonary binding kinetics of 125I-ANP in normoxic and chronically hypoxic rats. Exposure to 21 days of hypobaric (0.5 atm) hypoxia did not decrease specific binding of 125I-ANP in the kidney, but pulmonary binding decreased 35 and 75% after 1 and 3 days of hypoxia, respectively, and increased 200% after 3 days of normoxic recovery from 21 days of hypoxia. The total binding capacity for ANP to lung membrane fractions from normoxic rats, chronically hypoxic rats, and rats that had recovered from hypoxia was 488 +/- 59, 109 +/- 17, and 338 +/- 48 fmol/mg, respectively (P < 0.05 for hypoxic vs. normoxic or recovered lung membranes). The area under the 125I-ANP plasma concentration curve for normoxic and hypoxic rats and normoxic rats that were infused with the ANP C-receptor ligand C-ANF-(4-23) was 3,292 +/- 216, 5,022 +/- 466, and 8,205 +/- 1,059 disintegrations.min-1.ml-1, respectively [P < 0.05 for hypoxic vs. normoxic or C-ANF-(4-23)-infused rats]. We conclude that pulmonary ANP clearance is reduced during chronic hypoxia secondary to a downregulation in pulmonary ANP clearance receptors. Reduced pulmonary clearance of ANP may represent an adaptation that contributes to increased plasma ANP levels during chronic hypoxia.

Topics: Animals; Atrial Natriuretic Factor; Chronic Disease; Down-Regulation; Guanylate Cyclase; Hypoxia; Lung; Male; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor

1. Atrial natriuretic peptide (ANP) causes vasorelaxation in the pulmonary vasculature. ANP levels are elevated in conditions characterized by pulmonary hypertension and it has been hypothesized that ANP may be autoregulatory in the pulmonary circulation. 2. One route of ANP metabolism in vivo is by the action of the enzyme neutral endopeptidase (NEP). We have studied the effects of the NEP inhibitor, SCH 42495, in rats with established pulmonary hypertension secondary to chronic hypoxia. 3. Rats (n = 32) were divided into 4 groups. Normoxic controls were kept in air for 10 days (NC10) and all other animals were placed in a normobaric hypoxic chamber (F1 O2 10%). Chronic hypoxic controls were studied at 10 days (CHC10). After 10 days hypoxia the two remaining groups received oral treatment for a further 10 days, consisting of either SCH 42495 (30 mg kg-1, twice daily CHT20) or methyl cellulose vehicle (0.4%, twice daily, CHV20). 4. Animals were anaesthetized and blood collected for measurement of plasma ANP. Hearts were dissected and ventricles weighed and the histology of the pulmonary vasculature examined. 5. CHC10 rats had significant right ventricular hypertrophy (0.53 +/- 0.08) and pulmonary vascular remodelling (29.0 +/- 0.01%) and had gained significantly less body weight (33.2 +/- 5.5 g) than NC10 rats (0.31 +/- 0.04, 10.9 +/- 0.01%, and 59.2 +/- 11.9 g respectively). CHC10 rats had significantly elevated plasma ANP levels (58.4 +/- 9.9 pM) compared with NC10 rats (23.9 +/- 32 pM). Treatment with SCH 42495 caused a significant reduction in pulmonary vascular remodelling (25.0 +/- 0.01%) and right ventricular hypertrophy (0.52 +/- 0.09) in CHT20 rats compared with CHV20 controls (33.0 +/- 0.02% and 0.61 +/- 0.09 respectively). Pulmonary vascular remodelling was also significantly lower in CHT20 rats than CHC1O animals.6. Thus, short term inhibition of NEP causes regression of established pulmonary vascular remodelling and may be a useful therapeutic strategy in pulmonary hypertension.

Topics: Animals; Atrial Natriuretic Factor; Body Weight; Chronic Disease; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Lung; Male; Methionine; Myocardium; Neprilysin; Pulmonary Circulation; Rats; Rats, Wistar

Death in chronic heart failure (CHF) can be from progression of disease or sudden and unexpected. We have attempted to identify factors that predict sudden death in CHF. We followed up 44 patients with CHF for 12-50 (mean 36) months. 4 patients died of non-cardiovascular causes and were excluded from analysis. There were 7 sudden deaths (symptoms for less than 1 h in a previously stable patient) and 12 from progressive CHF. Patients who died of progressive CHF had lower left-ventricular ejection fractions and higher concentrations of atrial natriuretic factor than the 21 survivors, but there were no differences in these variables between survivors and those who died suddenly. However, the sudden death group had significantly (p < 0.05) greater inter-lead variability in the QT interval on the electrocardiogram (QT dispersion; 98.6 [95% CI 79.1-118] ms1/2) than survivors (53.1 [41.9-64.3] ms1/2) or the group who died from progressive CHF (66.7 [51.8-81.6] ms1/2). QT dispersion is a marker of myocardial electrical instability. The association of increased QT dispersion with sudden death suggests that patients at high risk of such death could be identified by means of this simple, reproducible test. This group might benefit from more intensive treatment.

Topics: Aged; Aged, 80 and over; Aldosterone; Analysis of Variance; Atrial Natriuretic Factor; Biomarkers; Cardiac Output, Low; Chronic Disease; Death, Sudden, Cardiac; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Norepinephrine; Retrospective Studies

Peripheral circulating levels of atrial natriuretic peptide may exhibit short-term variation compatible with a pulsatile pattern of secretion. We obtained samples every 2 min for 90 min from the antecubital vein of 16 patients with chronic cardiac failure and 13 controls. Overall levels were higher in the patients (median and quartiles 230 (125,325) vs. 26 (16,48) ng l-1; P < 0.001). In both groups there was considerable variability, with 10 (2-12) peaks, 9 (7-15) troughs (both defined as > 2 SD from the mean) and 16 (13-18) pulses (defined by computer) during the sampling period in controls, and a similar number in patients. We then carried out simultaneous sampling in the pulmonary artery, femoral artery and peripheral vein in eight subjects with normal cardiac function and six patients with impaired function due to valvular heart disease. The pattern of variability was preserved in all three sites in both groups, suggesting intermittent secretion rather than variable breakdown of the peptide in the lung. No changes in right atrial pressure or heart rate were observed to coincide with the variations, but levels of the peptide in the pulmonary artery correlated with right atrial pressure in patients (r = 0.87; P < 0.05). The mechanism of such periodicity and its pathophysiological importance remain unknown.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Chronic Disease; Female; Femoral Artery; Heart Diseases; Humans; Male; Middle Aged; Periodicity; Pulmonary Artery

1. We have investigated the effects of inhibition of neutral endopeptidase on the cardiovascular remodelling secondary to chronic hypoxia in rats using a novel neutral endopeptidase inhibitor, SCH 42495. 2. Rats were divided into four groups, two of which were maintained in a normobaric, hypoxic chamber (10% O2) and two in room air. Animals received either neutral endopeptidase inhibitor, SCH 42495 (30 mg/kg), or aqueous methyl cellulose vehicle (0.4%) twice daily by oral gavage. 3. At 1, 3, 7, 10 and 14 days, animals (n = 4 per group for days 1, 3, 7 and 14, and n = 8 for day 10) were killed. Hearts were dissected and weighed for determination of ventricular ratios, lungs were perfused with formol saline for histological examination of the pulmonary vasculature, and blood was collected for measurement of plasma atrial natriuretic peptide level. 4. Treatment with SCH 42495 caused a significant reduction in the pulmonary vascular remodelling and ventricular hypertrophy in hypoxic rats after 10 days. Plasma atrial natriuretic peptide levels were significantly elevated in both SCH 42495-treated and control hypoxic animals (n = 8) after 10 days when compared with the normoxic groups. However, there was no difference in plasma ANP levels between SCH 42495-treated and control hypoxic groups at day 10. 5. Treatment with SCH 42495 leads to a decrease in cardiovascular remodelling secondary to chronic hypoxia in rats. A local action of atrial natriuretic peptide within the pulmonary vasculature may be responsible for this effect. Modulation of atrial natriuretic peptide may have therapeutic potential in the management of conditions characterized by pulmonary hypertension and pulmonary vascular remodelling.

Topics: Animals; Atrial Natriuretic Factor; Chronic Disease; Heart Ventricles; Hypertrophy, Right Ventricular; Hypoxia; Male; Methionine; Neprilysin; Pulmonary Veins; Rats; Rats, Wistar

Topics: Adult; Atrial Fibrillation; Atrial Natriuretic Factor; Biopsy; Cardiomyopathies; Chronic Disease; Female; Heart Ventricles; Humans; Immunohistochemistry; Male; Middle Aged; Tachycardia

Renal response to atrial natriuretic peptide in chronic cholestasis was studied in anaesthetized rats and in their isolated perfused kidneys. Cholestasis was induced by bile duct section after ligature, while controls were sham operated. Three weeks after surgery, cholestatic rats showed moderate arterial hypotension, elevated diuresis and no differences in urinary sodium, glomerular filtration rate (GFR) and fractional sodium excretion (FENa), when compared to controls. Isolated kidneys of cholestatic rats had equal basal diuresis and less natriuresis than the controls. Cholestatic rats presented blunted natriuretic and diuretic responses to iv injections of atrial natriuretic peptide (ANP 0.5 microgram), associated with reduced increments in GFR and FENa, when compared with controls. Similarly, the diuretic-natriuretic response of isolated kidneys to ANP (3.5 x 10(-9) M) was greatly attenuated in this group. ANP did not increase perfusion pressure in cholestatic rats, as it did in controls. These results indicate that animals with chronic cholestasis present refractoriness to ANP, which might be mediated by a direct impairment at the renal vascular and tubular sites for ANP action.

Topics: Analysis of Variance; Animals; Atrial Natriuretic Factor; Cholestasis; Chronic Disease; Common Bile Duct; Diuresis; Female; Glomerular Filtration Rate; Kidney; Ligation; Male; Natriuresis; Rats; Rats, Sprague-Dawley; Renal Circulation; Vascular Resistance

High levels of endogenous atrial natriuretic peptide (ANP) are thought to compensate the condition of patients with heart failure by reducing preload and afterload. However, recent reports have indicated that a high plasma ANP level is a prognostic predictor in patients with heart failure. Therefore, the role of endogenous ANP has not been clearly established in patients with heart failure.. The plasma ANP and cGMP levels were determined in the femoral artery and the femoral vein of 97 patients with chronic congestive heart failure (CHF). The plasma ANP level decreased significantly, whereas the plasma cGMP levels increased significantly from the femoral artery to the femoral vein. Among patients with mild CHF (n = 52), the plasma cGMP level correlated with the ANP level, and the calculated ANP extraction level also correlated with the calculated cGMP production in the peripheral circulation (r = 0.70, p < 0.001). In contrast, these correlations were not found in patients with severe CHF (n = 45). Among these patients, the plasma cGMP levels seemed to reach a plateau despite high levels of plasma ANP, and the molar ratio of cGMP production to ANP extraction in the peripheral circulation was significantly lower than in patients with mild CHF (36.7 +/- 9.5 versus 183 +/- 17, p < 0.001). In patients with acute severe CHF (n = 9) and those with mild CHF, patients who were administered exogenous ANP, plasma cGMP levels increased in proportion to those of plasma ANP without saturation.. These results indicate that downregulation of ANP receptors coupled to guanylate cyclase may occur in the peripheral vascular beds of patients with chronic severe CHF.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Cardiac Output, Low; Chronic Disease; Down-Regulation; Extremities; Female; Femoral Artery; Femoral Vein; Guanylate Cyclase; Humans; Male; Middle Aged; Osmolar Concentration; Receptors, Atrial Natriuretic Factor

Neutral endopeptidase (NEP) inhibitors have been shown to strengthen the effects of endogenous atrial natriuretic peptide (ANP). It has been well documented that angiotensin I-converting enzyme (ACE) inhibitors act beneficially in chronic congestive heart failure (CHF). In the present study, renal and hormonal effects of SCH 34826, an orally active NEP inhibitor, were studied in a coronary-ligation model of experimental CHF in the rat. The effects were compared to those of captopril. The drugs were also administered in combination. In anaesthetized rats with CHF, SCH 34826 (90 mg kg-1 sc) elevated plasma ANP from 382 +/- 85 to 658 +/- 120 ng l-1 compared with vehicle (p = 0.002). In sham-operated control rats, plasma ANP also increased slightly from 52 +/- 6 to 70 +/- 9 ng l-1 (p = 0.05). Plasma renin activity did not change in either group. When given orally for 36 h (90 mg kg-1 b.i.d.), SCH 34826 enhanced natriuresis in controls but not in rats with CHF. Captopril (0.2 mg ml-1 in drinking water) enhanced natriuresis in CHF rats and both natriuresis and kaliuresis in controls. When SCH 34826 and captopril were combined, natriuresis was potentiated in control rats as compared with captopril alone; in rats with CHF, however, a brisk kaliuresis was seen. The excretion of cyclic guanosine monophosphate was enhanced in CHF rats by 52% during treatment with SCH 34826 but not with captopril or combination of the two drugs. Moreover, captopril suppressed aldosterone excretion both in CHF rats and controls when administered alone but not when combined with SCH 34826.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Chronic Disease; Cyclic GMP; Dioxolanes; Dipeptides; Drug Therapy, Combination; Heart Failure; Kidney; Male; Neprilysin; Rats; Rats, Wistar

1. The effect of blockade of nitric oxide synthesis in pulmonary endothelium by two L-arginine analogues was tested in isolated blood-perfused lungs of normal rats and rats exposed chronically to 10% O2. 2. In both groups of rats the analogues (N-monomethyl-L-arginine (L-NMMA) and N-nitro-L-arginine methyl ester (L-NAME)) enhanced hypoxic vasoconstriction. In normal rats, with rare exceptions, these analogues had little or no effect on pulmonary artery pressure (Ppa) at constant blood flow during normoxia. However, chronically hypoxic rats have pulmonary hypertension and in these rats the analogues always raised Ppa; the rise in Ppa after L-NMMA but not L-NAME could be partially reversed by L-arginine. L-NAME was more potent than L-NMMA. 3. To see whether the difference between rat groups was due to the high Ppa in chronically hypoxic rats, in control rats we raised Ppa passively by lung inflation to values higher than found in chronically hypoxic rats. L-NAME did not alter the effects of lung inflation on Ppa. 4. Ppa was also raised passively by plotting pressure-flow lines up to high flow rates; the lines were changed minimally by both analogues in control rats but in chronically hypoxic rats the lines were raised to higher pressures and steepened substantially. 5. In control rats, during vasoconstriction caused by hypoxia, endothelin 1 and almitrine, L-NAME caused further rises in pressure. We conclude that a stimulus for nitric oxide release in control rats is the narrowing of vessels caused by vasoconstriction rather than passive increases in intravascular pressure. 6. In chronically hypoxic rats arterioles are narrowed by growth of new muscle and there is some muscle tone even in normoxia. Thus narrowing of the vascular lumen is the stimulus common to both groups of rats which leads to nitric oxide synthesis and attenuation of Ppa by a negative feedback process. Narrowing is associated with a large increase in shear stress due to two factors; the pressure drop along a vessel segment is increased and the surface area of the lining of the affected segment is decreased. 7. Atrial natriuretic peptide caused dose-dependent pulmonary vasodilation in both rat groups but had a greater effect in chronically hypoxic rats. The action persisted and was enhanced after blockade of NO synthesis.

Topics: Almitrine; Animals; Arginine; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Endothelins; Endothelium, Vascular; Hypoxia; In Vitro Techniques; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; omega-N-Methylarginine; Pulmonary Circulation; Rats; Rats, Wistar; Respiration; Vasoconstriction

Neutral endopeptidase (NEP) inhibition is thought to blunt hypoxic pulmonary hypertension by reducing atrial natriuretic peptide (ANP) metabolism, but this hypothesis has not been confirmed. We measured NEP activity, guanosine 3',5'-cyclic monophosphate (cGMP) production, plasma ANP levels, and cardiac ANP synthesis in rats given an orally active NEP inhibitor (SCH-34826) during 3 wk of hypoxia. Under normoxic conditions, SCH-34826 had no effect on plasma ANP levels but reduced pulmonary and renal NEP activity by 50% and increased urinary cGMP levels (60 +/- 6 vs. 22 +/- 4 pg/mg creatinine; P < 0.05). Under hypoxic conditions, SCH-34826-treated rats had lower plasma ANP levels (1,259 +/- 361 vs. 2,101 +/- 278 pg/ml; P < 0.05), lower right ventricular systolic pressure (53 +/- 5 vs. 73 +/- 2 mmHg; P < 0.05), lower right ventricle weight-to-left ventricle+septum weight ratio (0.47 +/- 0.04 vs. 0.53 +/- 0.03; P < 0.05), and less muscularization and percent medial wall thickness of peripheral pulmonary arteries (22 +/- 5 vs. 45 +/- 8% and 17 +/- 1 vs. 25 +/- 1%, respectively; P < 0.05 for all values) than did rats treated with vehicle alone. These values were not affected by SCH-34826 under normoxic conditions. SCH-34826 decreased right ventricular ANP tissue levels in hypoxic rats (27 +/- 10 vs. 8 +/- 1 ng/mg protein; P < 0.05) but did not affect steady-state ANP mRNA levels. We conclude that NEP inhibition blunts pulmonary hypertension without increasing plasma ANP levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Cyclic GMP; Dioxolanes; Dipeptides; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Imidazoles; Male; Muscle, Smooth, Vascular; Myocardium; Neprilysin; Pyrazines; Rats; Rats, Sprague-Dawley; RNA, Messenger

Cyclosporin A has markedly improved graft survival in transplant patients but its side effects, such as renal toxicity and hypertension, pose management problems in transplant recipients. This toxicity has been attributed to prostaglandin inhibition. Concurrent administration of misoprostol (a prostaglandin E1 analog) prevents chronic cyclosporin A-induced nephrotoxicity but not hypertension in rats.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Creatinine; Cyclosporine; Drug Therapy, Combination; Electrolytes; Glomerular Filtration Rate; Heart Rate; Hypertension; Kidney Diseases; Misoprostol; Osmolar Concentration; Prostaglandins; Rats; Rats, Sprague-Dawley; Renal Circulation; Renin

Plasma renin activity (PRA) and aldosterone increase with exercise. Acute hypoxia interferes with this hormonal response to exercise, but the effects of chronic or intermittent hypoxia on exercise-induced hormonal changes are not well understood. The hormonal response to exercise was studied in two groups of subjects who were expected to become hypoxic during exercise (high altitude natives at high altitude and patients with moderate to severe chronic obstructive pulmonary disease or COPD), and normal controls. Both the high altitude natives and COPD patients became hypoxic with maximal exercise. The rate of rise of PRA and epinephrine was significantly less in the two study groups than the normal subjects. Changes in aldosterone levels with exercise were similar to PRA but the differences among groups were not significant. Differences between the groups were not seen for changes in atrial natriuretic polypeptide and norepinephrine during exercise. These results support the concept that hypoxia interferes with the renin-aldosterone and adrenal medullary response to exercise.

Topics: Adult; Aldosterone; Altitude; Atrial Natriuretic Factor; Chronic Disease; Epinephrine; Exercise; Exercise Test; Female; Heart Rate; Humans; Hypoxia; Lung Diseases, Obstructive; Male; Middle Aged; Norepinephrine; Oxyhemoglobins; Regression Analysis; Renin; Severity of Illness Index

To evaluate the possible role of atrial natriuretic peptides ANF (1-98) and ANF (99-126) as diagnostic parameters of atrial distension, measurements of peptide levels were performed in 47 patients with chronic ischemic and/or left sided valvular heart disease. Plasma samples were drawn from the pulmonary artery (PA) and superior vena cava (SVC) during diagnostic right heart catheterization. Forty of the patients also underwent left heart haemodynamic measurements, and in 28 patients two dimensional echocardiography with determination of left atrial diameter was performed. Enhanced plasma concentrations of both peptides were observed with increasing severity of heart failure assessed by the NYHA classification. Mean plasma levels of both peptides were closely correlated to mean pulmonary artery pressure (ANF (1-98): n = 47, r = 0.69 (SVC)/r = 0.72 (PA), p < 0.0001; ANF (99-126): n = 46, r = 0.75 (SVC)/r = 0.68 (PA), p < 0.0001) and mean pulmonary capillary wedge pressure (ANF (1-98): n = 47, r = 0.69 (SVC)/r = 0.72 (PA), p < 0.0001; ANF (99-126): n = 46, r = 0.70 (SVC)/r = 0.64 (PA), p < 0.0001). Positive correlations were also obtained between peptide levels and mean right atrial pressure and left ventricular end-diastolic pressure. When patients with high right atrial pressures (n = 2) were excluded from analysis, a significant correlation was found between peptide levels and echocardiography assessed left atrial diameter. The present study demonstrates the close correlation between concentrations of both atrial peptides and cardiopulmonary haemodynamics in patients with chronic heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Dilatation, Pathologic; Echocardiography; Female; Heart Atria; Heart Valve Diseases; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Protein Precursors

To evaluate the role of endogenous atrial natriuretic peptide (ANP) in patients with congestive heart failure (CHF), the relationship between plasma ANP and cyclic guanosine monophosphate (cGMP) levels and the prognosis of patients with CHF was examined. In patients with chronic mild to moderate CHF, there was a positive correlation between plasma ANP and cGMP levels (r = 0.81, p less than 0.001). However, there was no significant correlation between these plasma levels in patients with chronic severe CHF, in whom the cGMP concentration reached a plateau in spite of high levels of ANP. The ANP extraction level and the cGMP production level in the pulmonary and systemic circulation correlated significantly in patients with mild CHF. In contrast, there was no significant correlation between the 2 parameters in patients with severe CHF, and the molar ratios of cGMP production to ANP extraction in the pulmonary and systemic circulation were significantly lower than those in patients with mild CHF. In 44 patients with chronic severe CHF who were followed up over 2 years, plasma ANP levels provided more sensitive and specific prognostic information than any other parameters. These results indicate that ANP receptors coupled to guanylate cyclase may be down-regulated in patients with chronic severe CHF, suggesting that high plasma ANP levels as a prognostic predictor may be associated with limitations of compensation by endogenous ANP.

Topics: Atrial Natriuretic Factor; Chronic Disease; Cyclic GMP; Follow-Up Studies; Heart Failure; Humans; Prognosis; Pulmonary Artery; Regression Analysis; Second Messenger Systems; Sensitivity and Specificity

This study was designed to evaluate the role of endogenous atrial natriuretic peptide in the pulmonary circulation in patients with chronic heart failure.. Plasma atrial natriuretic peptide concentrations in patients with heart failure have been reported to be higher than those in normal subjects and to increase as the severity of heart failure progresses. Although endogenous atrial natriuretic peptide is thought to improve the condition of patients with heart failure by reducing preload and afterload, recent findings have indicated that a high plasma atrial natriuretic peptide level is a prognostic predictor in patients with heart failure.. To evaluate the pathophysiologic role of endogenous atrial natriuretic peptide in the pulmonary circulation, plasma atrial natriuretic peptide and cyclic guanosine monophosphate (cGMP) levels were determined in the main pulmonary artery and pulmonary capillary wedge region in 80 patients with chronic congestive heart failure (New York Heart Association functional classes II to IV).. The plasma atrial natriuretic peptide level decreased significantly from the main pulmonary artery to the pulmonary capillary wedge region, whereas the plasma cGMP level increased significantly from the main pulmonary artery to the pulmonary capillary wedge region. In patients with mild chronic heart failure (n = 50), the plasma atrial natriuretic peptide level correlated with the cGMP level in the main pulmonary artery (gamma = 0.71, p less than 0.001). The atrial natriuretic peptide extraction level, calculated as (Atrial natriuretic peptide in the main pulmonary artery--Atrial natriuretic peptide in the pulmonary capillary wedge region) x Cardiac output x (1-hematocrit/100) (ng/min), also correlated with the cyclic guanosine monophosphate production level, calculated as (cGMP in the pulmonary capillary wedge region--cGMP in the main pulmonary artery) x Cardiac output x (1-hematocrit/100) (nmol/min) (gamma = 0.78, p less than 0.001). In contrast, such correlations were not found in patients with severe chronic heart failure (n = 30). In these patients, the atrial natriuretic peptide extraction level was significantly higher but there was no significant difference in the cGMP production level between the two groups (mild and severe chronic heart failure). Therefore, the molar ratio of cGMP production to atrial natriuretic peptide extraction in the pulmonary circulation was significantly lower in patients with severe chronic heart failure (88 +/- 16 vs. 480 +/- 41, p less than 0.001).. These results indicate that down-regulation of atrial natriuretic peptide receptors coupled to guanylate cyclase may occur in the pulmonary vascular beds of patients with severe chronic heart failure.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Chronic Disease; Cyclic GMP; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Pulmonary Artery; Pulmonary Circulation

60% of chronic caval dogs with ascites did not respond to atrial natriuretic peptide (ANP) (75 ng.kg-1.min-1) with a natriuresis (TIVC-NR; delta UNaV = 2 +/- 0.8 mu eq/min) whereas the remaining 40% responded normally (TIVC-R; delta UNaV = 216 +/- 50 mu eq/min). Since proximal tubule neutral endopeptidase 24:11 (NEP) destroys most of intrarenal luminal ANP and kinins, we attempted to convert TIVC-NR into TIVC-R by providing NEP inhibition with SQ 28603 at 30 mg/kg. This potent and specific NEP inhibitor produced a natriuresis when administered alone to nine TIVC-NR dogs (delta UNaV = 67 +/- 2 mu eq/min) and permitted a natriuresis in the presence of ANP (delta UNaV = 97 +/- 18 mu eq/min). A natriuretic response to ANP could also be induced in TIVC-NR dogs by providing renal arterial bradykinin or intravenous captopril, a kininase inhibitor. Urodilatin, a natriuretic peptide not destroyed by intrarenal NEP was without effect in TIVC-NR dogs but increased UNaV when given to TIVC-R and normal dogs. Providing bradykinin to TIVC-NR now permitted an increment in delta UNaV (62 mu eq/min) when urodilatin was reinfused. TIVC-R dogs could be converted into TIVC-NR by pretreating with a specific bradykinin antagonist before infusing ANP. We conclude that TIVC-NR dogs are deficient in intrarenal kinins but are converted to responding dogs after NEP inhibition because of increased kinin delivery to the inner medullary collecting duct.

Topics: Alanine; Animals; Ascites; Atrial Natriuretic Factor; Chronic Disease; Cyclic GMP; Dogs; Female; Kidney Tubules; Kinins; Male; Neprilysin; Protease Inhibitors; Receptors, Bradykinin; Receptors, Neurotransmitter; Sodium

We have previously reported a fivefold increase of plasma atrial natriuretic factor (ANF) in patients with congestive heart failure (CHF) compared with normal subjects. However, given the marked increase of ANF under basal conditions, the extent to which ANF secretion can further increase under physiological stress is not been clarified in CHF. We therefore evaluated ANF secretion during ergometric exercise in 11 patients with CHF, with peripheral venous ANF samples obtained at rest and peak exercise. In seven patients, simultaneous peripheral venous and right ventricular ANF samples were obtained to estimate myocardial ANF secretion. Hemodynamic characteristics of exercise included a significant increase of heart rate, mean arterial pressure, and cardiac output (all P < 0.01); reduction of systemic vascular resistance (P < 0.001); and increase of right atrial and pulmonary wedge pressures (P < 0.001). ANF was abnormally elevated at baseline (108 +/- 58 fmol/ml) yet increased further to 183 +/- 86 fmol/ml with exercise (P < 0.003). A step-up of right ventricular ANF, particularly during exercise, was consistent with active myocardial secretion, despite elevated baseline ANF levels.

Topics: Adult; Aged; Atrial Natriuretic Factor; Chronic Disease; Ergometry; Exercise; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardium; Neurotransmitter Agents; Pulmonary Gas Exchange; Pulmonary Wedge Pressure

Endothelin is an extremely potent vasoconstrictor that may have a role in the pathogenesis of acute myocardial ischaemia. Atrial natriuretic factor is an endogenous antagonist of endothelin. To find the pattern and possible importance of circulating endothelin in ischaemic heart disease, concentrations in normal controls and those in patients with stable and unstable angina, acute myocardial infarction, and chronic cardiac failure were compared. The relation between circulating concentrations of endothelin and atrial natriuretic factor in the aftermath of myocardial infarction was also examined.. Eighteen patients with acute myocardial infarction, 10 with unstable angina, 10 with stable angina, 12 with chronic cardiac failure, and 10 normal controls were studied. Endothelin concentration was measured in venous plasma by radioimmunoassay. In patients with acute myocardial infarction simultaneous concentrations of endothelin and atrial natriuretic factor were measured on admission and at one, four, and 24 hours.. Mean concentrations (SEM) of endothelin were 5.72 (0.19) fmol/ml in controls, 6.56 (0.48) fmol/ml in stable angina, 6.41 (0.48) fmol/ml in unstable angina, and 13.83 (0.95) fmol/ml in chronic cardiac failure. In acute myocardial infarction concentrations were 8.81 (0.69) fmol/ml on admission, 11.85 (1.02) fmol/ml at one hour, 11.88 (1.10) fmol/ml at four hours, and 7.30 (0.49) fmol/ml at 24 hours. Concentrations of atrial natriuretic factor at the same times were 68.1 (13.1) pg/ml, 8.4 (1.5) pg/ml, 24.4 (4.1) pg/ml, and 42.0 (6.9) pg/ml.. Plasma endothelin is raised in chronic heart failure and in the aftermath of acute myocardial infarction but not in stable or unstable angina. After myocardial infarction endothelin concentrations are raised whereas concentrations of atrial natriuretic factor are relatively low. The role of endothelin in the pathogenesis of acute myocardial infarction and its interactions with other humoral factors require further investigation.

Topics: Angina Pectoris; Angina, Unstable; Atrial Natriuretic Factor; Chronic Disease; Endothelins; Heart Failure; Humans; Myocardial Infarction; Time Factors

The purpose of this study was to investigate the therapeutic potential of prolonged inhibition of atrial natriuretic factor (ANF) degradation in patients with severe chronic heart failure.. The effects of repeated doses of the endopeptidase inhibitor candoxatrilat (150 mg i.v.) were examined over a 24-hour period in patients with severe chronic heart failure (New York Heart Association class III-IV). Plasma alpha-hANF(99-126) was elevated at baseline (235 +/- 59 pg/ml), increased 2.5-fold at 2 hours after the first dose, and remained significantly elevated throughout the 24-hour protocol. In contrast, pro-hANF(31-67) decreased from 3,151 +/- 616 to 2,072 +/- 362 pg/ml (p less than 0.05). Cardiac index (CI) increased only transiently after the first dose of candoxatrilat (CI, 2.11 +/- 0.2 to 2.67 +/- 0.28 l/min/m2, p less than 0.05). Sodium excretion increased sixfold (p less than 0.05) 2 hours after the first dose of candoxatrilat and remained significantly elevated throughout the protocol. Degree of natriuresis and diuresis in response to candoxatrilat was closely related to baseline cardiac output. Glomerular filtration rate and volume excretion did not change significantly. Pulmonary capillary wedge pressure fell from 23 +/- 3 to 18 +/- 3 mm Hg (p less than 0.05) and remained below baseline throughout the 24 hours. Arterial pressure, heart rate, and total peripheral resistance did not change significantly during the 24-hour period. Urinary cGMP excretion increased fivefold (p less than 0.05), whereas urinary ANF immunoreactivity and plasma cGMP levels remained unchanged. Excretion of prostacyclin metabolite 6-keto-PGF-1 alpha increased 3.3-fold (p less than 0.05). Plasma norepinephrine and epinephrine levels decreased significantly after candoxatrilat and remained suppressed over the 24-hour period. There was also a transient reduction in plasma vasopressin, aldosterone levels, and plasma renin activity. Hematocrit, total protein content, and plasma albumin concentrations did not change, indicating that no fluid shift into the extravascular space had occurred.. 1) The inhibition of ANF degradation causes sustained drop in left and right atrial pressures that appears to be mediated by an inhibition of neurohumoral activity; 2) concomitant inhibition of bradykinin breakdown (which in turn stimulates renal prostacyclin synthesis) contributes to natriuresis; 3) the close correlation between renal response and baseline cardiac index indicates that an inadequate renal perfusion secondary to low cardiac output diminishes the efficacy of this treatment modality. This spectrum of action would be advantageous for a first-line diuretic agent early in the course of disease rather than in patients with advanced chronic heart failure.

Topics: Aged; Atrial Natriuretic Factor; Cardiac Output; Chronic Disease; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Female; Heart Failure; Hemodynamics; Hormones; Humans; Kidney; Male; Middle Aged; Neprilysin; Time Factors

The levels of several regulatory peptides were measured in peripheral plasma samples from individuals with chronic cardiac failure (CCF) and matched controls in both the resting state and during a short period of maximal exercise. Basal levels of noradrenaline (NA; 705 +/- 114 vs 195 +/- 54 ng.l-1; mean +/- SEM; P < 0.05), plasma renin activity (PRA; 12.9 +/- 2.9 vs 2.1 +/- 0.3 ng AI ml-1.h-1; P < 0.05) and aldosterone (ALDO; 325 +/- 49 vs 87 +/- 8 ng.l-1; P < 0.05) were all raised in the patients with CCF, and increased further with exercise. Basal circulating levels of atrial natriuretic peptide (ANP) were also significantly higher in the CCF group compared to controls (136 +/- 35 vs 27 +/- 5 ng.l-1; P < 0.01), but the response to exercise was attenuated, so that at peak exercise, no significant difference was observed. Basal circulating levels of gastrin-releasing peptide (GRP) (29 +/- 4 vs 40 +/- 4 ng.l-1; P < 0.05) and secretin (13 +/- 1 vs 32 +/- 4 ng.l-1; P < 0.05) were significantly lower in the CCF group when compared to controls and there was no significant change in the levels of either peptide with exercise. Levels of neurokinin A (NKA), neuropeptide Y (NPY) and neurotensin (NT) were somewhat higher in patients, but the differences were not significant, and there were no changes during exercise. There were also no significant differences in the levels of vasoactive intestinal peptide (VIP), glucose-dependent insulinotropic polypeptide (GIP), insulin or glucagon in either experimental group both before and during exercise. We have therefore identified different circulating levels of certain regulatory peptides in patients with CCF, but the significance of these remains unclear.

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Chronic Disease; Exercise; Exercise Test; Female; Gastrointestinal Hormones; Heart Failure; Humans; Male; Middle Aged; Neuropeptides; Norepinephrine; Peptides; Renin; Rest

The purpose of the study was to explore the dynamics of the concentration of atrial natriuretic hormone (ANH) in response to changes in arterial pressure including those induced by hypertonic crisis, 7-day hypotensive monotherapy with the drugs having different action mode, and the acute test with the basic hypotensive drugs. 75 patients suffering from arterial hypertension were entered into the study. Measurements of the concentration of ANH in blood plasma were performed by radioimmunoassay with the aid of the kits manufactured by the Amersham Company (Great Britain). The activity of renin and aldosterone was determined by radioimmunoassay according to the standard technique. A strong positive correlation was revealed between the concentration of ANH and the level of both systolic and diastolic AP. A significant rise of the concentration of ANH elicited by hypertonic crisis reflects the growth of the tension of the depressor mechanisms by which AP is regulated. The lack of significant changes in the level of ANH during the acute pharmacological tests and effective continuous treatment with the hypotensive drugs attests to the existence of the complex mechanisms that regulate ANH secretion, determined not only by the level of AP.

Topics: Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Captopril; Chronic Disease; Humans; Hydrochlorothiazide; Hypertension; Middle Aged; Nifedipine; Propranolol; Renin

Nonspecific baroreflex loading maneuvers such as head-down tilt readily suppress stimulated arginine vasopressin levels in normal humans. To test the hypothesis that the increased arginine vasopressin levels in patients with congestive heart failure would not respond normally to baroreflex loading, 12 patients with congestive heart failure had arginine vasopressin levels and osmolality determined in the supine position and after 15 min of 30 degrees head-down tilt. Arginine vasopressin was increased to 6.5 +/- 2.0 pg/ml at control measurement and did not decrease. Eight patients underwent further study after osmotic stimulation with mannitol. Mannitol increased osmolality from 287 +/- 9.2 to 294 +/- 7.8 mOsm/kg (p less than 0.001) and from 288 +/- 9 to 299 +/- 8.2 mOsm/kg (p less than 0.01) on two occasions. No significant suppression of arginine vasopressin was seen during head-down tilt after mannitol infusion compared with values in a time control period. These results are consistent with an abnormality in baroreflex suppression of arginine vasopressin secretion in chronic congestive heart failure and suggest that such a defect may contribute to long-term high levels of arginine vasopressin in this condition.

Topics: Adult; Aged; Analysis of Variance; Arginine Vasopressin; Atrial Natriuretic Factor; Chronic Disease; Female; Heart Failure; Hemodynamics; Humans; Male; Mannitol; Middle Aged; Posture; Pressoreceptors; Reflex; Time Factors

The differential effects of the alpha-2 adrenergic agonist, clonidine, on blood pressure, renal sympathetic nerve activity (RSNA) and renal responses were investigated in conscious as well as anesthetized congestive heart failure (CHF) rats and normal control animals. After the stepwise increments of i.v. clonidine infusion (5, 15 and 30 micrograms/hr for 1 hr), mean arterial pressure gradually decreased in CHF, but increased significantly in the control animals at the higher doses. Urinary volume, sodium and potassium excretions were significantly higher in the normal control animals after the clonidine 30-micrograms/hr infusion compared with the CHF rats. There were almost immediate decreases in RSNA in both the CHF and control groups. Although the control animals reduced RSNA to about 5%, the CHF rats retained 36.5% of their respective control values after clonidine administration. Base-line plasma immunoreactive atrial natriuretic peptide were increased 7-fold in the CHF rats compared to controls. After clonidine, immunoreactive atrial natriuretic peptide increased more than 3-fold in the normal rats, whereas no changes were observed in the CHF group. Our data show that clonidine decreases RSNA in CHF and that the natriuretic and that diuretic effects of an alpha-2 receptor agonist are blunted in experimental CHF. Furthermore, the different mean arterial pressure response in the CHF and control groups at higher doses of clonidine may suggest down-regulation of the vascular alpha-2 adrenergic receptor in CHF.

Topics: Animals; Atrial Natriuretic Factor; Chronic Disease; Clonidine; Diuresis; Epinephrine; Heart Failure; Hemodynamics; Infusions, Intravenous; Male; Natriuresis; Norepinephrine; Rats; Rats, Inbred Strains; Sympathetic Nervous System

Endothelin is a newly discovered potent vasoconstrictor peptide. To explain the clinical significance of endothelin in patients with chronic liver diseases, we measured the plasma concentration of endothelin in patients with chronic hepatitis (n = 15), cirrhosis with ascites (n = 8) and cirrhosis without ascites (n = 12), and we compared the findings with the plasma concentration of endothelin in normal controls (n = 14). The plasma endothelin concentration was significantly higher in patients with cirrhosis with ascites than in normal controls (8.3 +/- 2.3 pg/ml vs. 3.3 +/- 1.4 pg/ml, mean +/- S.D., p less than 0.001), whereas no significant difference was observed between normal controls and the other groups of patients (cirrhosis without ascites = 5.0 +/- 1.3 pg/ml; chronic hepatitis = 3.8 +/- 1.2 pg/ml). In patients with cirrhosis, the plasma endothelin concentration showed a significant negative correlation with creatinine clearance (r = -0.73, p less than 0.01), but no significant correlation was observed between plasma endothelin concentration and fractional excretion of filtered sodium. Furthermore, plasma endothelin levels were significantly higher in patients with endotoxemia than in those without (10.1 +/- 2.1 pg/ml vs. 4.9 +/- 1.2 pg/ml, p less than 0.001). From these results, elevated plasma endothelin, which has a close relation to endotoxemia, may play a contributory role in kidney dysfunction in patients with cirrhosis.

Topics: Aldosterone; Analysis of Variance; Arginine Vasopressin; Ascites; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Cross Reactions; Endothelins; Endotoxins; Hepatitis; Humans; Kidney Function Tests; Liver Cirrhosis; Liver Function Tests; Radioimmunoassay; Reference Values; Renin

1. The effects of the continuous infusion of atrial natriuretic peptide on the development of pulmonary hypertension were studied in rats exposed to chronic hypoxia. 2. Continuous intravenous infusion of two doses of synthetic rat atrial natriuretic peptide, 300 ng/h per rat (0.10 pmol/h per rat) and 800 ng/h per rat (0.28 pmol/h per rat), attenuated the development of pulmonary hypertension in rats exposed to chronic hypoxia (fractional concentration of oxygen in inspired air = 10%) for 7 days: (i) the pulmonary artery pressure (mean +/- SD) in the vehicle-treated hypoxic group was 45 +/- 6 mmHg compared with 28 +/- 6 mmHg in the vehicle-treated normotoxic group (n = 8, P less than 0.001); (ii) treatment with atrial natriuretic peptide in normoxia did not alter the pulmonary artery pressure, systemic blood pressure or heart rate; (iii) treatment with atrial natriuretic peptide in hypoxia resulted in a lower pulmonary artery pressure in the group treated with 800 ng of atrial natriuretic peptide/h per rat (38 +/- 8 mmHg, P less than 0.05 compared with the vehicle-treated hypoxic group) without affecting the systemic blood pressure or heart rate. 3. Chronic hypoxia resulted in an extension of vascular smooth muscle towards the periphery of the lung with the development of muscle in normally non-muscularized vessels (remodelling).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Chronic Disease; Hypertension, Pulmonary; Hypoxia; Infusion Pumps, Implantable; Male; Muscle Development; Muscle, Smooth, Vascular; Pulmonary Artery; Rats; Rats, Inbred Strains

In eight patients (63 +/- 7.9 years) with angiographically documented dilated cardiomyopathy, we studied the acute effects of a beta-adrenergic stimulation with dobutamine on the plasma levels of atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP). For this purpose, a four-point dose-response curve was prepared for dobutamine starting with an initial dose of 2.5 micrograms kg-1 min-1, which was increased by 2.5 micrograms kg-1 min-1 at a time up to altogether 10 micrograms kg-1 min-1. Each stage lasted 15 min. ANP and cGMP were determined from the mixed venous blood before the start (t0), at 5 micrograms kg-1 min-1 after 30 min (t1), at 10 micrograms kg-1 min-1 after 60 min (t2) and after subsidence of the drug effect after 90 min (t3). ANP dropped from 380 +/- 151 pg ml-1 (normal range up to 55 pg ml-1) by 38% to 235 +/- 90 pg ml-1 after 30 min and by another 17% to 171 +/- 45 pg ml-1 after 60 min. After the effect of dobutamine had subsided, an increase by 41% to 325 +/- 139 was reached. There was a parallel drop of the mean cGMP level from 5.4 +/- 1.4 pmol.ml-1 by 28% to 3.89 +/- 1.4 pmol.ml-1 (30 min) and by another 14% to 3.2 +/- 0.7 pmol.ml-1 (60 min). After 90 min it was 18% below the initial value, being 4.4 +/- 1.3 pmol.ml-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Chronic Disease; Cyclic GMP; Dobutamine; Dose-Response Relationship, Drug; Heart Failure; Hemodynamics; Humans; Male; Middle Aged

A canine model of chronic heart failure was produced by multiple sequential intracoronary embolizations with microspheres. Twenty closed-chest dogs underwent three to nine intracoronary embolizations performed 1-3 wk apart. Embolizations were discontinued when left ventricular (LV) ejection fraction was less than 35%. LV ejection fraction was 64 +/- 2% at baseline and decreased to 21 +/- 1% at 3 mo after the last embolization (P less than 0.001). During the same period, LV end-diastolic pressure increased from 6 +/- 1 to 22 +/- 3 mmHg (P less than 0.001); LV end-diastolic volume increased from 64 +/- 3 to 101 +/- 6 6 ml (P less than 0.001), and cardiac output decreased from 2.9 +/- 0.2 to 2.3 +/- 0.1 l/min (P less than 0.01). These changes were accompanied by significant increases of pulmonary artery wedge pressure and systemic vascular resistance. Plasma norepinephrine increased from 332 +/- 17 pg/ml at baseline to 791 +/- 131 pg/ml at 3 mo after the last embolization (P less than 0.01); plasma levels of atrial natriuretic factor increased from 12.7 +/- 10.0 to 28.8 +/- 8.6 pmol/l (P less than 0.01), whereas plasma renin activity remained unchanged. Gross and microscopic postmortem examination showed patchy myocardial fibrosis and LV hypertrophy. We conclude that multiple intracoronary embolizations with microspheres, separated in time, can lead to chronic heart failure in dogs. The preparation is stable and reproducible and manifests many of the sequelae of heart failure that result from loss of contractile myocardium.

Topics: Animals; Atrial Natriuretic Factor; Cardiac Output; Cardiac Output, Low; Chronic Disease; Coronary Disease; Disease Models, Animal; Dogs; Embolism; Heart Ventricles; Microspheres; Norepinephrine; Pulmonary Wedge Pressure; Renin; Stroke Volume; Vascular Resistance; Ventricular Function, Left

Seventy-six patients with chronic heart failure, stages I-III, that developed after different heart diseases were examined. Catheterization of the right heart was carried out in 51 patients. The concentration of immunoreactive atrial natriuretic factor (ANF) in peripheral blood plasma and in the blood from the right atrium was increased in patients and rose as heart failure progressed. No correlation was discovered between the character of heart disease and the concentration of immunoreactive ANF in the plasma. The latter one was directly dependent on the wedging pressure in the pulmonary artery and on the pressure in the right atrium. The level of immunoreactive ANF in the atrium was higher than in the periphery. However, that was not of statistical power.

Topics: Adult; Atrial Natriuretic Factor; Cardiac Catheterization; Cardiomyopathy, Dilated; Chronic Disease; Coronary Disease; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Radioimmunoassay; Rheumatic Heart Disease

Serum atrial natriuretic peptide (ANP), plasma renin activity (PRA), angiotensin II (AII) and aldosterone levels have been studied in patients with chronic bilateral ureteric obstruction resulting from high pressure chronic retention of urine (HPCR), both in the obstructed state and during the post-obstructed period. Increased ANP levels observed during chronic obstruction fell rapidly following urinary tract decompression by urethral catheterisation. Serum ANP resurged briefly within 24 h but stabilised thereafter at a lower level. PRA was initially suppressed but rose after catheterisation, the increase lagging behind the changes seen for ANP. Rising levels of AII and aldosterone followed this trend but, unlike PRA, levels were not completely suppressed in the obstructed state. The observed hormonal changes probably reflect homeostatic mechanisms directed to the maintenance of sodium and water balance during obstruction and to limitation of the diuresis following its relief.

Topics: Aged; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Chronic Disease; Diuresis; Humans; Middle Aged; Renin; Ureteral Obstruction; Urinary Catheterization; Urinary Retention

The present study was designed first to investigate the pulmonary hypertensive effects of chronic hypoxia in spontaneously hypertensive rats and second to compare the cardiovascular effects of atrial natriuretic factor on rats exposed to hypoxia and on control rats kept at sea level. Catheters were placed in the femoral and pulmonary arteries for measurement of mean systemic arterial pressure and mean pulmonary arterial pressure. The cardiac output was measured by thermodilution method. It was found that 4 weeks of simulated 18,000-foot hypoxia led to polycythemia, right ventricular hypertrophy, and pulmonary hypertension, which resulted from an increased pulmonary vascular resistance. However, systemic arterial pressure was not significantly different between the two groups of rats. Atrial natriuretic factor administration decreased systemic arterial pressure and pulmonary arterial pressure to a lesser extent in the hypoxic group compared with the sea level control group. It is concluded that these animals showed an impaired response to atrial natriuretic factor after long-term exposure to hypoxia.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Chronic Disease; Dose-Response Relationship, Drug; Heart Rate; Hypoxia; Male; Myocardium; Organ Size; Pulmonary Artery; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Stroke Volume

A 28-year-old woman had hypothalamic disorders (amenorrhea, obesity, psychiatric abnormalities, polydipsia and fever) and chronic glomerulonephritis. She also suffered from general edema associated with cyclical oliguria and polyuria. Her body weight and plasma osmolality increased during the oliguria phase lasting 2 to 8 days and decreased after paroxysmal polyuria accompanied by the natriuresis. These episodes occurred repeatedly, regardless of the treatment with or without diuretics. The release of arginine vasopressin in response to increased plasma osmolality was exaggerated, but changes in plasma volume did not affect arginine vasopressin release. Plasma atrial natriuretic hormone increased in response to a rise in plasma arginine vasopressin and plasma volume during the oliguria phase, thereby resulting in the diuresis and natriuresis. The renin-angiotensin-aldosterone system was secondarily activated by body fluid depletion and diuretics, and this might play an additive role in general swelling. Plasma gonadal hormones did not change to explain the edema. The mechanism of this cyclical edema remains unknown, but it is likely that hypothalamic dysfunction related to psychiatric abnormalities may exaggerate arginine vasopressin release, and enhanced renal sympathetic activity may cause retention of Na and water, and the increase in atrial natriuretic hormone release responding to the plasma volume expansion may bring about the diuresis and natriuresis.

Topics: Adult; Aldosterone; Arginine Vasopressin; Atrial Natriuretic Factor; Body Weight; Chronic Disease; Edema; Female; Follicle Stimulating Hormone; Glomerulonephritis; Growth Hormone; Humans; Hydrocortisone; Hypothalamic Diseases; Luteinizing Hormone; Oliguria; Osmolar Concentration; Plasma; Polyuria; Prolactin; Thyrotropin; Thyroxine; Water-Electrolyte Balance

Continuous ambulatory measurement of pulmonary arterial pressure was used to investigate changes following right heart catheterisation in patients with chronic heart failure. Ten males, mean age 56 years, with chronic heart failure, underwent 24 hour pressure recording using a micromanometer tipped catheter with in vivo calibration and frequency modulated recording. Eight patients were taking diuretics and 3 vasodilators. Blood was drawn for catecholamines, plasma renin activity and atrial natriuretic peptide 1 hour before catheterisation (-1 h), at the time of catheterisation (0 h) and 1, 2, 3, 4 and 6 hours later and aldosterone, cortisol and growth hormone at -1, 0 and 6 hours. Analysis of variance was used to determine changes in pulmonary arterial pressure, heart rate and hormones from the time of catheterisation in lying, sitting and standing postures. There was no significant change in pulmonary arterial pressure or heart rate over the 12 hours following or 24 hours after catheterisation in any posture. In the majority of patients plasma noradrenaline, plasma renin activity, atrial natriuretic peptide, aldosterone and cortisol were elevated. There was no significant change in hormone levels during the 6 hours following catheterisation. These findings suggest that the effect of invasive haemodynamic monitoring and chronic medical therapy on central haemodynamics is minor, and that a delay between insertion of catheters and measurement of pressure is unnecessary.

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Cardiac Catheterization; Chronic Disease; Electrocardiography, Ambulatory; Evaluation Studies as Topic; Heart Failure; Heart Rate; Hormones; Humans; Hydrocortisone; Male; Middle Aged; Norepinephrine; Pulmonary Wedge Pressure; Renin

Atrial natriuretic peptide (hANP 4-28) was infused for 1 h (0.3 microgram/kg/min) in 11 normal awake dogs and seven awake dogs with chronic left ventricular dysfunction, induced 16 weeks earlier by repetitive DC shock. The responses were similar in the two groups and included decreases in arterial pressure (107-99 mm Hg), heart rate (83-72 beats/min), and cardiac output (3.6-2.8 L/min), without changes in right or left ventricular filling pressures. Systemic vascular resistance (SVR) tended to rise during the infusion and was significantly increased (2,847-3,442 dyn s cm-5, p less than .05) during the postinfusion recovery period. Regional blood flows (microspheres) during infusion revealed a decrease in skin and splanchnic flow. Despite the apparent vasoconstrictor effect, plasma norepinephrine (PNE), renin activity (PRA), and arginine vasopressin (AVP) levels all fell during ANP infusion. These data suggest that ANP exerts a cardioinhibitory effect, possibly similar to that of arginine vasopressin (AVP), and that the net systemic vasoconstrictor effect of ANP in these dogs is mediated by a complex interrelationship between direct vascular effects, neurohormonal inhibition, and central reflex activation.

Topics: Animals; Atrial Natriuretic Factor; Cardiac Output; Chronic Disease; Dogs; Heart Diseases; Heart Rate; Heart Ventricles; Hemodynamics; Hormones; Neurotransmitter Agents; Regional Blood Flow; Renal Circulation; Sodium

The changes in plasma immunoreactive atrial natriuretic factor (iANF) and urinary Na excretion that occur in response to an oral load of Na and to infusion of synthetic atrial natriuretic factor (ANF) were examined in conscious dogs with an arteriovenous (AV) fistula and chronic compensated high-output heart failure. After ingestion of a meal containing 125 meq Na, plasma iANF and right atrial pressure increased from high basal levels of 506 +/- 46 pg/ml and 96 +/- 5 mmH2O to peak responses of 728 +/- 43 pg/ml (P less than 0.05) and 104 +/- 6 mmH2O (P less than 0.05). These increases were associated with a brisk postprandial natriuresis and diuresis of a magnitude previously observed in normal dogs. Synthetic ANF infusions that achieved plasma iANF levels of similar and higher magnitude to those observed during the feeding experiments did not produce a significant natriuresis in these AV fistula dogs. In separate series of experiments, chronic effects of normal and low-Na diets on daily Na excretion and postabsorptive plasma iANF, renin, and aldosterone were studied in normal and AV fistula dogs. During the normal Na diet of 40 meq/day, both groups had normal levels of renin and aldosterone, but Na balance was achieved in AV fistula animals in the presence of a fourfold elevation in plasma iANF compared with normal dogs (P less than 0.05). During 2 wk of Na restriction, cumulative negative Na balance and marked stimulation of renin and aldosterone were similar in normal and AV fistula animals, but plasma iANF did not change significantly in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Absorption; Aldosterone; Animals; Arteriovenous Shunt, Surgical; Atrial Natriuretic Factor; Cardiac Output, Low; Chronic Disease; Diet, Sodium-Restricted; Dogs; Eating; Female; Kidney; Renin; Sodium

The levels and molecular form of atrial natriuretic peptide-like immunoreactivity (ANP-LI) in human atrial tissue were investigated. The levels of right atrial ANP-LI were significantly higher in mitral disease than in other cardiac or noncardiac diseases. The increased ANP-LI was mainly accounted for by an increase in beta-human ANP-LI (beta-hANP-LI). Both total ANP-LI and beta-hANP-LI levels were associated with the presence of atrial fibrillation and with increased atrial pressure. Plasma beta-hANP-LI levels were also increased in mitral disease. These results suggest that human atrium with hemodynamic overloads is characterized by increased tissue levels of ANP and by a shift to the beta-hANP form.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Heart Atria; Heart Diseases; Heart Valve Diseases; Hemodynamics; Humans; Middle Aged; Mitral Valve; Molecular Structure; Myocardium; Radioimmunoassay

Elucidation of the role of (elevated) endogenous atrial natriuretic factor (ANF) in chronic heart failure has been hampered by a lack of specific inhibitors. We used a newly developed monoclonal antibody that has been shown to specifically block both exogenously and endogenously released ANF in vivo. For assessment of the vasodilatory action of ANF in chronic heart failure, either this antibody against ANF or ascites (control serum) was injected in rats with myocardial infarction and failure and in sham animals. Ascites did not alter central hemodynamics in either the sham or infarcted group. Antibody significantly increased right atrial pressure, left ventricular end-diastolic pressure, and systemic vascular resistance (SVR) in the infarction group but did not affect these variables in the sham group. Because renal blood flow, as measured by radioactive microspheres, decreased significantly in all four groups, probably due to nonspecific renal vasoconstrictor effects of the ascites, a separate group of infarcted animals was treated with purified ANF antibody (devoid of nonspecific effects) or mouse IgG as a control injection. In these animals, right atrial pressure increased from 1.1 +/- 0.7 to 2.6 +/- 0.7 mm Hg (p less than 0.001). Although SVR, renal blood flow velocity (measured by Doppler probe), and renal vascular resistance did not change in the infarcted animals after administration of purified ANF antibody, a significant correlation was found between baseline plasma ANF values and the change in SVR exerted by purified ANF antibody (r = 0.758, p less than 0.02, n = 9); that is, SVR increased in rats with high baseline plasma ANF (greater than 350 pg/ml), but decreased in animals with plasma ANF less than 200 pg/ml. These results suggest that moderately elevated endogenous plasma ANF levels in chronic heart failure do affect central hemodynamics, primarily by reducing venous pressure (e.g., by decreasing intravascular volume or by venous dilation). Arterial vasodilation, however, appears to emerge when plasma ANF is greatly increased.

Topics: Animals; Antibodies, Monoclonal; Atrial Natriuretic Factor; Cardiac Output, Low; Chronic Disease; Hemodynamics; Male; Myocardial Infarction; Rats; Rats, Inbred Strains; Vasodilator Agents

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Chronic Disease; Heart Rate; Hemodynamics; Humans; Male; Pericardiectomy; Pericarditis, Constrictive; Stroke Volume

The aim of the present study was to determine whether left atrial size--a likely indicator of atrial stretching--correlates with the plasma concentration of atrial natriuretic peptide and whether this relation is different in patients in sinus rhythm and in those with atrial fibrillation. Arterial plasma concentrations of immunoreactive atrial natriuretic peptide (ir-ANP), adrenaline, noradrenaline, aldosterone, and vasopressin were measured in 13 patients in sinus rhythm without apparent heart failure and in 13 patients in atrial fibrillation. The two groups were matched for left atrial diameter and the ratio of the left atrial diameter to the diameter of the aortic root (assessed by echocardiography). There were no significant differences in age, heart rate, blood pressure, or left ventricular end diastolic diameter between the two groups. Left atrial diameters varied from 33 to 60 mm. The mean (SD) plasma concentration of ir-ANP was significantly higher (35 (21) pmol/l) in the patients with atrial fibrillation than in those in sinus rhythm (12 (11) pmol/l). The concentration of plasma aldosterone was also higher in patients with atrial fibrillation (831 (366) v 523 (211) pmol/l). Concentrations of adrenaline, noradrenaline, and vasopressin were similar in both groups. None of the hormone concentrations correlated with left atrial dimensions. These results indicate that plasma concentrations of ir-ANP and aldosterone are highly sensitive indicators of changes in haemodynamic function during atrial fibrillation. They also underscore the difficulties of correlating echocardiographic assessment of patients with plasma concentrations of a vasoactive hormone.

Topics: Aldosterone; Arginine Vasopressin; Atrial Fibrillation; Atrial Natriuretic Factor; Chronic Disease; Epinephrine; Heart Atria; Hemodynamics; Humans; Middle Aged; Myocardium; Norepinephrine

Despite intensive investigation, the pathogenesis of sodium retention in patients with chronic liver disease is not fully known. We have studied 19 chronic liver disease patients, 13 without (group 1) and six with (group 2) histories of clinical sodium retention (ascites or edema) by varying dietary sodium intake. The patients were placed on a 20 mmol/day constant diet for 1 wk, followed by a constant 100 mmol/day sodium diet for 1 wk under strict metabolic conditions. After 5 days of equilibration on each diet, blood and urine samples were collected for plasma atrial natriuretic factor levels and urinary sodium excretion. Group 1 patients (n = 6) achieved near sodium balance in 5 days on both a 20-mmol (urinary sodium output = 17 +/- 3 mmol/day) and a 100-mmol sodium diet (urinary sodium output = 80 +/- 5 mmol/day). Atrial natriuretic factor levels in these patients tended to be elevated, but the increase was not significantly greater than that in normal control subjects (10 +/- 4 pg/ml to 19 +/- 4 pg/ml) on the same diets. In contrast, group 2 patients (n = 5) were in significant positive sodium balance on both the 20 mmol/day sodium diet (mean urinary sodium output = 9.5 +/- 3.3 mol/day) and the 100 mmol/day sodium diet (urinary sodium output = 37 +/- 13 mmol/day). This occurred despite significantly elevated baseline atrial natriuretic factor levels and a significant increase in plasma atrial natriuretic factor levels after sodium challenge (62 +/- 9 pg/ml, p less than 0.05) on a 100 mmol/day sodium diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Ascites; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Edema; Heart Atria; Humans; Hypertension, Portal; Kidney; Liver Cirrhosis; Sodium; Sodium, Dietary; Time Factors

A prospective longitudinal study of 25 pregnant women (30 pregnancies) with chronic hypertension, a group prone to development of preeclampsia, was conducted to explore the relationship between the renin-angiotensin-aldosterone system and the development of superimposed preeclampsia. In women with chronic hypertension in whom preeclampsia did not develop (17 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated, beginning in the first trimester and continuing throughout pregnancy as found previously in normotensive pregnant women (n = 58). Plasma estradiol and progesterone levels also increased progressively. In women with chronic hypertension in whom preeclampsia developed (13 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated in the first trimester as in the other groups. However, later in pregnancy significant differences were observed. Blood pressure began to rise in the second trimester. Initially the renin-angiotensin-aldosterone system remained stimulated, but in the early third trimester, when preeclampsia was diagnosed, plasma renin activity and urine aldosterone excretion decreased, and atrial natriuretic factor increased. These data provide information that may be useful in the recognition of superimposed preeclampsia, and in the investigation of its pathogenesis.

Topics: Adult; Analysis of Variance; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Estradiol; Female; Humans; Hypertension; Kidney; Longitudinal Studies; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Progesterone; Prospective Studies; Renin-Angiotensin System

We investigated whether rats with high-output heart failure [aortocaval (AC) shunts] release atrial natriuretic factor (ANF) and excrete sodium after moderate volume expansion (VE) as do sham-operated controls. Mean arterial blood pressure was lower (92.5 +/- 4.4 vs. 114.0 +/- 1.3 mmHg) and relative heart weight was higher (545.6 +/- 35.1 vs. 253.8 +/- 9.8 mg/100 g body wt) in animals with AC shunts than in their controls. Central venous pressure (CVP) was elevated (3.61 +/- 0.36 vs. 0.37 +/- 0.94 mmHg) and heart rate decreased (332.5 +/- 8 vs. 370.0 +/- 9.9 beats/min) in AC rats. This group also presented lower basal urinary sodium excretion (UNaV), urinary volume, and hematocrit than their sham-operated controls. Basal plasma COOH- and NH2-terminal ANF levels were greatly elevated in AC shunt animals (165.43 +/- 55.73 and 1,692.98 +/- 305.63 fmol/ml, respectively) when compared with the controls (14.27 +/- 1.49 and 331.67 +/- 29.84 fmol/ml, respectively). VE was performed in conscious rats 3 times at 15-min intervals with human plasma protein fraction. The effect of VE on CVP, left-ventricular end-diastolic pressure, the increases in plasma COOH- and NH2-terminal ANF, and the diuretic and natriuretic responses were similar in both experimental groups. U(NA)V was positively correlated with plasma COOH- (r = 0.50, P less than 0.01) and NH2- (r = 0.60, P less than 0.001) terminal ANF only in the controls. One main peak of immunoreactive ANF corresponding to the elution time of a small peptide such as ANF-(99-126) was detected in the plasma of AC animals after VE. We conclude that ANF release and natriuresis are conserved after moderate VE in a rat model of moderate high-output experimental heart failure.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output, Low; Chronic Disease; Diastole; Diuresis; Male; Natriuresis; Plasma Substitutes; Rats; Rats, Inbred Strains

The response in terms of production of atrial natriuretic factor to maximal cardiopulmonary exercise was investigated in 13 patients with mild heart failure (New York Heart Association function class II) secondary to previous myocardial infarction. Exercise induced a rapid and gradually increasing production of atrial natriuretic factor. The concentration at the termination of the test was statistically higher than at rest (64.5 +/- 9.7 versus 119.4 +/- 18.3 pmol/l. P = 0.001). Resting levels of the natriuretic factor correlated well to levels at peak exercise (r = 0.797, P = 0.001). The increase in concentration from rest to peak exercise (atrial natriuretic factor delta) was inversely correlated to the peak consumption of oxygen (r = -0.584, P = 0.036), indicating that the response to exercise is not attenuated in the patients with most marked functional impairment. The relationship between resting levels of atrial natriuretic factor and peak consumption of oxygen did not reach statistical significance (r = -0.421, P = 0.152), but a significant inverse relationship was observed between concentration at peak exercise and peak consumption of oxygen (r = -0.671, P = 0.012). Levels of atrial natriuretic factor during peak exercise are related to functional impairment in mild heart failure and may discriminate between the functional capacity of patients belonging in the same class of clinical function.

Topics: Aged; Atrial Natriuretic Factor; Chronic Disease; Exercise; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Oxygen Consumption

Alpha-atrial natriuretic peptide (ANP) levels, plasma renin activity, and plasma aldosterone levels were measured in 103 patients with coronary heart disease (CHD) having signs of various circulatory failures. The parameters were studied in relation to central hemodynamic values, and their dependence on the stage of chronic circulatory failure. Alpha-ANP was found to be one of the factors of the humoral systems implicated in the pathogenesis of chronic circulatory failure in CHD patients. The plasma level of alpha-ANP was found to be related to the state of the renin-angiotensin-aldosterone system both in healthy subjects and CHD patients.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Chronic Disease; Coronary Disease; Female; Heart Failure; Humans; Male; Middle Aged; Renin-Angiotensin System

The content of human precordial natriuretic peptide (alpha-HPNP) was examined in 26 patients suffering of chronic ischemic heart disease with different stages of circulatory insufficiency. It is suggested that alpha-HPNP participates in the pathogenesis of circulatory insufficiency in patients with chronic ischemic heart disease and depended on the stage of circulatory insufficiency.

Topics: Adult; Aged; Atrial Natriuretic Factor; Chronic Disease; Coronary Disease; Heart Failure; Humans; Middle Aged

A 40-year old female was admitted with complaints of general fatigue and dyspnoea brought on by effort. There were edema on the face, a diffuse and slightly hard goiter on the neck and non-pitting edema in the lower legs. Laboratory findings showed low levels of serum T3 (0.37 ng/ml) and T4 (2.0 micrograms/dl), a very high level of serum TSH (549.8 microU/l), positive thyroid test (x 400) and positive microsome test (x 102,400). The chest roentgenogram showed an enlargement (CTR 62%) of the cardiac silhouette in the shape an ice bag, and the electrocardiogram revealed low QRS voltage with T-wave flattening in all leads. Remarkable pericardial effusion was shown on the two-dimensional echocardiogram. Judging from the indications of hypothyroidism, positive antithyroid antibody and pericardial effusion. This patient was diagnosed as having myxedema heart due to chronic thyroiditis. The levels of plasma alpha-hANP did not elevate so much as the levels in normal controls after right atrial (RA) pacing, although mean right atrial pressure was higher than in normal controls after RA pacing. The levels of plasma alpha-hANP after RA pacing in euthyroid state were higher than those in hypothyroid state. The levels of plasma alpha-hANP after RA pacing became higher after the administration of ATP or db-cAMP both in euthyroid and hypothyroid states. These results indicate that the impaired alpha-hANP secretion in myxedema heart is improved by the administration of thyroxine, ATP or db-cAMP.

Topics: Adenosine Triphosphate; Adult; Atrial Natriuretic Factor; Bucladesine; Chronic Disease; Drug Therapy, Combination; Female; Heart Diseases; Humans; Myxedema; Thyroiditis; Thyroxine

The natriuretic, diuretic, and hypotensive responses to infused atrial natriuretic peptide (ANP) were measured in rats 4 weeks after myocardial infarction induced by coronary artery ligation. Rat [1-28]-ANP was infused intravenously in doses of 0.1, 0.3, and 1.0 microgram/kg/min for 30 min each under pentobarbital anesthesia. There was a marked natriuresis, diuresis, and fall in blood pressure in rats with infarction but each response was significantly attenuated when compared with sham-operated controls (ANOVA: p less than 0.01, p less than 0.05, and p less than 0.01, respectively). Urinary cyclic guanosine monophosphate (cGMP) excretion in rats with infarction was higher than that of controls but rose to the same absolute level in both groups in response to ANP infusion (0.3 microgram/kg/min). Reduced ANP responsiveness may result from impaired postreceptor mechanisms or from physiological antagonism by angiotensin II. Reduced ANP responsiveness may partly explain impaired salt handling in heart failure.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Coronary Vessels; Cyclic GMP; Female; Heart Failure; Myocardial Infarction; Rats; Rats, Inbred Strains; Sodium; Urodynamics

Atrial natriuretic factor may play a role in the regulation of blood pressure, renal function, and volume homeostasis in normal and pathologic states. Atrial natriuretic factor and plasma renin activity were measured by radioimmunoassay in pregnant women with normal blood pressure (n = 29), chronic hypertension (n = 17), and preeclampsia (n = 18) during the first, second, and third trimesters and in the postpartum period. Serial data were obtained in 11 patients. Nonpregnant age-matched women were used as controls (n = 14). In normal gestation and in chronic hypertension, atrial natriuretic factor levels were in the same range as that in the control group. Mean atrial natriuretic factor was significantly higher in the antepartum and postpartum periods in severe preeclampsia. There was an inverse relationship between atrial natriuretic factor and plasma renin activity in pregnancies complicated by chronic hypertension or preeclampsia. Although fluctuations in atrial natriuretic factor levels did not predict preeclampsia, atrial natriuretic factor did correlate with the severity of the disease.

Topics: Atrial Natriuretic Factor; Chronic Disease; Eclampsia; Female; Humans; Hypertension; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Renin

The aim of this paper was to study atrial natriuretic factor, plasma renin activity and antidiuretic hormone values during paroxysmal atrial arrhythmias with different ventricular rates before and after pharmacological cardioversion and during chronic atrial flutter-fibrillation. The study was carried out: 1) during acute arrhythmias (atrial flutter-fibrillation or supraventricular tachycardia) and after restoration of normal sinus rhythm in 2 patients without heart disease, in 13 with chronic heart disease and in 6 with acute myocardial infarction; 2) during chronic atrial flutter-fibrillation in 5 patients with chronic ischemic heart disease, without congestive heart failure. Atrial natriuretic factor, aldosterone, plasma renin activity and antidiuretic hormone values were measured by radio-immunoassay. During paroxysmal atrial arrhythmias atrial natriuretic factor levels were higher than normal in all patients, particularly in those with supraventricular tachycardia. Most of the aldosterone measurements were above the normal range. As far as plasma renin activity and antidiuretic hormone values are concerned, levels higher than the normal range were found in the patients with severe hemodynamic impairment. Central venous pressure was above normal in all patients except in the 2 without heart disease, and there was a positive correlation between atrial natriuretic factor and central venous pressure values. After restoration of normal sinus rhythm atrial natriuretic factor values returned to normal except in acute myocardial infarction patients, in 1 chronic ischemic heart disease patient with congestive heart failure and in 3 patients with mitral valve disease. In all patients with chronic atrial flutter-fibrillation and in 5 patients with acute atrial flutter-fibrillation and low rate, above normal atrial natriuretic factor values were found with normal central venous pressure values. Atrial distension due to high central venous pressure values, lack of atrial contraction and rhythmic detension of the atrial stretch receptors, may be considered the major stimuli responsible for atrial natriuretic factor release during acute paroxysmal atrial arrhythmias and atrial flutter-fibrillation with low ventricular rate, respectively.

Topics: Acute Disease; Adult; Aged; Aldosterone; Atrial Fibrillation; Atrial Flutter; Atrial Natriuretic Factor; Blood Pressure; Central Venous Pressure; Chronic Disease; Female; Humans; Male; Middle Aged; Renin; Tachycardia, Supraventricular; Vasopressins

The chronic reserve for the secretion of atrial natriuretic factor (ANF) was studied in conscious dogs with an arteriovenous (a-v) fistula, a model of high-output heart failure. After the first 7 days of marked sodium retention after creation of the a-v fistula, the animals regained sodium balance for the subsequent 3 wk. This compensatory natriuresis occurred in the presence of significant increases in right atrial pressure and was associated with marked and sustained elevations in plasma ANF and with the return of plasma renin and aldosterone to base-line values. The cardiac reserve for ANF secretion was further evaluated in these dogs with compensated high-output heart failure during additional progressive elevations in cardiac filling pressures induced by 3 wk of deoxycorticosterone acetate (DOCA) administration. During the DOCA regimen, plasma ANF increased an additional twofold from its high base line. Arterial blood pressure increased by 6-12 mmHg, and plasma renin activity was suppressed. However, the animals consistently retained sodium, and the high plasma levels of ANF were unable to counterbalance the sodium-retaining actions of DOCA. After termination of DOCA, the dogs exhibited a marked natriuresis, and all the hemodynamic and hormonal parameters returned to pre-DOCA control levels. This longitudinal study demonstrates that the cardiac reserve for chronic ANF secretion is well maintained in dogs with an a-v fistula during progressive cardiac volume overload. The present results suggest that the ANF endocrine system may represent one chronic compensatory mechanism to achieve sodium balance in heart failure when there is concomitant normalization of the renin-aldosterone system.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Desoxycorticosterone; Dogs; Female; Heart Atria; Heart Failure; Hemodynamics; Natriuresis; Renin

Topics: Aged; Atrial Natriuretic Factor; Chronic Disease; Drug Administration Schedule; Electrocardiography, Ambulatory; Furosemide; Heart Failure; Humans; Male; Middle Aged; Random Allocation; Sodium

Radioimmunoassay was used in 39 patients with chronic glomerulonephritis and secondary hypertension to measure atrial natriuretic peptide concentration in blood plasma. The latter concentration appeared unrelated to the patients' age, duration and gravity of hypertension, the degree of renal insufficiency, hyperhydration and activation of renin-angiotensin-aldosterone++ system. The conclusion is made on minor contribution of this short-acting peptide to pathogenesis of arterial hypertension in chronic glomerulonephritis.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Female; Glomerulonephritis; Humans; Hypertension; Male; Middle Aged; Renin-Angiotensin System

In order to study long term changes in plasma atrial natriuretic peptide (ANP) in chronic heart failure, plasma ANP levels were determined in rats after myocardial infarction due to coronary artery ligation and in sham-operated controls. In addition, effects of oral captopril treatment and sodium loading on plasma ANP were studied. In accordance with earlier reports plasma ANP paralleled both infarct size and signs of cardiac dysfunction. The highest plasma ANP levels were found in rats having over 45% of their left ventricle infarcted while rats with mild-to-moderate-size infarcts had only slightly elevated plasma ANP levels as compared with controls. These differences in plasma ANP levels between experimental and control groups remained remarkably stable during the three-month observation period. Plasma renin activity (PRA) was elevated in infarcted rats but no differences could be found between rats with varying infarct sizes. Captopril treatment decreased the high plasma ANP levels in rats with the largest infarcts, probably by unloading the failing heart. During increased sodium intake, plasma ANP levels increased in sham-operated controls but not in rats with heart failure. Thus, sodium loading, as compared with cardiac insufficiency, appears to be a weak stimulus for ANP release in rats. I conclude that plasma ANP is a sensitive marker, better than PRA, in long term follow-up of cardiac dysfunction.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Captopril; Chronic Disease; Coronary Vessels; Heart Diseases; Ligation; Male; Myocardial Infarction; Natriuresis; Rats; Rats, Inbred Strains; Renin; Sodium Chloride

The acute hemodynamic effect (right atrial pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac index, heart rate, blood pressure) and neurohumoral response (alpha-ANP, plasma renin activity, aldosterone, angiotensin II) of Bunazosin, oral alpha 1 blocker, was investigated in 28 patients with congestive heart failure at rest and immediately after exercise. Bunazosin reduced alpha-ANP, but, other neurohumoral factors did not change. Bunazosin produced significant hemodynamic improvements both at rest and after exercise. Its chronic effect was also investigated in 11 patients in 28 days after taking oral Bunazosin. Improvement of hemodynamics at acute phase was also preserved at chronic phase without deterioration of neurohumoral factors. It is concluded that Bunazosin may be an effective Balanced vasodilator both at acute and chronic phases in patients with congestive heart failure.

Topics: Adrenergic alpha-Antagonists; Atrial Natriuretic Factor; Chronic Disease; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Quinazolines

Previous studies have shown that indomethacin administered during the early phase of experimental myocarditis may exacerbate the disease process. It is unknown whether late administration of this agent is safe. Therefore, the effect of indomethacin administration during the late phase of coxsackievirus B3 murine myocarditis was investigated. Forty 3-week-old CD1 mice each received a 3 x 10(4) median tissue culture-infective dose of coxsackievirus intraperitoneally. On day 10 of infection, mice were randomized to receive either indomethacin or normal saline solution for 10 days, and 10 mice from each group were killed on days 20 and 30 of infection. Heart weight and size and serum atrial natriuretic peptide were similar in both groups on days 20 and 30. On day 20, pathologic scores for the degree of inflammation and necrosis were 1.7 and 1.0 for the indomethacin group versus 1.4 and 1.7 for the saline solution group. On day 30, pathologic scores were 0.3 and 0.6 for the indomethacin group versus 0.5 and 0.6 for the saline solution group. In addition, mineralization was absent in indomethacin-treated animals on day 20 after infection, but it was present in half of the control animals at that time. The degree of mineralization did not differ on day 30 between the two groups. These findings suggest that indomethacin given in the late phase of coxsackievirus myocarditis has no deleterious effects at 30 days.

Topics: Animals; Atrial Natriuretic Factor; Chronic Disease; Coxsackievirus Infections; Disease Models, Animal; Enterovirus B, Human; Indomethacin; Mice; Myocarditis; Myocardium; Necrosis; Organ Size; Random Allocation

In chronic cardiac failure, various neurohumoral mechanisms are activated to sustain blood volume, blood pressure, and organ perfusion. Using the coronary artery ligation model of heart failure in the rat, we have measured changes in vasoactive hormone secretion and related these changes to salt and water status during a 1-month period. When compared with controls, rats with infarction had a marked rise in plasma atrial natriuretic peptide (294 +/- 59 vs. 79 +/- 10 pg/ml, p less than 0.001) although there was no increase in total exchangeable body sodium. Plasma renin activity and plasma aldosterone concentrations were the same for both rats with infarction and controls. Similarly, there were no significant differences in plasma arginine vasopressin, plasma osmolality, or plasma sodium concentration in rats with infarction. Ventricular norepinephrine levels were reduced in animals with infarction (p less than 0.01). Plasma atrial natriuretic peptide levels were raised in this model of chronic left ventricular failure. However, there was no salt retention and little stimulation of the renin-angiotensin-aldosterone system or vasopressin. The results suggest that high circulating atrial natriuretic peptide levels may prevent or limit salt and water retention, either directly or indirectly, by inhibiting the renin-angiotensin-aldosterone system.

Topics: Aldosterone; Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Catecholamines; Chronic Disease; Female; Ion Exchange; Myocardial Infarction; Myocardium; Neurotransmitter Agents; Osmolar Concentration; Rats; Rats, Inbred Strains; Renin; Sodium

Topics: Animals; Atrial Natriuretic Factor; Chronic Disease; Dose-Response Relationship, Drug; Hypertension, Pulmonary; Hypoxia; Male; Rats; Rats, Inbred Strains

The role of catecholamine in atrial natriuretic peptide (ANP) secretion and its secretory mechanism in normal humans is not well defined; therefore, we studied the relationship among ANP, catecholamine, and atrial pressures in 25 patients without cardiovascular disease and in 35 patients with chronic congestive heart failure (CHF, 20 in mitral valve disease and 15 in dilated cardiomyopathy). In patients without cardiovascular disease, right atrial pressure at rest showed a positive correlation (r = 0.80, p less than 0.001) with ANP concentration, whereas left atrial pressure did not. The relation narrowed (r = 0.82) when the bicycle ergometer exercise in the supine position was conducted. Neither adrenalin nor noradrenalin significantly correlated with ANP concentration. In patients with mitral valve disease and dilated cardiomyopathy, the significant relations (r = 0.56 p less than 0.001, r = 0.85 p less than 0.001, respectively) between left atrial pressures and ANP concentrations at rest were observed, and following exercise, induced more significant relations. Right atrial pressures did not correlate positively with ANP concentrations. The increments of ANP concentrations induced by exercise load were markedly reduced compared with those of patients without cardiovascular disease. Although concentrations of both noradrenalin and adrenalin in patients with mitral valve disease and dilated cardiomyopathy at rest were much higher than those without cardiovascular disease, only noradrenalin had a highly positive correlation with ANP concentrations (r = 0.88 p less than 0.001, r = 0.78 p less than 0.001, respectively). Furthermore, the circulating ANP molecular weight forms in all patients studied were analyzed by gel chromatography coupled with radioimmunoassay.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Natriuretic Factor; Chromatography, Gel; Chronic Disease; Epinephrine; Exercise Test; Female; Heart Atria; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Molecular Weight; Norepinephrine; Pressure; Radioimmunoassay

In 14 patients with arterial hypertension secondary to chronic renal parenchymal disease and impaired renal function, 24-h ambulatory and casual blood pressure readings plasma, angiotensin II, aldosterone, arginine vasopressin and atrial natriuretic peptide, creatinine clearance, plasma lipids and lipoproteins, and body weight were determined after consecutive 3-week periods on placebo and sustained release verapamil 240 mg/day. Verapamil reduced the mean 24-h ambulatory blood pressure from 152/104 to 142/97 mm Hg. Blood pressure was significantly reduced during the daytime and the evening, but not at night. Casual blood pressure was also significantly reduced from 176/106 mm Hg to 154/96 mm Hg. No significant changes were found in the hormones, creatinine clearance, plasma lipids and lipoproteins, heart rate or body weight. The atrial natriuretic peptide level was significantly correlated with the calculated creatinine clearance (r = -0.797). Thus, sustained release verapamil 240 mg as a single daily dose had a moderate hypotensive effect in patients with chronic renal disease without inducing tachycardia, activation of the renin-angiotensin-aldosterone system, or increasing body weight, and without altering renal function and plasma lipids and lipoproteins. The negative correlation between atrial natriuretic peptide and glomerular filtration rate supports the hypothesis that the extracellular volume increases during progression of renal disease.

Topics: Adult; Aldosterone; Angiotensin II; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Delayed-Action Preparations; Female; Humans; Hypertension, Renal; Kidney Diseases; Male; Middle Aged; Verapamil

Throughout the course of chronic congestive heart failure cardiac and peripheral compensatory mechanisms are at play, most of them under the influence of the neuroendocrine system. The reserves of heart rate and contractility are regulated essentially by the noradrenergic system (NAS), but this mechanism is partial and transient owing to the gradual decrease in the density and sensitivity of myocardial beta-adrenergic receptors induced by overstimulation. Adaptation of the heart to exercise may be reduced. This escape phenomenon is also observed with almost all cardiotonic drugs which interfere with cyclic adenosine monophosphate (cAMP), in contrast with the paradoxically favourable effects of beta-blockers in small doses or of drugs that are both agonists and antagonists of beta-adrenergic receptors. The mechanisms which contribute to the induction of left ventricular hypertrophy are imperfectly known. The noradrenergic system and the renin-angiotensin-aldosterone system (RAAS) are probably not the only ones involved. The setting in action of Frank-Sterling heterometric regulation, at first during exercise then permanently, requires an increase in filling pressure obtained by venous constriction (predominantly controlled by the NAS) and, mostly, by an increase in circulating blood volume. NAS and RAAS intervene in the kidneys to produce water-and-salt retention.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Chronic Disease; Heart Failure; Hemodynamics; Humans; Kinins; Norepinephrine; Prostaglandins E; Renin-Angiotensin System; Sympathetic Nervous System; Vasoconstriction; Vasodilation

1. The relationship between plasma atrial natriuretic peptide (ANP) and body sodium was determined in rats 1 month after myocardial infarction induced by coronary artery ligation. After operation rats received a normal or a low salt diet, and total exchangeable body sodium was measured sequentially. 2. Rats with infarction receiving a normal salt intake did not retain sodium when compared with sham-operated controls. Rats receiving a low salt diet had a 10% decrease in body sodium (P less than 0.01). The decrease was the same in rats with infarction as in controls. 3. Plasma ANP was similar in control rats irrespective of salt status. Plasma ANP levels were markedly elevated in rats with infarction irrespective of salt status (P less than 0.01). 4. The rise in plasma ANP was correlated with cardiac hypertrophy and infarct size in animals fed both normal and low salt diets. However, there was no relationship between plasma ANP and exchangeable body sodium. 5. These results suggest that in this model of heart failure plasma ANP is raised by increased left atrial stretch in proportion to the severity of left ventricular dysfunction. In contrast, plasma ANP concentrations do not appear to be elevated as a consequence of increased right atrial pressure caused by sodium retention and expanded extracellular volume.

Topics: Animals; Atrial Natriuretic Factor; Chronic Disease; Coronary Vessels; Diet, Sodium-Restricted; Female; Ligation; Myocardial Infarction; Rats; Rats, Inbred Strains; Sodium; Time Factors

Atrial natriuretic peptide (ANP), angiotensin II (AII) and aldosterone (Aldo) in plasma were determined at supine rest in 16 normotensive and 9 hypertensive patients with chronic glomerulonephritis and in 18 control subjects (Study 1). In addition, 12 of the normotensive, 7 of the hypertensive patients and 11 of the control subjects were studied with the same parameters after an exercise test (Study 2). Study 1 showed that supine ANP, AII and Aldo did not differ significantly between the groups. In Study 2, ANP increased after exercise in the normotensive patients (8.4 vs. 11.4 pmol/l (median), p less than 0.05) and control subjects (7.6 vs. 9.3 pmol/l, p less than 0.02) but not in the hypertensives (7.6 vs. 7.9 pmol/l, p greater than 0.10), and after exercise ANP was increased in the normotensive patients compared with the controls (p less than 0.02). After exercise, an enhanced increase of Aldo was found in the hypertensives but not in the normotensive patients compared with the controls, whereas the increase of AII did not differ significantly between the groups. It is concluded that patients with chronic glomerulonephritis and relatively well preserved renal function do not have major abnormalities of ANP at rest or during exercise. In the normotensive patients, however, ANP increased to a higher level than in the controls, but the difference was small and further studies are needed to define the role of ANP in blood pressure regulation of early stage chronic glomerulonephritis.

Topics: Adult; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Exercise Test; Glomerulonephritis; Heart Rate; Humans; Male; Middle Aged; Potassium

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Diuresis; Glomerular Filtration Rate; Hematocrit; Hypothyroidism; Kidney; Kidney Concentrating Ability; Male; Potassium; Rats; Rats, Inbred Strains; Sodium; Thyroidectomy

Atrial natriuretic peptide (ANP), angiotensin II (AII), aldosterone (Aldo), arginine vasopressin (AVP) in plasma, urinary excretion of prostaglandin E2 (PGE2) and urinary sodium excretion rate (UNaV) were determined in 11 normotensive patients with chronic glomerulonephritis and a normal glomerular filtration rate (GFR) and in 14 healthy control subjects before, during and after intravenous infusion of a 2.5% sodium chloride solution. During basal conditions ANP was increased in patients compared with controls (9.8 pmol/l (median) versus 7.2 pmol/l, p less than 0.01). After sodium infusion ANP was unchanged in the patients but significantly increased in the controls. AII, Aldo, AVP in plasma and urinary PGE2 excretion were the same in patients and controls. The urinary sodium excretion rate was significantly increased in patients compared with controls during sodium infusion (p less than 0.05). No correlations were found between ANP and UNaV, AII or Aldo in either patients or controls. The relationship between serum osmolality (Sosm) and AVP was normal in the patients. It can be concluded that in normotensive patients with chronic glomerulonephritis and normal GFR, ANP is increased during basal conditions and the response to acute volume expansion may be blunted. The renin-angiotensin system, the osmoregulatory system and urinary PGE2 excretion are normal and respond in a normal way to volume expansion. It is suggested that the increased level of ANP can be viewed as a compensatory phenomenon to an abnormal sodium or volume homeostasis in the early stages of chronic glomerulonephritis.

Topics: Adolescent; Adult; Aldosterone; Angiotensin II; Arginine Vasopressin; Atrial Natriuretic Factor; Chronic Disease; Female; Glomerular Filtration Rate; Glomerulonephritis; Humans; Male; Middle Aged; Prostaglandins E; Saline Solution, Hypertonic; Sodium

1. The natriuretic and diuretic effects of three atrial natriuretic peptide (ANP) infusion rates were examined in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. 2. The natriuretic and diuretic effects of ANP were observed in controls and rats with infarction, but the effects were significantly attenuated in the latter. 3. Rats with chronic left heart failure were less sensitive to the renal effects of ANP compared with controls. 4. Impaired sodium and water excretion in chronic heart failure may be due partly to an attenuated renal response to ANP.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Coronary Vessels; Diuresis; Dose-Response Relationship, Drug; Female; Heart Failure; Infusions, Intravenous; Kidney; Myocardial Infarction; Natriuresis; Rats; Rats, Inbred Strains

Water, sodium, and potassium balance and urinary excretion of norepinephrine and aldosterone were investigated in rats with left ventricular failure due to left ventricular infarction, and measurements were obtained of plasma levels of atrial natriuretic factor (ANF). Increased plasma levels of ANF in relation to the size of the infarction and to the right atrial and left ventricular end-diastolic pressure were found. The augmented levels of ANF were not able to prevent an accumulation of sodium in the rats with myocardial infarction in which urinary excretion of norepinephrine and aldosterone was unchanged in comparison to control values. Plasma levels of ANF in the pulmonary artery, aorta, and renal vein of six conscious dogs were studied during the development of heart failure due to rapid right ventricular pacing. A threefold increase in ANF was found: ANF levels did not differ between the pulmonary artery and the aorta, but a reduction in ANF of about 30% was reported in the renal vein in comparison to the arteries. A close positive correlation between right atrial pressure and plasma levels of ANF was noted. No correlation could be demonstrated between mean pulmonary arterial pressure and ANF or between the stimulated plasma renin concentration and plasma ANF values.

Topics: Acute Disease; Animals; Atrial Natriuretic Factor; Chronic Disease; Dogs; Heart Failure; Kidney; Male; Rats; Rats, Inbred Strains

To define the relationship between plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP) and hemodynamic parameters in patients with chronic pulmonary artery hypertension, we measured plasma concentrations of the peptide in 15 patients during right heart catheterization. Eleven patients had chronic obstructive pulmonary disease and 4 had pulmonary vascular disease of diverse etiology. At rest, plasma concentrations of IR-ANP positively correlated with mean pulmonary artery pressure (r = 0.70, p less than 0.01) and pulmonary vascular resistance (r = 0.88, p less than 0.001), but not with right atrial pressure. Nine of these patients, all with chronic obstructive pulmonary disease, were also evaluated during exercise. Plasma concentrations of IR-ANP increased from 131 +/- 22 to 191 +/- 30 pg/ml (p less than 0.003) at maximal exercise, whereas pulmonary artery pressure increased from 29 +/- 1.5 to 56 +/- 2.5 mm Hg and right atrial pressure from 5 +/- 1 to 13 +/- 2 mm Hg. Increases of plasma IR-ANP concentrations correlated with changes in pulmonary artery pressure and right atrial pressure but not with changes in pulmonary capillary wedge pressure. These findings suggest that ANP is released in response to an increase in pulmonary artery pressure and are consistent with the hypothesis that ANP could modulate the pulmonary vascular tone in patients with pulmonary artery hypertension.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiac Catheterization; Chronic Disease; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Lung Diseases, Obstructive; Male; Middle Aged; Physical Exertion; Pulmonary Artery; Radioimmunoassay; Rest

Topics: Adult; Aged; Atrial Natriuretic Factor; Chronic Disease; Female; Heart Atria; Humans; Male; Middle Aged; Renal Dialysis

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Female; Humans; Male; Middle Aged; Pulmonary Circulation; Respiratory Insufficiency

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Chronic Disease; Coronary Disease; Female; Heart Failure; Humans; Male; Middle Aged

The plasma levels of atrial natriuretic peptide were determined by radioimmunoassay in 24 patients with chronic liver disease, including three patients with alcoholic liver disease, four with chronic active hepatitis, 13 with liver cirrhosis, and four with hepatocellular carcinoma. When compared with normal subjects (180 +/- 12 pg/ml), the plasma levels of atrial natriuretic peptide in cirrhotic patients (349 +/- 64 pg/ml) were significantly elevated (p less than 0.001) but not in other disease groups. In patients with chronic liver disease the plasma levels of atrial natriuretic peptide were correlated significantly with plasma renin activity but not with plasma aldosterone, and furthermore showed a negative correlation with indocyanine green disappearance rate. These results suggest that the increased plasma levels of atrial natriuretic peptide, which appear to be associated with an increase in plasma renin activity and with hepatic dysfunction, may participate in maintaining homeostasis of sodium and fluid volume in patients with chronic liver disease.

Topics: Aldosterone; Atrial Natriuretic Factor; Carcinoma, Hepatocellular; Chronic Disease; Female; Hepatitis, Chronic; Humans; Liver Cirrhosis; Liver Diseases; Liver Diseases, Alcoholic; Liver Function Tests; Liver Neoplasms; Male; Middle Aged; Radioimmunoassay

Using a radioimmunoassay for atrial natriuretic peptide (ANP) we studied plasma concentrations of immunoreactive ANP in order to investigate the pathophysiological role of ANP in patients with various diseases. Plasma ANP levels were elevated in patients with congestive heart failure (394 +/- 260 pg/ml, n = 8) and chronic renal failure (219 +/- 86 pg/ml, n = 11). In patients undergoing hemodialysis plasma ANP levels were markedly high and decreased after hemodialysis from 433 +/- 166 pg/ml to 204 +/- 92 pg/ml (n = 11). ANP was removed from blood to dialysate (21 +/- 13 pg/ml of dialysate, n = 6, dialysate flow: 500 ml/min). Plasma ANP level was conversely correlated with creatinine clearance (r = -0.812, p less than 0.001) in patients with renal diseases (n = 29). In patients with atrial fibrillation, pace maker implantation, lung disease, chronic glomerulonephritis, nephrotic syndrome, essential hypertension, liver disease and cerebrovascular disease, plasma ANP levels were not significantly different from those in normal subjects (70 +/- 32 pg/ml, n = 28). These results suggest that ANP may be a circulating hormone playing pathophysiological roles in congestive heart failure and chronic renal failure.

Topics: Adult; Atrial Natriuretic Factor; Cardiovascular Diseases; Cerebrovascular Disorders; Chronic Disease; Female; Humans; Kidney Diseases; Liver Diseases; Lung Diseases, Obstructive; Male; Middle Aged; Radioimmunoassay; Renal Dialysis

Conscious two-kidney, one-clip (2-K, 1-C) hypertensive rats and their normotensive sham-operated controls were infused during 13 days with synthetic ANF (Arg 101 - Tyr 126) at 35 pmol/hr/rat by means of osmotic minipumps connected to the jugular vein. The initial blood pressure of 186 +/- 6 mmHg maximally decreased to 118 +/- 7 mmHg at day 5 and slowly rose afterwards without reaching basal values. A concomitant drop in pressure natriuresis and diuresis was observed. No changes were observed in ANF-infused sham-operated rats. Urinary aldosterone excretion declined in ANF-treated rats from a basal value of 63.38 +/- 21.04 micrograms/24 hr to 13.36 +/- 3.78 micrograms/24 hr the last infusion day. No change in urinary aldosterone was observed in either non-infused 2-K, 1-C or ANF-infused sham-operated rats. Plasma aldosterone was significantly higher only in non-treated 2-K, 1-C rats. Renal aldosterone clearance was significantly lower in ANF-infused 2-K, 1-C rats than in the other experimental groups. Plasma renin activity (PRA) was lower in treated (3.92 +/- 2.26 AI ng/ml/hr) than in non-treated (9.08 +/- 2.32 AI ng/ml/hr) hypertensive rats, and not different from ANF-infused or non-infused sham-operated rats. No differences in body weight between infused and non-infused rats, or hematocrit between any group were observed. Atrial immunoreactive ANF was not different in any group. These results demonstrate that chronic administration of ANF not only reduces blood pressure and PRA in 2-K, 1-C hypertensive rats but also plasma and urinary aldosterone. Whether the latter is a direct inhibitory effect or secondary to the normalization of PRA is not known. The hypotensive response may be due to a direct effect on vascular smooth muscle but a role of renin cannot be excluded. Because blood pressure returned toward basal values during the last days of the observation period, the possibility of a tachyphylactic effect of ANF on vascular smooth muscle cannot be excluded.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Diuresis; Drug Evaluation, Preclinical; Hypertension; Male; Natriuresis; Rats; Rats, Inbred Strains; Renin; Sodium

In patients with chronic cardiac disease plasma concentrations of atrial natriuretic peptide are elevated. The close relationships obtained between right (and/or left) atrial pressure and the peptide concentrations suggest a non-resetting phenomenon of the pressure induced release mechanism in the presence of a maintained responsiveness to acute stimuli.

Topics: Atrial Natriuretic Factor; Blood Pressure; Cardiomyopathy, Dilated; Chronic Disease; Coronary Disease; Heart Atria; Heart Diseases; Heart Valve Diseases; Hemodynamics; Humans; Physical Exertion; Pressure

Plasma concentrations of the atrial natriuretic peptide (ANP) were measured during cardiac catheterization in 289 patients with heart disease. It was elevated in all types of cardiac disease investigated, irrespective of the nature and duration of the disease. Close relationships were observed between the elevated ANP concentrations and the increased right and/or left atrial pressure. Further increments in ANP concentration were measured during exercise in direct response to the rise in mean pulmonary artery pressure. Thus, ANP concentrations may be regarded as a non-invasive marker of the haemodynamic burden in cardiac disease.

Topics: Atrial Natriuretic Factor; Cardiomyopathies; Cardiomyopathy, Dilated; Chronic Disease; Heart Diseases; Heart Valve Diseases; Hemodynamics; Humans; Osmolar Concentration; Physical Exertion; Rest