atrial-natriuretic-factor and Coronary-Disease

Topics: Adrenomedullin; Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Coronary Disease; Diabetes Mellitus; Humans; Hypertension; Liver Failure; Mice; Natriuretic Peptide, Brain; Oxidative Stress; Peptides; Rats

B-type natriuretic peptide (BNP), a neurohormone synthesized in the cardiac ventricles, is released as preproBNP and then enzymatically cleaved to the N-terminal-proBNP (NT-proBNP) and BNP upon ventricular myocyte stretch. Blood measurements of BNP and NT-proBNP 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. The BNP assay currently available in North American markets, approved for use as a diagnostic aid in CHF and a prognostic marker in acute coronary syndromes (ACS), has particular advantages because it is available at the point of care and has had considerable use in clinical studies. In general, a BNP level less than 100 pg/mL has strong negative predictive value for CHF. In addition, BNP levels can be used to gauge the effect of short-term treatment of acutely decompensated CHF. BNP has been shown to be a reliable and independent predictor of sudden cardiac death. In the absence of renal dysfunction, NT-proBNP has also been shown to be of diagnostic value in CHF, related to CHF severity, predictive of sudden death, and prognostic for death in ACS. This article reviews the literature concerning the use of these peptides in a variety of clinical scenarios.

Topics: Acute Disease; Aged; Atrial Natriuretic Factor; Biomarkers; Coronary Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Sensitivity and Specificity; Severity of Illness Index

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biopsy; Coronary Angiography; Coronary Disease; Electrocardiography; Heart Failure; Humans; Hypertension

This update reviews the remarkable progression in several cardiovascular gene transfer domains. The first chemical gene therapy protocols to stimulate angiogenesis in ischemic myocardium are discussed and both the great expectations as well as remaining hurdle are highlighted. In experimental models of restenosis and heart failure gene therapy shows promising results. Important question regarding vector-related limitations and suboptimal in vivo delivery systems will require expeditious attention for gene therapy to become a more widely applicable option in cardiovascular diseases.

Topics: Animals; Arteriosclerosis; Atrial Natriuretic Factor; Cardiovascular Diseases; Coronary Disease; Endothelial Growth Factors; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Heart Failure; Humans; Hypertension; Lymphokines; Mice; Neovascularization, Physiologic; Rabbits; Superoxide Dismutase; Thrombosis; Tissue Plasminogen Activator; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Congestive heart failure is a syndrome common in the United States, especially in elderly patients. The most common etiology is coronary artery disease. A number of general factors contribute to the heart failure syndrome, including loss of muscle, decreased myocardial contractility, pressure or volume overload, or restricted filling. All of these factors may play a role in a given patient as, for example, with coronary artery disease. Although systolic dysfunction with a reduced ejection fraction is the most common heart failure syndrome, up to 40% of patients may have a relatively preserved ejection fraction with diastolic dysfunction. As the heart begins to fail, a number of compensatory mechanisms are activated. These include increased heart rate, the Frank-Starling mechanism, increased catecholamines, activation of the renin-angiotensin system, and release of atrial natriuretic peptides. Although these mechanisms are initially helpful to the cardiovascular system, they frequently overshoot, initiating a vicious cycle. For example, with a decrease in cardiac output, there is a reflex increase in systemic vascular resistance in order to maintain perfusion pressure. This increase in resistance, however, acts as a load on the left ventricle and further reduces cardiac output. The best evidence for the existence of this vicious cycle is the beneficial change in hemodynamics produced by vasodilator drugs and the ACE inhibitors. Thus, an understanding of pathophysiology allows for the selection of rational therapy. An unresolved problem in heart failure patients is how best to reduce the high incidence of sudden death, which is one of the major challenges for the future.

Topics: Aged; Arginine Vasopressin; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Catecholamines; Coronary Disease; Heart Failure; Hemodynamics; Humans; Incidence; Myocardial Contraction; Renin-Angiotensin System; United States

In this review, the authors examine the biochemical mechanism involved in synthesis and release of ANF and its physiological effects concerning kidney and cardiovascular system. In addition, the authors underline the possible interactions of ANF with other hormones, particularly with the renin-angiotensin-aldosterone system and with vasopressin. Finally, the authors consider the possible physiopathological implications of ANF in the genesis of hypertension and hydrosaline retention.

Topics: Animals; Atrial Natriuretic Factor; Cardiovascular Diseases; Coronary Disease; Heart Failure; Hemodynamics; Humans; Hypertension; Kidney; Renin-Angiotensin System

Circulating biomarkers can offer insight into subclinical cardiovascular stress and thus have the potential to aid in risk stratification and tailoring of therapy.. We measured plasma levels of 4 cardiovascular biomarkers, midregional pro-atrial natriuretic peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), and copeptin, in 3717 patients with stable coronary artery disease and preserved left ventricular ejection fraction who were randomized to trandolapril or placebo as part of the Prevention of Events With Angiotensin Converting Enzyme (PEACE) trial. After adjustment for clinical cardiovascular risk predictors and left ventricular ejection fraction, elevated levels of MR-proANP, MR-proADM, and CT-proET-1 were independently associated with the risk of cardiovascular death or heart failure (hazard ratios per 1-SD increase in log-transformed biomarker levels of 1.97, 1.48, and 1.47, respectively; P≤0.002 for each biomarker). These 3 biomarkers also significantly improved metrics of discrimination when added to a clinical model. Trandolapril significantly reduced the risk of cardiovascular death or heart failure in patients who had elevated levels of ≥2 biomarkers (hazard ratio, 0.53; 95% confidence interval, 0.36-0.80), whereas there was no benefit in patients with elevated levels of 0 or 1 biomarker (hazard ratio, 1.09; 95% confidence interval, 0.74-1.59; P(interaction)=0.012).. In patients with stable coronary artery disease and preserved left ventricular ejection fraction, our results suggest that elevated levels of novel biomarkers of cardiovascular stress may help identify patients who are at higher risk of cardiovascular death and heart failure and may be useful to select patients who derive significant benefit from angiotensin-converting enzyme inhibitor therapy.

Topics: Adrenomedullin; Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Coronary Disease; Death; Endothelin-1; Female; Glycopeptides; Heart Failure; Humans; Indoles; Male; Middle Aged; Peptide Fragments; Prognosis; Protein Precursors; Risk; Stress, Physiological; Stroke Volume

The heart secretes natriuretic peptides (NPs) in response to myocardial stretch. Measuring NP concentrations is a helpful tool in guiding treatment. It has been suggested that sodium ion and hyperosmolality could affect NP excretion. If this is true, peri-operative NP measurements could be inconsistent when hypertonic solutions are used. With different osmolalities but equal volumes of hydroxyethyl starch (HES)--and hypertonic saline (HS)--infusions, this double-blinded study tested the hypothesis that osmolality modulates the excretion of NPs.. Fifty coronary surgery patients were randomized to receive within 30 min 4 ml/kg either HS or HES post-operatively. Samples for analysis of atrial NP (ANP), brain NP (BNP), plasma and urine sodium and osmolality and urine oxygen tension were obtained before and 60 min after starting the infusions and on the first post-operative morning. The haemodynamic parameters were measured at the same time points.. Plasma osmolality and sodium increased only in the HS group. Changes in plasma BNP and ANP levels did not differ between the groups (P=0.212 and 0.356). There were no correlations between NP levels and osmolality or sodium at any time point. In the HS group, urine volume was higher (3295 vs. 2644 ml; P<0.05) and the need for furosemide treatment was less (0.4 vs. 3.8 mg; P<0.01) than in the HES group.. The absence of effects of plasma sodium content or hyperosmolality on NP release validates the value of NPs as a biomarker in peri-operative patients.

Topics: Aged; Anesthesia; Atrial Natriuretic Factor; Cardiopulmonary Bypass; Coronary Disease; Data Collection; Double-Blind Method; Female; Hemodynamics; Humans; Hydroxyethyl Starch Derivatives; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Osmolar Concentration; Plasma Substitutes; Postoperative Period; Saline Solution, Hypertonic; Sodium; Treatment Outcome; Urodynamics

This study was performed to determine the secretion pattern and prognostic value of A-type (ANP) and B-type (BNP) natriuretic peptide in patients undergoing cardiac surgical procedures. We measured ANP and BNP in patients undergoing coronary artery bypass grafting (CABG) with (n = 28) or without (n = 32) ventricular dysfunction and in patients undergoing mitral (n = 21) or aortic (n = 24) valve replacement, respectively. Postoperative mortality was recorded up to 730 days after operation. ANP, but not BNP, concentrations were closely associated with volume reloading of the heart after aortic cross-clamp in all patients. The secretion pattern of BNP during surgery was much less uniform. BNP, but not ANP, concentrations correlated with aortic cross-clamp time (r(2) = 0.32; P = 0.006) and postoperative troponin I concentrations (r(2) = 0.22; P = 0.0009) in bypass patients, and preoperative BNP increases were associated with a more frequent postoperative (2-yr) mortality in these patients. Markedly increased preoperative BNP concentrations in mitral (3-fold) and aortic (14-fold) valve disease patients did not further increase during cardiopulmonary surgery. The data suggest that ANP is primarily influenced by intravascular volume reloading of the heart after cross-clamp, whereas the secretion of BNP is related to other factors, such as duration of ischemia and long-term left ventricular pressure and/or excessive intravascular volume. BNP, but not ANP, was shown to be a mortality risk predictor in patients undergoing CABG.. A-type natriuretic peptide is primarily influenced by volume reloading of the heart after cross-clamp, whereas the secretion of B-type natriuretic peptide (BNP) is related to the duration of ischemia and long-term left ventricular pressure and/or volume overload. Preoperative BNP, but not postoperative BNP, concentrations predict long-term outcome after coronary artery bypass grafting.

Topics: Aged; Anesthesia, General; Atrial Natriuretic Factor; Biomarkers; Cardiac Surgical Procedures; Coronary Artery Bypass; Coronary Disease; Female; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Postoperative Complications; Prognosis; Prospective Studies; Troponin I; Ventricular Function, Left

There is growing evidence from recent studies that atrial natriuretic peptide (ANP) plays an important part in coronary blood flow regulation and in atherosclerosis. Transition T2238-->C in the atrial natriuretic peptide (ANP) precursor gene, which leads potentially to the translation of ANP with 2 additional arginines, has been suggested to be associated with salt-sensitive hypertension. According to our knowledge, this study is the first to look for the potential association of the ScaI ANP gene polymorphism with the history of nonfatal myocardial infarction and the extent of coronary artery disease (CAD).. The study was performed in 847 consecutive, white patients (719 men and 128 women) with significant coronary artery stenosis confirmed by means of elective coronary angiography (at least 1 coronary artery with > or =50% lumen narrowing). Screening for the T2238-->C substitution was performed by means of polymerase chain reaction of genomic DNA, followed by ScaI digestion and agarose gel electrophoresis.. We found a significant association of the A2A2 ScaI ANP genotype with a higher incidence of positive history of nonfatal myocardial infarction (odds ratio 1.85, 95% CI 1.33-2.58) and multiple-vessel CAD (odds ratio 1.45, 95% CI 1.02-2.06). The ScaI ANP genotype distribution did not differ with age, sex, body mass index, plasma lipids, hypertension, diabetes mellitus, and family history of CAD in studied groups.. Our results suggest that the ScaI ANP polymorphism may be associated with nonfatal myocardial infarction and the extent of CAD. However, the precise mechanism of this association remains to be determined.

Topics: Atrial Natriuretic Factor; Coronary Angiography; Coronary Disease; Female; Genotype; Humans; Male; Middle Aged; Myocardial Infarction; Polymorphism, Single Nucleotide

To study the effect of Yiqi Wenyang Huoxue Lishui principle (YWHL, a therapeutic principle with Chinese medicine for reinforcing Qi warming Yang, activating blood circulation and promoting urination) on some neuroendocrine factors in patients with congestive heart failure (CHF).. Forty-nine patients of CHF with heart function of grade III-IV were randomly divided into 2 groups. The 29 cases in the treated group were treated with YWHL and the 20 cases in the control group treated with captopril. Changes of angiotensin II (AT II), atrial natriuretic peptide (ANP), endothelin (ET), nitric oxide (NO) and alpha-granule membrance protein -140 (GMP-140) were observed.. After treatment, plasma level of AT II, ANP, ET, and NO lowered in both groups with insignificant difference, but the GMP-140 reduced more significantly in the treated group (P < 0.05).. YWHL showed a regulatory effect of neuroendicrine system partially similar to that of angiotensin-converting enzyme inhibitor, it possibly can improve the ventricular remodeling and would be beneficial to prevent the thrombus formation and improve heart failure by means of inhibiting platelet activity.

Topics: Adult; Aged; Angiotensin II; Atrial Natriuretic Factor; Coronary Disease; Drugs, Chinese Herbal; Female; Heart Failure; Humans; Male; Middle Aged; Neurosecretory Systems; P-Selectin; Phytotherapy

Atrial natriuretic peptide (ANP) exerts a dilatory effect on coronary arteries in humans. We investigated the effects of ANP on pacing-induced myocardial ischemia during enflurane anesthesia in patients with coronary artery disease (CAD). In 20 patients with CAD, myocardial ischemia was induced by atrial pacing before and after an i.v. infusion of ANP (50 mg x kg(-1) min(-1), n = 10) or placebo (n = 10). We studied the effects of ANP or placebo on pacing-induced changes in central hemodynamics, myocardial blood flow and regional myocardial indices of lactate uptake (RMLU), and oxygen consumption (RMVO2) and extraction (RMO2E). ST-segment depression was less pronounced during pacing with ANP compared with control pacing (-0.09 +/- 0.01 vs -0.24 +/- 0.02 mV; P < 0.001). RMLU decreased to -11.1 micromol/min during control pacing compared with -0.7 micromol/min during pacing with ANP (P < 0.01). ANP did not affect pacing-induced changes in RMVO2, RMO2E, or the rate pressure product. Placebo did not affect pacing-induced changes in ST-segment depression or RMLU. In conclusion, ANP attenuates ischemic ST-segment depression and lactate release during pacing-induced myocardial ischemia in patients with CAD. The antiischemic effect of ANP was not accompanied by any improvement in the regional myocardial oxygen supply/demand relationship.. We evaluated the effects of i.v. atrial natriuretic peptide (50 ng x kg(-1) x min(-1)) on pacing-induced myocardial ischemia during general anesthesia in patients with coronary artery disease. In contrast to placebo, atrial natriuretic peptide attenuated ST-segment depression and myocardial lactate production and improved left ventricular function during pacing-induced ischemia.

Topics: Adult; Aged; Anesthesia, General; Anesthetics, Inhalation; Atrial Natriuretic Factor; Blood Pressure; Cardiac Pacing, Artificial; Coronary Circulation; Coronary Disease; Coronary Vessels; Electrocardiography; Enflurane; Female; Heart Rate; Humans; Infusions, Intravenous; Lactates; Male; Middle Aged; Myocardial Ischemia; Myocardium; Oxygen Consumption; Placebos; Vasodilator Agents; Ventricular Function, Left

Long-term angiotensin-converting enzyme (ACE) inhibition may reduce ischemic events in patients with coronary artery disease, but whether it protects against acute ischemia or the effects of preexisting left ventricular (LV) dysfunction on potential anti-ischemic properties is unknown. We performed a double-blind trial in 25 patients with exercise-induced ischemia. The effects of perindoprilat on pacing-induced myocardial ischemia were examined. Fourteen patients received perindoprilat and 11 patients received placebo. Based on LV function, 2 subgroups were formed in the perindoprilat group: 7 patients with LV dysfunction (LV ejection fraction <0.40), and 7 patients with normal LV function. After receiving the study medication, the pacing test was repeated. During the first pacing test both groups developed ischemia. After perindoprilat administration, the increase in systemic vascular resistance and LV end-diastolic pressure were significantly blunted (p <0.05). Further, the ischemia-induced increase in arterial and cardiac uptake of norepinephrine was inhibited by perindoprilat, and the increase in atrial natriuretic peptide was less pronounced; also, ST-segment depression was reduced by 32% compared with placebo (all p <0.05). In the group with LV dysfunction, perindoprilat reduced LV end-diastolic pressure significantly by 67% and myocardial lactate production was prevented, but this did not happen in the group with normal LV function. In addition, the increase in arterial norepinephrine was reduced by 74% and 33%, respectively (p <0.05). These results indicate that perindoprilat reduced acute, pacing-induced ischemia in normotensive patients. In patients with (asymptomatic) LV dysfunction these effects were more pronounced than in patients with normal LV function.

Topics: Adult; Aged; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Cardiac Catheterization; Coronary Disease; Double-Blind Method; Electrocardiography; Exercise Test; Humans; Indoles; Lactic Acid; Male; Middle Aged; Norepinephrine; Ventricular Dysfunction, Left; Ventricular Function, Left

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

The purpose of this study was to determine whether endurance exercise training could buffer neuroendocrine activity in chronic heart failure patients.. Neuroendocrine activation is associated with poor long-term prognosis in heart failure. There is growing consensus that exercise may be beneficial by altering the clinical course of heart failure, but the mechanisms responsible for exercise-induced benefits are unclear.. Nineteen heart failure patients (ischemic disease; New York Heart Association [NYHA] class II or III) were randomly assigned to either a training group or to a control group. Exercise training consisted of supervised walking three times a week for 16 weeks at 40% to 70% of peak oxygen uptake. Medications were unchanged. Neurohormones were measured at study entry and after 16 weeks.. The training group (n = 10; age = 61 +/- 6 years; EF = 30 +/- 6%) and control group (n = 9; age = 62 +/- 7 years; EF = 29 +/- 7%) did not differ in clinical findings at study entry. Resting levels of angiotensin II, aldosterone, vasopressin and atrial natriuretic peptide in the training and control groups did not differ at study entry (5.6 +/- 1.3 pg/ml; 158 +/- 38 pg/ml; 6.1 +/- 2.0 pg/ml; 37 +/- 8 pg/ml training group vs. 4.8 +/- 1.2; 146 +/- 23; 4.9 +/- 1.1; 35 +/- 10 control group). Peak exercise levels of angiotensin II, aldosterone, vasopressin and atrial natriuretic peptide in the exercise and control groups did not differ at study entry. After 16 weeks, rest and peak exercise hormone levels were unchanged in control patients. Peak exercise neurohormone levels were unchanged in the training group, but resting levels were significantly (p < 0.001) reduced (angiotensin -26%; aldosterone -32%; vasopressin -30%; atrial natriuretic peptide -27%).. Our data indicate that 16 weeks of endurance exercise training modified resting neuroendocrine hyperactivity in heart failure patients. Reduction in circulating neurohormones may have a beneficial impact on long-term prognosis.

Topics: Aged; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Coronary Disease; Exercise; Female; Heart Failure; Humans; Male; Middle Aged; Neurosecretory Systems; Physical Endurance; Prognosis; Stroke Volume; Treatment Outcome; Vasopressins

To investigate the effect of Shenmai injection (SMI) on neuroendocrine function in the patients with heart failure (HF).. Sixty patients with HF were randomly divided into the treated group administered with SMI combined with western medicine, and the control group administered with western medicine alone. The change of cardiac function was observed, and plasma neuropeptide Y (NPY), endothelin (ET) and atrial natriuretic polypeptide (ANP) were determined by immunoradiometric assay.. The total effective rate and markedly effective rate were higher in the treated group than that of the control group, the level of NPY, ET and ANP of both groups were higher than healthy subjects. The plasma NPY, ET and ANP of both groups were significantly reduced after treatment, the effect of treated group was better than that of control group.. SMI could improve the HF patient's cardiac function, reduce the level of plasma NPY, ET and ANP, their neuroendocrine activity was affected at the same time.

Topics: Aged; Atrial Natriuretic Factor; Coronary Disease; Drugs, Chinese Herbal; Endothelins; Female; Heart Failure; Humans; Infusions, Intravenous; Male; Middle Aged; Neuropeptide Y

The effects of recombinant alpha-human atrial natriuretic peptide (alpha-hANP) infusion an acute left ventricular dysfunction provoked by exercise were examined in 14 men with coronary artery disease. Patients performed symptom-limited, graded exercise on a supine bicycle ergometer. Plasma alpha-hANP and guanosine 3',5'-monophosphate (cyclic GMP) concentrations as well as hemodynamic variables were measured at rest, during and after exercise. In 14 patients whose pulmonary artery wedge pressure was > 20 mm Hg at peak exercise, the same exercise protocol was repeated at 30 minutes after starting intravenous alpha-hANP infusion (0.05 microgram.kg-1.min-1). In 8 of these patients, a Webster thermodilution catheter was advanced into the coronary sinus for measurement of coronary sinus blood flow. From the control exercise test, plasma alpha-hANP concentration increased from 86 +/- 20 pg/ml at rest to 188 +/- 32 pg/ml at peak exercise (p < 0.001), and plasma cyclic GMP concentration increased from 4.8 +/- 1.9 pmol/ml at rest to 7.2 +/- 2.9 pmol/ml at peak exercise (p < 0.001). Both plasma alpha-hANP and cyclic GMP concentrations showed a significant positive correlation with pulmonary artery wedge pressure during control exercise. With alpha-hANP infusion, systolic and diastolic pulmonary artery pressures and pulmonary artery wedge pressure were significantly decreased at all time points during exercise testing. Heart rate was increased and systolic blood pressure was significantly decreased at rest and at 3 minutes of exercise. Diastolic blood pressure, systemic vascular resistance, and pulmonary vascular resistance were significantly decreased at rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Atrial Natriuretic Factor; Coronary Circulation; Coronary Disease; Cyclic GMP; Exercise Test; Hemodynamics; Humans; Male; Middle Aged; Ventricular Dysfunction, Left

To compare the hemodynamic, antiischemic, metabolic, and neurohumoral effects of intravenous esmolol (beta 1 blocking agent) and gallopamil (verapamil-like calcium channel blocker), 14 patients with angiographically proven CAD and reproducible ST segment depression were studied at rest and during exercise under control conditions and after an intravenous bolus injection of esmolol (0.5 mg/kg/1 min, followed by an infusion with 0.2 mg/kg/min) or gallopamil (0.025 mg/kg/3 min). In contrast to gallopamil, esmolol significantly reduced systolic blood pressure (175.7 vs. 160 mm Hg) and heart rate (107.4 vs. 96.9 min-1) during exercise as well as cardiac output (11.57 vs. 9.38 l/min) and significantly enhanced systemic vascular resistance both at rest (1241 vs. 1479 dynes.s.cm-5) and during exercise (805 vs. 947 dynes.s.cm-5). On the other hand, exercise filling pressures and lactate levels (3.66 vs. 3.05 mmol/l) were significantly reduced by gallopamil only. Thus, the significant improvement of exercise tolerance by both esmolol and gallopamil is based on different mechanisms of action: esmolol improves myocardial ischemia by appreciably reducing myocardial oxygen consumption, whereas gallopamil primarily improves oxygen supply and ventricular performance. Plasma catecholamines, atrial natriuretic factor, and aldosterone levels as well as plasma renin activity were identically influenced by esmolol and gallopamil, respectively. A reflex activation of the sympathetic system did not occur.

Topics: Adrenergic beta-Antagonists; Aged; Aldosterone; Atrial Natriuretic Factor; Coronary Angiography; Coronary Circulation; Coronary Disease; Drug Therapy, Combination; Electrocardiography; Exercise Test; Female; Gallopamil; Hemodynamics; Humans; Infusions, Intravenous; Lactates; Lactic Acid; Male; Middle Aged; Myocardial Ischemia; Norepinephrine; Propanolamines; Renin; Single-Blind Method

Whereas angiotensin-converting enzyme inhibitors are now indicated for all grades of chronic heart failure, the 2 adverse effects that limit use of these drugs are systemic hypotension and renal dysfunction. The recognized clinical correlates such as hyponatremia and high diuretic dose, which predict occurrence of these adverse effects in severe chronic congestive heart failure (CHF), are rarely evident in patients with mild-to-moderate CHF. Accordingly, we studied 36 patients with stable, moderate CHF in a double-blind, placebo-controlled, crossover fashion to evaluate by multiple discriminate regression analysis the pathophysiologic determinants of changes in blood pressure, glomerular filtration rate, and urinary sodium excretion after initial converting enzyme inhibition with captopril 25 mg. A captopril-mediated decrease in mean arterial pressure was predicted by 3 factors (r2 = 0.74): the decrease in serum angiotensin II (F ratio = 10.3, p < 0.01), the decrease in plasma norepinephrine (F = 8, p = 0.02), and, inversely by pretreatment mean arterial pressure (F = 5.6, p = 0.04), patients with higher initial values exhibiting greater decreases in response to captopril. A captopril-mediated decline in glomerular filtration rate, determined by radioisotope elimination, was also predicted by 3 factors (r2 = 0.67): a decrease in renal plasma flow (F = 48.6, p < 0.01), low pretreatment glomerular filtration rate (F = 11.1, p < 0.01), and low absolute post-treatment serum angiotensin II (F = 5, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Blood Pressure; Captopril; Coronary Disease; Double-Blind Method; Female; Glomerular Filtration Rate; Heart Failure; Humans; Male; Natriuresis; Norepinephrine; Placebos; Renal Plasma Flow; Sodium

The present study evaluated the effect of right atrial appendicectomy on the release of atrial natriuretic peptide (ANP) and subsequent changes in postoperative haemodynamics in 20 men undergoing coronary artery bypass graft surgery. The right atrial appendix was removed in ten patients and saved in ten. Serum ANP, sodium levels and urinary sodium excretion were measured before and on days 1, 7 and 30 after surgery. Haemodynamic parameters were monitored before surgery and on day 30. Serum ANP levels fell significantly in patients undergoing appendicectomy (P < 0.05); haemodynamic parameters were unchanged. Hence, appendicectomy reduced serum ANP levels in the short term, though these tended to rise again with time; cardiac function was not affected by lowered levels of serum ANP. Consequently, saving the appendix in right atrial appendicectomy improves natriuresis and may decrease diuretic requirement.

Topics: Adult; Aged; Atrial Natriuretic Factor; Coronary Artery Bypass; Coronary Disease; Cytoplasmic Granules; Heart Atria; Hemodynamics; Humans; Male; Microscopy, Electron; Middle Aged

It has been shown that atrial natriuretic peptide (ANP), an endogenous vasodilator, dilates coronary arteries and decreases coronary vascular resistance. The purpose of this study was to determine whether an intravenous administration of ANP attenuated exercise-induced myocardial ischemia in 14 patients with stable effort angina pectoris.. The first 12 patients (patients 1-12) who had exercise-induced ST segment depression underwent treadmill exercise testing and the last seven patients (patients 8-14) underwent the exercise 201Tl-single-photon emission computed tomography (SPECT) study while synthetic 28-amino acid alpha-human ANP (0.1 micrograms/kg per minute) or saline was intravenously infused in a double-blind, cross-over manner. The duration of exercise testing was the same during ANP and saline infusion, which was determined in preliminary exercise testings in each patient to cause a transient perfusion defect and/or ischemic ST segment depression. During saline infusion, all 12 patients developed exercise-induced ischemic ST segment depression, whereas no significant ST segment depression appeared during ANP infusion. Average ST segment depression during ANP infusion was significantly less (p < 0.01) than that during saline infusion (0.0 +/- 0.0 versus 0.2 +/- 0.1 mV, mean +/- SD). The averaged extent and severity scores assessed by 201Tl-SPECT were smaller (p < 0.05) during ANP infusion than during saline infusion (extent score: 0.22 +/- 0.20 versus 0.42 +/- 0.20; severity score: 18.77 +/- 23.45 versus 38.24 +/- 24.04, respectively). ANP decreased resting systolic blood pressure from 125 +/- 15 to 110 +/- 15 mm Hg (p < 0.01) but did not alter resting heart rate. At peak exercise, systolic blood pressure, heart rate, and the rate-pressure products did not differ during ANP and saline infusion. At peak exercise, plasma ANP increased from 98 +/- 45 to 4,383 +/- 2,782 pg/ml and cGMP increased from 3.6 +/- 1.7 to 34.5 +/- 16.1 pmol/ml during ANP infusion; values were significantly higher than those during saline infusion (from 96 +/- 42 to 133 +/- 66 pg/ml and from 3.4 +/- 1.8 to 4.6 +/- 1.8 pmol/ml, respectively).. An intravenous administration of ANP attenuated exercise-induced myocardial ischemia in patients with stable effort angina pectoris. Although the mechanism by which ANP attenuated myocardial ischemia was not defined, increased myocardial perfusion to the ischemic region might be an important factor.

Topics: Adult; Aged; Angina Pectoris; Atrial Natriuretic Factor; Coronary Circulation; Coronary Disease; Double-Blind Method; Electrocardiography; Exercise Test; Female; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Pain; Physical Exertion; Sodium Chloride; Tomography, Emission-Computed, Single-Photon

Circulating organ-specific autoantibodies are serological markers of destruction or impairment of the relevant endocrine tissue cells and may be associated with abnormal hormone levels with or without clinical evidence of overt disease. We sought organ-specific cardiac antibodies in patients with autoimmune polyendocrinopathy because of increasing evidence that the heart has endocrine characteristics (secretion of atrial natriuretic peptide [ANP] and other peptide hormones). Serum samples from 166 patients with polyendocrinopathy, 80 with autoimmunity confined to one gland, and 200 healthy blood donors were tested for these antibodies by means of immunofluorescence on human heart. Skeletal muscle was used to identify cross-reacting antibodies. Organ-specific cardiac antibodies were detected in significantly more of the patients with autoimmune polyendocrinopathy (28 [17%]) than of those with autoimmunity confined to one gland (1 [1%]) or of normal subjects (7 [3.5%]; p = 0.0001). Among the patients with autoimmune polyendocrinopathy, the prevalence of systemic hypertension was higher in those with cardiac autoantibodies than in those without (5/28 [18%] vs 2/80 [3%]; p = 0.01); the same was true for a family history of hypertension (11 [42%] vs 5 [7%]; p = 0.0001). There were no significant differences in mean basal or stimulated ANP concentrations between patients with or without antibodies or between patients and controls. 5 of the 22 antibody-positive patients had ANP concentrations outside the normal range, but these disturbances were not associated with systemic hypertension or a family history of the disorder. Patients with autoimmune polyendocrinopathy can have organ-specific cardiac antibodies, which may represent novel serological markers for an autoimmune form of systemic hypertension in the absence of overt cardiac disease.

Topics: Adult; Aged; Atrial Natriuretic Factor; Autoantibodies; Autoimmune Diseases; Biomarkers; Coronary Disease; Diabetes Mellitus, Type 1; Family Health; Female; Humans; Hypertension; Immunoglobulin G; Male; Middle Aged; Myocardium; Organ Specificity; Thyroid Diseases

To evaluate the antiischemic effects of intravenous milrinone, 20 patients with angiographically proved coronary artery disease and stable angina were studied at rest and during exercise under control conditions and after an intravenous loading injection of milrinone (50 micrograms/kg/10 min) followed by an infusion with 0.5 micrograms/kg/min. Hemodynamic parameters, epinephrine, norepinephrine, and atrial natriuretic factor were assessed. Control ergometry revealed ischemia; however, during exercise with intravenous milrinone, ischemia was eliminated. Because of unloading effects, there was also a significant decrease in ST segment depression (p less than 0.001). Heart rate increased significantly (p less than 0.001) at rest but increased significantly less after exercise testing (p less than 0.001). The changes in mean arterial pressure, cardiac output, and myocardial oxygen consumption during exercise were not significantly different between the milrinone and control phase. Intravenous milrinone delayed the onset of angina (p less than 0.001) and significantly shortened the duration of anginal attacks (p less than 0.05); exercise duration in the milrinone phase was longer than in the control phase (p = 0.051). Because of vasodilatation, a mild secondary increase in norepinephrine was observed during the milrinone phase, and there was a significantly smaller increase in atrial natriuretic factor during exercise while receiving milrinone as a result of preload reduction (p less than 0.05). Intravenous milrinone produced beneficial hemodynamic and antiischemic effects in patients with coronary artery disease, stable angina, and reproducible ST segment depression probably by enhancing myocardial contractility and reducing preload and afterload.

Topics: Aged; Angina Pectoris; Atrial Natriuretic Factor; Cardiotonic Agents; Coronary Disease; Drug Evaluation; Electrocardiography; Exercise Test; Female; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Milrinone; Norepinephrine; Phosphodiesterase Inhibitors; Pyridones

Studies of the effects of atrial natriuretic peptide on the coronary circulation have yielded conflicting results in animals and have not been fully investigated in human subjects. To further characterize the direct coronary hemodynamic actions of atrial natriuretic peptide in humans and to assess the safety of its administration in patients with coronary artery disease, incremental doses of synthetic atrial natriuretic peptide and nitroglycerin were infused into the left coronary artery in 14 patients, 11 of whom had coronary artery disease. Both agents caused dose-related increases in total coronary sinus blood flow. The largest dose of atrial natriuretic peptide given to all patients (100 micrograms) increased mean coronary sinus blood flow from 127 +/- 7 to 149 +/- 9 ml/min (p less than 0.05) and decreased coronary vascular resistance from 0.93 +/- 0.07 to 0.81 +/- 0.05 mm Hg/ml per min (p less than 0.05); mean arterial blood pressure and heart rate were not affected by this dose of atrial natriuretic peptide. The greatest changes in coronary sinus blood flow (+25%) and coronary vascular resistance (-18%) after atrial natriuretic peptide administration occurred in the patients with coronary artery disease and no other associated cardiovascular disease. The maximal effects of atrial natriuretic peptide were similar to those of nitroglycerin, and no untoward effects were observed. Thus, atrial natriuretic peptide is a direct coronary vasodilator in humans. Its maximal dose effects are similar to those of nitroglycerin and were well tolerated in this small group of patients. The physiologic importance and therapeutic potential of atrial natriuretic peptide in patients with coronary artery disease merit further investigation.

Topics: Atrial Natriuretic Factor; Coronary Circulation; Coronary Disease; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Nitroglycerin; Stimulation, Chemical; Thermodilution; Vasodilator Agents; Ventricular Function, Left

Ibopamine is a novel oral dopamine analogue with positive inotropy and diuretic effects. In a double-blind, randomized study, the drug was investigated in 10 patients (mean age 49 +/- 10 years, six male, four female) with mild heart failure (NYHA classes II: six patients, III: four patients). Effects of single oral doses of 200 mg ibopamine, of 40 mg furosemide, and of 200 mg ibopamine plus 40 mg furosemide were compared in each patient at 3-day-intervals. One h after application, systolic and diastolic blood pressure increased from 119 +/- 11 to 124 +/- 8, and from 75 +/- 4 to 80 +/- 6 mm Hg (p less than 0.01) in the ibopamine group, while changes in both other groups and changes of the heart rate were insignificant. During 2 h after drug ingestion urinary flow was raised from 124 +/- 81 to 227 +/- 166 ml/2 h in the ibopamine group (p less than 0.05), while the application of furosemide (with or without ibopamine) resulted in several fold increases of urinary flow. After ibopamine, the 2-h-creatinine-clearance rose from 123 +/- 73 to 130 +/- 85 ml/min (not significant). Sodium excretion remained unchanged by ibopamine, potassium excretion was increased from 2.9 +/- 1.7 to 4.0 +/- 3.3 mmol/h (p less than 0.05), while effects of furosemide were several fold of those of ibopamine. Atrial natriuretic factor concentrations in plasma increased significantly after ibopamine and after ibopamine plus furosemide (p less than 0.01), but remained constant after furosemide alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Atrial Natriuretic Factor; Blood Pressure; Cardiomyopathy, Dilated; Coronary Disease; Cyclic GMP; Deoxyepinephrine; Diuretics; Dopamine; Electrolytes; Female; Furosemide; Heart Failure; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuresis; Urodynamics

UK 69 578 is a competitive inhibitor of endopeptidase 24.11 (the enzyme that degrades atrial natriuretic factor) in vitro. In vivo, UK 69 578 has renal and cardiovascular effects similar to low-dose atrial natriuretic factor infusion, and may be a useful agent in hypertension and heart failure.

Topics: Animals; Atrial Natriuretic Factor; Clinical Trials as Topic; Coronary Disease; Cyclohexanecarboxylic Acids; Dogs; Dose-Response Relationship, Drug; Double-Blind Method; Drug Evaluation; Drug Evaluation, Preclinical; Half-Life; Humans; Infusions, Intravenous; Male; Middle Aged; Natriuresis; Nephrectomy; Neprilysin; Rats; Rats, Inbred Strains; Time Factors

Plasma atrial natriuretic peptide (ANP) was measured during dynamic exercise in 10 patients with coronary heart disease before and after single dose atenolol 50 mg and acebutolol 200 mg, respectively. Systolic blood pressure, heart rate and the rate-pressure product increased during exercise before and after beta-blockade, but levels were lower after beta-blockade. Plasma ANP levels at rest were unchanged after atenolol, but rose after acebutolol (p less than 0.01). During exercise plasma ANP increased significantly both before and after beta-blockade, but plasma ANP levels were higher after acebutolol at all workloads (p less than 0.05), whereas plasma ANP levels after atenolol were higher at 125 W exclusively (p less than 0.05). The augmented ANP levels during exercise after beta-blockade probably reflect catecholamine-stimulated ANP release, whereas the elevated plasma ANP levels after acebutolol at rest might be a beta-adrenoceptor-mediated ANP release due to the intrinsic sympathomimetic effect of acebutolol.

Topics: Acebutolol; Aged; Atenolol; Atrial Natriuretic Factor; Clinical Trials as Topic; Coronary Disease; Exercise Test; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Random Allocation

The cardiac release and total body and renal clearances and the hemodynamic, renal and endocrine effects of increasing doses of atrial natriuretic peptide were investigated in 12 patients with severe chronic congestive heart failure. Immunoreactive arterial plasma levels of atrial natriuretic peptide were 10-fold higher than normal and there was no correlation between aortic atrial natriuretic peptide and cardiac filling pressures. The heart released atrial natriuretic peptide into the coronary sinus. The kidney, though a major clearance site, accounted for only 33% of the total body clearance. Administration of 0.3 micrograms/kg per min atrial natriuretic peptide produced significant changes in heart rate (95 +/- 4 to 85 +/- 4 beats/min) and mean arterial (92 +/- 8 to 77 +/- 9 mm Hg), right atrial (13 +/- 3 to 8 +/- 2 mm Hg) and mean pulmonary artery occluded (27 +/- 3 to 14 +/- 3 mm Hg) pressures. Atrial natriuretic peptide increased cardiac index (2.25 +/- 0.18 to 2.83 +/- 0.3 liters/min per m2) and stroke work index (21 +/- 1.5 to 29 +/- 3.4 g/m2), whereas systemic vascular resistance (1,424 +/- 139 to 1,033 +/- 97 dynes.s.cm(-5)) decreased. Infusion of 0.1 microgram/kg per min atrial natriuretic peptide increased urinary flow 128%, fractional excretion of sodium 133% and fractional excretion of potassium 35%. The filtration fraction increased from 29 +/- 2 to 31 +/- 4%. This represented a disproportionate rise in glomerular filtration rate over renal plasma flow. Plasma aldosterone and norepinephrine decreased whereas plasma renin activity remained unchanged. In association with these hemodynamic, excretory and endocrine changes, the urinary excretion of cyclic guanosine monophosphate doubled. Placebo had no effect. These results showed that, despite high circulating levels of atrial natriuretic peptide, administration of this hormone in heart failure is associated with potentially beneficial hemodynamic, renal and endocrine effects.

Topics: Adult; Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Coronary Disease; Female; Heart Valve Diseases; Hemodynamics; Humans; Kidney; Male; Middle Aged; Renin-Angiotensin System

Pathophysiological studies suggest that A-type natriuretic peptides (ANPs) might provide valuable information beyond B-type natriuretic peptides (BNPs) about cardiac dysfunction in patients with coronary heart disease (CHD). We aimed to assess the predictive value of midregional pro-A-type natriuretic peptide (MR-proANP) for recurrent cardiovascular disease (CVD) events in stable CHD patients for whom information on N-terminal proBNP (NT-proBNP) was already available.. Plasma concentrations of MR-proANP and NT-proBNP were measured at baseline in a cohort of 1048 patients aged 30-70 years with CHD who were participating in an in-hospital rehabilitation program. Main outcome measures were cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke.. During a median follow-up of 8.1 years, 150 patients (incidence 21.1 per 1000 patient-years) experienced a secondary CVD event. MR-proANP was associated with a hazard ratio (HR) of 1.89 (95% CI, 1.01-3.57) when the top quartile was compared to the bottom quartile in the fully adjusted model (P for trend = 0.011). For NT-proBNP the respective HR was 2.22 (95% CI, 1.19-4.14) with a P for trend = 0.001. Finally, MR-proANP improved various model performance measures, including c-statistics and reclassification metrics, but without being superior to NT-proBNP.. Although we found an independent association of MR-proANP as well as NT-proBNP when used as single markers with recurrent CVD events after adjustment for established risk factors, the results of a simultaneous assessment of both markers indicated that MR-proANP fails to provide additional prognostic information to NT-proBNP in the population studied.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cohort Studies; Coronary Disease; Female; Humans; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Proportional Hazards Models; Socioeconomic Factors; Statistics, Nonparametric

Atrial natriuretic peptide (ANP, also known as NPPA) and brain natriuretic peptide (BNP, also known as NPPB) have been determined as genetic factors for several diseases, including stroke and myocardial infarction, in human and rat models. To investigate the potential association between polymorphisms of the NPPA gene and stroke in a Korean population, nine single-nucleotide polymorphisms (SNPs) of NPPA and NPPB genes were genotyped in a total of 941 Korean subjects, including 674 stroke patients (109 hemorrhagic and 565 ischemic) and 267 unaffected controls. Genotype comparisons of the targeted alleles revealed that there were no significant associations between stroke patients and control subjects, or among hemorrhagic, ischemic, and control groups. However, in logistic analysis for Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification of ischemic stroke, nonsynonymous rs5065 (STOP152Arg) and rs5067 in 3'UTR of NPPA, which were in complete linkage disequilibrium, showed significant associations with cardioembolic stroke. These two SNPs showed higher frequencies in cardioembolic stroke patients than those in controls and ischemic patients with small-vessel occlusion (p=0.002, adjusted p=0.02). It was also found that NPPA rs5065C allele in all of the Korean subjects existed as heterozygous compared with Caucasian and African populations. Although further replications in larger cardioembolic stroke subjects are required, our preliminary findings suggest that the nonsynonymous rs5065C of the NPPA gene, which could produce a new or dysfunctional transcript, is possibly associated with cardioembolism.

Topics: Aged; Atrial Natriuretic Factor; Case-Control Studies; Coronary Disease; Embolism; Female; Genotype; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Stroke

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

Polymorphisms within individual natriuretic peptide genes have been associated with risk factors for cardiovascular disease, but their association with clinical outcomes was previously unknown. This study aimed to investigate the association between genetic variants in key genes of the natriuretic peptide system with cardiovascular outcomes in patients with coronary artery disease. Coronary disease patients (n=1810) were genotyped for polymorphisms within NPPA, NPPB, NPPC, NPR1 and NPR2. Clinical history, natriuretic peptide concentrations, echocardiography, all-cause mortality and cardiovascular hospital readmissions were recorded over a median 2.8 years. Minor alleles of NPPA rs5068, rs5065 and rs198358 were associated with less history of hypertension; minor alleles of NPPA rs5068 and rs198358 was also associated with higher circulating natriuretic peptide levels (p=0.003 to p=0.04). Minor alleles of NPPB rs198388, rs198389, and rs632793 were associated with higher circulating BNP and NT-proBNP (p=0.001 to p=0.03), and reduced E/E(1) (p=0.011), or LVESVI (p=0.001) and LVEDVI (p=0.004). Within NPPC, both rs11079028 and rs479651 were associated with higher NT-proBNP and CNP (p=0.01 to p=0.03), and rs479651 was associated with lower LVESVI (p=0.008) and LVEDVI (p=0.018). NPR2 rs10758325 was associated with smaller LVMI (p<0.02). A reduced rate of cardiovascular readmission was observed for minor alleles of NPPA rs5065 (p<0.0001), NPPB rs632793 (p<0.0001), rs198388 (p<0.0001), rs198389 (p<0.0001), and NPR2 rs10758325 (p<0.0001). There were no associations with all-cause mortality. In established cardiovascular disease, natriuretic peptide system polymorphisms were associated with natriuretic peptide levels, hypertension, echocardiographic indices and the incidence of hospital readmission for cardiovascular events.

Topics: Aged; Atrial Natriuretic Factor; Coronary Disease; Female; Genotype; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Polymorphism, Genetic; Receptors, Atrial Natriuretic Factor

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

We compared the diagnostic performance of N-terminal pro-brain natriuretic peptide (NT-proBNP) with a newly developed assay for the midregional part of pro-atrial natriuretic peptide (MR-proANP) concerning the detection of impaired left ventricular ejection function (LVEF) among patients with coronary artery disease (CAD).. Plasma levels of MR-proANP and NT-proBNP were determined in 102 consecutive patients with a history of ST-elevation myocardial infarction. Plasma levels of both markers were measured during a mean follow-up period of 687 days after acute myocardial infarction. Univariate analyses revealed inverse correlations between MR-proANP levels and LVEF (r=-0.39; p<0.001), NT-proBNP levels and LVEF (r=-0.39; p<0.001) and a positive correlation between MR-proANP and NT-proBNP (r=0.75; p<0.001). After adjustment for traditional risk factors, MR-proANP was the strongest predictor for LVEF (p=0.001) in multivariate analysis, being even superior to NT-proBNP. The area under the ROC curve (AUC) indicated moderate performance (AUC=0.73; p<0.01) of MR-proANP regarding the detection of a reduced LVEF<50%. The AUC of NT-proBNP for detection of impaired LVEF<50% was 0.68 (p=0.019). The negative predictive values of both markers were 86% for MR-proANP at a cut-off >135 pmol/L and NT-proBNP at a cut-off >560 pmol/L. At these cut-offs, the specificity of MR-proANP was 90%, and the specificity of NT-proBNP was 84%.. MR-proANP is a useful indicator for the exclusion of a preserved left ventricular function in patients with coronary artery disease. The study demonstrates that the diagnostic performance of MR-proANP is comparable to the "gold standard" NT-proBNP.

Topics: Atrial Natriuretic Factor; Biomarkers; Coronary Disease; Echocardiography; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Sensitivity and Specificity; Ventricular Dysfunction, Left

The association between atrial natriuretic peptide (ANP) polymorphism and coronary heart disease (CHD) was studied in Chinese population. The genotypes of ANP T2238C and ANP C-664G were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) methods in 158 consecutive CHD patients and 165 controls. It was found that the distribution of A2A2 genotype in CHD group was significantly higher than that in control group (P<0.05). Stepwise Logistic regression analysis revealed that male, smoking, history of hypertension, history of diabetes, family history of hypertension, high level of serum cholesterol, and ANP T2238C polymorphism were the possible risk factors in patients with CHD (P<0.05). However, there was no significant difference between the patients with CHD and the control group in the distribution of ANP C-664G polymorphism (P>0.05). The results suggest that A2A2 T2238C genotype could be one of the risk factors for CHD (P<0.05, OR: 1.80, 95 % CI: 1.03-3.15).

Topics: Aged; Asian People; Atrial Natriuretic Factor; Coronary Disease; Female; Genotype; Humans; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Risk Factors

High circulating concentrations of N-terminal fragments of A- and B-type natriuretic peptides (NT-proANP and NT-proBNP) identify patients with impaired cardiac function. ProANP-derived peptides are particularly sensitive to increased preload of the heart and proBNP-derived peptides to increased afterload; therefore, combining the information from the ANP and BNP systems into a single analyte could produce an assay with increased diagnostic and prognostic power.. We prepared a hybrid peptide containing peptide sequences from both NT-proBNP and NT-proANP (referred to as NT-proXNP) by recombinant techniques and used it to develop a RIA combining weighed concentrations of NT-proANP and NT-proBNP into a new virtual analyte, NT-proXNP. We used the novel method to measure the circulating concentrations in healthy persons and in patients with cardiac disorders. We also characterized the assay by HPLC analysis of the immunoreactive molecular forms in human plasma and serum.. The results from the novel assay correlated well with independent home-made NT-proANP and NT-proBNP assays (r2 = 0.75-0.85) as well with the arithmetic sum of NT-proANP and NT-proBNP (r2 = 0.92). Patients with valvular heart disease (VHD) and coronary artery disease (CAD) had significantly increased NT-proXNP concentrations. The areas under the curve (AUC) of the NT-proXNP assay in detecting VHD and CAD (0.961 and 0.924, respectively) were significantly larger than the AUC of either NT-proANP (0.947 and 0.872) or NT-proBNP (0.913 and 0.782) assays. HPLC analysis showed that the novel NT-proXNP assay detects two major classes of circulating immunoreactivity corresponding to peptides derived from NT-proANP and NT-proBNP.. Our novel immunoassay mimics the physiologic signaling system working in the body by converging the information obtained from the activation of ANP and BNP into a single virtual analyte, NT-proXNP. It appears to have a diagnostic efficiency equal to or slightly better than that of individual NT-proANP or NT-proBNP assays.

Topics: Adult; Aged; Atrial Natriuretic Factor; Chromatography, High Pressure Liquid; Coronary Disease; Heart Valve Diseases; Humans; Immune Sera; Iodine Radioisotopes; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Protein Precursors; Radioimmunoassay; Recombinant Fusion Proteins; Reference Values

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

Atrial natriuretic peptide and brain natriuretic peptide are known to be indices for heart failure. Atrial natriuretic peptide and brain natriuretic peptide changes in off-pump and on-pump coronary artery bypass grafting is hypothesized to be correlated to clinical implications of coronary artery bypass grafting. 20 consecutive off-pump and 20 consecutive on-pump coronary artery bypass grafting patients were studied. Perioperative atrial natriuretic peptide and brain natriuretic peptide values were measured and statistically analyzed in terms of 14 factors related to myocardial damage and recovery. Postoperative atrial natriuretic peptide plateaued on the third postoperative day and it decreased gradually down to the preoperative level by one month in the off-pump group. Postoperative brain natriuretic peptide plateaued, showed very slow decrease and it never reached down to the preoperative level. The peak brain natriuretic peptide level was correlated with aortic cross-clamp time, postoperative pleural effusion, and postoperative atrial fibrillation (p < 0.01). The atrial natriuretic peptide change reflected surgical prevention of ventricular remodeling. Brain natriuretic peptide > 450 microg.mL(-1) had strong predictive power for atrial fibrillation and pleural effusion and is a useful marker for management of coronary surgery patients.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Cardiopulmonary Bypass; Chi-Square Distribution; Coronary Angiography; Coronary Artery Bypass; Coronary Disease; Female; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Postoperative Care; Probability; Prognosis; Prospective Studies; Sensitivity and Specificity; Severity of Illness Index; Survival Rate; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; C-Reactive Protein; Carotid Artery Diseases; Clinical Trials as Topic; Combined Modality Therapy; Coronary Disease; Electrocardiography; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Myocardial Revascularization; Natriuretic Peptide, Brain; Stents

Topics: Acute Disease; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Coronary Disease; Creatinine; Glycated Hemoglobin; Humans; Inflammation; Kidney Diseases; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Syndrome

increased ANP levels after uncomplicated coronary artery surgery (CAS) indicate functional reduction.. prospective, randomized. Preoperative upto the 12 week postoperative.. Thoracic and Cardiovascular Surgery, University of Düsseldorf.. 15 patients (mean age: 58+/-6.1 years; 13 months, 2 weeks; no myocardial infarction, no congestive heart failure) with 3 vessel disease.. levels of atrial natriuretic peptide (ANP) (pg/ml; radioimmunoassay), Troponin T (TnT) (ng/ml; ELISA test), haemodynamic parameters, ECG monitoring, m-mode echocardiography (Echo).. increase of ANP, TnT levels during extracorporeal circulation (ECC), decrease after operation.. Maximal increase of ANP from preoperative 90+/-10 (M+/-SEM) pg/ml (p<0.05) up to intraoperative 380+/-38 pg/ml. Ten days postoperative ANP (26+/-33 pg/ml) still threefold increased compared to preoperative level. Increasement of TnT from preoperative 0.02+/-0.01 ng/ml upto intraoperative 3.44+/-0.47 ng/ml. Ten days postoperative TnT concentration normal (0.13+/-0.11 ng/ml). Correlation of ANP and TnT five min after bypass up to 6 hrs postoperative (p<0.05, r =3.4). Increase of left atrial diameter preoperative 42.2+/-1.1 mm up to 46.8+/-1.2 mm (p<0.05) 10 days postoperative. LVEDD, EF changed from preoperative 51.1+/-0.9 mm, 73+/-2% to 54.5+/-1.2 mm, 65+/-4% 10 days postoperative.. Threefold increase of ANP 10 days postoperative and return of TnT levels to normal under consideration of datas of echo show, that ANP is suitable to indicate the meanterm, functional, myocardial reduction. Increased ANP levels, atrial dilatation and dysfunction are important signs of cardial functional reduction after CAS.

Topics: Adult; Aged; Atrial Natriuretic Factor; Coronary Artery Bypass; Coronary Disease; Dilatation, Pathologic; Extracorporeal Circulation; Female; Heart Atria; Humans; Male; Middle Aged; Postoperative Period; Prospective Studies; Troponin T; Ventricular Dysfunction

We prospectively tested the hypothesis that atrial enlargement and increased level of atrial natriuretic peptide, N-terminal atrial natriuretic peptide and brain natriuretic peptide would predict atrial fibrillation after coronary artery bypass grafting.. Eighty-eight elective coronary artery bypass grafting patients had preoperative echocardiographic assessment. The level of atrial natriuretic peptide, N-terminal atrial natriuretic peptide and brain natriuretic peptide were measured preoperatively. Patients were ECG- monitored during the whole hospital stay.. Thirty one (35.2%) patients had postoperative atrial fibrillation. In univariate analysis increased age (P=0.003), enlargement of left and right atria (P=0.002 and P=0.004, respectively) and increased level of preoperative atrial natriuretic peptide and N-terminal atrial natriuretic peptide (P=0.016 and P=0.03, respectively) were associated with postoperative atrial fibrillation. There was correlation between the age and level of N-terminal atrial natriuretic peptide (r=0.45 and P<0.001). In multivariate analysis only age and the left atrial enlargement were independent predictors of postoperative atrial fibrillation (P=0.02 and P=0.01).. Left atrial enlargement was independent predictor for postoperative atrial fibrillation. However, atrial peptides were associated with age and did not independently predict postoperative atrial fibrillation. In addition, the wide variation of the peptide levels renders the implementation of this measure in clinical practice superfluous.

Topics: Age Factors; Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Coronary Artery Bypass; Coronary Disease; Female; Heart Atria; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Protein Precursors; Risk Factors

Conflict exists regarding the usefulness of measuring plasma B type natriuretic peptide (BNP) concentrations for identifying impaired left ventricular (LV) systolic function during mass screening. Various cardiac abnormalities, regardless of degree of LV dysfunction, are prone to carry a high risk of cardiovascular events.. To examine the validity of plasma BNP measurement for detection of various cardiac abnormalities in a population with a low prevalence of coronary heart disease and LV systolic dysfunction.. Participants in this cross sectional study attended a health screening programme in Iwate, northern Japan. Plasma BNP concentrations were determined in 1098 consecutive subjects (mean age 56 years) by direct radioimmunoassay. All subjects underwent multiphasic health checkups including physical examination, ECG, chest radiography, and transthoracic echocardiography.. Conventional diagnostic methods showed 39 subjects to have a wide range of cardiac abnormalities: lone atrial fibrillation or flutter in 11; previous myocardial infarction in seven; valvar heart disease in seven; hypertensive heart disease in six; cardiomyopathy in six; atrial septal defect in one; and cor pulmonale in one. No subjects had a low LV ejection fraction (< 40%). To assess the utility of plasma BNP measurement for identification of such patients, receiver operating characteristic analysis was performed. The optimal threshold for identification was a BNP concentration of 50 pg/ml with sensitivity of 89.7% and specificity of 95.7%. The area under the receiver operating characteristic curve was 0.970. The positive and negative predictive values at the cutoff level were 44.3% and 99.6%, respectively.. Measurement of plasma BNP concentration is a very efficient and cost effective mass screening technique for identifying patients with various cardiac abnormalities regardless of aetiology and degree of LV systolic dysfunction that can potentially develop into obvious heart failure and carry a high risk of a cardiovascular event.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Coronary Disease; Cross-Sectional Studies; Electrocardiography; Female; Humans; Japan; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction, Left

Most patients (about 85%) seen in the ED to rule out an acute coronary event do not have acute coronary disease. In addition, the presenting ECG findings have been nondiagnostic in 50% of patients with acute MI. Our current knowledge of atherosclerosis as being a chronic low-grade inflammatory process triggered the search for reliable serum markers that have improved the diagnostic accuracy management and prognosis of this prevalent disease. Newer and potential inflammatory markers currently under investigation deserve watching in future reports. These among others include those markers produced by the arterial wall itself, that is, cell adhesion molecules (CAM), inter-cellular adhesion molecules (ICAM), and vascular adhesion molecules (VCAM). The expression of CAM is a marker of dysfunctional endothelial cells. It is likely that more cardiac markers will be reported in the future. Time will tell.

Topics: Acute Disease; Atrial Natriuretic Factor; Biomarkers; Coronary Disease; Female; Humans; Male; Natriuretic Peptide, Brain; Pregnancy-Associated Plasma Protein-A; Syndrome

In patients with acute coronary syndromes (ACS), troponin I (TnI), C-reactive protein (CRP), and B-type natriuretic peptide (BNP) each predict adverse cardiac events. Little is known, however, about the utility of these biomarkers in combination.. Baseline measurements of TnI, CRP, and BNP were performed in 450 patients in OPUS-TIMI 16. Elevations in TnI, CRP, and BNP each were independent predictors of the composite of death, myocardial infarction (MI), or congestive heart failure (CHF). When patients were categorized on the basis of the number of elevated biomarkers at presentation, there was a near doubling of the mortality risk for each additional biomarker that was elevated (P=0.01). Similar relationships existed for the endpoints of MI, CHF, and the composite, both at 30 days and through 10 months. In a validation cohort of 1635 patients in TACTICS-TIMI 18, the number of elevated biomarkers remained a significant predictor of the composite endpoint after adjustment for known clinical predictors: patients with one, two, and three elevated biomarkers had a 2.1- (P=0.006), 3.1- (P<0.001), and 3.7- (P=0.001) fold increase in the risk of death, MI, or CHF by 6 months.. Troponin, CRP, and BNP each provide unique prognostic information in patients with ACS. A simple multimarker strategy that categorizes patients based on the number of elevated biomarkers at presentation allows risk stratification over a broad range of short- and long-term major cardiac events.

Topics: Acute Disease; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Cohort Studies; Coronary Disease; Heart Failure; Humans; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; Risk Assessment; Syndrome; Troponin I

Experimental studies have demonstrated that adrenomedullin (AM) has a positive inotropic action and exerts inhibitory effects against ventricular remodelling as an autocrine and paracrine factor. However, there is no clinical evidence for AM acting as a local regulator in the human heart. We measured the levels of various molecular forms of AM, i.e. an active form of mature AM (AM-m), an intermediate inactive form of glycine-extended AM (AM-Gly) and total AM (AM-T=AM-m+AM-Gly), in plasma and pericardial fluid using our newly developed immunoradiometric assay in consecutive 67 patients undergoing coronary artery bypass graft surgery. Pericardial fluid and plasma cAMP, atrial natriuretic peptide and brain natriuretic peptide levels were also measured. The relationships between pericardial fluid AM levels and ventricular functions and other hormone levels were analysed. The level of each molecular form of AM in pericardial fluid was closely correlated with that of the other molecular forms of AM in the fluid. However, levels were not correlated with those in plasma. AM-T levels were slightly higher in pericardial fluid than in plasma (+72%; P<0.05), whereas AM-m levels and AM-m/AM-T ratios were markedly higher in pericardial fluid than in plasma (AM-m, +994%; AM-m/AM-T ratio, +443%; both P<0.01). AM-m, AM-Gly and AM-T levels in pericardial fluid were correlated with indices of left ventricular function, and with atrial natriuretic peptide and brain natriuretic peptide levels. Interestingly, AM and cAMP levels were positively correlated in plasma, but negatively correlated in pericardial fluid. In addition, AM-m, AM-Gly and AM-T levels in pericardial fluid were higher in patients with acute coronary syndrome than in those with stable ischaemic heart disease (AM-m, +80%; AM-Gly, +96%; AM-T, +83%; all P<0.01). These results suggest that AM in pericardial fluid reflects cardiac synthesis, and that enhanced cardiac secretion of AM is associated with left ventricular dysfunction, ventricular overload and myocardial ischaemia. Considering that AM has positive inotropic, coronary vasodilatory and anti-remodelling actions, increased cardiac AM may play a compensatory role in the ischaemic and failing myocardium.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Coronary Artery Bypass; Coronary Disease; Cyclic AMP; Female; Humans; Immunoradiometric Assay; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptides; Pericardial Effusion; Ventricular Function, Left

Fluctuations in the level of blood natriuretic peptides (ANP and BNP) were compared between 41 patients who underwent conventional coronary artery bypass (CCAB) and 19 patients who underwent off-pump coronary artery bypass (OPCAB). A blood sample was collected before surgery, and 6, 12 and 24 hours; 2, 3, 5 and 7 days; and 1 month after the end of extracorporeal circulation. There were no significant differences in left ventricular ejection fraction (LVEF) before and after surgery in either group or between the two groups. On average, 3.3 +/- 1.0 bypass grafts were used for the CCAB group, and 2.2 +/- 0.8 grafts for the OPCAB group. Furthermore, the maximum postoperative creatine phosphokinase-MB (CK-MB) level for the CCAB group was 49.1 +/- 17.5 IU/l, whereas that for the OPCAB group was significantly lower at 23.2 +/- 24.8 IU/l. The preoperative level of blood ANP for the CCAB group was 24.6 +/- 19.9 pg/ml while that for the OPCAB group was 39.3 +/- 29.5 pg/ml, but there was no significant difference between the two groups. In both groups, the level of blood ANP reached a peak three days after the end of extracorporeal circulation and then decreased after that point. Although the level of blood ANP for the OPCAB group decreased to 51.4 +/- 26.4 pg/ml one month after the end of extracorporeal circulation, that for the CCAB group one month after the end of extracorporeal circulation remained significantly high at 61.3 +/- 30.6 pg/ml, when compared to that before surgery. Furthermore, the preoperative level of blood BNP for the CCAB group was 40.0 +/- 35.2 pg/ml and that for the OPCAB group was 75.5 +/- 59.7 pg/ml, but there was no significant difference between the two groups. Then, in both groups, the level of blood BNP reached a peak 2-5 days after the end of extracorporeal circulation and then decreased after that. Whereas the level of blood BNP for the OPCAB group decreased to 96.4 +/- 56.0 pg/ml one month after the end of extracorporeal circulation, that for the CCAB group one month after the end of extracorporeal circulation remained significantly high at 160.3 +/- 106.2 pg/ml when compared to that before surgery. The levels of ANP and BNP increased postoperatively for both OPCAB and CCAB groups since the following events caused a great degree of stress on the heart: general anesthesia, cardiac herniation, stabilizer compression, regional blood flow blockage and reperfusion injury. Although the level of natriuretic peptides for the CCAB group remain

Topics: Aged; Atrial Natriuretic Factor; Coronary Artery Bypass; Coronary Disease; Female; Humans; Male; Middle Aged; Minimally Invasive Surgical Procedures; Natriuretic Peptide, Brain; Postoperative Period

A noninvasive biochemical testing method for early detection and monitoring the condition of cardiac complications in hemodialysis (HD) patients would be useful and might lead to improved survival. The aim of this study is to clarify the pathophysiological significance of plasma brain natriuretic peptide (BNP) levels in HD patients with and without coronary artery disease (CAD). We measured plasma atrial natriuretic peptide (ANP) and BNP levels on Monday, Wednesday, and Friday before and after HD in 28 consecutive patients who underwent HD three times weekly. In addition, we measured plasma ANP and BNP levels in 21 HD patients with CAD and 27 HD patients without CAD and studied the relationships between BNP levels and cardiac function and clinical variables. Plasma ANP levels significantly decreased after HD on Monday, Wednesday, and Friday, and predialysis plasma ANP levels on Monday were significantly greater than those on other days. Plasma BNP levels did not change after HD on Monday; however, they significantly decreased after HD on Wednesday and FRIDAY: Predialysis plasma BNP levels on Monday were greater than those on other days, and postdialysis plasma BNP levels on Monday were greater than predialysis plasma BNP levels on WEDNESDAY: Plasma BNP levels in HD patients with CAD were significantly greater than those in HD patients without CAD and significantly correlated with left ventricular (LV) ejection fraction (r = -0.69), end-diastolic volume index (r = 0.59), and end-systolic volume index (r = 0.84) determined by left ventriculography. Conversely, plasma BNP levels in HD patients without CAD significantly correlated with LV mass index (r = 0.54) determined by echocardiography and mean systolic blood pressure (r = 0.72) determined by 48-hour ambulatory blood pressure monitoring. These results suggest the following: (1) plasma BNP levels before and after HD in chronic HD patients directly correlate with the degree of body fluid retention, and the day of the week on which the sample is obtained should be considered for its evaluation; (2) plasma BNP levels reflect LV function in HD patients with CAD; and (3) plasma BNP levels reflect LV mass and blood pressure in HD patients without CAD.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Coronary Disease; Female; Heart Ventricles; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis

There are few stable and reproducible large-animal models of chronic heart failure produced by ischaemic damage to the myocardium. Here we characterize a novel method of inducing myocardial damage in closed-chest sheep by catheter delivery of thrombogenic coils, and compare this with a newly described open-artery model of cardiac injury in sheep. Sham controls were compared with animals subjected to (a) 90 min of coronary artery occlusion/reperfusion by PTCA (percutaneous transluminal coronary angioplasty) balloon, and (b) permanent coronary artery occlusion induced by catheter delivery of thrombogenic coils (seven sheep/group). Both balloon occlusion/reperfusion and permanent coil occlusion resulted in well-defined anteroapical infarcts, as documented by ECG changes, significant rises in creatine kinase (both groups P<0.001) and troponin-T (both groups P<0.05), and post-mortem examination. Washout of enzymes was much more rapid in the reperfused group (P<0. 01). Infarction resulted in significant reductions in left ventricular (LV) ejection fraction (both groups P<0.01) and regional wall abnormalities. Ejection fraction 7 days post-coil (21.3+/-4.2%) was significantly lower (P<0.01) than that 7 days post-balloon (38. 8+/-4.5%). Coil-induced infarction was associated with acutely reduced arterial pressure (P<0.05), and increases in heart rate (P<0. 05), atrial pressures (P<0.05), plasma brain natriuretic peptide levels (P<0.05) and adrenaline levels (P<0.05). Rises seen in plasma endothelin levels in sham controls were blunted in the coil group (P<0.001). Haemodynamic changes were less marked in the balloon group. In conclusion, restriction of coronary artery occlusion to 90 min results in infarction, but less LV dysfunction with reduced early remodelling, compared with permanent occlusion. Acute changes in biochemical markers, haemodynamics, neurohormones and LV function confirm that these are excellent models of open- and closed-artery myocardial infarction leading to asymptomatic LV dysfunction.

Topics: Analysis of Variance; Animals; Atrial Natriuretic Factor; Biomarkers; Coronary Disease; Disease Models, Animal; Hemodynamics; Hormones; Myocardial Infarction; Myocardial Reperfusion Injury; Sheep; Ventricular Dysfunction, Left

Carperitide, a recombinant form of alpha-hANP, possesses potent diuretic, natriuretic, and vasodilatory activity, and inhibits the renin-aldosterone system and sympathetic nervous activity. However, its beneficial effects on ischemic myocardium have not been studied fully. We examined carperitide's effects on infarct size, hemodynamics, and arrhythmia frequency in anesthetized dogs (n = 20) subjected to a 90-min coronary artery occlusion/6-h reperfusion protocol. Intravenous infusion of carperitide (0.2 microg/kg/min) commenced 15 min after occlusion and continued during occlusion/reperfusion. Ventricular fibrillation developed in two of 10 control versus three of 10 treated dogs (p = NS). Hemodynamics, collateral blood flow to the ischemic wall measured 10 min after occlusion, and extent of area at risk were comparable for the two groups. Infarct size/area at risk was smaller in treated than in control dogs (4.5 +/- 2.1% vs. 27.8 +/- 7.8%, respectively; p < 0.05). During occlusion, carperitide tended to increase collateral blood flow (+39%) and significantly decreased left ventricular systolic pressure (-13%) and end-diastolic pressure (-40%) compared with baseline. In control dogs, collateral blood flow tended to decrease (-8.3%), whereas most hemodynamic parameters did not change significantly with respect to baseline. The number of arrhythmias recorded during occlusion/reperfusion was similar in the two groups. Intravenous administration of carperitide limited infarct size, but did not reduce incidence of ventricular arrhythmias after 90-min coronary occlusion/6-h reperfusion in anesthetized dogs. Although the beneficial effects of carperitide may be attributable to concomitant changes in hemodynamics and collateral blood flow, the precise mechanisms require further investigation.

Topics: Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cardiotonic Agents; Collateral Circulation; Coronary Disease; Cyclic GMP; Dogs; Female; Humans; Male; Myocardial Infarction; Myocardial Reperfusion; Peptide Fragments

Neurohormones may influence vascular tone both during and after exercise. Neuropeptide Y (NPY), which is costored and released with norepinephrine (NE) during sympathetic activity, is a potent vasoconstrictor with a relatively long half-life. We therefore examined its possible association with the ischemic response to exercise in patients with coronary artery disease.. Twenty-nine male patients with effort-induced angina pectoris underwent a symptom-limited exercise test. In addition to conventional ST-segment analysis, we examined ischemia on the basis of heart rate (HR)-adjusted ST-segment changes through calculation of the ST/HR slope during the final 4 minutes of exercise and of the ST/HR recovery loop after exercise. Blood samples were taken before, during, and after exercise for an analysis of several neurohormones. Mean ST-segment depression was -223+/-20.2 microV (P:<0.0001) just before the termination of exercise, followed by a gradual normalization, but it remained significant after 10 minutes (-49+/-8.9 microV, P:<0.0001). At the end of exercise, the ST/HR slope, which reflects myocardial ischemia, was -6.0+/-0.77 microV/HR. In most patients, ST-segment levels at a given HR were lower during recovery than during exercise, here referred to as ST "deficit." Exercise increased the plasma levels of NPY, NE, epinephrine, and N-terminal proatrial natriuretic peptide, but big endothelin remained unchanged. Although NE and epinephrine peaked at maximal exercise, the highest levels of NPY and N-terminal proatrial natriuretic peptide were observed 4 minutes after exercise. The maximal increase in the NPY correlated significantly with ST-segment depression at 3 minutes after exercise (r=-0.61, P:= 0.0005), the ST deficit at the corresponding time point (r=-0.66, P:= 0.0001), and the duration of ST-segment depression after exercise (r= 0.42, P:=0.02). In contrast, no such correlations were found for NE.. The present study has for the first time demonstrated a correlation between plasma NPY levels and the degree and duration of ST-segment depression after exercise in patients with coronary artery disease, which suggests that NPY may contribute to myocardial ischemia in these patients.

Topics: Analysis of Variance; Angina Pectoris; Atrial Natriuretic Factor; Coronary Disease; Electrocardiography; Endothelin-1; Endothelins; Epinephrine; Exercise Test; Heart Rate; Humans; Male; Middle Aged; Neuropeptide Y; Norepinephrine; Protein Precursors; Time Factors

The aim of the present study was to examine the effects of atrial natriuretic peptide (ANP) on the responses to coronary artery occlusion. In chloralose-urethane anaesthetised mongrel dogs either saline (controls) or human synthetic ANP was infused intravenously (10 microg kg(-1) + 0.1 microg kg(-1) min(-1)), starting 30 min before and continuing 10 min during a 25 min occlusion of the left anterior descending coronary artery (LAD). ANP infusion resulted in a fall in mean arterial blood pressure (by 17 +/- 2 mmHg, p < 0.05), a transient (max. at 5 min) increase in coronary blood flow (by 24 +/- 5 ml min(-1), p < 0.05), and a reduction in coronary vascular resistance (by 0.27 +/- 0.05 mmHg ml(-1), p < 0.05). When the LAD coronary artery was occluded, there was a less marked elevation in left ventricular end-diastolic pressure (LVEDP) in the ANP-treated dogs than in the controls (9.0 +/- 0.9 versus 12.2 +/- 0.8 mmHg, p < 0.05). Compared to the controls, ANP reduced the number of ventricular premature beats (VPBs, 26 +/- 12 versus 416 +/- 87, p < 0.05), the number of episodes of ventricular tachycardia per dogs (VT, 0.7 +/- 0.3 versus 12.4 +/- 4.2, p < 0.05), and the incidences of VT (45% versus 100%, p < 0.05) and ventricular fibrillation (VF 18% versus 57%, p < 0.05) during occlusion. Reperfusion of the ischaemic myocardium at the end of the occlusion period led to VF in all the control dogs (survival from the combined ischaemia-reperfusion insult was therefore 0%), but VF following reperfusion was much less in the dogs given ANP (survival 64%; p < 0.05). The severity of myocardial ischaemia, as assessed from changes in the epicardial ST-segment and the degree of inhomogeneity, was significantly less marked in dogs given ANP. We conclude that ANP protects the myocardium from the consequences of myocardial ischaemia resulting from acute coronary artery occlusion and reperfusion in anaesthetized dogs.

Topics: Analysis of Variance; Animals; Atrial Natriuretic Factor; Coronary Disease; Dogs; Female; Hemodynamics; Infusions, Intravenous; Male; Myocardial Ischemia; Myocardial Reperfusion

Plasma levels of ANP (pg/ml; radioimmunoassay) as a parameter for postischemic dysfunction and levels of Troponin T (TnT) (ng/ml; ELISA test) as a parameter for postischemic cellular damage were determined in 15 patients with coronary artery disease (CAD) (mean age: 58 +/- 6.1 years; 13 m, 2 w; with no history of myocardial infarction and no signs for congestive heart failure) prior to, during and after extracorporal circulation (ECC). Under standardized conditions during the ECC basic parameters concerning the cardial hemodynamic (heart rate (HR); systolic (RRsys, mmHg), diastolic pressure (RR dia, mmHg) central venous pressure (CVP, mmHg); left atrial pressure (LAP, mmHg); left ventricular enddiastolic pressure (LVEDP, mmHg)) and ECG monitoring blood samples were performed: 1) prior to operation (op); 2) prior to CPB; 3) 1 h CPB; 4) 5 min after CPB; 5) 1 h after CPB; 6) 6 h postoperative (postop); 7) 24 h postop; 8) 48 h postop; 9) 10 days postop. Also the left atrial diameter (LAD, mm) and the left ventricular enddiastolic diameter at Q (LVEDD, mm) pre- and postop were documented with m-mode echocardiography (Echo) and ejection fraction (EF, %) was calculated. The bypass operations were performed with intermittent aortic cross-clamping with open venae cavae (CVP: 0-5 mmHg) and moderate hypothermia. For the determination of ANP levels and TnT levels in arterial and venous blood, a double-antibody (AB) radioimmunoassay and an ELISA test were used. Concerning the patients with CAD there was a maximal increase of ANP from preoperative 90 +/- 10 (M +/- SEM) pg/ml (p < 0.05) up to intraoperative 380 +/- 38 pg/ml. Ten days postop, the ANP level was with 262 +/- 33 pg/ml still increased threefold in comparison to the preoperative level. TnT showed an increase from preoperative 0.02 +/- 0.01 ng/ml up to intraoperative 3.44 +/- 0.47 ng/ml. Ten days postop the TnT concentration was at the preoperative level with 0.13 +/- 0.11 ng/ml. Five minutes after bypass up to 48 h postop, ANP and TnT levels were correlated (p < 0.05, r = 3.4). There was an increase of the LAD from preoperative 42.2 +/- 1.1 mm up to 46.8 +/- 1.2 mm (p < 0.05) 10 days postop as determined by m-mode echo. LVEDD and EF changed from preoperative 51.1 +/- 0.9 mm and 73 +/- 2% to 54.5 +/- 1.2 mm and 65 +/- 4% 10 days postop. The significant increase of TnT (172-fold) indicates the cellular, myocardial injury, caused by the operation without signs in ECG recordings and no signs of congestive heart f

Topics: Adult; Aged; Atrial Natriuretic Factor; Coronary Artery Bypass; Coronary Disease; Echocardiography; Enzyme-Linked Immunosorbent Assay; Extracorporeal Circulation; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Reperfusion Injury; Postoperative Complications; Troponin T

To investigate whether oxygen uptake (VO2) kinetics during low intensity exercise are related to clinical signs, symptoms, and neurohumoral activation independently of peak oxygen consumption in chronic heart failure.. Comparison of VO2 kinetics with peak VO2, neurohormones, and clinical signs of chronic heart failure.. Tertiary care centre.. 48 patients with mild to moderate chronic heart failure.. Treadmill exercise testing with "breath by breath" gas exchange monitoring. Measurement of atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and noradrenaline. Assessment of clinical findings by questionnaire.. O2 kinetics were defined as O2 deficit (time [rest to steady state] x DeltaVO2 -sigmaVO2 [rest to steady state]; normalised to body weight) and mean response time of oxygen consumption (MRT; O2 deficit/DeltaVO2).. VO2 kinetics were weakly to moderately correlated to the peak VO2 (O2 deficit, r = -0.37, p < 0.05; MRT, r = -0.49, p < 0.001). Natriuretic peptides were more closely correlated with MRT (ANF, r = 0.58; BNP, r = 0.53, p < 0.001) than with O2 deficit (ANF, r = 0.48, p = 0.001; BNP, r = 0.37, p < 0.01) or peak VO2 (ANF, r = -0.40; BNP, r = -0.31, p < 0.05). Noradrenaline was correlated with MRT (r = 0. 33, p < 0.05) and O2 deficit (r = 0.39, p < 0.01) but not with peak VO2 (r = -0.20, NS). Symptoms of chronic heart failure were correlated with all indices of oxygen consumption (MRT, r = 0.47, p < 0.01; O2 deficit, r = 0.39, p < 0.01; peak VO2, r = -0.48, p < 0. 01). Multivariate analysis showed that the correlation of VO2 kinetics with neurohormones and symptoms of chronic heart failure was independent of peak VO2 and other variables.. Oxygen kinetics during low intensity exercise may provide additional information over peak VO2 in patients with chronic heart failure, given the better correlation with neurohormones which represent an index of homeostasis of the cardiovascular system.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Coronary Disease; Exercise; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Oxygen Consumption; Regression Analysis; Statistics, Nonparametric; Time Factors

Atrial natriuretic peptide secretion on exercise testing may be exaggerated by left ventricular dysfunction due to multivessel coronary disease rather than by scintigraphically detectable myocardial ischemia. The measurement of plasma atrial natriuretic peptide levels during exercise test may provide additional information regarding the severity of coronary heart disease.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Coronary Disease; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Myocardial Ischemia; Physical Exertion; Radiopharmaceuticals; Stroke Volume; Thallium Radioisotopes; Tomography, Emission-Computed, Single-Photon; Ventricular Dysfunction, Left

Plasma atrial natriuretic peptide (ANP) concentration increases during ventricular arrhythmias and rapid ventricular pacing but less is known about plasma brain natriuretic peptide (BNP) and endothelin (ET-1). In the present study concentrations of ANP, the amino terminal part of the proANP (NT-proANP), BNP, and ET-1 were measured in the coronary sinus and femoral artery before and at the end of rapid ventricular pacing in 15 patients with coronary arterial disease. The changes were compared with the changes in mean arterial blood pressure, pulmonary capillary wedge pressure (PCWP), transcardiac differences in pH, pCO2, lactate, and norepinephrine. There was an increase in PCWP and a transient decrease in blood pressure after initiation of pacing. Pacing caused a decrease in ST-segment, transcardiac difference of norepinephrine, lactate extraction, pCO2 difference, and an increase in pH difference. Concentration of ANP in the coronary sinus and femoral artery and its transcardiac difference increased during pacing (P < 0.001), whereas changes in NT-proANP were small and BNP and ET-1 levels remained unchanged. The change in transcardiac ANP difference correlated with the change in lactate (r = 0.53, P < 0.05) but not that of norepinephrine, PCWP, or blood pressure. The results show that the plasma concentration of ANP increases more than that of NT-proANP during rapid ventricular pacing. Ischemia-induced release of ANP and its diminished elimination may contribute to the increased plasma ANP level.

Topics: Aged; Angina Pectoris; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Coronary Disease; Endothelin-1; Energy Metabolism; Female; Heart Rate; Heart Ventricles; Hemodynamics; Humans; Lactic Acid; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain

Thirty patients with chronic heart failure after conventional treatment for two weeks with cardiac diuretic and vasodilator were divided into two groups. There was addition of betaloc into Group A, but Group B kept the original treatment plan for 8 weeks. Group C consisted of 16 normal controls. The results showed that: 1. The level of plasma endothelin(ET), norepinephrine(NE), atrial natriuretic peptide(ANP) in Group A and B were higher than those in Group C. 2. The decreasing degrees of ET, NE, ANP, heart function score and the increasing degrees of CI and LVEF in Group A were more than those in Group B. 3. The change of ET was related to the changes of the others. Therefore, the beta-blocker may be associated with the decrease of the plasma concentration of ET, NE and ANP and improve heart function. It is considered that the degree of change of plasma ET may be the simple and reliable index which evaluate the degree of improving heart function.

Topics: Adrenergic beta-Antagonists; Adult; Atrial Natriuretic Factor; Coronary Disease; Endothelins; Female; Heart Failure; Humans; Male; Metoprolol; Middle Aged; Norepinephrine

The purpose of this study was to investigate whether atrial and brain natriuretic peptides (ANP and BNP, respectively) represent autocrine/paracrine factors and are accumulated in pericardial fluid.. ANP and BNP, systemic hormones produced by the heart, have elevated circulating levels in patients with heart failure. Recent evidence suggests that the heart itself is one of the target organs for these peptides.. With an immunoreactive radiometric assay, we measured the concentrations of these peptides in plasma and pericardial fluid simultaneously in 28 patients during coronary artery bypass graft surgery.. The pericardial levels of BNP were markedly elevated in patients with impaired left ventricular function. We investigated the correlation of ANP and BNP levels in plasma or pericardial fluid with left ventricular hemodynamic variables. None of the hemodynamic variables correlated with ANP levels in plasma or pericardial fluid. Both plasma and pericardial fluid levels of BNP were significantly related to left ventricular end-diastolic and systolic volume indexes (LVEDVI and LVESVI, respectively). In addition, BNP pericardial fluid levels had closer relations with LVEDVI (r = 0.679, p < 0.0001) and LVESVI (r = 0.686, p < 0.0001) than did BNP plasma levels (LVEDVI: r = 0.567, p = 0.0017; LVESVI: r = 0.607, p = 0.0010). BNP levels in pericardial fluid but not in plasma correlated with left ventricular end-diastolic pressure (r = 0.495, p = 0.0074).. BNP levels in pericardial fluid served as more sensitive and accurate indicators of left ventricular dysfunction than did BNP levels in plasma. Thus, BNP may be secreted from the heart into the pericardial space in response to left ventricular dysfunction, and it may have a pathophysiologic role in heart failure as an autocrine/paracrine factor.

Topics: Aged; Atrial Natriuretic Factor; Autocrine Communication; Biomarkers; Cardiac Output, Low; Cardiac Volume; Coronary Artery Bypass; Coronary Disease; Diastole; Female; Hemodynamics; Humans; Hypertension; Male; Mitral Valve Insufficiency; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Paracrine Communication; Pericardial Effusion; Radioimmunoassay; Systole; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

Superior long-term patency rates of the internal mammary artery (IMA) versus saphenous vein (SV) after coronary artery bypass grafting are well documented. Higher production rates of vasodilating and platelet-inhibiting mediators (prostacyclin and nitric oxide) by the IMA seem to have a major impact on its long-term durability and resistance to coronary artery graft disease. For the right gastroepiploic artery (RGEA) marked release of protective mediators is reported as well. The vasodilating effect of cyclic guanosine monophosphate (cGMP) released after stimulation by atrial natriuretic peptide might serve as another graft protective system. The aim of the present study was to determine cGMP release by IMA, RGEA, and SV after atrial natriuretic peptide challenge.. Samples of human IMA (n = 19), RGEA (n = 7), and SV (n = 18) discarded during coronary artery bypass grafting were stimulated with 10(-6) mol/L atrial natriuretic peptide after a resting phase in nutrient medium. Release of cGMP was determined by 125-iodide radioimmunoassay.. Basal cGMP production rates of the IMA (759.9 +/- 277.0 fmol/cm2) and RGEA (739.9 +/- 186.0 fmol/cm2) were higher than production rates of SV (281.2 +/- 64.0 fmol/cm2). Application of atrial natriuretic peptide led to a statistically significant increase of cGMP release in IMA grafts (1,939.3 +/- 778.0 fmol/cm2), whereas RGEA (618.4 +/- 141.3 fmol/cm2) and SV (221.7 +/- 64.5 fmol/cm2) remained at basal levels (p < 0.05).. From these data we conclude that the IMA in comparison with the RGEA and SV produces more extracellular cGMP when stimulated by atrial natriuretic peptide. This effect might support the cGMP-mediated protective properties of nitric oxide and could underline the extraordinary suitability of the IMA as a bypass conduit.

Topics: Abdominal Muscles; Arteries; Atrial Natriuretic Factor; Coronary Artery Bypass; Coronary Disease; Culture Techniques; Cyclic GMP; Epoprostenol; Humans; Internal Mammary-Coronary Artery Anastomosis; Iodine Radioisotopes; Mammary Arteries; Nitric Oxide; Omentum; Platelet Aggregation Inhibitors; Radiopharmaceuticals; Saphenous Vein; Vascular Patency; Vasodilator Agents

We evaluated the effects of myocardial infarction (MI) on the hemodynamics and the expression of atrial natriuretic peptide (ANP) mRNA in rats with streptozotocin-induced diabetes. Eight weeks after streptozotocin injection, the diabetic rats and age-matched nondiabetic controls underwent coronary artery ligation. One week later, the left ventricular end-diastolic pressure, systolic blood pressure, infarct size, and serum ANP levels did not differ significantly between the diabetic and nondiabetic rats. Compared with control animals without MI, the atrial ANP/beta-actin mRNA ratio in rats with MI was increased to 195% in diabetic animals and 213% in nondiabetic animals. In the left ventricle, however, the ANP/beta-actin mRNA ratio in diabetic animals with MI was increased to only 131% compared with control animals, whereas the corresponding increase in nondiabetic animals was 240% (p<0.05). Thus, the modulation of ANP mRNA expression after MI was impaired in the left ventricle, but not in the atria, of diabetic rats. A reduced myocardial expression of ANP could increase the morbidity and mortality associated with cardiovascular disorders in patients with diabetes.

Topics: Animals; Atrial Natriuretic Factor; Body Weight; Coronary Disease; Diabetes Mellitus, Experimental; Heart Atria; Heart Ventricles; Hemodynamics; Ligation; Male; Myocardial Infarction; Myocardium; Organ Size; Rats; Rats, Wistar; RNA, Messenger

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

In 15 patients with end-stage renal failure and proven coronary heart disease, profile haemodialysis with decreasing ultrafiltration rate and hyperionic, decreasing dialysate solute concentration was compared with conventional, extracorporeal bicarbonate haemodialysis (Na+D = 138 mmol/l). Body fluid distribution and the release of vasoactive hormones (plasma renin activity, aldosterone, norepinephrine, epinephrine, and atrial natriuretic peptide) were investigated. Haemodialysis with constant ultrafiltration rate and constant dialysate composition (A) was followed by two dialysis profiles: decreasing ultrafiltration rate (B) and additional hyperionic, decreasing dialysate sodium concentration (C). In all 15 patients, the dialysis procedures (A) - (C) were used for 2 weeks each with six sessions, the last being taken for investigation. Body fluid distribution was calculated. In patients with serum sodium above 136 mmol/l, the conventional dialysis (A) as well as the Uf profile (B) showed a net fluid shift from extracellular volume (ECV) to intracellular volume (ICV). Using the profile with hyperionic, decreasing Na+D (C), the reverse fluid shift with decreasing ICV was achieved not only in those with serum Na+ <136 mmol/l, but also in those with serum Na+ > or = 136 mmol/l. The release of vasoactive hormones decreased already at profile haemodialysis (B) compared with (A) and was further reduced in (C). These results would suggest, profile dialyses B and C to have less impact on the cardiovascular system in elderly patients assuming higher patient comfort compared with the standard dialysis procedure. A higher benefit was obtained in C compared with B, presumably due to the additional prevention of the ICV shift and plasma volume depletion in patients with initial serum sodium > or = 136 mmol/l using transiently hyperionic Na+D. These results show that in elderly patients, hyperionic profile haemodialysis (Na+D > Na+S) had less impact on cardiovascular regulation than conventional bicarbonate dialysis.

Topics: Aged; Aging; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Coronary Disease; Epinephrine; Extracellular Space; Female; Humans; Intracellular Fluid; Kidney Failure, Chronic; Male; Middle Aged; Norepinephrine; Renal Dialysis; Renin; Sodium; Ultrafiltration

To examine associations of N-terminal and C-terminal components of the proatrial natriuretic peptide [ANP (1-98) and ANP (99-126), respectively], with echocardiographic measurements of left ventricular structure and performance and with the function of the aortic and mitral valves in old age. To compare the predictive value of the atrial peptides and echocardiographic data for short-term mortality.. A population based survey with 1.5-year mortality follow-up.. University hospital.. Three-hundred and thirty-three people aged 78-88 years.. (i) Plasma ANP (1-98) and ANP (99-126); (ii) M-mode and Doppler echocardiographic measurements of left atrial diameter; left ventricular diameters, mass and fractional shortening; peak transmitral velocities; aortic valve area, aortic regurgitation jet length and mitral regurgitant jet area; (iii) total and cardiovascular 1.5-year mortality.. ANP (1-98) correlated with left atrial diameter (r = 0.33; P < 0.001), left ventricular mass (r = 0.19; P < 0.001), fractional shortening (r = -0.16; P < 0.01) and the early-to-atrial peak transmitral velocity ratio (r = 0.23; P < 0.001). Also, ANP (1-98) predicted the degree of aortic valve obstruction and the severity of aortic and mitral regurgitation. Associations of ANP (99-126) with echocardiographic data were much weaker. Aortic valve stenosis and ANP (1-98) were independent predictors of age- and sex-adjusted total and cardiovascular mortality at 1.5 years of entry.. Circulating ANP (1-98) correlates with left atrial size, with left ventricular mass and performance and with the severity of aortic and mitral valve dysfunction in persons representing the general elderly population. ANP (1-98) also predicts both total and cardiovascular mortality.

Topics: Aged; Aged, 80 and over; Atrial Function; Atrial Natriuretic Factor; Coronary Disease; Echocardiography, Doppler; Female; Heart; Heart Valve Diseases; Humans; Male; Prognosis; Prospective Studies; Ventricular Function, Left

Resting plasma levels of atrial natriuretic peptide and B-type natriuretic peptide rise with left ventricular dysfunction, but little is known about effects of cardiac ischaemia on atrial natriuretic peptide and B-type natriuretic peptide levels during exercise. We investigated exercise levels of atrial natriuretic peptide and B-type natriuretic peptide in patients with suspected angina to determine whether these measurements could improve non-invasive assessment of coronary disease severity.. One hundred patients performed an exercise test (Bruce protocol) within 2 weeks of coronary angiography. Plasma levels of atrial natriuretic peptide and B-type natriuretic peptide were measured at rest and at peak exercise. Multivariate regression analysis was used to assess effects of age, sex, coronary anatomy, exercise time and ventricular function on atrial natriuretic peptide and B-type natriuretic peptide levels. Increasing age and female sex were significantly associated with higher resting atrial natriuretic peptide levels; age alone was associated with higher exercise atrial natriuretic peptide levels. As expected, left ventricular end-diastolic pressure and disease of left anterior descending and circumflex coronary arteries were associated with increased resting B-type natriuretic peptide levels. However, the usual rise in B-type natriuretic peptide levels during exercise was independently reduced by disease of the right coronary artery.. This paradoxical effect of right coronary artery disease limits the value of natriuretic peptide measurements as predictors of coronary disease severity. Impaired release of B-type natriuretic peptide may reduce exercise tolerance in patients with right coronary artery disease.

Topics: Age Factors; Angina Pectoris; Atrial Natriuretic Factor; Coronary Angiography; Coronary Disease; Exercise; Exercise Test; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Sex Factors

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are homeostatic hormones secreted from the human heart which protect both cardiac and the renal function. It is well known that these hormones increase in patients along with increases in the severity of congestive heart failure or acute myocardial infarction. However, as yet there are no reports in the literature on changes of the secreted level of ANP or BNP in surgical patients undergoing cardiopulmonary bypass (CPB). We evaluated the relationship between ANP, BNP, and perioperative cardiac and renal functions in patients with heart failure caused by CPB. We selected 45 patients of elective open heart surgery. We measured plasma level of ANP in all 45 cases, and BNP in 18 cases at preoperation, postoperation, and postoperatively three days after, respectively. At the same time, the cardiac index (CI) was measured. These cases were divided into the following groups. Group A1 (n = 23): cases in which the preoperative ANP was less than 40 pg/ ml. Group A2 (n = 22): cases in which the preoperative ANP was more than 40. Group B1 (n = 8): cases in which the preoperative BNP is increased to the level of 5 times as mach as the normal level. Group B2 (n = 8): cases in which the preoperative BNP is increased to the level of 5 times as much as the normal level. Group B2 (n = 10): cases in which the preoperative BNP was more than that of 10 times as mach as normal level. We then carried out a comparative study of the perioperative cardiac and renal functions in group A1 and A2, and group B1 and B2, respectively. In the terms of preoperative cardiac and renal function, there were no significant differences between groups A1 and A2, and there were no significant differences in urinary volume during CPB or post operative CI. However, the urinary volume during CPB of group B1 was significantly more than that of B2. Furthermore, the incidence of postoperative CI in group B1. Furthermore, the incidence of postoperative CI in group B1 was significantly higher than in B2. The preoperative and post operative third day BNP level had significant negative correlations with postoperative CI and postoperative third day CI, respectively (r = -0.641, -0.514, p = 0.008, 0.012). The postoperative ANP and BNP levels tend to a mean level roughly similar to one another because of the easing of cardiac stress by surgery and postoperative management. According to these results and several instances in the literature, a

Topics: Aged; Atrial Natriuretic Factor; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Coronary Artery Bypass; Coronary Disease; Female; Heart; Heart Valve Prosthesis Implantation; Hemodynamics; Humans; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins

There is continuing interest in the link between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and cardiovascular diseases. Studies on various ethnic populations have shown conflicting evidence as to the association of the DD genotype with an increased risk of myocardial infarction. We examined the relationship between various cardiovascular hormones and ACE gene polymorphism in 149 subjects who underwent cardiac catheterization and had normal cardiac function. The distribution of the II, ID, and DD genotypes was 68, 67, and 14, respectively. Although serum ACE activity was higher in DD and ID than in II (II 9.7+/-0.5 IU/l, ID 12.2+/-0.5, DD 12.8+/-1.2; p < 0.005), other factors of the renin-angiotensin system such as plasma renin activity and plasma concentrations of angiotensin II and aldosterone were not different among the three genotypes. Plasma catecholamines did not differ among the ACE genotypes either, however, plasma atrial natriuretic peptide (ANP) was significantly lower in the subjects carrying the D allele (II 38+/-5 pg/ml, ID 26+/-2, DD 21+/-3; p < 0.05). In particular, the DD genotype showed a low plasma ANP level although the left ventricular mass index was greater than the other genotypes (II 133+/-5 g/m2, ID 137+/-6, DD 165+/-7; p < 0.05). The low plasma ANP in the DD genotype may contribute to the increased risk of cardiovascular diseases.

Topics: Atrial Natriuretic Factor; Blood Chemical Analysis; Catecholamines; Coronary Angiography; Coronary Disease; Female; Genotype; Humans; Lipids; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Renin-Angiotensin System; Stroke Volume; Ventricular Function, Left

We evaluated the analytical characteristics and clinical usefulness of a commercially available IRMA kit for measuring plasma concentrations of atrial natriuretic peptide (ANP) in healthy subjects and in patients with heart failure. The method uses two monoclonal antibodies prepared against sterically remote epitopes of the ANP molecule; the first antibody is coated on the solid-phase beads, and the second is radiolabeled with 125I. Fifty-nine healthy subjects and 77 patients with heart failure were studied. After subjects had rested 20 min in a recumbent position, blood samples were collected from a brachial vein into ice-chilled disposable polypropylene tubes containing aprotinin and EDTA. Plasma samples were immediately separated by centrifugation and stored at -20 degrees C until assay. The working range (CV <15%) was 10-2000 ng/L. The detection limit (2.13 +/- 0.91 ng/L) was similar to those reported for other IRMAs but was much better than those of RIAs. For healthy subjects, the results of this method (18.0 +/- 10.6 ng/L, range 4.7-63 ng/L, median 16.7 ng/L, n = 59) were similar to those generally reported for the most accurate methods, i.e., those using preliminary extraction and chromatographic purification of plasma samples. Measured plasma ANP was significantly associated with the severity of clinical symptoms, i.e., NYHA class (ANOVA, P <0.0001), and with the left ventricular ejection fraction (n = 62, r = 0.618, P <0.0001). Patients with severe heart failure showed greatly increased values (NYHA III-IV: 257.4 +/- 196.6 ng/L, n = 23).

Topics: Adult; Aged; Aorta; Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Coronary Disease; Drug Stability; Female; Humans; Immunoradiometric Assay; Male; Middle Aged; Posture; Pulmonary Artery; Reagent Kits, Diagnostic; Reference Values; Sensitivity and Specificity; Vena Cava, Inferior

Coronary angioplasty has been the favoured model in studying ischemic preconditioning in humans, but results have remained controversial, possibly due to some artefacts related to coronary balloon angioplasty as an ischemia model. We examined this issue by monitoring the sequential metabolic, functional and neurohumoral changes during repeated vessel occlusion in coronary angioplasty performed in patients with chronic angina pectoris. Two groups of patients undergoing two successive balloon inflations of approximately 2 min duration were studied. These balloon inflations were preceded by a short inflation performed immediately after introduction of the balloon into the stenosis. The aim of this primary inflation was to establish adequate coronary blood flow with the deflated balloon in the stenosis and to guarantee that the subsequent two balloon inflations were truly comparable in time. Group I consisted of 23 patients, in whom the changes in the degree of angina, pulmonary capillary wedge pressure (PCWP), atrial natriuretic peptide (ANP) and circulating catecholamines during the procedure were studied. The sequential changes in myocardial metabolism were monitored in group II of nine patients by determining the lactate extraction ratios and femoroarterial coronary sinus (Fa-CS) differences in pH and pCO2 before and after each balloon inflation. In group I, PCWP and total catecholamines increased similarly during both balloon inflations, but ANP remained unchanged. In group II patients the lactate extraction ratios turned negative, the Fa-CS pH-differences increased and the pCO2-differences decreased during vessel occlusions, the changes being somewhat more prominent during the second balloon inflation. To study adaptation to ischemia, the group I patients were divided into two subgroups with and without signs of ischemic dysfunction during balloon inflations (PCWP increase > 5 mmHg and < 5 mmHg, respectively), and the group II patients were divided into two subgroups with and without metabolic ischemia (lactate-producers and non-producers). The ANP levels were constantly higher in the patients demonstrating ischemic dysfunction during balloon inflations, but catecholamine levels increased only after the second balloon inflation. The anginal pain experienced by the patients and the signs of metabolic ischemia were identical during both balloon inflations. We conclude that acute ischemic preconditioning does not occur in patients with repeated vessel occl

Topics: Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Catecholamines; Constriction, Pathologic; Coronary Disease; Female; Humans; Ischemic Preconditioning, Myocardial; Male; Middle Aged; Myocardium; Pulmonary Wedge Pressure

Endothelin-1 and cyclic guanosine monophosphate (c-GMP) peripheral vein plasma levels increase during coronary angioplasty, but the reason for this increase has not been elucidated. The purpose of this study was to investigate whether these changes are related to myocardial ischaemia, or to mechanical artery injury induced during the procedure. Thirty-two patients with stable angina pectoris and a single lesion were studied. They were aged 56 +/- 8 and were undergoing balloon angioplasty. Eight arteries were totally occluded and 24 were partially occluded. Blood samples were drawn from a peripheral vein after coronary artery engagement with the guiding catheter (baseline), after the first balloon inflation, immediately after the end of the procedure, and 4 h later. In the total occlusion group endothelin-1 increased by 7% (P ns), whereas in the partial occlusion group it increased by 45% after the procedure (P < 0.001). c-GMP in the partial occlusion group increased by 41% (P < 0.001) after the procedure whereas in the total occlusion group it increased by 5% (P ns). Thus, the increase in endothelin-1 and c-GMP peripheral vein plasma levels after coronary angioplasty is related to myocardial ischaemia rather than to mechanical artery injury.

Topics: Adult; Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Coronary Disease; Coronary Vessels; Cyclic GMP; Diagnosis, Differential; Endothelins; Female; Humans; Male; Middle Aged; Myocardial Ischemia

This study examines acute changes in circulating levels of atrial natriuretic peptide (ANP) and insulin-like growth factor (IGF-1) during short periods of myocardial ischemia experienced at coronary angioplasty. Ten patients (mean age 55.7 +/- 3.9 years, nine men) undergoing angioplasty to the left anterior descending coronary artery were studied. Angioplasty of the left anterior descending coronary artery was performed with the balloon inflations maintained at 6 to 10 atm for 20 to 90 seconds. Blood was sampled from the coronary sinus for ANP, IGF-1 (both total and free), and lactate levels at (1) after catheterization of the coronary sinus, (2) after the initial left coronary angiography, (3) immediately after balloon deflation, and (4) 5 minutes after deflation. ANP levels (pmol/L +/- SEM) rose significantly at the end of balloon deflation (13.4 +/- 2.8; p < 0.01) compared with baseline levels (8.8 +/- 1.9). This rise was sustained for at least 5 minutes after balloon deflation (13.7 +/- 3.1; p < 0.01). ANP levels were not affected by the injections of angiographic contrast media. Free IGF-1 levels rose after injections of radiographic contrast but not after balloon inflation or deflation. Total IGF-1 levels did not change significantly at any of the sampling times. Lactic acid (mmol/L) levels rose at the end of balloon inflation (2.66 +/- 0.6) compared with baseline (2.13 +/- 0.7; p < 0.05) but returned to normal within 5 minutes of balloon deflation. Neither lactic acid levels nor release of ANP or IGF-1 correlated with the initial left ventricular end-diastolic pressure or the degree of electrocardiographic ST depression during the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Constriction, Pathologic; Coronary Disease; Female; Humans; Insulin-Like Growth Factor I; Lactates; Lactic Acid; Male; Middle Aged; Myocardial Ischemia; Recurrence

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations were measured in patients with dialysis-dependent chronic renal failure and in patients with coronary artery disease exhibiting normal or elevated left ventricular end-diastolic pressure (LVEDP) (n = 30 each). Blood samples were obtained from the arterial line of the arteriovenous shunt before, 2 h after the beginning of, and at the end of hemodialysis in patients with chronic renal failure. In patients with coronary artery disease arterial blood samples were collected during cardiac catheterization. BNP and ANP concentrations were determined by radioimmunoassay after Sep Pak C18 extraction. BNP and ANP concentrations decreased significantly (P < 0.001) during hemodialysis (BNP: 192.1 +/- 24.9, 178.6 +/- 23.0, 167.2 +/- 21.8 pg/ml; ANP: 240.2 +/- 28.7, 166.7 +/- 21.3, 133.0 +/- 15.5 pg/ml). The decrease in BNP plasma concentrations, however, was less marked than that in ANP plasma levels (BNP 13.5 +/- 1.8%, ANP 40.2 +/- 3.5%; P < 0.001). Plasma BNP and ANP concentrations were 10.7 +/- 1.0 and 60.3 +/- 4.0 pg/ml in patients with normal LVEDP and 31.7 +/- 3.6 and 118.3 +/- 9.4 pg/ml in patients with elevated LVEDP. These data demonstrate that BNP and ANP levels are strongly elevated in patients with dialysis-dependent chronic renal failure compared to patients with normal LVEDP (BNP 15.6-fold, ANP 2.2-fold, after hemodialysis; P < 0.001) or elevated LVEDP (BNP 6.1-fold, ANP 2.0-fold, before hemodialysis; P < 0.001), and that the elevation in BNP concentrations was more pronounced than that in ANP plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Coronary Disease; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Renal Dialysis; Ventricular Pressure

The regulation of cytosolic Ca2+ concentration during excitation-contraction coupling is altered in the failing human heart. Previous studies have focused on disturbances in Ca2+ release and reuptake from the sarcoplasmic reticulum (SR), whereas functional studies of the cardiac Na(+)-Ca2+ exchanger, another important determinant of myocyte homeostasis, are lacking for the failing human heart. Using a cardiac Na(+)-Ca2+ exchanger cDNA recently cloned from a guinea pig cDNA library, we investigated the gene expression of the cardiac Na(+)-Ca2+ exchanger in relation to the SR Ca(2+)-ATPase. Expression of both genes was quantified in left ventricular myocardium from 24 failing human cardiac explants and 7 control heart samples in relation to beta-myosin heavy chain mRNA by slot blot analysis. Compared with patients with nonfailing hearts, patients with dilated cardiomyopathy (DCM, n = 13) showed a 55% increase in Na(+)-Ca2+ exchanger mRNA levels (P < .05 versus control value) and a 41% increase in patients with coronary artery disease (CAD, n = 11). In the same hearts, SR Ca(2+)-ATPase mRNA levels were decreased by 50% in DCM and by 45% in CAD (P < .05 for both versus control value). There was a positive correlation between Na(+)-Ca2+ exchanger and SR Ca(2+)-ATPase mRNA levels both in normal and failing human hearts, albeit with different slopes and intercepts of the regression line. The Na(+)-Ca2+ exchanger protein levels as assessed by Western blot analysis and normalized to beta-myosin heavy chain protein were increased in DCM and CAD (P < .05 and P < .01 versus control value, respectively), whereas SR Ca(2+)-ATPase protein levels were reduced (P < .05 for both groups versus control values). Thus, the Na(+)-Ca2+ exchanger gene expression is enhanced in failing human hearts and may, in part, compensate for the depressed SR function with regard to diastolic Ca2+ removal.

Topics: Adult; Animals; Atrial Natriuretic Factor; Base Sequence; Blotting, Western; Calcium; Calcium-Transporting ATPases; Cardiomyopathy, Dilated; Carrier Proteins; Coronary Disease; Female; Gene Expression; Gene Library; Guinea Pigs; Humans; Male; Middle Aged; Molecular Sequence Data; Myocardium; Myosins; Oligodeoxyribonucleotides; Rats; Reference Values; Restriction Mapping; RNA, Messenger; Sarcoplasmic Reticulum; Sodium; Sodium-Calcium Exchanger

This paper reports the therapeutic effect of microwave acupuncture (MWA) and its influence on the plasma level of cardionatrion. Twenty-eight cases with coronary heart disease (CHD) were systemically observed and investigated. Atrial natriuretic polypeptides (ANP) were determined by radioimmunoassay. Plasma level of ANP was elevated, the rising rate being 100%. The therapeutic effect of MWA in the 28 cases with CHD was 85.7%, the ECG improving rate was 82.2%. Effect of MWA was briefly discussed. The authors consider that the therapeutic effect of MWA in the treatment of CHD could be ascertained, and the measurement of plasma ANP concentration is a useful method and an objective parameter for further research.

Topics: Acupuncture Points; Acupuncture Therapy; Aged; Atrial Natriuretic Factor; Coronary Disease; Female; Humans; Male; Microwaves; Middle Aged

To evaluate the behavior of circulating endothelin and atrial natriuretic peptide (ANP) during coronary artery bypass graft (CABG) surgery, blood samples from patients with coronary artery disease (n = 8) were investigated before, during and after operation. Plasma levels of endothelin and ANP were determined using the radioimmunoassay method. Baseline plasma levels were compared to those of normal volunteers (n = 6). Left ventricular function at rest and as a response to isometric exercise was evaluated using radionuclide ventriculography before and after coronary bypass surgery. The mean endothelin value was found to be within normal limits, however the mean ANP value was slightly higher than control. Patients had significantly improved left ventricular systolic and diastolic function after surgery. The mean endothelin level was higher than initial values immediately after extra-corporeal circulation and returned to initial values in two hours. However, ANP values were increased and remained higher than initial values. Baseline endothelin values were negatively correlated with systolic function parameters, whereas endothelin and heart rate had a positive correlation before extra-corporeal circulation. Coronary artery bypass graft surgery may cause an increase in the circulating endothelin level either due to endothelial injury or due to myocardial ischemia and hypothermia. Following surgery, increased endothelin levels returned to normal values immediately.

Topics: Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Coronary Artery Bypass; Coronary Disease; Endothelins; Female; Gated Blood-Pool Imaging; Heart Rate; Humans; Male; Middle Aged; Renin; Ventricular Function, Left

The concentrations of plasma ANF and plasma and urinary cyclic GMP were measured at rest and during exercise in 12 normal subjects (reference group) and 20 patients with coronary artery disease (coronary group). In both groups, plasma ANF and c GMP increased during exercise and fell one hour after (F = 3.8, p = 0.029 and F = 13.3, p = 0.0001, respectively) whereas the urinary c GMP increased one hour after exercise (F = 5.3, p = 0.029). In the control group, ANF increased on effort and fell during recovery to above its resting value whereas the plasma c GMP remained unchanged throughout the test. In the coronary group, no significant increase in ANF was observed on effort (wide dispersion of values) whereas the c GMP increased during effort and fell to below testing value during the recovery phase. The ANF of the coronary group was globally higher than the ANF of the control group (F = 4.7, p = 0.04). The plasma c GMP of the coronary group was comparable to that of the controls (F = 2.1, p = 0.15) despite higher concentrations at rest (p < 0.05) and during exercise (p < 0.05). However, there was a positive interaction between the efforts of exercise and the pressure of coronary disease on the concentration of plasma c GMP (F = 6.7, p = 0.0024). There was no difference in urinary c GMP between control and coronary subjects (F = 1, p = 0.33).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Natriuretic Factor; Coronary Disease; Cyclic GMP; Female; Humans; Male; Middle Aged; Physical Exertion; Reference Values

Percutaneous transluminal coronary angioplasty (PTCA) is frequently associated with vasoconstriction involving large vessels as well as microcirculation, but the potential mechanisms remain poorly defined. In this study, we tested the hypothesis that endothelial disruption during PTCA is associated with an increase in circulating levels of endothelin, a potent endothelium-derived vasoconstrictor peptide. Circulating levels of endothelin and other potential vasoactive mediators such as atrial natriuretic factor, epinephrine and norepinephrine were measured immediately before and after PTCA in 23 patients with coronary artery disease. Although there was no change in the endothelin levels after angiography alone (43 +/- 5 vs 44 +/- 7 pg/ml, p = 0.5), there was a significant increase after PTCA (32 +/- 8 to 37 +/- 10 pg/ml, p < 0.005). The increase in endothelin was associated with a significant increase in atrial natriuretic factor (78 +/- 57 to 129 +/- 131 ng/ml, p = 0.01) and a decrease in epinephrine and norepinephrine levels (111 +/- 64 to 59 +/- 36 pg/ml, p = 0.005, and 1,131 +/- 500 to 811 +/- 311 pg/ml, p = 0.003, respectively). Circulating levels of endothelin did not correlate with the percent coronary stenosis before or after PTCA or the presence or absence of angiographically visible thrombus. These findings suggest that endothelial injury during PTCA may be associated with increased circulating levels of endothelin and its counter-regulatory hormone, atrial natriuretic factor, and also with a reciprocal decrease in epinephrine and norepinephrine levels. Thus, these humoral changes may modulate changes in coronary vascular tone after PTCA.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Confounding Factors, Epidemiologic; Coronary Disease; Endothelins; Epinephrine; Female; Humans; Linear Models; Male; Middle Aged; Norepinephrine

The present study was designed to investigate whether brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations correlate with left ventricular end-diastolic pressure (LVEDP), pulmonary capillary wedge pressure (PCWP), diastolic pulmonary arterial pressure (DPAP), right atrial pressure (RAP), or ejection fraction (EF). Plasma BNP and ANP levels were determined by commercial radioimmunoassays (Peninsula) after Sep Pak C18 extraction in blood samples withdrawn from the pulmonary artery and the left ventricle or from the left ventricle and the femoral vein in 85 patients undergoing diagnostic cardiac catheterization. Linear and nonlinear regression analysis and the paired sample t-test were applied to the data. Pulmonary arterial plasma BNP and ANP levels showed a close nonlinear correlation with LVEDP (BNP: r = 0.94, p < 0.001; ANP: r = 0.81, p < 0.001), a significant linear correlation with PCWP, DPAP, and RAP, and a significant negative correlation with EF. ANP concentrations decreased significantly from the pulmonary artery to the left ventricle and from the left ventricle to the femoral vein (p < 0.001). BNP levels also decreased significantly between the left ventricle and the femoral vein (p < 0.001), but there was no significant difference between pulmonary arterial and left ventricular BNP concentrations. BNP and ANP concentrations correlated significantly between pulmonary arterial and left ventricular blood samples (BNP: r = 0.99, ANP: r = 0.93, p < 0.001) and between left ventricular and peripheral blood samples (BNP: r = 0.99, ANP: r = 0.94, p < 0.001). The present data suggest that peripheral plasma BNP and ANP levels are useful non-invasive indices of cardiac performance.

Topics: Atrial Function, Right; Atrial Natriuretic Factor; Cardiac Catheterization; Coronary Disease; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Pulmonary Wedge Pressure; Radioimmunoassay; Regression Analysis; Stroke Volume; Ventricular Function, Left

We assayed the concentrations of atrial natriuretic factor and guanosine 3',5'-phosphate in the plasma and urine of six healthy subjects, 12 patients with coronary artery disease and 11 patients with congestive heart failure. Patients with coronary artery disease had normal levels of atrial natriuretic factor in the plasma and urine and a normal excretion of guanosine 3',5'-phosphate, while those with congestive heart failure had a raised level of atrial natriuretic factor in the plasma, an increased excretion of 3',5'-guanosine phosphate and normal excretion of atrial natriuretic factor. Thus, measurement of atrial natriuretic factor in the urine can not replace the assay of the peptide in plasma.

Topics: Aged; Atrial Natriuretic Factor; Coronary Disease; Cyclic GMP; Female; Heart Failure; Humans; Male; Middle Aged; Reference Values

Ten patients with coronary artery disease and stable angina (mean age fifty-seven) were included in the study. Five of the patients had normal left ventricular function, 5 had local hypokinesia or akinesia; 8 had one-stem and 2 had two-stem disease, but all had left anterior descending (LAD) lesions ranging from 75% to 100%. Ejection fraction varied between 35% and 75% (mean 59%). Immunoreactive atrial natriuretic polypeptide (ANP) levels in the femoral vein (FV) and the coronary sinus (CS) were measured before, immediately after, and up to twenty-four hours after percutaneous transluminal coronary angioplasty (PTCA) of the LAD. ANP secretion increased by 83% (FV) and 11% (CS) within minutes after PTCA and reached control levels after thirty to sixty minutes. In patients with hypokinesia of the anterior wall, ANP secretion was significantly lower, 48% (FV) and 11% (CS) respectively. ANP secretion during PTCA was higher in patients with concomitant increase in pulmonary capillary pressure (PCP) but was also observed without an increase of PCP, suggesting ventricular ANP secretion. IN conclusion, transient myocardial ischemia leads to immediate ANP secretion even in the absence of significant pressure elevation in the left atrium. As a part of the continuous medical education program of the American College of Angiology the second part of the paper reviews the mechanisms that allow the ischemic heart to counteract the ischemic condition and thus to escape from myocardial infarction. A review of this subject is presently not available in the literature.

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Atrial Function, Left; Atrial Natriuretic Factor; Coronary Disease; Female; Humans; Male; Middle Aged; Myocardial Contraction; Myocardial Ischemia; Myocardium; Oxygen Consumption; Pulmonary Wedge Pressure; Time Factors; Ventricular Function, Left

Topics: Angina Pectoris; Atrial Natriuretic Factor; Coronary Disease; Electrocardiography; Female; Humans; Male; Middle Aged; Physical Exertion; Rest

The inter-relationships between ischaemia-induced metabolic changes and atrial natriuretic peptide (ANP) release were studied in 18 patients undergoing elective percutaneous transluminal coronary angioplasty (PTCA). Transcardiac differences in ANP, lactate, pH, pCO2 and O2 saturation were analysed before and after balloon inflation. The patients were divided into ischaemia and non-ischaemia groups on the basis of the change in lactate extraction ratio during balloon inflation. The ischaemia group (patients with a decrease in lactate extraction ratio) showed an increase of 27 +/- 15 pg.ml-1 in the transcardiac ANP difference, whereas a decrease of 27 +/- 17 pg.ml-1 occurred in the non-ischaemia group (no decrease in lactate extraction ratio). The change between the two patient groups was statistically significant (P < 0.05). Metabolic 'pre-conditioning' was not observed in patients with successive dilatations, therefore data from all the dilatations were combined and evaluated by regression analysis. A correlation coefficient of 0.40 (P < 0.05) was obtained between the PTCA-induced changes in transcardiac ANP and lactate differences. We conclude that transient myocardial ischaemia induced by PTCA increases circulating ANP concentrations in patients with signs of metabolic ischaemia, but not in those without.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Coronary Circulation; Coronary Disease; Energy Metabolism; Female; Heart Rate; Humans; Lactates; Lactic Acid; Male; Middle Aged; Myocardial Ischemia; Myocardium

Recent studies suggest that plasma levels of alpha-hANP may reflect the severity of heart failure, but mechanism whereby ANP secretion increase is not known. Changes in alpha-hANP concentration in the arterial (A-ANP) and coronary sinus blood (CS-ANP) during and after the cardiopulmonary bypass (CPB) were measured to investigate the role of ANP in patients undergoing cardiac surgery. Fifteen patients were divided into 2 group; Group I, valvular heart disease (n = 9), Group II, coronary artery disease (n = 6). Both A-ANP and CS-ANP were significantly higher in the Group I than Group II before and during CPB. The difference between two groups decreased and was insignificant after CPB. The CS-ANP was twice as high as A-ANP at simultaneous sampling point. Significant correlations between the changes in PCWP (delta PCWP) and delta A-ANP (p < 0.01), delta RAP and delta A-ANP (p < 0.02) and an inverse linear correlation between CI and A-ANP (p < 0.01) were observed. Not a significant correlation was found between ANP and urine volume, urinary sodium excretion and other renal functional parameters during and after CPB. Hypothermia and the use of mannitol in large quantities were considered to be factors. In the Group I, A-ANPs were also measured in the postoperative follow-up period. A-ANP remained elevated above 100 pg/ml in patients with poor and decreased below 100 pg/ml with good prognostic signs 3 to 6 months postoperatively. From these results, it is suggested that alpha hANP is secreted from the atrial wall to the coronary sinus vein and the levels of alpha-hANP in the perioperative and follow-up period after heart surgery, especially in the valvular heart disease, are considered to reflect the cardiac performance.

Topics: Aortic Valve; Arteries; Atrial Natriuretic Factor; Cardiopulmonary Bypass; Coronary Disease; Coronary Vessels; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve

We studied the effect of a volume load induced by a 45 degrees Trendelenburg position on atrial natriuretic peptide (ANP) secretion in awake and anaesthetized patients with coronary artery disease undergoing aortocoronary bypass surgery. ANP was measured in different parts of the circulation before and after induction of high dose fentanyl anaesthesia at fixed times prior to and after extracorporeal circulation. METHOD. In eight patients with coronary artery disease (NYHA classification II-III), who received neither diuretic nor positive inotropic therapy, ANP was measured in the various parts of the circulation: in a peripheral vein, a radial artery, in the pulmonary artery and in the coronary sinus. The measurements were made in the supine and 45 degrees Trendelenburg position. Measurements of mean arterial pressure (MAP), central venous pressure (RAP), pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), cardiac index (CI) and heart rate (HR) were taken simultaneously. The measurements were taken in the awake patient, during steady-state high-dose fentanyl anaesthesia with 50% O2 in N2O and after extracorporeal circulation. RESULTS. Compared to measurements in a control group, ANP levels were significantly higher in all parts of the circulation in patients with coronary artery disease, although clinical symptoms of heart failure were absent. After extracorporeal circulation, significantly higher levels of ANP were found at all measurement sites; however the concentration gradient of ANP between coronary sinus and arterial or venous blood was reduced. In awake and anaesthetized patients a change in body position, causing a significant increase in filling pressures, did not produce an increase in ANP levels at all measurement sites. The induction of high-dose fentanyl anaesthesia did not have an influence on plasmatic ANP levels. CONCLUSION. The results of this study lead to the following conclusions: 1. ANP levels in patients with CAD are increased, even if clinical heart failure symptoms are absent. 2. ANP is secreted in the coronary vessels. Following dilution in the atrial blood, it is metabolized to inactive compounds in the periphery. 3. Basic ANP levels are not changed by high-dose fentanyl anaesthesia. Marked increases of the filling pressures do not correlate with atrial ANP levels either before or after induction of anaesthesia. 4. After extracorporeal circulation ANP levels are significantly increased in all parts of t

Topics: Aged; Anesthesia; Atrial Natriuretic Factor; Coronary Artery Bypass; Coronary Disease; Female; Fentanyl; Hemodynamics; Humans; Male; Middle Aged; Posture

To study neurohumoral control mechanisms of the hemodynamic response to ventricular tachycardia, arterial blood pressure, plasma atrial natriuretic peptide (ANP) and catecholamine levels were monitored during simulated ventricular tachycardia before and after administration of beta blockade. Tachycardia was simulated by ventricular pacing at 150 beats/min for 150 seconds in 9 patients without and 14 with angiographically demonstrable coronary artery disease (CAD). The effects of intravenous propranolol (0.15 mg/kg) were evaluated in 7 control subjects and in 13 patients with CAD. Arterial blood pressure decreased to its minimum within 5 seconds after onset of pacing in all patients, the decrease being 27 and 30% (p = not significant) in the groups without and with CAD, respectively. Propranolol did not affect the initial decline, but blunted subsequent recovery. The ANP baseline levels were similar in both groups, increasing by 60% (p less than 0.05) and 71% (p less than 0.02) in the groups without and with CAD, respectively, during ventricular pacing. After administration of propranolol the increase in ANP was 180% in both groups. Rapid ventricular pacing did not affect catecholamine levels before propranolol, but after propranolol norepinephrine increased by 71 (p less than 0.02) and 97% (p less than 0.01) in patients without and with CAD, respectively. There was a significant correlation (r = 0.53, p = 0.001) between pacing-induced ANP and norepinephrine changes, but changes in arterial blood pressure did not correlate with those in either of these hormones. Thus, beta-adrenergic blockade blunts blood pressure recovery during simulated ventricular tachycardia. However, this is partly counterbalanced by increased circulating norepinephrine levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analysis of Variance; Atrial Natriuretic Factor; Blood Pressure; Cardiac Pacing, Artificial; Catecholamines; Coronary Disease; Epinephrine; Female; Humans; Male; Middle Aged; Norepinephrine; Propranolol; Regression Analysis; Time Factors

Atrial natriuretic factor release during transient myocardial ischemia was investigated in 29 patients with coronary artery disease and symptoms of angina (Canadian Cardiovascular Association classes II-III). Eleven patients (group I) underwent single-vessel percutaneous transluminal coronary angioplasty. Repeat determinations of mean pulmonary artery wedge pressure and blood sampling from pulmonary artery for atrial natriuretic factor measurements were performed at baseline, and at 2, 5, and 15 minutes after percutaneous transluminal coronary angioplasty was begun. Baseline atrial natriuretic factor levels (34.6 +/- 4.5 pg/ml) rose to 56.3 +/- 7.3 pg/ml (p = 0.02) and decreased at 5 minutes (43.7 +/- 5.7 pg/ml, not significant) and 15 minutes (35.3 +/- 4.4 pg/ml, not significant). Changes in atrial natriuretic factor concentrations were significantly correlated with those in mean pulmonary artery wedge pressure (2 minutes: r = 0.69, p = 0.02; 5 minutes: r = 0.90, p less than 0.001). In group II (n = 10) the increase in atrial natriuretic factor after dye load occurred later (baseline: 25.8 +/- 2.1; 60 minutes: 40.6 +/- 2.6 pg/ml; p = 0.005) than that observed in group I after percutaneous transluminal coronary angioplasty. In group III, atrial natriuretic factor during angina rose as early (baseline 11.3 +/- 1.3; 5 minutes: 20 +/- 2.3 pg/ml; p = 0.006) as after percutaneous transluminal coronary angioplasty. Results indicate that transient myocardial ischemia stimulates atrial natriuretic factor release, probably through changes in cardiac function.

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Coronary Disease; Female; Heart Rate; Humans; Male; Middle Aged; Pulmonary Wedge Pressure

The correlations between myocardial redox and energy states and atrial natriuretic peptide (ANP) secretion were studied in the perfused rat heart by exposing the hearts to global and low-flow ischemia for varying periods. Atrial and ventricular energy states and immunoreactive ANP in the effluent perfusate were measured. The basal secretion rate of ANP was 2.7 +/- 0.2 ng/min.g dry wt and it was stimulated 2.6 +/- 0.4, 4.0 +/- 0.6, 11.2 +/- 2.1 and 13.3 +/- 3.2-fold (means +/- S.E.) at the time point of 2 min after 5, 10, 20 and 30-min periods of ischemia, respectively. The increase in ANP release during the post-ischemic period was statistically significant and showed positive linear correlation with the atrial and ventricular lactate/pyruvate ratios (r = 0.92 and 0.89, respectively) and negative non-linear correlation with the atrial and ventricular phosphorylation potentials (r = -0.97 and -0.94, respectively). In agreement with the enhanced release of ANP after global ischemia, low-flow ischemia also increased ANP release. Cellular damage was not evidently responsible for the increased secretion, because only ANP1-28, the processed form of the peptide, was detected in the perfusates and no processing of exogenous proANP during or after ischemia was observed. These results indicate that myocardial ischemia stimulates ANP release and suggest that cellular redox and energy states may be linked to ANP release during ischemia/reperfusion. Thus, ANP release during and after ischemia in vivo may be due not only to atrial distention but also to changes in energy metabolism.

Topics: Animals; Atrial Natriuretic Factor; Coronary Disease; Energy Metabolism; Female; Myocardial Reperfusion; Myocardium; Oxidation-Reduction; Oxygen Consumption; Rats; Rats, Inbred Strains

Infusions of atrial natriuretic factor (ANF) are frequently associated with attenuated natriuretic and diuretic responses in patients with congestive heart failure. However, ANF infusions result in systemic vasodilation, suggesting that end organ responsiveness to ANF may not be uniformly decreased. To determine if the vasodilator effects of ANF were altered in heart failure, strain-gauge plethysmography was utilized to measure forearm blood flow responses to the intraarterial infusion of ANF using a dose range that was low enough to avoid systemic effects. In 9 control subjects, ANF infusions of 0.5, 1.0, 2.0 and 4.0 micrograms/min/100 ml forearm volume significantly increased forearm blood flow from 3.21 +/- 1.71 to 5.69 +/- 3.14, 6.20 +/- 2.57, 6.64 +/- 2.53 and 6.97 +/- 2.49 ml/min/100 ml forearm volume, respectively (all p less than 0.01). In 7 patients with heart failure, ANF infusion significantly increased forearm blood flow from 2.19 +/- 0.98 to 3.18 +/- 1.70, 3.76 +/- 2.0 and 4.42 +/- 2.80 ml/min/100 ml forearm volume for the 0.5, 1.0 and 2.0 micrograms doses, respectively (all p less than 0.05). By analysis of variance, the forearm blood flow responses pooled over all doses were not significantly different between the 2 groups. At the 2.0 micrograms dose, the peak increase in forearm blood flow in normal subjects represented a 107% increase over baseline compared with a 102% increase in patients with heart failure. In summary, these data demonstrate that intraarterial administration of ANF in patients with heart failure resulted in dose-related increases in forearm blood flow. The responses were not significantly different from normal subjects expressed both as an absolute response and as a percent increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Analysis of Variance; Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Coronary Disease; Dose-Response Relationship, Drug; Female; Forearm; Heart Failure; Humans; Male; Middle Aged; Plethysmography; Regional Blood Flow; Vasodilation

Human atria through release of atrial natriuretic peptide play an important role in extracellular fluid homeostasis. This study investigates the perioperative role of atrial natriuretic peptide, renin, angiotensin, aldosterone, and vasopressin in patient response to cardiopulmonary bypass after coronary artery bypass operations. Serum levels of these hormones were measured, along with hemodynamic profiles, urine output, and urine electrolytes, before induction of anesthesia, after discontinuation of cardiopulmonary bypass, 1 hour postoperatively, and 3 hours postoperatively. Serum levels of atrial natriuretic peptide were found to be significantly elevated immediately after discontinuation of cardiopulmonary bypass. These elevations did not correspond temporally to elevated central venous pressure or tachycardia. Significant natriuresis and diuresis were observed during the first postoperative hour. This diuresis failed to correspond temporally with alterations noted in serum levels of atrial natriuretic peptide, renin, angiotensin, aldosterone, and vasopressin. The mechanism responsible for the increases in serum atrial natriuretic peptide and the postoperative natriuresis and diuresis after cardiopulmonary bypass remain unknown.

Topics: Aged; Atrial Natriuretic Factor; Cardiopulmonary Bypass; Coronary Disease; Diuresis; Female; Heart Arrest, Induced; Hemodynamics; Homeostasis; Humans; Male; Middle Aged; Natriuresis; Postoperative Period; Time Factors

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

Doppler echocardiographic transmitral peak early velocity normalized to the time-velocity integral during diastole is equivalent to volumetric peak filling rate normalized to stroke volume. To compare the pathophysiologic validity of normalized and nonnormalized peak early flow velocity, pulsed Doppler echocardiography with simultaneous high fidelity left ventricular pressure measurements was performed in 52 patients with coronary artery disease. Left ventricular loading conditions were changed by intravenous administration of norepinephrine in 15 patients and synthetic atrial natriuretic polypeptide in 15 others. Norepinephrine increased nonnormalized and normalized peak early flow velocities in association with significantly elevated end-diastolic, peak systolic and mitral valve opening pressures and decelerated the time constant of left ventricular isovolumetric pressure decline. Atrial natriuretic polypeptide did not change either nonnormalized or normalized peak early flow velocity, despite significant reductions in end-diastolic, peak systolic and mitral valve opening pressure and an accelerated time constant. Normalized peak early flow velocity showed the highest univariate correlation with long-term change in mitral valve opening pressure (n = 52, r = 0.67, p less than 0.0001). It provided a modest univariate correlation (n = 30, r = 0.74, p less than 0.0001) with immediate change in mitral valve opening pressure during norepinephrine infusion, whereas this correlation was lower (n = 30, r = 0.57, p less than 0.001) during polypeptide infusion. However, multivariate regression analysis relating normalized peak velocity with long- and short-term changes in end-diastolic, peak systolic and mitral valve opening pressures, time constant and constant of left ventricular chamber stiffness improved the correlation coefficients (r = 0.80 to 0.85, all p less than 0.0001). In contrast, neither univariate nor multivariate correlations of nonnormalized velocity with long- and short-term changes in these hemodynamic variables were satisfactory. Thus, nonnormalized peak early flow velocity does not directly reflect underlying hemodynamic changes in humans. Normalization to mitral stroke volume clarifies the dependence of peak early flow velocity on the determinants of early diastolic filling. When left ventricular early diastolic filling is evaluated by Doppler echocardiography, normalized peak early flow velocity should be taken into consideration.

Topics: Atrial Natriuretic Factor; Blood Flow Velocity; Cineangiography; Coronary Circulation; Coronary Disease; Echocardiography, Doppler; Evaluation Studies as Topic; Female; Hemodynamics; Humans; Male; Middle Aged; Mitral Valve; Norepinephrine; Regression Analysis; Stroke Volume

We determined the time-course of the release of atrial natriuretic factor (ANF) during cardiopulmonary bypass (CPB) in six patients undergoing coronary artery bypass (CAD) and eight patients undergoing valve replacement for mitral stenosis (MS). Before CPB, the arterial ANF was significantly higher in MS patients than in CAD patients (243 +/- 38 and 29 +/- 5.8 pg/ml respectively, P less than 0.01). With the onset of CPB, the acute pressure unloading of the atria induced a significant, rapid decrease of ANF only in MS patients (-64% of pre-CPB value at 5 min) and no major changes in CAD patients. Clamping of the aorta induced a further progressive reduction of ANF release to almost zero in both groups. Readmission of coronary flow to the empty atria with declamping resulted in an increase in the plasma level of ANF in both groups to reach the concentration present in MS patients before CPB. After CPB, the ANF levels decreased in CAD patients while remaining elevated in MS patients. These data suggest that ANF release from human atria depends on atrial filling pressure and other unknown factors.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiopulmonary Bypass; Coronary Disease; Female; Heart Valve Prosthesis; Hemodynamics; Humans; Intraoperative Complications; Male; Middle Aged; Mitral Valve Stenosis; Myocardial Reperfusion Injury; Postoperative Complications; Reference Values; Saphenous Vein

In 34 patients undergoing routine coronary angioplasty, concentrations of atrial natriuretic peptide (ANP), plasma renin (PR), and plasma aldosterone (PA) were estimated before, during, and after vessel occlusion and were correlated with hemodynamic changes. For the group as a whole, averaged right atrial pressure rose significantly (p less than 0.001) from 4.4 +/- 1.8 mm Hg at baseline to 6.7 +/- 3.0 mm Hg during vessel occlusion, and average right atrial ANP concentrations increased significantly (p less than 0.005) from 50.1 +/- 18.8 pg/ml to 59.7 +/- 21.4 pg/ml during balloon inflation. Data analysis of subgroups did not show any differences in right atrial pressure elevations between patients with left anterior descending artery (LAD) or right coronary artery (RCA) disease; ANP elevation was significant only in patients with LAD occlusion (p less than 0.001). In individual patients no statistically significant correlations were found to be present between changes in right atrial pressures and changes in atrial ANP concentrations. During vessel occlusion, PR dropped from 0.86 +/- 1.11 ng/ml/hr to 0.65 +/- 0.85 ng/ml/hr (p less than 0.001) in all patients, and PA decreased from 63.0 +/- 50.9 ng/ml to 52.2 +/- 43.4 ng/ml (p less than 0.01). Our data support the concept that, although an increase in right atrial pressure leads to ANP release in the majority of patients, atrial pressure and stretch are not the only regulatory factors of ANP release in humans.

Topics: Aldosterone; Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Blood Pressure; Coronary Disease; Heart Atria; Humans; Middle Aged; Renin

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

Atrial natriuretic factor (ANF) release is modulated by several haemodynamic factors, including ventricular and atrial wall stretch. Dipyridamole infusion, which is commonly used as a pharmacological stressor in patients with coronary artery disease, can acutely increase ventricular and atrial pressure via myocardial ischaemia. The aim of this study was to assess whether dipyridamole infusion (up to 0.84 mg kg-1 over 10') can affect ANF release in man. Nineteen patients (13 men, 6 women) with a history of chest pain were studied. Their drug regimen was interrupted and instead they were administered a dipyridamole infusion, combined with two-dimensional echocardiography and 12-lead ECG monitoring. Plasma ANF was measured by RIA while the patients rested, and after dipyridamole infusion. Eight patients had no evidence of myocardial ischaemia, as measured by electrocardiographic and/or echocardiographic criteria, during dipyridamole infusion: among them, ANF values were similar while they were at rest and at peak dipyridamole administration (23.9 +/- 9.5 vs 23.4 +/- 6.9 pg ml-1, P = ns). Eleven patients had dipyridamole-induced transient ischaemia (regional ventricular dyssynergy and/or ST segment depression): among them, ANF values rose significantly at peak dipyridamole administration (31.8 +/- 13.8 vs 65.5 +/- 36.4, P less than 0.01). We conclude that dipyridamole infusion does not increase ANF release in man in the absence of ischaemia. The induction of myocardial ischaemia acutely increases ANF release, probably through a rise in ventricular and atrial wall stress.

Topics: Atrial Natriuretic Factor; Coronary Angiography; Coronary Disease; Dipyridamole; Female; Humans; Male; Middle Aged

Percutaneous transluminal coronary angioplasty provides the opportunity to study ischemic alterations in the setting of acute transient coronary occlusions in man. In 124 patients changes in hemodynamics, global and regional left ventricular function, collateral flow and mitral valve incompetence, alterations in the concentrations of atrial natriuretic peptide, renin and aldosterone concentrations as well as metabolic changes were studied. In 39 patients with single vessel disease presenting with isolated stenosis in the left anterior descending artery (LAD), but normal global as well as regional left ventricular function hemodynamic and ventriculographic abnormalities were found to be present during intraluminal occlusion for 60 seconds. The mean heart rate increased from 76.3 +/- 15.8 to 80.4 +/- 14.9 beats/min (p less than 0.01) and the mean end diastolic volume index (EDVI) increased from 92.8 +/- 17.1 to 104.6 +/- 17.1 ml/m2 (p less than 0.001). The end systolic volume index (ESVI) also increased from 27.5 +/- 11.3 to 48.2 +/- 12.1 ml/m2 (p less than 0.001). By contrast, mean global left ventricular ejection fraction showed a highly significant reduction from 70.7 +/- 8.8 to 53.8 +/- 7.9% (p less than 0.001). This was paralleled by a reduction in circumferential fibre shortening velocity (VCF) from 1.44 +/- 0.48 to 0.81 +/- 0.31 L/s during LAD occlusion (p less than 0.001). Mean end diastolic left ventricular pressure (EDP) rose significantly from 17.0 +/- 6.8 to 30.1 +/- 9.0 mm Hg (p less than 0.001). In the left ventricular segments supplied by the LAD there was a significant drop in regional shortening. Compensatory increase of regional wall motion in the segments supplied by the right coronary artery (RCA) or circumflex artery (ACX) could not be documented. In the group as a whole the end systolic pressure-volume curves were found to be shifted to the right and the end diastolic pressure-volume curves were elevated, indicating a decrease of contractility and an increase of chamber stiffness. During four consecutive balloon inflations 60 patients showed a significant (p less than 0.001) reduction in peak dp/dtmax and peak dp/dtmin values within the first 30 seconds after coronary artery occlusion and a highly significant (p less than 0.001) increase in left ventricular end diastolic pressures. These changes proved to be reproducible and were found to be almost identical in the four consecutive inflation cycles. The effects of reperfusion were also

Topics: Adenosine Triphosphate; Adult; Aged; Aldosterone; Angina Pectoris; Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Collateral Circulation; Coronary Circulation; Coronary Disease; Energy Metabolism; Female; Hemodynamics; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Myocardial Contraction; Myocardial Infarction; Myocardium; Renin; Stroke Volume

Atrial amyloid deposits are common in the ageing human heart and contain alpha-atrial natriuretic peptide (proANP99-126) immunoreactivity. However, atrial myocytes secrete both amino and carboxy terminal fragments of the ANP prohormone (proANP1-126) and also express an homologous, but separate brain natriuretic peptide (BNP). Characteristic amyloid deposits were identified in the atria of 9/22 patients (26-63 years of age) with end-stage heart failure. Amyloid fibrils displayed immunoreactivity for both amino and carboxy terminal fragments of proANP1-126 and for the distinct BNP sequence. As in other endocrine organs, both mature and precursor peptide sequences appear to be constituents of amyloid fibrils. Whilst immunoreactivity for cardiac peptide hormones is co-localized in atrial amyloid deposits, it is uncertain whether the increase in natriuretic peptide expression which accompanies cardiac failure contributes to the incidence of isolated atrial amyloidosis.

Topics: Adolescent; Adult; Amyloid; Amyloidosis; Atrial Natriuretic Factor; Cardiomyopathies; Coronary Disease; Female; Heart Atria; Heart Diseases; Heart Valve Diseases; Humans; Immunohistochemistry; Male; Microscopy, Electron; Middle Aged; Muscle Proteins; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Protein Precursors

To study the release of plasma atrial natriuretic factor (ANF) and to explain the mechanism underlying its increase during myocardial ischemia, we measured plasma ANF and mean pulmonary capillary wedge pressure (PCW) before, during and after percutaneous transluminal coronary angioplasty (PTCA) in eight patients. All patients were free of calcium channel antagonists and beta-blocking drugs. Evidence of myocardial ischemia was observed in all patients with an increase of PCW from 3.2 +/- 1.2 to 10.6 +/- 2.9 mm Hg (mean +/- SD; p less than 0.001). Heart rate and mean blood pressure did not change significantly. We observed an increase of plasma ANF during PTCA, from 53 +/- 24 to 100 +/- 37 pmol/L (mean +/- SD; p less than 0.005). There was a correlation between absolute values of ANF and PCW before and during PTCA (r = 0.64, p less than 0.01). After PTCA, ANF levels remained increased for at least twenty minutes (p less than 0.005 vs basal state) despite a decrease in PCW. Thus, increase of PCW during this very short-term left ventricular ischemic dysfunction induces an increase of plasma ANF, which persists during a certain time when PCW returns to normal.

Topics: Aged; Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Blood Pressure; Coronary Disease; Evaluation Studies as Topic; Female; Heart Rate; Humans; Male; Middle Aged; Pulmonary Wedge Pressure

Topics: Adult; Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Coronary Disease; Female; Humans; Male; Middle Aged; Radioimmunoassay; Tumor Necrosis Factor-alpha

To investigate myocardial ischemia during exercise, submaximal exercise testing with electrocardiogram and thallium 201-myocardial scintigraphy was performed in non-insulin-dependent diabetics. The relationship between plasma atrial natriuretic polypeptide (ANP) levels in response to exercise and cardiac function assessed by echocardiography was also examined. The following results were obtained: 1) Twelve of the 66 diabetics (18.2%) had ischemic ST-segment changes in exercise ECGs, compared with 4 of 75 control subjects (5.3%)(p less than 0.05). Of the 12 diabetics with positive exercise ECGs, 10 were asymptomatic. 2) The washout rate in thallium-201 myocardial scintigraphy was significantly less in diabetics with positive exercise ECGs (36.5 +/- 4.1%) than in controls (51.9 +/- 2.8%)(p less than 0.05). 3) Although no difference in heart rate were observed between diabetics and controls, diabetic patients had significantly higher systolic blood pressure than controls during all stages of exercise and at maximal exertion. Rate pressure products in stages 1 and 2 were significantly higher in diabetics than in controls. 4) The increase of plasma ANP concentration during moderate exercise (VO2 max 60%) was significantly greater in diabetics than in controls (32.3 +/- 11.9 pg/ml vs. 15.0 +/- 1.7 pg/ml)(p less than 0.02). 5) There was a significant correlation between the increase in plasma ANP during exercise and the levels of left ventricular diastolic function (A/R:r = 0.504, p less than 0.05, IRT:r = 0.587, p less than 0.02), assessed by echocardiography, in diabetics. In conclusion, this study demonstrated that the frequency of asymptomatic myocardial ischemia during exercise was higher in diabetics than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Atrial Natriuretic Factor; Blood Pressure; Coronary Disease; Diabetes Complications; Diabetes Mellitus; Electrocardiography; Exercise; Heart; Heart Rate; Humans; Middle Aged

In an attempt to identify which parameters predict survival in advanced dilated cardiomyopathy, 232 patients presenting for assessment for cardiac transplantation were investigated and followed for 10 +/- 12 months (range 2 weeks to 5 years). Etiology of dilated cardiomyopathy included ischemic heart disease (33%), idiopathic (42%) and miscellaneous (25%). In each patient, 26 parameters were recorded. Whole group survival was 68% at 1 year, 56% at 2 years, 41% at 3 years and 25% at 4 years. On Cox multivariate regression analysis, 3 parameters predicted survival: New York Heart Association symptom class (p less than 0.0001), pulmonary capillary wedge pressure (p less than 0.008) and plasma atrial natriuretic factor level (p less than 0.002). On paired testing of actuarial survival curves, plasma noradrenaline also held predictive value (p less than 0.002), as did left ventricular ejection fraction less than or equal to 20% on radionuclide ventriculography (p = 0.007) and presence of greater than or equal to 4 beats of ventricular tachycardia on Holter monitoring (p = 0.007). Treatment with amiodarone did not appear to influence survival. Conventional determinants of prognosis in cardiomyopathy (symptom class, wedge pressure, nonsustained ventricular tachycardia and ejection fraction) do not alone always adequately differentiate survival in this group of high risk patients. More attention to plasma noradrenaline and to atrial natriuretic factor levels may give important additional information in the context of assessment of patients for transplantation.

Topics: Adolescent; Adult; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Child; Coronary Disease; Echocardiography; Electrocardiography, Ambulatory; Heart Transplantation; Hemodynamics; Humans; Middle Aged; Multivariate Analysis; Norepinephrine; Predictive Value of Tests; Prognosis; Radionuclide Ventriculography; Renin; Survival Analysis

A tissue kallikrein has been isolated from rat heart extracts by DEAE-Sepharose and aprotinin-affinity column chromatography. The purified cardiac enzyme has both N-tosyl-L-arginine methyl ester esterolytic and kinin-releasing activities, and displays parallelism with standard curves in a kallikrein radioimmunoassay, indicating it to have immunological identity with tissue kallikrein. The enzyme is inhibited by aprotinin, antipain, leupeptin and by high concentrations of soybean trypsin inhibitor, but stimulated by lima-bean or ovomucoid trypsin inhibitor and low concentrations of soybean trypsin inhibitor. By using a specific monoclonal antibody to tissue kallikrein in Western blot as well as active-site labelling with [14C]di-isopropyl fluorophosphate, the cardiac enzyme was identified as a protein of 38 kDa, a molecular mass identical with that of tissue kallikrein. Immunocytochemistry at the electron-microscopic level localized this enzyme to the sarcoplasmic reticulum and granules of rat atrial myocytes. Two cardiac kallikrein precursors, (38 and 40 kDa) were identified from the translation in vitro of heart mRNA by immunoprecipitation and electrophoresis of [35S]methionine-labelled cell-free translation products. Kallikrein mRNA in the rat heart was also demonstrated by dot-blot analysis using a tissue kallikrein cDNA probe. These results indicate that the tissue kallikrein gene is expressed in the rat heart and that the purified enzyme is indistinguishable from tissue kallikrein with respect to enzymic and immunological characteristics.

Topics: Animals; Atrial Natriuretic Factor; Binding Sites; Blotting, Western; Coronary Disease; Hydrogen-Ion Concentration; Immunohistochemistry; Kallikreins; Myocardium; Rats; Rats, Inbred Strains; RNA, Messenger

Plasma levels of atrial natriuretic peptide (ANP) were determined in 34 male patients undergoing diagnostic right heart catheterization. Patients with effort angina exhibited significant higher ANP levels at rest (259 +/- 42 pg/ml; n = 7) than patients without signs of coronary heart disease (78 +/- 30 pg/ml; n = 8). Patients with effort angina also had higher ANP levels at rest than patients exhibiting impaired cardiac function on exertion without signs of ischemia (105 +/- 15 pg/ml; n = 4), patients with only minimal functional alterations due to infarction residues (95 +/- 27 pg/ml; n = 7), or patients with only borderline changes of ST-segments during exertion (61 +/- 19 pg/ml; n = 8). In contrast, mean pulmonary capillary or right atrial pressures were not significantly different between the various groups of patients. The patients with effort angina also exhibited the highest ANP levels during bicycle exercise (846 +/- 238 pg/ml). There was only a weak to moderate linear correlation between ANP levels and pulmonary or right atrial pressures in the whole group of patients (r = 0.1-0.6). The plasma levels of epinephrine and norepinephrine and of ANP were not significantly correlated, with the exception of norepinephrine levels during exercise (r = 0.54). Our observations suggest that in patients with effort angina there may exist additional stretch-independent factors stimulating the release of ANP, possibly associated with repetitive myocardial ischemia.

Topics: Angina Pectoris; Atrial Natriuretic Factor; Coronary Disease; Epinephrine; Exercise Test; Heart Failure; Hemodynamics; Humans; Male; Norepinephrine

Vasopressin, the renin-angiotensin system and atrial natriuretic factor (ANF) interact in regulating blood pressure. While the vasoconstrictor effect of vasopressin and the renin-angiotensin system is well documented, the direct vascular effect of ANF is unclear. We studied in anaesthetized dogs the coronary vascular effects of agonists and antagonists of vasopressin and the renin-angiotensin system under control and ischaemic conditions, respectively. In addition, the action of ANF and its relationship to the renin-angiotensin system was analysed. A coronary artery was cannulated and perfused by a bypass system from the femoral arteries of the same animal. Coronary vasoconstriction by vasopressin was potentiated when myocardial ischaemia was induced by lowering coronary perfusion pressure while coronary constriction by angiotension I and II was mitigated. A vasopressin receptor blocker slightly reduced coronary blood flow at high doses (intrinsic activity) while the angiotensin II receptor blocker increased coronary flow in myocardial ischaemia. ANF effects were ambiguous at lower doses (1 ng (kg)-1 i.c.) with coronary constriction in 79% of dogs. At higher doses (1 microgram kg-1) ANF consistently induced coronary dilation. The angiotensin II receptor blocker saralasin significantly reduced this coronary dilator effect of ANF. Thus, in conclusion, a vasoconstrictor effect of endogenous vasopressin could not be shown by this study. In contrast, endogenous angiotensin II might participate in control of coronary blood flow during myocardial ischaemia. The coronary dilator effect of ANF at least in part appears to be due to interference with the renin-angiotensin system.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Captopril; Coronary Circulation; Coronary Disease; Dogs; Renin-Angiotensin System; Saralasin; Vasoconstriction; Vasopressins

Atrial natriuretic peptide (ANP) levels were measured prior to and at 1 and 5 minutes postcontrast left ventriculography with an ionic contrast agent (diatrizoate), and a nonionic agent (iopamidol) and the results were compared. Since ionic contrast agents have been found to cause an increase in left ventricular end-diastolic pressure (LVEDP) and nonionic agents have been found to have less of an effect on LVEDP, we investigated the response of ANP levels, which have been found to increase secondary to increased LVEDP (atrial pressure), with both agents. A group of 38 patients who were scheduled for left heart catheterization for suspected coronary artery disease was included (19 in each group) and blood samples for ANP levels were drawn from the left ventricles. At the same time, heart rate, LVEDP, and left ventricular systolic pressure (LVSP) were also measured. It was found that the LVEDP increased significantly for both agents at 1 minute postventriculography, but no further change occurred at 5 min. Heart rate increased significantly in the diatrizoate group at 1 minute with a return of heart rate to preventriculography levels at 5 min, while the ANP level and LVSP remained unchanged at 1 minute postventriculography with both agents but increased significantly at 5 min in the diatrizoate group only. This difference in ANP response is not correlated with the LVEDP. The response of ANP may be related to heart rate and/or LVSP.

Topics: Atrial Natriuretic Factor; Blood Pressure; Coronary Disease; Diatrizoate; Electrocardiography; Female; Heart; Heart Rate; Heart Ventricles; Humans; Iopamidol; Male; Middle Aged; Osmolar Concentration; Radiography

According to several reports of close correlations between pulmonary artery pressure and ANF plasma levels it would be convenient to replace invasive pressure monitoring by ANF determination. Mean pulmonary artery and right atrial pressures and pulmonary artery as well as peripheral venous ANF plasma concentrations were measured in 24 patients before and after coronary angioplasty (PTCA) continuously at rest and during exercise: At rest, both pressure and ANF-values remained unchanged before and after PTCA. At exercise, there was a decrease of mean pulmonary artery pressure (from 41.3 +/- 8.6 to 31.5 +/- 7.4 mmHg, p less than 0.001), mean right atrial pressure (from 11.9 +/- 3.0 to 9.0 +/- 2.3 mmHg, p less than 0.001), pulmonary artery (282.5 +/- 191.0 to 207.3 +/- 157.2 pg/ml, p less than 0.05) and peripheral venous (112.7 +/- 48.0 to 97.1 +/- 53.2 pg/ml, n.s.) ANF concentration after PTCA. We found no correlation between PTCA-induced changes of right arterial pressures and ANF concentrations, while changes of pulmonary artery pressures were significantly correlated to changes of peripheral venous (r = 0.79, p less than 0.001) as well as pulmonary artery (r = 0.59, p less than 0.01) ANF concentrations at exercise. In 6 of the 24 patients, however there was an inverse relationship between changes of pulmonary artery pressures and ANF concentrations. - Our data demonstrate a significant correlation between changes of ANF plasma level and pulmonary artery pressure values at exercise after PTCA. In the individual case however invasive pressure monitoring cannot be replaced by determination of ANF plasma levels.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Blood Pressure; Coronary Disease; Heart Atria; Humans; Middle Aged; Pulmonary Artery; Pulmonary Wedge Pressure

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

This study investigated the plasma concentrations of human atrial natriuretic peptide (hANP) of blood samples obtained from the aorta and coronary sinus (CS) in 19 male patients (mean age of 52.8 +/- 2.1 years) with ischemic heart disease before and during atrial pacing. The plasma concentrations of hANP were measured by radioimmunoassay, and the secretion rate of hANP was calculated on the basis of the CS-aorta difference in plasma hANP concentration and the CS flow rate recorded at blood sampling. Before atrial pacing, aortic plasma hANP concentration showed a significant positive correlation with mean pulmonary capillary wedge pressure (r = 0.67, p less than 0.002) or mean pulmonary artery pressure (r = 0.71, p less than 0.001), and a significant negative correlation with left ventricular ejection fraction (r = -0.50, p less than 0.05). During atrial pacing, aortic plasma hANP concentration increased from 67 +/- 13 (SEM) to 151 +/- 33 pg/ml (p less than 0.01), CS plasma hANP concentration from 727 +/- 121 to 1205 +/- 228 pg/ml (p less than 0.01), and the hANP secretion rate from 45.4 +/- 14.8 to 86.8 +/- 28.2 ng/min (p less than 0.05, n = 12). The aortic plasma hANP concentration was significantly correlated with the CS plasma hANP concentration (r = 0.81, p less than 0.001) or the hANP secretion rate (r = 0.70, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Coronary Circulation; Coronary Disease; Humans; Male; Middle Aged

Myocardial infarction and heart failure are associated with an elevation in plasma levels of atrial natriuretic peptide (ANP). The early stages of myocardial ischaemia and infarction are associated with serious ventricular arrhythmias. We examined the possibility that ANP may function in early ischaemia to alter the susceptibility of the heart to arrhythmias by perfusing rat hearts (n = 12 in each group) with various concentrations of ANP during periods of aerobic perfusion and regional ischaemia. The complications associated with the release of endogenous ANP were precluded by carrying out the experiments with an isolated Langendorff (nonrecirculating) preparation in which the atrial effluent does not gain access to the ventricular coronary arteries. When compared with control hearts, ANP (0.02, 0.2, 0.6, or 2.0 nM) had no significant influence on the ventricular arrhythmias (ventricular premature beats, tachycardia, and fibrillation) elicited by 30-min regional myocardial ischaemia. Heart rate and coronary flow were also unchanged. We conclude that in the isolated rat heart during myocardial ischaemia ANP probably has no significant mediatory or modulatory role in the pathogenesis of serious ventricular arrhythmias.

Topics: Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Coronary Disease; Heart; Heart Rate; Hemodynamics; In Vitro Techniques; Male; Perfusion; Rats; Rats, Inbred Strains

The effect of an acute and sustained reduction in atrial pressure on atrial natriuretic factor (ANF) and vasoactive hormone secretion was studied in 9 patients with congestive heart failure (CHF). Intravenous nitroglycerin was titrated to reduce the pulmonary artery wedge pressure by 30 to 50% and maintain this reduction for 4 hours. After 60 minutes of nitroglycerin administration, the mean decrement in wedge pressure was 10.0 +/- 1.7 (standard error) mm Hg (35%) and plasma ANF was 65.3 +/- 13.9 pmol/liter (35%). The initial decrease, sustained reduction and later increase in plasma ANF levels closely paralleled the changes in pulmonary arterial wedge (r = 0.94, p less than 0.0001) and right atrial pressures (r = 0.91, p less than 0.0001) during and immediately after the nitroglycerin infusion. Plasma aldosterone and cortisol levels increased during the first 2 hours of the nitroglycerin infusion, but there was little change in plasma norepinephrine or plasma renin activity. Although levels were elevated in CHF, plasma ANF still responded rapidly to changes in atrial pressure. A sustained reduction in pressure produced a sustained reduction in ANF levels. These findings provide further support for a regulatory role of ANF, even in chronic CHF.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Cardiomyopathy, Dilated; Coronary Disease; Female; Heart Failure; Humans; Male; Middle Aged; Nitroglycerin; Pulmonary Wedge Pressure; Vasoconstriction

The effects of atrial natriuretic peptide (ANP) on transmural myocardial blood flow distribution and the reactive hyperemic response in the presence and absence of flow-limiting coronary stenosis were examined in chronically instrumented conscious dogs. Ten-second coronary occlusion without subsequent flow restriction resulted in marked reactive hyperemic responses (Doppler flow probes), mean flow debt repayment was 481 +/- 55%. When the 10-second coronary occlusions were followed by a 20-second partial restriction that allowed normal preocclusion coronary inflow, the subsequent reactive hyperemia was significantly augmented, mean flow debt repayment was 938 +/- 91% (p less than 0.05). Pretreatment with ANP (3 micrograms/kg) did not alter the flow debt repayment after a 10-second occlusion without restriction (474 +/- 30%, NS) but attenuated the augmentation of reactive hyperemia resulting from the 20-second inflow restriction, flow debt repayment (613 +/- 66%, NS). Regional myocardial blood flow to the ischemic region was measured during restricted inflow after a 10-second coronary occlusion before and after ANP pretreatment. Before ANP, subendocardial flow decreased (0.54 +/- 0.04 ml/min/g) and subepicardial flow significantly increased (1.03 +/- 0.12 ml/min/g) when compared with the nonischemic zone (subendocardial, 1.03 +/- 0.09 ml/min/g; subepicardial, 0.87 +/- 0.09 ml/min/g, p less than 0.05), indicating maldistribution of the restricted inflow. The resultant subendocardial-to-subepicardial ratio in the ischemic region was significantly decreased when compared with the nonischemic region (0.56 +/- 0.03 vs. 1.18 +/- 0.04, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Coronary Circulation; Coronary Disease; Dogs; Drug Evaluation, Preclinical; Hyperemia; Microspheres; Time Factors; Vasodilation; Wakefulness

Topics: Aged; Aldosterone; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Coronary Disease; Electrophysiology; Female; Hemodynamics; Humans; Hydrocortisone; Male; Middle Aged; Norepinephrine; Renin; Tachycardia; Vasopressins

To study the effects of myocardial ischemia on plasma atrial natriuretic peptide (ANP) levels, immunoreactive ANP levels in the pulmonary artery (ANP-PA) and femoral vein (ANP-V) were measured before and during percutaneous transluminal coronary angioplasty (PTCA). Ten patients (group 1), seven of whom had no symptoms during PTCA, maintained a normal mean pulmonary capillary wedge pressure (PCWP) of less than or equal to 13 mm Hg during PTCA, whereas five patients (group 2), all of whom had symptoms and signs of ischemia during PTCA, had an increased PCWP of greater than or equal to 20 mm Hg. ANP levels did not differ significantly between the two groups before PTCA, but ANP-PA (p less than 0.02) and ANP-V (p less than 0.01) during PTCA were higher in group 2 than in group 1. ANP-V at rest and during exercise was measured in 11 patients with and 14 patients without anginal symptoms and ischemic ST changes on the ECG during exercise. The values did not change significantly in either group, and there were no difference between the groups. Thus myocardial ischemia during PTCA may lead to left ventricular dysfunction serious enough to increase PCWP and subsequently plasma ANP levels in some patients. Myocardial ischemia induced by dynamic exercise seems to be unrelated to significant changes in the plasma ANP level.

Topics: Adult; Angioplasty, Balloon; Atrial Natriuretic Factor; Coronary Disease; Femoral Vein; Humans; Middle Aged; Physical Exertion; Pulmonary Artery; Pulmonary Wedge Pressure

The tissue distribution and possible neuroendocrine nature of atrial natriuretic factor (ANF) were studied, using the avidin-biotin-peroxidase technique and antibodies to ANF, chromogranin (Ch), and neuron-specific enolase (NSE). Tissues examined included: Group 1, formalin-fixed and fresh frozen atrial tissue from adjacent areas of the hearts from two heart-lung-transplant patients; Group 2, the entire atria and sampling of other areas from formalin-fixed hearts of five gunshot wound or automobile accident victims; and Group 3, formalin-fixed right auricular tissue from 19 open-heart-surgery patients. In each case of Group 3, the ANF score, expressed as the product of the percentage of stained areas by the staining intensity, was correlated with age, weight, height, blood pressure, ejection fraction, and degree of coronary arterial stenosis. It was found that: (a) ANF was limited to atrial myocytes; the staining was significantly stronger in the right atrium, diffuse and most intense in auricles and pectinate muscles, diffuse and strong in subendocardium, focal and weak in other areas; (b) although ANF has been reported to be a peptide hormone stored in dense-core granules, it does not seem to belong to the diffuse neuroendocrine system because Ch and NSE were consistently absent in cardiac myocytes; and (c) although the limited numbers of evaluable clinical parameters do not significantly correlate with ANF scores, a change in the pattern and intensity of ANF staining was noted in some cases of Group 3.

Topics: Adult; Atrial Natriuretic Factor; Autoantibodies; Chromogranin A; Chromogranins; Coronary Disease; Endocardium; Heart Atria; Humans; Immunoenzyme Techniques; Myocardium; Pericardium; Phosphopyruvate Hydratase

The diuretic and natriuretic effects of r-alpha-ANP (99-126) were investigated in rats with chronic ischaemic heart failure (IHF) produced by left coronary artery ligation. The plasma concentration of immunoreactive ANP (IrANP) was significantly higher, 91.8 +/- 16.0 pm in the IHF rats compared to 31.0 +/- 4.9 pm in sham-operated controls. In the control rats, ANP infusion (0.25-1.0 micrograms kg 1 mm 1) increased urine flow rate (V) and urinary sodium (UNa V) excretion. At the highest dose level, both V and UNa V were increased approximately fivefold. The diuresis and natriuresis seen in the control group after the infusion of ANP were blunted in the IHF rats. A bilateral surgical renal denervation in the IHF rats did not alter the renal dopamine levels, but induced a significant decrease in renal noradrenaline content, and almost completely restored the renal responsiveness to the ANP infusions. We conclude that renal denervation reversed the blunted renal excretory response to ANP in IHF rats. Thus, in experimental IHF, there seems to be a functional antagonism between efferent renal sympathetic nerve activity and ANP.

Topics: Animals; Atrial Natriuretic Factor; Coronary Disease; Diuresis; Kidney; Natriuresis; Neurons; Peptide Fragments; Rats; Rats, Inbred Strains; Sympathectomy; Sympathetic Nervous System

Atrial natriuretic factor (ANF) was determined in pulmonary and systemic arterial plasma during diagnostic left and right heart catheterization in twenty-three patients. In twenty of these patients ANF was subsequently measured in systemic arterial plasma during nuclear magnetic resonance (NMR) imaging of the heart with computation of left heart chamber volumes and left ventricular mass. Left ventricular end-diastolic pressure was the strongest independent predictor of pulmonary arterial plasma ANF, whereas cardiac index best predicted aortic plasma ANF. Both pulmonary and aortic plasma ANF correlated with systolic and diastolic pulmonary arterial pressure, left ventricular end-diastolic pressure and cardiac index. Left atrial volume index and left ventricular mass index did not correlate with systemic arterial plasma ANF whereas a positive linear correlation between left ventricular end-diastolic volume index and ANF could be demonstrated (r = 0.61, P less than 0.01). Left ventricular end-diastolic volume index was the most important independent predictor of systemic arterial plasma ANF. Systemic arterial plasma ANF might be a simple marker of left ventricular dilatation in patients with heart disease.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Cardiac Catheterization; Cardiac Volume; Coronary Disease; Female; Heart Atria; Heart Ventricles; Hemodynamics; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged

The fate of atrial natriuretic peptide (ANP) was studied by arterial and venous catheterization in ischemic heart disease patients, and arterio-venous blood sampling in healthy kidney donors at the time of transplantation. In vitro ANP degradation was examined using healthy human plasma. In ischemic heart disease, the plasma ANP concentration at the inferior vena cava was 62.6% of that at the left ventricle, and that at the superior vena cava was 82.8%. Arterio-venous gradients were similar from pulmonary artery to vein (88.3%), from celiac artery to the hepatic vein (75.5%) and from the femoral artery to vein (85.4%). In the donor for kidney transplantation, renal arterio-venous gradient was also similar at 77.1%. No platelet consumption of ANP was noted, and the molecular forms of ANP present in the circulation were similar in samples obtained from both the coronary sinus and the superior or inferior vena cava. We conclude that no specific organ plays a dominant role in ANP degradation, and that ANP molecular forms may not be altered during circulation.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Blood Platelets; Coronary Disease; Female; Humans; Kidney Transplantation; Male; Middle Aged; Renal Artery; Renal Veins

The secretion of atrial natriuretic factor (ANF) and its adaptation to pharmacologic and hemodynamic interventions were investigated in 36 patients with sinus rhythm. To provoke standardized secretion of ANF all patients underwent two periods of rapid right ventricular pacing for 4 min with a 15 min interval. Immediately after the first pacing eight patients received 5 mg verapamil, 10 patients 5 mg atenolol and 10 patients 4 mg molsidomine intravenously. Eight patients remained untreated and served as controls. The amounts of atrial pressure increments due to pacing were identical (70% over basal pressure) in all patients. After molsidomine, but not after the other drugs, basal right atrial pressure was lowered. In controls the secretion of ANF due to the second stimulation was significantly (2.5-fold) larger than the secretion induced by the first stimulation. In patients receiving verapamil the secretion response after the second pacing was blunted. Atenolol did not affect the release of ANF. After molsidomine the upward regulation of the ANF secretion rate - seen in controls - was abolished. Thus, the myoendocrine cells are capable for a fast upward regulation of their ANF secretion rate after repeated stimuli. Verapamil directly blocks stimulated ANF secretion, whereas beta-blockade shows no effect. Molsidomine seems to impair enhanced ANF release by lowering basal atrial pressure.

Topics: Adult; Aged; Atenolol; Atrial Natriuretic Factor; Blood Pressure; Cardiac Catheterization; Cardiac Pacing, Artificial; Coronary Disease; Cyclic GMP; Female; Humans; Male; Middle Aged; Molsidomine; Verapamil

To evaluate the risk of ischemia in 17 patients with significant coronary artery disease, the influence of enoximone was analyzed under the following conditions: (1) at rest (RC) and during exercise (ExC) under control conditions and (2) at rest (RE) and during exercise (ExE) after administration of enoximone (0.75 mg/kg, intravenously). During ExC all patients had ischemia (angina, and ST segment alterations); metabolic markers of ischemia (MMI) increased, as did the mean pulmonary artery pressure, from 19 to 41 mm Hg. However, during ExE ischemia was abolished (no angina, decrease in mean pulmonary artery pressure to 24 mm Hg, and improvement in MMI) and there was some improvement in left ventricular pump function, whereas pre- and afterload decreased (pulmonary artery pressure by 40%, systemic vascular resistance by 10%), and heart rate, arterial pressure, and myocardial oxygen consumption (MVO2) were all unchanged (p greater than 0.05). Comparative hemodynamics at RE vs RC showed a decrease in pulmonary artery pressure (by 25%) and pulmonary vascular resistance (by 19%) and an increase in heart rate (by 11%), whereas arterial pressure and MVO2 were unchanged (p greater than 0.05). Enoximone did not induce changes in plasma catecholamine, prostaglandin, or thromboxane levels (p greater than 0.05), whereas the atrial natriuretic factor decreased (by 15%), probably because of unloading of the atria during exercise. We concluded that enoximone induces beneficial hemodynamic effects in coronary artery disease without causing ischemia, probably by enhancing myocardial contractility, vasodilation, and improved diastolic properties.

Topics: Atrial Natriuretic Factor; Catecholamines; Coronary Circulation; Coronary Disease; Enoximone; Hemodynamics; Humans; Imidazoles; Lactates; Lactic Acid; Middle Aged; Neurotransmitter Agents; Phosphodiesterase Inhibitors; Prostaglandins

The relations between atrial natriuretic peptide (ANP) binding sites in the renal medulla, plasma ANP concentration, and ventricular dysfunction have been studied in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. Plasma ANP concentration was measured by radioimmunoassay, and quantitation of receptors was performed by computerized in vitro autoradiography with 125I-labeled alpha-rat ANP (1-28) as the radioligand. When compared with controls, rats with myocardial infarction had markedly elevated plasma immunoreactive ANP concentrations (462 +/- 82 versus 124 +/- pg/ml, p less than 0.01) and reduced densities of ANP binding in the inner renal medulla (2.93 +/- 0.19 versus 3.53 +/- 0.22 fmol/mg protein, p less than 0.01). Extensive myocardial infarction was associated with a significant decrease in receptor numbers in the inner medulla (33.6 +/- 5.7 versus 95.6 +/- 9.6 fmol/mg protein, p less than 0.01) without significantly altering the affinity constant (1.76 +/- 0.51 versus 1.03 +/- 0.15 x 10(9) M-1, p greater than 0.05). Right ventricular weight increased in proportion to infarct size (r = 0.71, p less than 0.01), and both were correlated with plasma immunoreactive ANP levels (r = 0.74, p less than 0.01 and r = 0.75, p less than 0.01, respectively). Binding densities in the inner medulla of rats with infarcts were negatively correlated with right ventricular weight, plasma immunoreactive ANP concentrations, and also with infarct size (r = -0.92, p less than 0.001; r = -0.78, p less than 0.001; r = -0.77, p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Coronary Disease; Kidney Medulla; Myocardial Infarction; Myocardium; Organ Size; Rats; Rats, Inbred Strains; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Cardiac Pacing, Artificial; Coronary Disease; Cyclic GMP; Electric Stimulation; Electrocardiography; Female; Heart Atria; Humans; Male; Middle Aged

The adaptation of the secretory rate of atrial natriuretic factor to repeated adequate stimuli and the influence of the calcium antagonist verapamil on the release of atrial natriuretic factor were investigated in 16 patients. In eight patients (Group 1) right atrial pressure was abruptly increased by rapid right ventricular pacing for 4 min (stimulation I). After a 15 min interval, the identical stimulation was repeated (stimulation II). Eight patients (Group 2) underwent the same protocol but received 5 mg of verapamil intravenously after stimulation I. Pacing increased right atrial pressure in both groups identically by 70%. In Group 1, release of atrial natriuretic factor caused by the second stimulation (median 290 pg/ml over basal) was significantly (2.5-fold) larger than atrial natriuretic factor release induced by the first stimulation (median 116 pg/ml over basal). In the verapamil-treated patients (Group 2), the effect of right atrial pressure increase on release of atrial natriuretic factor was abolished after stimulation II. In both groups, changes in plasma concentrations of cyclic guanosine monophosphate corresponded to changes in atrial natriuretic factor concentrations. Thus, the myoendocrine cells are apparently capable of a fast upward regulation of their response to repeated secretory stimuli. Verapamil appears to block the stimulatory effect of a sudden increase in right atrial pressure upon release of atrial natriuretic factor.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Coronary Disease; Cyclic GMP; Female; Heart Atria; Humans; Male; Middle Aged; Verapamil

Although atrial natriuretic peptide (ANP) is known to be secreted through the coronary sinus into the systemic circulation, its actual secretion rate has not been thoroughly investigated. The immunoreactive ANP concentrations in plasma samples from the ascending aorta and coronary sinus in 11 patients with the coronary artery disease were measured and the coronary sinus flow rate using the continuous thermodilution method was simultaneously determined at the time of sampling. These variables were also determined during the intravenous infusion of synthetic alpha-human ANP at 0.025 microgram/kg.min in 7 of the 11 patients. In the basal state, the plasma concentration of ANP was 61 +/- 6 (standard error) pg/ml in the aorta and 541 +/- 40 pg/ml in the coronary sinus, and the coronary sinus flow index was 57.3 +/- 12.3 ml/min.m2. Thus, the secretion rate of ANP was determined to be 14.4 +/- 2.8 ng/min.m2. The secretion rate of ANP correlated significantly with the plasma concentration of ANP in the aorta (r = 0.65, p less than 0.05). The ANP infusion, which decreased pulmonary artery wedge pressure from 8.0 +/- 0.6 to 6.3 +/- 0.4 mm Hg (p less than 0.01), elevated the plasma concentrations of ANP in the aorta and coronary sinus by 701% (p less than 0.001) and 33% (p less than 0.05), respectively, and decreased the secretion rate of ANP by 40% (p less than 0.05). These results suggest that the circulating plasma concentration of ANP may reflect the secretion rate of ANP and that an increase in circulating ANP directly or indirectly reduces ANP secretion.

Topics: Aorta; Atrial Natriuretic Factor; Blood Flow Velocity; Coronary Circulation; Coronary Disease; Coronary Vessels; Female; Humans; Male; Middle Aged; Secretory Rate; Veins

The elevation of cardiac filling pressure induces the release of atrial natriuretic peptide into the circulation. Ischemia during exercise in patients with coronary artery disease may manifest itself with elevation of cardiac filling pressure before the onset of electrocardiographic changes or chest pain. Thus, patients with ischemic heart disease might have an elevated circulating atrial natriuretic peptide after exercise. The present study investigated the effect of exercise on circulating atrial natriuretic peptide in patients with and without ischemic heart diseases. Group 1 was composed of five patients who had ischemic heart disease by clinical history, previous myocardial infarction, angina or angiographically proven coronary artery disease and positive electrocardiogram during exercise. Group 2 was composed of five patients without ischemic heart disease and negative electrocardiogram response. Heart rate, blood pressure, and atrial natriuretic peptide were measured during routine treadmill exercise testing using the Bruce protocol. Our results indicate that the rate of rise of heart rate (12.3 +/- 1.8 vs. 8.5 +/- 0.7 beats/min/min), blood pressure (7.1 +/- 1 vs. 4.2 +/- 0.8 mm Hg/minute), and atrial natriuretic peptide (4.1 +/- 1 vs. 1.4 +/- 0.3 pg/ml/min) was significantly elevated in patients with ischemic heart disease compared to the group 2 patients. These findings suggest that the disproportionate elevation of atrial natriuretic peptide after exercise in ischemia may be caused by elevation of cardiac filling pressure, which may provide a noninvasive method for the diagnosis of ischemic heart disease.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Coronary Disease; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Physical Exertion

Alpha human atrial natriuretic polypeptide (alpha-hANP) was intravenously infused into 7 patients with ischemic heart disease who had almost normal cardiac function at a rate of 0.025 micrograms/kg/min for 15 min. During infusion of alpha-hANP, left ventricular (LV) systolic pressure decreased from 144 +/- 19 (SD) to 129 +/- 22 mmHg (p less than 0.01), LV end diastolic pressure (EDP) from 15 +/- 5 to 13 +/- 4 mmHg (p less than 0.05), mean aortic pressure from 102 +/- 14 to 91 +/- 14 mmHg (p less than 0.01), time constant of LV pressure fall (T) from 100 +/- 15 to 88 +/- 13 msec (p less than 0.05), systemic vascular resistance (SVR) from 1711 +/- 206 to 1424 +/- 340 dynes.sec.cm-5 (p less than 0.05) and coronary vascular resistance (CVR) from 8.5 +/- 1.2 to 7.4 +/- 1.3 x 10(4) dynes.sec.cm-5 (p less than 0.05). There was a linear correlation between percent changes in SVR and those of CVR (r = 0.92, p less than 0.01), and the fall in CVR was approximately 68% of that in SVR. Increases occurred in heart rate from 63 +/- 7 to 66 +/- 8 beats/min (p less than 0.05), LV dp/dt from 1558 +/- 266 to 1627 +/- 238 mmHg/sec (p less than 0.05), LV dp/dt/p from 22.9 +/- 3.2 to 25.6 +/- 3.7/sec (p less than 0.01), and myocardial oxygen consumption (from 7.9 +/- 2.4 to 9.8 +/- 2.1 ml/min, p less than 0.05), while mean right atrial and mean pulmonary arterial pressures and pulmonary vascular resistance were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiac Output; Coronary Circulation; Coronary Disease; Heart Function Tests; Heart Ventricles; Hemodynamics; Humans; Lactates; Male; Middle Aged; Oxygen Consumption; Pulmonary Circulation

The interaction between atrial natriuretic factor [synthetic human ANF-(103-126)] and angiotensin II (Ang II) and its influence on reperfusion arrhythmias, cardiodynamics, enzyme loss and metabolic changes were investigated in isolated ischaemic working rat hearts. Acute regional myocardial ischaemia was induced by coronary artery occlusion which was associated with ventricular fibrillation. Perfusion with 1 X 10(-9) mol/l Ang II markedly aggravated these arrhythmias. Perfusion with 1 X 10(-7) mol/l ANF, in contrast, gave protection against ventricular fibrillation and prevented Ang II-induced aggravation of ventricular fibrillation. Atrial natriuretic factor improved cardiodynamics, in particular, during reperfusion, whereas Ang II impaired cardiodynamics and increased the release of creatine kinase and lactate dehydrogenase. These adverse effects of Ang II were absent when ANF was simultaneously perfused. Compared with control hearts, myocardial tissue levels of glycogen, ATP and creatine phosphate were increased in hearts perfused with either ANF or ANF plus Ang II, whereas lactate levels decreased. Perfusion with Ang II alone led to deterioration in these metabolic parameters. These results in isolated working rat hearts suggest that ANF protects against the consequences of ischaemia and reperfusion and that functional antagonism between ANF and Ang II may contribute to this.

Topics: Angiotensin II; Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Coronary Circulation; Coronary Disease; Myocardial Reperfusion Injury; Rats; Rats, Inbred Strains; Ventricular Fibrillation

Radionuclide angiographic measurements of left ventricular ejection fraction were performed at rest and during exercise in 10 normal persons and 11 patients with coronary artery disease. Exercise was continued on a supine bicycle exercise table up to a symptom-limited maximum. Plasma levels of atrial natriuretic peptide (ANP) were also determined at rest and during exercise. Ejection fraction in the normal volunteers was 59 +/- 3% (mean +/- SEM) at rest and increased significantly (p less than 0.01) to 69 +/- 3% during exercise. Ejection fraction in the patients was 47 +/- 5% at rest and did not change significantly during exercise (51 +/- 7%). Plasma ANP in the normals rose significantly (p less than 0.01) from 62 +/- 16 pg/ml at rest to 454 +/- 94 pg/ml during exercise. Plasma ANP in the patients also rose significantly (p less than 0.01) from 231 +/- 102 pg/ml to 794 +/- 170 pg/ml. The response of plasma ANP to exercise was enhanced significantly (p less than 0.05) in the patients as compared with the normals in relation to ejection fraction by analysis of covariance. In both the normals and the patients, plasma ANP was inversely and significantly correlated with ejection fraction during exercise (r = -0.46, p less than 0.05, n = 21), however, not at rest. Because it has been reported that plasma ANP is correlated positively with pulmonary artery wedge pressure, the estimation of plasma ANP during an exercise stress test might be used for the evaluation of cardiac reserve in coronary artery disease.

Topics: Adult; Aged; Atrial Natriuretic Factor; Coronary Disease; Erythrocytes; Exercise; Exercise Test; Female; Heart; Humans; Male; Middle Aged; Radionuclide Angiography; Stroke Volume; Technetium

1. In order to examine the concentration of neuropeptide Y-like immunoreactivity (NPY-LI) and atrial natriuretic peptide (ANP) in the circulation in man, blood was sampled from the iliac vein, the inferior vena cava, the superior vena cava, the pulmonary artery and the femoral artery in 13 patients undergoing cardiac catheterization. 2. Plasma NPY-LI levels were similar at all points sampled and no arteriovenous differences were found. Plasma ANP concentration in the pulmonary artery was greater than in peripheral venous blood but there was a strong correlation between the two. 3. The concentration of NPY-LI and ANP in peripheral venous blood reflects central venous and arterial concentrations.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiac Catheterization; Coronary Disease; Female; Femoral Artery; Femoral Vein; Humans; Male; Middle Aged; Neuropeptide Y; Pulmonary Artery; Venae Cavae

Plasma levels of atrial natriuretic peptide (ANP) and tissue content of the peptide were measured simultaneously in 18 patients with coronary heart disease (group A) and 10 patients with aortic or mitral dysfunction (group B) undergoing open heart surgery. Plasma levels of ANP were significantly higher in patients with valvular heart disease compared to those with coronary heart disease (816 +/- 246 pg/ml versus 232 +/- 58 pg/ml, p less than 0.005). Similarly, tissue levels of ANP in the right atrium of group B doubled that of group A (227 +/- 46 micrograms/g versus 129 +/- 15 micrograms/g, p less than 0.025). Plasma levels and tissue content of ANP were not correlated. However, plasma ANP levels and mean pulmonary artery pressure were positively correlated (r = 0.688, p less than 0.05). Chronic stimulation of ANP secretion leads to a tissue accumulation of natriuretic peptide in heart atrium.

Topics: Aged; Aortic Valve; Atrial Natriuretic Factor; Coronary Artery Bypass; Coronary Disease; Female; Heart Atria; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Myocardial Infarction

We studied the effect of an increase in heart rate and/or in right atrial pressure (RAP) on the release of atrial natriuretic peptide (ANP) in 18 patients. In group 1 (n = 6), right ventricular stimulation (100, 120, 140 and 150 bpm) was used to increase RAP by asynchronous contraction of the right atrium and ventricle. Mean RAP increased from 3.9 +/- 0.2 to 8.3 +/- 0.6 mmHg (mean +/- SEM). Median ANP levels increased from 120 to 440 pg ml-1 (P less than 0.05). In group 2 (n = 6), right atrial stimulation below 140 bpm did not have any effect on ANP or RAP, but at a rate above 140 bpm RAP increased from 5.8 +/- 0.5 to 7.5 +/- 0.5 mmHg and ANP from 226 to 396 pg ml-1 (P less than 0.05). In group 3 (n = 6), RAP or ANP were not influenced by continuous right atrial stimulation at 110 bpm. Plasma cyclic GMP levels paralleled the changes in plasma ANP. Thus, an acute increment of RAP results in a release of ANP, but acceleration of heart rate alone has no effect on ANP secretion.

Topics: Atrial Natriuretic Factor; Blood Pressure; Cardiac Pacing, Artificial; Coronary Disease; Heart Rate; Humans

Left ventricular end-diastolic pressure and the concentration of atrial peptides in plasma were measured before and after the administration of contrast material into the left ventricle of 12 patients during cardiac catheterization. A positive relationship between changes in left ventricular end-diastolic pressure and the circulating level of atrial peptides was found in all 12 patients. Increases in plasma atrial peptide levels were detected within less than one minute after injection of the contrast agent. We conclude that the release of atrial peptides in the human is modulated rapidly by changes in atrial pressure. The rapid release of peptides from the atria in response to an increase in atrial pressure, coupled with evidence that atrial peptides reduce cardiac filling pressure, is consistent with the possibility that the atrial peptides may serve as part of a negative feedback system that enables the heart to influence its own filling pressure.

Topics: Adult; Aged; Aged, 80 and over; Angiocardiography; Atrial Natriuretic Factor; Cardiac Volume; Contrast Media; Coronary Disease; Female; Heart Atria; Humans; Male; Middle Aged; Pressure; Time Factors

At rest, during cardiac catheterization, aortic plasma levels of immunoreactive atrial natriuretic peptide did not differ between 10 controls with atypical chest pains and normal coronary arteries and 9 patients with stable angina pectoris and coronary arterial disease (55.2 +/- 19.8 vs. 64.8 +/- 19.8 pg/ml, NS). Nor did atrial natriuretic peptide values differ between the two groups during or after atrial pacing (150 beats/minute), which induced electrocardiographic and metabolic signs of acute myocardial ischaemia in the patients with coronary arterial disease but in none of the controls. Pacing, when carried out for more than 300 seconds, induced an increase of plasma atrial natriuretic peptide that correlated with duration of pacing (r = 0.80, P less than 0.001), and similarly in controls and patients with coronary arterial disease. In a second part of the study, which included 2 controls and 2 patients with coronary arterial disease, post-pacing coronary sinus concentrations of atrial natriuretic peptide were 10-20 times higher than peripheral levels (415- greater than 890 pg/ml). The concentration of atrial natriuretic peptide rose as blood from the caval veins (34 +/- 7 pg/ml) entered the right atrium (56 +/- 24 pg/ml), but thereafter was unchanged in the pulmonary artery (51 +/- 3 pg/ml) and the aorta (46 +/- 9 pg/ml). In conclusion, the results gave no evidence for ischaemic heart disease without congestive cardiac failure to be associated with altered levels of atrial natriuretic peptide. It was confirmed that atrial pacing stimulates the secretion of atrial natriuretic peptide which is produced by the heart and released via the coronary sinus into the circulation.

Topics: Atrial Natriuretic Factor; Cardiac Catheterization; Cardiac Pacing, Artificial; Coronary Disease; Humans; Myocardial Infarction; Myocardium; Radioimmunoassay

To elucidate the secretory form of atrial natriuretic polypeptide from the atrium, the molecular form of atrial natriuretic polypeptide in the perfusate from the isolated beating rat heart and in plasma taken at the coronary sinus of 10 patients during cardiac catheterization has been investigated using high performance gel permeation chromatography and reverse phase high performance liquid chromatography coupled with radioimmunoassay for atrial natriuretic polypeptide. Atrial natriuretic polypeptide in the perfusate from the rat heart showed a single peak eluting at the position of a low molecular weight form of atrial natriuretic polypeptide, without any detectable amounts of atrial natriuretic polypeptide with high molecular weights. The major component of atrial natriuretic polypeptide in the rat heart perfusate co-migrated with rat alpha-atrial natriuretic polypeptide in reverse phase high performance liquid chromatography. In 9 out of 10 patients atrial natriuretic polypeptide in plasma taken at the coronary sinus revealed a single peak of atrial natriuretic polypeptide emerging at the position of human alpha-atrial natriuretic polypeptide in gel filtration. Only one plasma sample had a small quantity of high molecular weight forms with the predominant low molecular weight form of atrial natriuretic polypeptide. The major component of atrial natriuretic polypeptide in the plasma extract from the coronary sinus was identified with human alpha-atrial natriuretic polypeptide. These results indicate that alpha-ANP, a 28-amino acid polypeptide, is secreted as a cardiac hormone into the coronary blood stream from the atrium.

Topics: Animals; Atrial Natriuretic Factor; Coronary Circulation; Coronary Disease; Female; Heart; Heart Valve Diseases; Humans; In Vitro Techniques; Male; Middle Aged; Perfusion; Rats; Rats, Inbred Strains; Species Specificity

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

To evaluate the relationship between plasma levels of immunoreactive atrial natriuretic hormone (IR-ANH) and different hemodynamic parameters in man, we studied 34 patients undergoing right heart catheterization. Plasma levels of IR-ANH in blood samples withdrawn from the femoral vein (n = 28), right ventricle (n = 27), and left ventricle (n = 17) were determined by radioimmunoassay. Right atrial pressure, pulmonary arterial wedge pressure, heart rate, and mean arterial pressure were found to be independent and significant predictors of IR-ANH plasma levels. The closest correlations were between right atrial pressure and either right ventricular IR-ANH levels (r = .78, p greater than .001) or femoral vein IR-ANH levels (r = .52, p less than .006). Five patients with isolated left ventricular failure had elevated IR-ANH levels out of proportion to their right atrial pressure levels. Pulmonary arterial wedge pressure also correlated with right ventricular IR-ANH levels (r = .46, p less than .002) and with femoral vein IR-ANH levels (r = .58, p less than .002). A single patient with isolated right heart failure had markedly elevated IR-ANH levels despite normal pulmonary arterial wedge pressure. Right ventricular levels were twice femoral vein levels and were closely correlated (181 +/- 40 vs 90 +/- 20 pmol/liter; r = .90, p less than .001). Right ventricular and left ventricular levels were almost identical (155 +/- 46 vs 146 +/- 43 pmol/liter; r = .99, p less than .001). Patients with volume overload states had elevated IR-ANH levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiac Catheterization; Coronary Disease; Female; Femoral Vein; Heart Diseases; Heart Valve Diseases; Heart Ventricles; Hemodynamics; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Mitral Valve

Atrial natriuretic factor, a peptide found in mammalian cardiac atria, has natriuretic and vasodilatory properties that may be important in the regulation of intravascular volume. To study factors related to its release in human subjects, intracardiac pressures and plasma atrial natriuretic factor concentrations in the central circulation were measured in 34 patients with a variety of cardiovascular disorders. Plasma atrial natriuretic factor concentration increased from the inferior vena cava to the right atrium (76 +/- 24 to 162 +/- 37 pg/ml, p less than 0.001) and from the vena cava to the aorta (76 +/- 24 to 177 +/- 46 pg/ml, p less than 0.001). Mean right atrial pressure was positively correlated with atrial natriuretic factor concentration in the pulmonary artery (r = 0.58, p less than 0.001), and mean pulmonary capillary wedge pressure was positively correlated with concentration in the aorta (r = 0.64, p less than 0.001). In six patients whose atrial natriuretic factor concentrations were measured at two different levels of atrial pressure, increased atrial pressure was accompanied by increased atrial natriuretic factor concentration in the pulmonary artery (p less than 0.01) and aorta (p less than 0.01). Atrial natriuretic factor levels measured in fresh myocardium from a patient undergoing cardiac transplantation showed tissue concentrations in the atria 500-fold higher than tissue concentrations in the ventricles. These data document that atrial natriuretic factor is found in human atrial myocardium and suggest that it may be released in response to increased atrial pressure. Such a secretory release mechanism is consistent with the hypothesis that atrial natriuretic factor plays a role in the regulation of circulatory volume.

Topics: Adult; Aged; Aorta; Atrial Natriuretic Factor; Cardiac Catheterization; Cardiomyopathy, Dilated; Coronary Disease; Female; Heart Atria; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Pressure; Pulmonary Artery; Pulmonary Wedge Pressure

The plasma concentrations of atrial natriuretic peptides (ANP) were measured during cardiac catheterization in 137 patients with heart disease. Atrial natriuretic peptides were elevated in all types of cardiac disease investigated, including valve disease, coronary heart disease and cardiomyopathy. The highest plasma ANP concentrations were found in patients with the most marked impairment of ventricular function and mitral valve disease. In patients with coronary heart disease, a significant, direct linear correlation was found between left ventricular filling pressure and plasma ANP concentrations (r = 0.42, P less than 0.001). Similarly, in patients with cardiomyopathy, a linear relationship was found between mean pulmonary artery pressure and plasma ANP concentration (r = 0.80, P less than 0.01). These observations suggest that measurement of ANP may be of value as a non-invasive humoral marker in the diagnosis of various cardiac diseases.

Topics: Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Coronary Disease; Heart Diseases; Heart Valve Diseases; Humans; Radioimmunoassay

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

The hemodynamic and renal electrolyte/function effects of a synthetic peptide (ANF) corresponding to the sequence of the 26 amino acids contained in atrial natriuretic factor (ANF) were assessed in closed-chest dogs in which acute left ventricular failure was produced by coronary artery embolization with 50 micron plastic microspheres. Coronary embolization produced a sustained reduction in cardiac contractility (LV dP/dtmax) and cardiac output which averaged 42 and 44%, respectively. Following a 45 min equilibration period after heart failure induction, most of the hemodynamic functions stabilized. At this time, ANF infused intravenously at 100 pmol/kg per min X 30 min (n = 9) did not lower mean arterial pressure although it increased cardiac output (P less than 0.05) by 17% at only one time period. With the exception of a fall in coronary resistance and an increase in myocardial blood flow, a higher dose of ANF (200 pmol/kg per min) did not consistently alter hemodynamic function. Fractional excretion of sodium (FE Na%) increased 3.4-fold with ANF at 100 pmol/kg per min and 1.8-fold with the 200 pmol/kg per min dose. Neither dose of ANF produced significant effects on renal blood flow (RBF) or glomerular filtration rate (GFR). Plasma angiotensin II which was 91 +/- 20 fmol/ml at baseline increased to 175 +/- 25 fmol/ml (P less than 0.05) 45 min after heart failure induction. However, neither dose of ANF significantly reduced these high circulating angiotensin II levels. These results demonstrate that an infusion of a synthetic ANF stimulated saluresis without altering RBF or GFR, and improved cardiac output in dogs with acute left ventricular failure.

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; Coronary Disease; Creatinine; Dogs; Electrolytes; Female; Heart Failure; Hemodynamics; Kidney Function Tests; p-Aminohippuric Acid; Renal Circulation; Time Factors

The diuretic-natriuretic responses of eight assay rats to extracts of atrial tissue obtained 3 months after left coronary ligation were less than the responses to extracts of tissue from sham-operated controls. The mean difference in diuresis (sham-operated response minus ligated response) was 370 (range 22 to 656) microliter/20 minutes (p less than 0.01) and in natriuresis 56 (range -92 to 222) microEq/20 minutes (p = 0.19). The differences in diuretic responses to these extracts was directly related to the severity of elevation of left ventricular end-diastolic pressure in these rats (r = -0.82, p = 0.01). These results in a model with varying degrees of left ventricular dysfunction suggest that myocardial damage is associated with a chronic decrease in atrial natriuretic factor. Reduced circulating atrial natriuretic factor therefore could contribute to the previously observed impaired ability of coronary ligated rats to excrete a saline load and to the sodium retention observed in clinical heart failure. Conclusive evidence will depend on the development of techniques to measure plasma levels of this hormone.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Coronary Disease; Disease Models, Animal; Heart; Male; Natriuresis; Organ Size; Rats; Rats, Inbred Strains