atrial-natriuretic-factor and Myocardial-Ischemia

Since December 2019, an outbreak of a new coronavirus, COVID-19, infection has been taking place. At present, COVID-19 has spread to most countries worldwide. The latest evidence suggests that cytokine storm syndrome (CSS) is an important cause of the transition from mild to critical pneumonia and critically ill patients' death. The sudden exacerbation of COVID-19 may be related to a cytokine storm. Therefore, early identification and active treatment of CSS may play very important roles in improving the patients' prognosis, and these tasks are given attention in the current treatment of new Coronavirus pneumonia. However, there is still no specific medicine for this purpose. This article reviews cytokine storms and conducts an exploratory review of pharmacotherapy for cytokine storms to provide a reference for clinical treatment.

Topics: alpha-Methyltyrosine; Angiotensin-Converting Enzyme 2; Antibodies, Monoclonal, Humanized; Antioxidants; Apoptosis; Atrial Natriuretic Factor; Azetidines; Benzyl Compounds; COVID-19; COVID-19 Drug Treatment; Cytokine Release Syndrome; Enzyme Inhibitors; Glucocorticoids; Glycoproteins; Humans; Hypoxia; Interleukin 1 Receptor Antagonist Protein; Myocardial Ischemia; Myocarditis; Myocytes, Cardiac; Oxidative Stress; Oxygen Inhalation Therapy; Respiration, Artificial; SARS-CoV-2; Sphingosine 1 Phosphate Receptor Modulators; Trypsin Inhibitors; Tumor Necrosis Factor Inhibitors

Experimental studies of acute myocardial infarction have revealed that up to half of the final infarct size may be due to reperfusion injury rather than the initial ischemic incident. Research over the past three decades has deepened our understanding of the molecular mechanisms underlying ischemic reperfusion injury and several therapeutic strategies to decrease the incidence and severity of reperfusion injury have been explored.. To discuss the promising therapies and future perspectives on methods to attenuate myocardial reperfusion injury.. Existing therapies that address reperfusion can be divided into two major groups comprising nonpharmacological and pharmacological interventions. Myriad pharmacological and nonpharmacological approaches to reduce lethal reperfusion injury have been employed. Although many initial clinical studies were negative, more recent proof-of-concept clinical trials are promising. To date, the most encouraging results are with ischemic postconditioning, remote ischemic preconditioning, ANP, adenosine, cyclosporine and exenatide.. Studies demonstrate that nonpharmacological and pharmacological conditioning can be used together as part of a multifaceted approach to improve clinical outcomes in patients with ischemic heart disease.

Topics: Adenosine; Animals; Atrial Natriuretic Factor; Clinical Trials as Topic; Combined Modality Therapy; Cyclosporine; Disease Models, Animal; Exenatide; Humans; Ischemic Postconditioning; Ischemic Preconditioning; Myocardial Ischemia; Myocardial Reperfusion Injury; Peptides; Venoms

Chronic renal failure (CRF) is related to cardiac diseases. Cardiac surgery is also related to postoperative acute kidney injury (AKI). It means heart and kidney have close relationship. We analyzed recent published data to understand how to manage CRF patients undergoing cardiovascular surgeries. We compared endovascular surgery and open procedure for aortic aneurysm, especially about contrast media-related renal damage, On or Off CABG or PCI for ischemic heart disease. We also discussed the relation between cardiopulmonary bypass and AKI and the risk factors causing AKI after CPB. Finally, we discussed prevention and treatment options of CPB related AKI, including furosemide, hANP mannitol, and statin. Published evidence in this area is still insufficient, but many studies are still carried out focusing on postoperative AKI. In the future we may be able to find the best answer for managing CRF patients undergoing cardiovascular surgeries.

Topics: Acute Kidney Injury; Aortic Aneurysm; Atrial Natriuretic Factor; Cardiopulmonary Bypass; Cardiovascular Diseases; Cardiovascular Surgical Procedures; Contrast Media; Coronary Artery Bypass; Furosemide; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mannitol; Myocardial Ischemia; Percutaneous Coronary Intervention; Perioperative Care; Postoperative Complications; Renal Insufficiency, Chronic; Thoracic Surgical Procedures

Postconditioning is an intervention in which controlled, brief, intermittent periods of ischaemia at the onset of reperfusion protect myocardium from the lethal consequences of reperfusion ('reperfusion injury'). Postconditioning has been demonstrated in humans with acute myocardial infarction and offers the possibility of further limiting infarct size in patients undergoing reperfusion therapy. We review current research that focuses on the molecular mechanisms of postconditioning. The molecular pathways are incompletely mapped but they probably converge on suppression of mitochondrial permeability transition pore opening during early reperfusion, an event that is thought to promote cell death at reperfusion. A number of upstream signalling pathways, activated by autacoid factors, converge on this crucial target and these offer a range of realistic possibilities for pharmacological induction of a postconditioned state.

Topics: Animals; Apoptosis Regulatory Proteins; Atrial Natriuretic Factor; Autacoids; Cardiotonic Agents; Drug Delivery Systems; Humans; Ischemic Preconditioning, Myocardial; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Myocardial Ischemia; Myocardial Reperfusion Injury; Narcotic Antagonists; Purinergic P1 Receptor Agonists; Purinergic P1 Receptor Antagonists; Receptors, Opioid; Receptors, Purinergic P1

Sudden cardiac death(SCD) from early myocardial ischemia is often lack of typically morphological findings and clinical manifestation, thus cases of SCD may be suspected as criminal cases. It is necessary to clarify the cause of death, which is significance for medico-legal investigation. This article reviewed the latest advancement in the studies on the application of inorganic ions, CK-MB, cTn, ANP and BNP for certification of death from SCD in order to provide a practical way for diagnosis of SCD in forensic pathology.

Topics: Atrial Natriuretic Factor; Autopsy; Biomarkers; Calcium; Cause of Death; Creatine Kinase, MB Form; Death, Sudden, Cardiac; Forensic Pathology; Humans; Myocardial Infarction; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Troponin

Since the discovery of atrial natriuretic peptide (ANP) more than 20 years ago, numerous studies have focused on the mechanisms regulating ANP secretion. From a physiological standpoint, the most important factor governing ANP secretion is mechanical stretching of the atria, which normally occurs when extracellular fluid volume or blood volume is elevated. In addition, the ability of several vasoconstrictors to increase ANP secretion can be traced to their indirect effects on atrial stretch via increases in cardiac preload or afterload. Whether vasoconstrictors such as angiotensin II and vasopressin have a direct positive or negative effect on ANP secretion has not been determined with certainty. Two paracrine factors derived from endothelial cells play important roles in modulating ANP secretion. Endothelin, a potent vasoconstrictor, stimulates ANP secretion and augments stretch induced ANP secretion. The dramatic increase in ANP release produced by cardiac ischemia appears to be mediated in part by endothelin. Nitric oxide (NO), an important vasodilator, is also produced by endothelial cells and inhibits ANP secretion acting through cyclic GMP as an intracellular messenger. Several recent studies have helped to define the cellular mechanism contributing to regulation of ANP secretion including stretch-activated ion channels, prostaglandins, cytochrome P450, G proteins and cell calcium. A number of steps in the cellular transduction of the ANP signal remain to be resolved. The release of ANP in disease states such as myocardial infarction and heart failure appears to be related to both mechanical and cellular events.

Topics: Animals; Atrial Natriuretic Factor; Biomechanical Phenomena; Calcium; Endothelins; Heart Atria; Humans; Myocardial Ischemia; Myocardium; Nitric Oxide; Prostaglandins

The serine proteases of the trypsin superfamily are versatile enzymes involved in a variety of biological processes. In the cardiovascular system, the importance of these enzymes in blood coagulation, platelet activation, fibrinolysis, and thrombosis has been well established. Recent studies have shown that trypin-like serine proteases are also important in maintaining cardiac function and contribute to heart-related disease processes. In this review, we describe the biological function of corin, tissue kallikrein, chymase and urokinase and discuss their roles in cardiovascular diseases such as hypertension, cardiac hypertrophy, heart failure, and aneurysm.

Topics: Animals; Aortic Aneurysm, Abdominal; Atrial Natriuretic Factor; Cardiomegaly; Chymases; Heart; Humans; Hypertension; Hypertension, Pulmonary; Myocardial Ischemia; Serine Endopeptidases; Tissue Kallikreins; Urokinase-Type Plasminogen Activator

The natriuretic peptides are a family of widely distributed polypeptide mediators that exert a range of actions in several body systems. In cardiovascular homeostasis, the endocrine roles of the cardiac-derived atrial and B-type natriuretic peptide (ANP and BNP) in regulating central fluid volume and blood pressure have been recognised for two decades. However, there is a growing realisation that natriuretic peptide actions go far beyond their endocrine effects and that local (autocrine/paracrine) regulatory actions within the heart and coronary vasculature may be of comparable importance, especially in disease states where tissue and circulating levels of the peptides rise markedly. In acute myocardial ischaemia, release of BNP occurs rapidly from ventricular myocardium, prompting speculation that the early activation of the natriuretic peptide receptor/cGMP signalling system may be an important autocrine/paracrine response in cardiac ischaemia. The autocrine/paracrine actions include inotropic effects, the acute regulation of coronary vascular tone and the attenuation of the susceptibility of myocardium to ischaemic injury. The effects of longer-term upregulation of natriuretic peptide expression in the heart could include the suppression of growth and proliferative responses in a variety of myocardial and vascular cells. In a variety of preparations, acute exposure of epicardial coronary arteries to pharmacological concentrations of natriuretic peptides evokes vasorelaxation, although in coronary microvessels, evidence for a vasorelaxant action of the peptides is less consistent. The mechanisms of the coronary vasorelaxant action are unclear but limited evidence suggests an endothelium-dependent component. In ischaemic myocardium, acute treatment with BNP prior to and during coronary artery occlusion exerts a markedly protective, concentration-dependent infarct-limiting action. This cytoprotective effect of the natriuretic peptide signalling pathway might conceivably represent an alternative endogenous salvage pathway in myocardium which is potentially exploitable therapeutically. Taken together, the acute actions of natriuretic peptides on the coronary vasculature and in myocardial ischaemia suggest a profile of activity that may be therapeutically beneficial in the management of patients with acute coronary syndromes.

Topics: Animals; Atrial Natriuretic Factor; Coronary Vessels; Heart Ventricles; Humans; Myocardial Ischemia

B-type natriuretic peptide (BNP) and the N-terminal fragment of its prohormone (N-proBNP) are released from the heart in response to increased wall stress. Assays for these peptides are now commercially available, and measurement of BNP and N-proBNP is becoming commonplace in patients with suspected heart failure. BNP and N-proBNP facilitate diagnosis and risk stratification in patients with heart failure, and may help guide response to therapy. This review focuses on the emerging role of BNP and N-proBNP measurement in patients with acute coronary syndromes (ACS). Although experimental studies demonstrate rapid BNP release in response to cardiac ischemia, it is unlikely that BNP will be used to diagnose cardiac ischemia, because many other conditions are also associated with modest BNP elevation. In contrast, BNP holds tremendous promise as a prognostic marker in patients with ACS. Studies to date have shown consistently that higher BNP levels are associated with worse clinical outcomes, and that BNP provides unique information to clinical variables, other biomarkers, and left ventricular ejection fraction. Future studies are needed to identify the therapeutic implications of BNP elevation in patients with ACS.

Topics: Acute Disease; Angina, Unstable; Atrial Natriuretic Factor; Cardiotonic Agents; Humans; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Protein Precursors; Syndrome

The role of the clinical laboratory in emergency cardiac medicine is rapidly evolving; with recent redefinitions of acute myocardial infarction (AMI) and unstable angina (UA) based on troponin levels, recommended acceleration of cardiac testing protocols, and increased clinical measurement of B-type natriuretic peptide (BNP). We briefly review the background pathophysiology of acute coronary syndromes (ACS) and congestive heart failure (CHF), along with an overview of the biochemistry and physiology of the natriuretic peptides.. The assay principles and performance characteristics of the rapid BNP assays are discussed. The performance characteristics of troponin assays are at the center of controversy regarding the redefinition of AMI and UA, and will be discussed.. We review the rapidly expanding evidence regarding the clinical utility of BNP for CHF patients. While BNP has gained wide acceptance as a rapid diagnostic tool, considerable controversy remains concerning its potential for prognosis, screening, and therapeutic monitoring. Although a thorough discussion of the use of cardiac markers is well beyond the scope of this review, overviews of the redefinitions of AMI and UA, and the trend toward accelerated testing protocols to obtain a quicker diagnosis or ruling-out of AMI are included. In addition to accelerating the retesting of existing markers, a recent test for ischemia modified albumin (IMA) promises another quantum leap in cardiac diagnoses.. The positive impact of these developments on the healthcare costs and overall improvement in the quality of healthcare delivery will be discussed. A brief analysis of the downstream costs of BNP testing is also offered.

Topics: Atrial Natriuretic Factor; Biomarkers; Emergencies; Heart Failure; Humans; Medical Laboratory Science; Myocardial Ischemia; Natriuretic Peptide, Brain

The natriuretic peptide family consists of four molecules that share significant amino acid sequence homologic characteristics and a looped motif. Atrial natriuretic peptide and brain natriuretic peptide are similar in their ability to promote natriuresis and diuresis, inhibit the renin-angiotensin-aldosterone axis, and act as vasodilators. Understanding of the actions of C-type natriuretic peptide and dendroaspis natriuretic peptide is incomplete, but these two new family members also act as vasodilators. Because of the rapid evolution of information about this peptide family, we reviewed the state of the art with respect to risk stratification and therapeutic ability.. English-language papers were identified by a MEDLINE database search covering 1966 through 1997 and supplemented with bibliographic references and texts.. The natriuretic peptides are counterregulatory hormones with prognostically important levels. They are similarly upregulated in heart failure and counteract neurohormones that induce vasoconstriction and fluid retention. BNP may be the superior prognosticator for risk stratification after myocardial infarction and is independent of left ventricular ejection fraction. Lastly, experimental trials suggest that administration of exogenous natriuretic peptides or inhibitors of their catabolism to patients with ischemic heart disease may be clinically beneficial.

Topics: Animals; Atrial Natriuretic Factor; Humans; Myocardial Infarction; Myocardial Ischemia; Vasodilation

1. The major cardiovascular and renal actions of alpha-atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and the fact that the heart is strategically located to sense changes in intravascular volume indicate the importance of these peptides in the overall control of the extracellular fluid volume under normal and pathophysiological conditions.2. This review examines the clinical and diagnostic significance of the measurement of plasma natriuretic peptides in diseases of the cardiovascular system with particular emphasis on the assessment of patients with heart failure. 3. Raised plasma levels of ANP and BNP have repeatedly been found in patients with heart disease originating from diverse causes including tachycardias, valvular stenosis or ventricular dysfunction. The raised circulating levels of natriuretic peptide (ANP, N-terminal proANP and BNP in particular) are associated with (i) raised atrial and pulmonary wedge pressures; (ii) reduced ventricular systolic and diastolic function; (iii) presence (and possibly geometric form) of left ventricular hypertrophy; and (iv) severe myocardial infarction. Although both plasma ANP and BNP are raised in the presence of left ventricular hypertrophy, BNP appears to be a better index of left ventricular hypertrophy.4. Several situations where the measurement of natriuretic peptides may be of benefit in the overall assessment of heart disease are discussed. However, it is emphasized that the measurement of plasma natriuretic peptides alone appears to be of limited value as a specific diagnostic tool, given that raised levels are a consequence of haemodynamic and structural abnormalities arising from diverse pathological processes. Despite these limitations, the major value of plasma natriuretic peptides in the examination of patients with suspected heart disease rests on the premise that: (i) a normal value would not be consistent with cardiac disease; (ii) the presence of markedly raised levels may help to target those for subsequent detailed assessment of underlying cardiac dysfunction; and (iii) markedly raised levels of plasma natriuretic peptides after myocardial infarction can identify those at high risk of death.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Heart Failure; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Prognosis; Risk Factors

Long-term controlled trials in heart failure in patients with asymptomatic left ventricular dysfunction indicate the potential of ACE inhibition to reduce ischaemic events, such as unstable angina and myocardial infarction. These effects occur after long-term medication and suggest structural rather than functional effects of ACE inhibitors. Such structural effects could include an improvement in endothelial function and less atherosclerosis of coronary and systemic arteries, as well as a reduction in cardiac size. Together, these effects may improve the myocardial oxygen supply/demand ratio. Neurohormonal activation is pivotal in heart failure and also occurs in patients with asymptomatic left ventricular dysfunction. ACE inhibitors modulate neurohormonal activation and, through that mechanism, may induce their beneficial effects in terms of cardiac remodelling and improved morbidity and mortality in heart failure patients. Neurohormonal activation also occurs during acute myocardial infarction, particularly in patients with diminished left ventricular dysfunction or heart failure. Recent studies indicate that short episodes of stress-induced myocardial ischaemia may also lead to significant increases in circulating norepinephrine, epinephrine and, in more severe ischaemia, in angiotensin II. This increase in vasoconstricting neurohormones results in significant systemic vasoconstriction and may also underlie the constriction of abnormal coronary segments observed during atrial pacing-induced stress. This ischaemia-induced neurohormonal activation is not dependent on the stress of angina, but correlates with the degree of myocardial ischaemia and also with the presence of left ventricular dysfunction. Acute ACE inhibition modulates this ischaemia-induced neurohormonal activation and the subsequent effects on systemic and coronary vascular tone. Consequently, acute ACE inhibition significantly reduces acute myocardial ischaemia. The significance of these observations is as yet unclear. However, they may be important in situations of severe myocardial ischaemia, such as unstable angina and acute myocardial infarction. Presumably, this potential of ACE inhibitors to reduce short-term stress-induced myocardial ischaemia as a result of their neurohormonal modulating and subsequent vasodilating effects gains in significance during chronic ACE inhibitor treatment, in parallel with a long-term improvement of coronary endothelial function.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Controlled Clinical Trials as Topic; Humans; Myocardial Infarction; Myocardial Ischemia; Norepinephrine; Peptidyl-Dipeptidase A

The purpose of this study was to determine the effect of human atrial natriuretic peptide (hANP) in patients who underwent coronary artery bypass grafting (CABG) on renal function.. Acute renal failure after cardiac surgery is associated with high morbidity and mortality.. A total of 504 patients who underwent CABG were divided into 2 groups: 1 group received hANP at 0.02 microg/kg/min from the start of cardiopulmonary bypass (hANP group), and 1 group did not receive hANP (placebo group). Various parameters were measured before and after surgery.. There was no difference in mortality between the 2 groups, but post-operative complications were less frequent in the hANP group (p = 0.0208). In the hANP group, serum creatinine (Cr) was significantly lower and urinary Cr and Cr clearance were significantly higher from post-operative day 1 to week 1. The maximum post-operative Cr level and percent increase of Cr were significantly lower in the hANP group (p < 0.0001). Patients with Cr exceeding 2.0 mg/dl included 1 in the hANP group and 8 in the placebo group, showing a significant difference (p = 0.0374). Four patients in the placebo group and none in the hANP group required hemodialysis, but the difference was not statistically significant.. Continuous infusion of low-dose hANP from the start of cardiopulmonary bypass effectively maintained post-operative renal function. Infusion of hANP prevents early post-operative acute renal failure and helps to achieve safer cardiac surgery. (. UMIN000001440).

Topics: Aged; Atrial Natriuretic Factor; Cardiopulmonary Bypass; Coronary Artery Bypass; Creatinine; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Infusions, Intravenous; Intraoperative Care; Kidney; Male; Myocardial Ischemia; Postoperative Complications; Renal Insufficiency; Treatment Outcome

Cardiac peptides are increased at rest in heart failure patients representing a useful diagnostic tool for this condition. Recently it has been demonstrated that cardiac peptides increase also during myocardial ischemia. Cardiac peptides increase during exercise in heart failure patients, but it has not been established yet if the increase is the same in ischemic and nonischemic patients.. There were studied 50 heart failure patients, 32 ischemic and 18 nonischemic, 35 males and 15 females aged 61.8 +/- 11.61 after the relief of congestive syndrome, which was submitted to a symptom-limited exercise stress test on a cycloergometer. Blood samples were obtained at rest and at a peak effort and the plasmatic values of NT-proBNP (NV<250 fmoles/mL) and of NT-proANP (NV<1950 fmoles/mL) were determined using the ELISA method.. At rest, both NT-proBNP and NT-proANP were more increased in nonischemic (1104.33 +/- 730; 3275.55 +/- 3424) than in ischemic patients (685.68 +/- 452.01, 2265.0 +/- 2552.32) with significant differences only for NT-proBNP (p=0.016). During exercise NT-proBNP increase from 836.40 +/- 596.34 to 1403.92 +/- 2126.21 and NT-proANP from 2628.80 +/- 2903.41 to 3701.30 +/- 3237.76, the final values being again more increased in nonischemic patients (NT-proBNP-2945.44 +/- 3257.89; NT-proANP-3174 +/- 2905); for NT-proBNP p<0.05. The results suggest that the stretching effect during exercise is more increased at the ventricular level in comparison with the atrial level (67% increase for NT-proBNP and only 40% for NT-proANP). Surprisingly, myocardial ischemia does not increase additionally cardiac peptides either at rest or during exercise. Our data suggest that the intracardiac pressure is more important than ischemia in determining the increase of cardiac peptides in heart failure patients because the left ventricular ejection fraction was lower in nonischemic patients (40.03 +/- 5.5 vs 38.11 +/- 4.07).. Cardiac peptides are increased, both at rest and during exercise, in nonischemic heart failure patients in comparison with ischemic ones, probably in relationship with the lower left ventricular systolic function.

Topics: Atrial Natriuretic Factor; Exercise Test; Female; Heart Failure; Humans; Linear Models; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index

Off-pump coronary artery bypass grafting (CABG) is an alternative to conventional CABG using cardiopulmonary bypass. Off-pump technique reduces the complications of CABG performed with extracorporeal circulatory assistance (Lancey et al. 2000; Mack et al. 2004a,b). The object of this study was to compare peri- and postoperative time courses of vasoactive peptides - atrial natriuretic poptide (ANP), brain natriuretic poptide (BNP) and endothelin-1 (ET-1) in off-pump versus on-pump CABG. 22 patients, who underwent on-pump (group A, n = 11) or off-pump CABG (group B, n = 11) were studied. The peri- and postoperative time courses of plasma ANP and BNP were similar in both groups. A statistically significant difference between ET-1 plasma level 2 h after surgery in the group A and ET-1 plasma level 2 h after surgery in the group B (2.46 + or - 1.14 pg/ml/Ht versus 0.74 + or - 0.09 pg/ml/Ht, p < 0.0001) was found. Different CABG techniques were not associated with significant changes in peri- and postoperative plasma ANP and BNP. By contrast, plasma ET-1 significantly rose in the group A 2 h after surgery, indicating endothelial damage.

Topics: Adult; Aged; Atrial Natriuretic Factor; Coronary Artery Bypass; Endothelin-1; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain

The aim of this study was to investigate what factor determines tachycardia-induced secretion of atrial and brain natriuretic peptides (ANP and BNP, respectively) in patients with hypertrophic cardiomyopathy (HCM). HCM patients with normal left ventricular (LV) systolic function and intact coronary artery (n = 22) underwent rapid atrial pacing test. The cardiac secretion of ANP and BNP and the lactate extraction ratio (LER) were evaluated by using blood samples from the coronary sinus and aorta. LV end-diastolic pressure (LVEDP) and the time constant of LV relaxation of tau were measured by a catheter-tip transducer. These parameters were compared with normal controls (n = 8). HCM patients were divided into obstructive (HOCM) and nonobstructive (HNCM) groups. The cardiac secretion of ANP was significantly increased by rapid pacing in HOCM from 384 +/- 101 to 1,268 +/- 334 pg/ml (P < 0.05); however, it was not significant in control and HNCM groups. In contrast, the cardiac secretion of BNP was fairly constant and rather significantly decreased in HCM (P < 0.01). The cardiac ANP secretion was significantly correlated with changes in LER (r = -0.57, P < 0.01) and tau (r = 0.73, P < 0.001) in HCM patients. Tachycardia potentiates the cardiac secretion of ANP, not BNP, in patients with HCM, particularly when it induces myocardial ischemia and LV diastolic dysfunction.

Topics: Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Cardiomyopathy, Hypertrophic; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Tachycardia; Ventricular Dysfunction, Left

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

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

Now that marathon racing is growing in popularity, many thousands of enthusiastic athletes are participating in various ultramarathons all over the world each year. However, it remains controversial whether such a sport contributes to the promotion of health. The occurrence of transient cardiac dysfunction and irreversible myocardial injury has been reported in association with such exercise in healthy individuals. Brain natriuretic peptide (BNP) is a cardiac hormone, as is atrial natriuretic peptide (ANP), and its measurement has been widely used for clinical evaluation of cardiac dysfunction. However, little is known about the response of plasma BNP to prolonged strenuous exercise. We hypothesized that confirmation of minimal cardiac dysfunction or myocardial injury may be made by measurements of plasma BNP.. Levels of plasma ANP, BNP, catecholamines, blood lactate, and serum cardiac troponin T (cTnT) were determined before and after a 100-km ultramarathon in 10 healthy men to examine the effects of the exercise on levels of ANP and BNP and correlations between the natriuretic peptides and cTnT as a marker for myocardial damage.. Whereas all variables significantly increased after the race, increased levels of ANP and BNP were most strongly correlated with increases in cTnT levels. The cTnT level after the race was greater than the upper reference limit in 9 of 10 men.. Such exercise significantly increased ANP and BNP levels in healthy men, and the increases could be partially attributed to myocardial damage during the race.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Epinephrine; Exercise; Hematocrit; Hemoglobins; Humans; Lactic Acid; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Norepinephrine; Reference Values; Retrospective Studies; Risk Factors; Running; Troponin T

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

Plasma neurohormones were analyzed for prediction of adverse outcomes and response to treatment in 415 patients with ischemic left ventricular dysfunction randomly assigned to receive carvedilol or placebo.. Atrial natriuretic peptide, brain natriuretic peptide (BNP), or norepinephrine (NE) levels above the group median were associated with increased mortality rates and heart failure. On multivariate analysis, both BNP and NE interacted with treatment to predict death or heart failure independent of age, New York Heart Association class, and left ventricular ejection fraction. For placebo, supramedian levels of BNP were associated with 3-fold the mortality rate of inframedian levels (20/104; 19% vs 6/99; 6%; P<0.01). For carvedilol, mortality rate was comparable in these 2 subgroups (12/109; 11% vs 8/94; 9%; NS). Corresponding rates for heart failure were 29/104 (28%) versus 3/99 (3%; P<0.001) for placebo and 16/109 (15%) versus 7/94 (7%; NS) for carvedilol. High NE levels did not predict additional benefit from carvedilol, which significantly reduced heart failure admissions only in those with NE levels below the median (13.1% to 4. 0%; P<0.01). In the 23% of the study population with supramedian BNP but inframedian levels of NE, carvedilol reduced hospital admission with heart failure by >90% (P<0.001).. Carvedilol reduced mortality rates and heart failure in those with higher pretreatment BNP levels but lesser activation of plasma NE. Neurohumoral profiling may guide introduction of beta-blockade in heart failure.

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Carbazoles; Carvedilol; Double-Blind Method; Heart Failure; Humans; Multivariate Analysis; Myocardial Ischemia; Natriuretic Peptide, Brain; Neuropeptides; Norepinephrine; Predictive Value of Tests; Prognosis; Propanolamines; Survival Analysis; Vasodilator Agents; Ventricular Dysfunction, Left

Angiotensin converting enzyme (ACE) inhibition after myocardial infarction is associated with an improvement in plasma fibrinolytic parameters. The aim of the present study was to determine whether acute ACE inhibition and angiotensin II type 1 (AT1) receptor antagonism have similar effects in patients with heart failure.. Twenty patients with moderately severe chronic heart failure received enalapril 10 mg and losartan 50 mg on 2 separate occasions in a single-blind, randomized, crossover design. Plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) antigen and activity were measured at baseline and 6 hours after the dose. Acute administration of losartan but not of enalapril reduced plasma t-PA (11%; P=0.003) and PAI-1 (38%; P<0.001) antigen concentrations, which was associated with increases in t-PA (29%; P=0.03) and decreases in PAI-1 (48%; P=0.01) activity. Changes in plasma fibrinolytic parameters were more marked during losartan treatment (P<0.02), with a 3-fold greater reduction in plasma PAI-1 antigen concentrations (P<0.05).. Acute AT1 antagonism in patients with heart failure is associated with a significant improvement in plasma fibrinolytic parameters that is greater than during ACE inhibition. These beneficial effects of AT1 antagonism and ACE inhibition would therefore appear to be mediated principally through suppression of angiotensin II.

Topics: Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Cardiomyopathy, Dilated; Cross-Over Studies; Enalapril; Female; Fibrinolysis; Heart Failure; Heart Rate; Hemodynamics; Humans; Losartan; Male; Myocardial Ischemia; Plasminogen Activator Inhibitor 1; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Single-Blind Method; Tissue Plasminogen Activator; Ventricular Dysfunction, Left

Proteinuria associated with acute heart disease was studied prospectively in 160 patients admitted to the coronary care unit with suspected AMI. Series 1 comprised 150 patients, divided into the following groups: AMI, 27 UAP, 43 AP, 22 NIP and 18 excluded. Albumin and creatinine were measured in the first urine passed after admission (sample 1) and the first morning urine the following 2 days (samples 2 and 3). The ACR was significantly higher in the AMI and UAP groups than in the other patient groups (p < 0.0001). There was no significant difference of ACR between the AMI and UAP in sample 1 (p = 0.31). In the AMI, UAP and AP groups ACR was significantly higher in sample 1 than in samples 2 and 3 (p < 0.005). In the NIP group there were no significant differences between sample 1 versus samples 2 and 3 (p = 0.06). Series 2 comprised 10 patients: 8 AMI, 1 UAP and 1 AMYO. ACR were measured in all specimens voided during the period of observation. ACR can oscillate within hours between normal concentrations and concentrations well into or above the microalbuminuric range. We propose the term episodic albuminuria for this reversible, switch-like change in renal function. The albuminuric episodes lasted 90-600 minutes. Maximum values for ACR were between 133-790 mumol/mol or 78-466 mg/g. In healthy, resting individuals ACR is < 50 mumol/mol (< 30 mg/g). The rapid changes in glomerular permeability may reflect systemic changes in endothelial permeability in the affected individuals. We speculate that atrial natriuretic peptide (ANP) may be a mediator of this type of albuminuria.

Topics: Adult; Aged; Albuminuria; Angina, Unstable; Atrial Natriuretic Factor; Biomarkers; Chest Pain; Creatinine; Female; Humans; Kidney Function Tests; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Myocarditis; Prospective Studies

Topics: Aged; Atrial Natriuretic Factor; Exercise Test; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Norepinephrine; Physical Endurance

Atrial natriuretic peptide (ANP) has been shown to dilate the coronary artery. The aim of this study was to determine whether, in patients with effort angina pectoris, intracoronary infusion of ANP attenuates pacing-induced myocardial ischemia either by dilating the stenotic lesion in a large coronary artery or by dilating collateral vessels.. We studied six patients who had total or subtotal occlusion in one coronary artery and well-developed, angiographically visible collateral vessels (group A) and five patients who had a significant stenosis in a large coronary artery with no visible collateral vessels (group B). Their heart rate was increased by atrial pacing both before and after intracoronary infusion of ANP (0.03 microgram/kg/min for 15 min) into the donor artery of collateral vessels in group A or into the stenotic artery in group B.. Before ANP infusion, all patients of both groups developed an ischemic ST-segment depression (> or = 0.1 mV) and angina-like chest pain from pacing tachycardia. After ANP infusion, significant ST-segment depression was induced by rapid pacing in only one out of six patients of group A, whereas it was noted in all patients of group B (P < 0.01). After ANP infusion, chest pain developed in one out of six patients in group A, whereas it appeared in four out of five patients in group B (P < 0.05). ANP significantly dilated the angiographically normal segment of the epicardial coronary artery, but it did not significantly change the severity of the stenotic lesion in either group. ANP did not change the basal arterial pressure or heart rate, nor did it change their response to pacing tachycardia.. Infusing ANP into the donor artery of collateral vessels, but not into the artery with culprit stenotic lesion, attenuated pacing-induced myocardial ischemia. Therefore, the beneficial effects of ANP in reducing pacing-induced myocardial ischemia may result from the increase in myocardial perfusion to the ischemic area caused by dilating the collateral vessels.

Topics: Aged; Angina Pectoris; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Collateral Circulation; Constriction, Pathologic; Coronary Vessels; Female; Humans; Infusions, Intravenous; Injections, Intralesional; Male; Middle Aged; Myocardial Ischemia; Vasodilation

To examine the relation between haemodynamics and atrial natriuretic peptide concentration during short term angiotensin converting enzyme inhibition.. Patients were randomly allocated to receive placebo or one of three doses of the angiotensin converting enzyme inhibitor ramipril.. Cardiac units of two tertiary referral hospitals.. 38 Patients with stable congestive heart failure caused by ischaemic heart disease.. Data were collected over a 24 hour period and assessed with the aim of distinguishing between the haemodynamic effects on plasma concentrations of atrial natriuretic peptide and the direct effects of the study drug, vasopressin concentrations, and angiotensin converting enzyme activity.. Pulmonary capillary wedge pressure was the main predictor of the plasma concentration of atrial natriuretic peptide. A higher plasma concentration of this peptide with a given pulmonary capillary wedge pressure was found after 24 hours of treatment with 2.5 mg and 5 mg of ramipril. Plasma concentration of the active metabolite, change in arginine vasopressin concentration or degree of angiotensin converting enzyme inhibition did not significantly predict change in plasma concentration of atrial natriuretic peptide or in the ratio of atrial natriuretic peptide concentration to pulmonary capillary wedge pressure.. A gradual increase in plasma concentration of atrial natriuretic peptide with a given pulmonary capillary wedge pressure, occurs during short term high degree inhibition of angiotensin converting enzyme. The causative mechanisms are yet to be identified. Such a change in the relation between central haemodynamics and atrial natriuretic peptide concentration may contribute to the beneficial effects of angiotensin converting enzyme inhibition in patients with congestive heart failure due to ischaemic heart disease.

Topics: Aged; Arginine Vasopressin; Atrial Natriuretic Factor; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Peptidyl-Dipeptidase A; Pulmonary Wedge Pressure; Ramipril; Renin

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

The effects of nisoldipine on regional myocardial perfusion and neuro-hormonal status were assessed in a double-blind, placebo-controlled study of 32 patients. All patients had ischaemic left ventricular dysfunction, with a left ventricular ejection fraction between 25% and 35%; per protocol, they were stratified according to concomitant use of ACE inhibitors. After baseline measurements at rest, including single photon emission computed tomography (SPECT) with Tc-MIBI, plasma neuro-hormones (norepinephrine, renin, arginine vasopressin, atrial natriuretic peptide) and echocardiography, the patients were randomized to nisoldipine (core coat tablet, 20 mg once daily; n = 16) or placebo (n = 16). Measurements were repeated after 8 weeks. SPECT data were analysed qualitatively (visual comparison by blinded observer) and quantitatively to derive an index of hypoperfusion representing the percentage of the left ventricular mass with Tc-MIBI activity below normal. At baseline, all patients had left ventricular areas with reduced Tc-MIBI uptake and 29 patients also had increases in plasma neuro-hormones. With nisoldipine, the extent of hypoperfusion (quantitative analysis) was reduced in 8/14 patients vs only 2/14 patients with placebo (P = 0.046, 2-tailed test). The benefit of nisoldipine was similar in patients with or without ACE inhibitor therapy and was also confirmed by the visual analysis of the data. Further, none of the neuro-hormones examined was significantly modified by nisoldipine. Thus, chronically underperfused areas are present at rest in patients with ischaemic left ventricular dysfunction, and nisoldipine significantly improved Tc-MIBI uptake in these areas without evidence of detrimental changes in plasma neuro-hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Coronary Circulation; Double-Blind Method; Echocardiography; Female; Heart; Humans; Male; Middle Aged; Myocardial Ischemia; Nisoldipine; Norepinephrine; Renin; Technetium Tc 99m Sestamibi; Tomography, Emission-Computed, Single-Photon; Ventricular Dysfunction, Left

Drugs facilitating the cardioprotective effects of natriuretic peptides are introduced in heart failure treatment. ANP and BNP also stimulate lipolysis and increase circulating concentrations of free fatty acids (FFAs); an aspect, however, thought to be confined to primates. We examined the lipolytic effect of natriuretic peptide infusion in healthy young men and evaluated the effect in a porcine model of myocardial ischemia and reperfusion. Six young healthy normotensive men underwent infusion with ANP, BNP, or CNP for 20 min. Blood samples were collected before, during, and after infusion for measurement of FFAs. In a porcine model of myocardial ischemia and reperfusion, animals were infused for 3 h with either BNP (n = 7) or saline (n = 5). Blood samples were collected throughout the infusion period, and cardiac tissue was obtained after infusion for lipid analysis. In humans, ANP infusion dose-dependently increased the FFA concentration in plasma 2.5-10-fold (baseline vs. 0.05 μg/kg/min P < 0.002) and with BNP 1.6-3.5-fold (P = 0.001, baseline vs. 0.02 μg/kg/min) 30 min after initiation of infusion. Infusion of CNP did not affect plasma FFA. In pigs, BNP infusion induced a 3.5-fold increase in plasma FFA (P < 0.0001), which remained elevated throughout the infusion period. Triglyceride content in porcine right cardiac ventricle tissue increased ∼5.5 fold in animals infused with BNP (P = 0.02). Natriuretic peptide infusion has similar lipolytic activity in human and pig. Our data suggest that short-term infusion increases the cardiac lipid content, and that the pig is a suitable model for studies of long-term effects mediated by natriuretic peptides.

Topics: Animals; Atrial Natriuretic Factor; Disease Models, Animal; Fatty Acids, Nonesterified; Female; Heart; Humans; Infusions, Intravenous; Lipolysis; Male; Models, Animal; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Sus scrofa; Triglycerides

The T2238C variant of the ANP gene is associated with higher risk of major cardiovascular events. The purpose of this study is to investigate if this polymorphism influences the response to antiplatelet agents and it is responsible of increased platelet reactivity, thus contributing to the adverse outcome. In patients undergoing elective percutaneous coronary intervention (PCI), loaded with antiplatelets, blood samples were withdrawn for genotyping, platelet reactivity assessment and for troponin T measurement to investigate the association between the polymorphism with residual platelet reactivity and with the incidence of PPMI. No significant differences in platelet reactivity nor in PPMI incidence were observed between groups. Nevertheless, higher ARU, PRU, and % PI were detected in diabetic patients, with PRU significantly higher in carriers versus non-carriers. We observed increased residual platelet reactivity exclusively in diabetic carriers of the T2238C variant undergoing elective PCI, suggesting the need of a more effective platelet inhibition in this category of patients.

Topics: Aged; Aspirin; Atrial Natriuretic Factor; Clopidogrel; Drug Resistance; Drug Therapy, Combination; Female; Genotype; Humans; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Pharmacogenomic Variants; Phenotype; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Risk Factors; Treatment Outcome

Following acute myocardial infarction, clinical studies show alterations in the blood levels of corin, a cardiac-selective activator of the natriuretic peptides pro-atrial natriuretic peptide (pro-ANP) and pro-B-type natriuretic peptide (pro-BNP). However, the temporal changes in circulating and cardiac corin levels and their relationships to the severity of myocardial infarction have not been studied. The main objective of this study was to examine the relationship between cardiac and circulating corin levels and their association with cardiac systolic function and infarct size during the early phase of acute myocardial infarction (<72 h) in a translationally relevant induced coronary ligation mouse model. This acute phase timeline was chosen to correlate with the clinical practice within which blood samples are collected from myocardial infarction patients. Heart and plasma samples were examined at 3, 24, and 72 hours post acute myocardial infarction. Plasma corin levels were examined by enzyme-linked immunosorbent assay, transcripts of cardiac corin, pro-ANP and pro-BNP by quantitative real-time polymerase chain reaction, cardiac corin expression by immunohistology, infarct size by histology and heart function by echocardiography. Plasma corin levels were significantly increased at 3 (P<0.05), 24 (P<0.001), and 72 hours (P<0.01) post-acute myocardial infarction. In contrast, cardiac corin transcript levels dropped by 5% (P>0.05), 69% (P<0.001) and 65% (P<0.001) and immunoreactive cardiac corin protein levels dropped by 30% (P<0.05), 76% (P<0.001) and 75% (P<0.001), while cardiac pro-ANP and pro-BNP transcript levels showed an opposite pattern. Plasma corin levels were negatively correlated with immunoreactive cardiac corin (P<0.01), ejection fraction (P<0.05) and fractional shortening (P<0.05), but positively correlated with infarct size (P<0.01). In conclusion, acute myocardial infarction induces rapid increases in plasma corin and decreases in cardiac corin levels. In the early phase of acute myocardial infarction, plasma corin levels are inversely correlated with heart function and may reflect the severity of myocardial damage.

Topics: Animals; Atrial Natriuretic Factor; Heart; Male; Mice; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; RNA, Messenger; Serine Endopeptidases; Time Factors

To investigate the relationship between zinc finger protein(ZFP580)and ventricular remodeling after myocardial is-chemia/reperfusion(I/R) injury in rats.. Seventy-two rats were divided into sham group and I/R groups which would be tested in se-ries time of 0.5 h, 1 h, 2 h, 4 h, 1 d,7 d,14 d,28 d after reperfusion to observe the expression of ZFP580 in rat myocardium. The H9C2 cells were cultured and treated with transforming growth factor-beta1 (TGF-β 1) to establish cardiac hypertrophy in vitro model in series time of 0 h, 8h, 16 h and 24 h. The cardiomyocyte hypertrophy morphology was measured. The mRNA levels of atrial natriuretic peptide(ANP), myosin heavey chain beta(β -MHC) and ZFP580 genes were quantified. The protein levels of MMP-3 and ZFP580 were quantified after H9C2 cells were transfected by lentiviral-mediated ZFP580 gene.. Myocardial I/R injury model was successfully established. Myocardial tis-sue in rats had large area infarction, and myocardial cells were eosinophilic changed. The increased level of ZFP580 protein was observed in the cardiomyocytes around infarction zone. The expression of TGF-β 1 in myocardium was up-regulated after myocardial I/R injury. TGF-β 1 (5 ng/ml) treatment could induce cardiomyocyte hypertrophy in H9C2 cells. TGF-β 1 treatment increased the cell size and mRNA levels of ANP andβ -MHC genes (. ZFP580 is probably related with ventricular remodeling after myocardial I/R injury by involving TGF-β 1 induced cardiomyocyte hypertrophy and attenuating MMP-3 production.

Topics: Animals; Atrial Natriuretic Factor; Cell Line; Matrix Metalloproteinase 3; Myocardial Ischemia; Myocardium; Myocytes, Cardiac; Myosin Heavy Chains; Rats; Reperfusion Injury; Transcription Factors; Transfection; Transforming Growth Factor beta1; Ventricular Remodeling

In forensic medicine, the diagnosis of death due to neurogenic shock is considered to be an aporia, as lacking objective indicators and presenting atypical symptoms in autopsy. Medico-legal disputes and complaints occasionally result from this ambiguity. To explore potential objective indicators of neurogenic shock, we set up a model of neurogenic shock by applying an external mechanical force on the carotid sinus baroreceptor in rabbits. The serum atrial natriuretic peptide (ANP) level was measured by radioimmunoassay in the control group (n = 8), survival group (n = 15) and death group (n = 5) both before and after the insult. The serum ANP level showed a significant increase after the insult in the death group compared with the serum obtained before the insult (P = 0.006), while the serum ANP level after the insult in the survival group and control group was not statistically significant compared with the serum obtained before the insult (P = 0.332 and P = 0.492, respectively). To verify the repeatability of the model and the postmortem behavior of serum ANP, five healthy adult rabbits underwent the same procedure as the experimental group. The mortality rate was consistent with the former experiment (20 %). There were no significant changes in serum ANP level in vitro and in vivo (within 48 and 24 h, respectively). But there was a significant decrease in serum ANP level at 48 h postmortem in vivo (P = 0.001). A female patient who expired due to neurogenic shock during a hysteroscopy was reported. Neither fatal primary disease nor evidence for mechanical injuries or intoxication was found according to the autopsy. The serum ANP level was assayed as a supplementary indicator and was found to be three-fold higher than the normal maximum limit. Combined with the animal experiment, this case highlights that serum ANP has the potential to be an objective indicator for the diagnosis of death due to neurogenic shock.

Topics: Adult; Animals; Atrial Natriuretic Factor; Biomarkers; Carotid Sinus; Female; Humans; Immunoglobulin E; Myocardial Ischemia; Myocardium; Rabbits; Radioimmunoassay; Shock

The atrium is the major site of ANP synthesis, which has been said to increase in heart failure as a result of increased production in the left ventricular (LV) myocardium. This is a key issue related to its diagnostic and prognostic capabilities. We aimed to evaluate protein levels of proANP and ANP and the enzymes that cleave the natriuretic peptides, corin and furin, in the LV tissue of heart transplant patients with dilated (DCM) and ischemic (ICM) cardiomyopathy compared with control donors (CNT). We also evaluate mRNA levels of ANP gene (NPPA) by RNA sequencing in the same tissue.. Seventy-three human LV tissue samples from ICM (n=30) and DCM (n=33) patients and CNT (n=10) were analyzed by Western blot and RNA sequencing. Comparing protein levels according to etiology, neither DCM nor ICM showed levels of proANP or ANP different from those of CNT. However, NPPA was increased in both groups compared to CNT (DCM 32 fold, p<0.0001; ICM 10 fold, p<0.0001). Corin (but not furin) was elevated in the ICM group compared to CNT (112 ± 24 vs. 100 ± 7, p<0.05), and its level was inversely related with LV ejection fraction (LVEF) (r=-0.399, p<0.05).. Patients present with elevated levels of NPPA but not of proANP or ANP proteins in LV tissue, which may be due to posttranscripcional regulation of NPPA or different pathways for ANP secretion between the atrium and ventricle. Moreover, there are differences between DCM and ICM in corin levels, indicating that a different molecular mechanism may exist that converge in this syndrome. Further, LV concentration of corin is inversely related to LVEF in ICM.

Topics: Adult; Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Case-Control Studies; Female; Furin; Gene Expression; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Ischemia; Protein Precursors; Sequence Analysis, RNA; Serine Endopeptidases

Carperitide is effective for heart failure (HF) owing to its diuretic and vasodilatory effects. This recombinant peptide may also have direct cardioprotective effects because carperitide reduces the severity of heart failure and limits infarct size. Because coronary vasodilation is an important cardioprotective treatment modality, we investigated whether carperitide increased coronary blood flow (CBF) and improved myocardial metabolic and contractile dysfunction during ischemia in canine hearts. We also tested whether carperitide is directly responsible for limiting the infarct size. We infused carperitide at 0.025-0.2 μg kg(-1) min(-1) into the canine coronary artery. A minimum dose of 0.1 μg kg(-1) min(-1) was required to obtain maximal vasodilation. To test the effects of carperitide on ischemic hearts, we reduced perfusion pressure in the left anterior descending coronary artery such that CBF decreased to one-third of the baseline value. At 10 min after carperitide was infused at a dose of 0.1 μg kg(-1) min(-1), we observed increases in CBF, fractional shortening (FS) and pH levels in coronary venous blood without concomitant increases in cardiac nitric oxide (NO) levels; these changes were attenuated using either the atrial natriuretic peptide receptor antagonist HS-142-1 or the NO synthase inhibitor L(ω)-nitroarginine methyl ester (L-NAME). Cyclic guanosine monophosphate (GMP) levels in the coronary artery were elevated in response to carperitide that also limited the infarct size after 90 min of ischemia and subsequent reperfusion. Again, these effects were blunted by L-NAME. Carperitide increases CBF, reduces myocardial contractile and metabolic dysfunction and limits infarct size. In addition, NO is necessary for carperitide-induced vasodilation and cardioprotection in ischemic hearts.

Topics: Animals; Atrial Natriuretic Factor; Coronary Circulation; Coronary Vessels; Cyclic AMP; Dogs; Female; Myocardial Contraction; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Nitric Oxide; Receptors, Atrial Natriuretic Factor; Vasodilation; Vasodilator Agents

In patients with heart failure, reactivation of a fetal gene program, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), is a hallmark for maladaptive remodeling of the LV. The mechanisms that regulate this reactivation are incompletely understood. Histone acetylation and methylation affect the conformation of chromatin, which in turn governs the accessibility of DNA for transcription factors. Using human LV myocardium, we found that, despite nuclear export of histone deacetylase 4 (HDAC4), upregulation of ANP and BNP in failing hearts did not require increased histone acetylation in the promoter regions of these genes. In contrast, di- and trimethylation of lysine 9 of histone 3 (H3K9) and binding of heterochromatin protein 1 (HP1) in the promoter regions of these genes were substantially reduced. In isolated working murine hearts, an acute increase of cardiac preload induced HDAC4 nuclear export, H3K9 demethylation, HP1 dissociation from the promoter region, and activation of the ANP gene. These processes were reversed in hearts with myocyte-specific deletion of Hdac4. We conclude that HDAC4 plays a central role for rapid modifications of histone methylation in response to variations in cardiac load and may represent a target for pharmacological interventions to prevent maladaptive remodeling in patients with heart failure.

Topics: Acetylation; Active Transport, Cell Nucleus; Animals; Atrial Natriuretic Factor; Blood Pressure; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cardiomyopathy, Dilated; Case-Control Studies; Cells, Cultured; Enzyme Induction; Epigenesis, Genetic; Gene Expression; Heart Failure; Heart Ventricles; Histone Deacetylases; Histones; Humans; In Vitro Techniques; Jumonji Domain-Containing Histone Demethylases; Male; Methylation; Methyltransferases; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Myocardial Ischemia; Myocytes, Cardiac; Natriuretic Peptide, Brain; Promoter Regions, Genetic; Protein Processing, Post-Translational; Rats; Rats, Sprague-Dawley; Repressor Proteins; Sarcoplasmic Reticulum Calcium-Transporting ATPases

The characteristics, in-hospital management, and outcomes of patients hospitalized with worsening heart failure (HF) have been described by large-scale registries performed mainly in the USA and Europe. However, little information is available in Japan. We thus clarified the characteristics and clinical status as well as in-hospital management and outcomes among patients hospitalized with worsening HF in Japan and compared them with those reported in previous studies.. The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) studied prospectively the characteristics and treatments in patients hospitalized with worsening HF. From the total cohort of JCARE-CARD, 1677 patients were randomly selected and their detailed data during acute phase were collected as another registry database in the present study. The characteristics, in-hospital management, and outcomes were analyzed.. The mean age was 70.7 years and 59.4% were male. Etiology was ischemic in 34.0% and mean left ventricular ejection fraction was 42.5%. Carperitide was highly used as in-hospital management in Japan (33.5%) compared to the use of nesiritide in the USA (8-11%). The use of angiotensin-converting enzyme inhibitors was lower and angiotensin II receptor blockers (ARB) were more commonly used in this study compared to other studies in the USA and Europe. In-hospital crude mortality rate was comparable among studies (4-8%), however, length of stay was longer in Japan (15-20 versus 4-9 days).. The characteristics, clinical status, and laboratory data on admission in patients hospitalized with worsening HF were similar between the present study and previous Japanese and western studies. Management was also similar except for higher use of carperitide and ARB. The most striking difference between Japanese registries and those from the USA and Europe was the longer length of stay.

Topics: Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Asian People; Atrial Natriuretic Factor; Cohort Studies; Disease Progression; Female; Heart Failure; Hospital Mortality; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Myocardial Ischemia; Natriuretic Agents; Natriuretic Peptide, Brain; Prospective Studies; Random Allocation; Registries; Treatment Outcome

Serial changes in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and atrial natriuretic peptide (ANP) concentrations are unknown in dogs with myocardial injury. The time-course secretory responses between NT-proBNP and ANP or cardiac troponin-T (cTnT) related to myocardial infarction (MI) were investigated in this study. Six dogs were anaesthetised and the left anterior descending artery was ligated. A transient decrease in cardiac function was detected 1h after MI but returned to baseline levels within 7 days and remained so for 6 months. Echocardiographic examination revealed focal ventricular dyskinesis throughout the study. Six months following MI, the left atrium to aorta ratio increased significantly although the relative wall thickness decreased significantly from baseline. Significantly elevated plasma NT-proBNP and cTnT concentrations were detected 1 day after MI and these gradually decreased over 28 days to baseline levels without left ventricular pressure elevation. Plasma ANP was elevated significantly 6 months after MI. The NT-proBNP assay is a helpful diagnostic indicator for identifying asymptomatic acute and subacute myocardial injury whereas plasma ANP concentration mainly reflects atrial dilation.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Disease Models, Animal; Dog Diseases; Dogs; Female; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Severity of Illness Index

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Dog Diseases; Female; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Prognosis; Risk Factors; Sensitivity and Specificity

In investigating death due to mechanical asphyxiation and drowning, a cardiac attack is important for discriminating between possible causes of death and as a contributory factor in death processes; however, general pathologies involving visceral congestion are often similar. The present study compared terminal cardiac dysfunction in these fatalities using the molecular pathology of atrial and brain natriuretic peptides (ANP and BNP) in the myocardium as markers of cardiac strain. Both mechanical asphyxiation (n=27) and drowning (n=23) showed significantly lower ANP and BNP mRNA expressions in bilateral ventricular walls than sudden cardiac deaths (n=36). In addition, right atrial wall BNP mRNA expression was lower in asphyxiation; however, immunostaining did not demonstrate any difference among these fatalities. Differences among the subtypes of asphyxiation or between fresh- and saltwater drowning were insignificant. These observations suggest a difference between primary heart failure in sudden cardiac death and terminal cardiac dysfunction secondary to fatal asphyxiation or drowning.

Topics: Adult; Aged; Aged, 80 and over; Asphyxia; Atrial Natriuretic Factor; Biomarkers; Death, Sudden, Cardiac; Drowning; Female; Forensic Pathology; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

The present study investigated the molecular pathology of atrial and brain natriuretic peptides (ANP and BNP) in the myocardium to evaluate terminal cardiac function in routine forensic casework with particular regard to fatal drug intoxication (n = 18; sedative-hypnotics, n = 10; methamphetamine, n = 8), hypothermia (cold exposure, n = 13), and hyperthermia (heatstroke, n = 10), compared with that in acute ischemic heart disease (AIHD, n = 35) and congestive heart disease (CHD, n = 11) as controls (total n = 87; within 48 h postmortem). Quantitative analyses of myocardial ANP and BNP messenger RNA demonstrated that their expressions in bilateral atrial and ventricular walls were high in methamphetamine intoxication and hypothermia, comparable to those in AIHD and CHD, but were low in sedative-hypnotic intoxication and hyperthermia. In pericardial fluid, both ANP and BNP levels were increased in hypothermia, while CHD cases had an elevated BNP level, and ANP level showed a tendency to increase in hyperthermia; however, immunohistochemistry showed no evident differences in myocardial ANP and BNP among the causes of death. These findings suggest terminal high cardiac strain in methamphetamine intoxication, decreased cardiac strain in sedative-hypnotic intoxication and hyperthermia (heatstroke), and persistent congestion in hypothermia (cold exposure).

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Autopsy; Cause of Death; Female; Gene Expression; Heart Atria; Heart Failure; Heart Ventricles; Heat Stroke; Humans; Hypnotics and Sedatives; Hypothermia; Illicit Drugs; Male; Methamphetamine; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Pathology, Molecular; Pericardial Effusion; Poisoning; Postmortem Changes; Prescription Drug Misuse; RNA-Directed DNA Polymerase; RNA, Messenger

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Female; Glycopeptides; Heart Failure; Humans; Hypertension; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Stroke Volume

Fractalkine (FKN) is a newly identified membrane-bound chemokine; its role in myocardial ischaemia and heart failure is largely unknown. We attempted to investigate the role of FKN in myocardial ischaemia and ischaemia or pressure overload-induced ventricular remodelling and heart failure.. FKN-induced changes of heart failure-related genes in cultured rat cardiac cells and the effect of FKN on cultured cardiomyocyte injury during anoxia/reoxygenation (A/R) were examined. The direct influence of FKN neutralization on heart failure and the potential mechanism was also investigated. In mice with failing hearts, myocardial FKN expression was correlated with the lung weight/body weight ratio, left ventricular fractional shortening, and brain natriuretic peptide expression. In cultured rat cells, exposure to FKN increased natriuretic peptide A expression in cardiomyocytes, matrix metalloproteinase-9 expression in fibroblasts, and intercellular adhesion molecule-1 expression in microvascular endothelial cells. FKN also promoted cardiomyocyte damage during A/R and neutralizing FKN antibody treatment improved heart failure induced by myocardial infarction or pressure overload. Neutralizing FKN or its receptor inhibited the activation of mitogen-activated protein kinases (MAPKs) in hypoxic cardiomyocytes or ischaemic myocardium.. FKN promotes myocardial injury and accelerates the progress of heart failure, which is associated with the activation of MAPKs.

Topics: Animals; Animals, Newborn; Antibodies, Neutralizing; Atrial Natriuretic Factor; Cells, Cultured; Chemokine CX3CL1; Disease Models, Animal; Endothelial Cells; Enzyme Activation; Fibroblasts; Heart Failure; Intercellular Adhesion Molecule-1; Male; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Myocardial Ischemia; Myocytes, Cardiac; Natriuretic Peptide, Brain; Rats; Recombinant Proteins; Severity of Illness Index; Time Factors; Ventricular Remodeling

Reactive oxygen species are important mediators that exert a toxic effect during ischemia-reperfusion (I/R) injury of various organs. Sulforaphane is known to be an indirect antioxidant that acts by inducing Nrf2-dependent phase 2 enzymes. In this study, we investigated whether sulforaphane protects heart against I/R injury. Sprague-Dawley rats received sulforaphane (500microg/kg/day) or vehicle intraperitoneally for 3 days and global ischemia was performed using isolated perfused Langendorff hearts. Hearts were perfused with Krebs-bicarbonate buffer for 20min pre-ischemic period followed by a 20min global ischemia and 50min reperfusion. Treatment with sulforaphane inhibited an increase in the post-ischemic left ventricular end-diastolic pressure (LVEDP) and improved the post-ischemic left ventricular developed pressure (LVDP), +/-dP/dt, and coronary flow as compared with the untreated control hearts. Pretreatment with 5-hydroxydecanoic acid (5-HD), a mitochondrial K(ATP) channel blocker, for 10min before ischemia attenuated the improvement of LVEDP, LVDP, +/-dP/dt, and coronary flow induced by sulforaphane. Sulforaphane markedly decreased the infarcted size and attenuated the increased lactate dehydrogenase level in effluent during reperfusion. Pretreatment with 5-HD also blocked these protective effects of sulforaphane. Post-ischemia increased the concentration of atrial natriuretic peptide in coronary effluent, which attenuated by sulforaphane treatment. Decreases on Mn-superoxide dismutase (SOD), catalase, and heme oxygenase-1 levels by I/R were increased by sulforaphane treatment and pretreatment of 5-HD blocked the sulforaphane effects. Increases in Bax and caspase-3 levels, and decrease in Bcl-2 level by I/R were attenuated by sulforaphane treatment. These results suggest that the protective effects of sulforaphane against I/R injury may be partly mediated through mitochondrial K(ATP) channels and antioxidant pathway.

Topics: Animals; Antioxidants; Atrial Natriuretic Factor; bcl-2-Associated X Protein; Caspase 3; Decanoic Acids; Disease Models, Animal; Drug Interactions; Free Radical Scavengers; Hydroxy Acids; In Vitro Techniques; Isothiocyanates; KATP Channels; L-Lactate Dehydrogenase; Male; Mitochondria; Myocardial Infarction; Myocardial Ischemia; Potassium Channel Blockers; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Sulfoxides; Thiocyanates

The cardiorenal syndromes (CRS) are composed of five recently defined syndromes which represent common clinical scenarios in which both the heart and the kidney are involved in a bidirectional injury process leading to dysfunction of both organs. Common to each subtype are multiple complex pathogenic factors, a precipitous decline in function and a progressive course. Most pathways that lead to CRS involve acute injury to organs which manifest evidence of chronic disease, suggesting reduced ability to sustain damage, maintain vital functions, and facilitate recovery. Prevention of CRS is an ideal clinical goal, because once initiated, CRS cannot be readily aborted, are not completely reversible, and are associated with serious consequences including hospitalization, complicated procedures, need for renal replacement therapy, and death. Principles of prevention include identification and amelioration of precipitating factors, optimal management of both chronic heart and kidney diseases, and future use of multimodality therapies for end-organ protection at the time of systemic injury. This paper will review the core concepts of prevention of CRS with practical applications to be considered in today's practice.

Topics: Anemia; Atrial Natriuretic Factor; Cardiotonic Agents; Dopamine; Heart Failure; Humans; Inflammation; Infusions, Intravenous; Kidney Diseases; Kidney Failure, Chronic; Myocardial Ischemia; Randomized Controlled Trials as Topic; Renal Circulation; Sleep Apnea, Obstructive; Sodium; Sodium Potassium Chloride Symporter Inhibitors; Syndrome

Both prevention and attenuation of ischemic heart disease are important issues, and there are three different strategies to save patients from the deleterious sequelae of ischemic injury. The first strategy is to remove the causes of ischemic heart disease; the second is to attenuate on-going ischemic and reperfusion injury; the third is to prevent the progression of cardiac remodeling and chronic heart failure following ischemic injury.. For prevention of acute myocardial infarction, it is widely accepted to treat high risk patients with aspirin and/or statins. On the other hand, several medications such as angiotensin converting enzyme inhibitors, aldosterone receptor antagonists and beta blockers have been used for the prevention of post-infarction heart failure in patients who have suffered from an acute myocardial infarction. However, at present we do not have an adjunctive drug therapy to reduce infarct size in the acute phase in patients with myocardial infarction. Recently, the J-WIND trials suggested that an infusion of human atrial natriuretic peptide in the acute phase and oral administration of nicorandil in the chronic phase of infarction result in a better outcome in patients with a myocardial infarction. In this article we propose potential mechanisms for cardioprotection in patients with an acute myocardial infarction.

Topics: Atrial Natriuretic Factor; Cardiotonic Agents; Disease Progression; Heart Failure; Humans; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Nicorandil; Randomized Controlled Trials as Topic; Risk Factors; Vasodilator Agents

The insulin-like and vasodilatatory polypeptide relaxin (RLX), formerly known as a pregnancy hormone, has gained interest as a potential humoral mediator in human heart failure. Controversy exists about the relation between plasma levels of RLX and the severity of heart failure. The present study was designed to determine the course of RLX, atrial, and brain natriuretic peptide (NT-proANP and NT-proBNP) during physical exercise in patients with ischemic heart disease (IHD) and to relate hormone levels to peak cardiac power output (CPO) as a measure of cardiopulmonary function with prognostic relevance. 40 patients with IHD were studied during right-heart-catheterization at rest and during supine bicycle ergometry. RLX, NTproBNP, and NTproANP were determined before, during exercise, and after recovery. NT-proANP and NT-proBNP levels increased during maximal charge, and recovery while RLX levels decreased. Cardiac power output at maximal charge correlated inversely with NTproANP and NTproBNP but positively with RLX. Patients with high degree heart failure (CPO<1.96 W) had higher NTproANP and NTproBNP and lower RLX levels than patients with low degree heart failure. While confirming the role of NTproANP and NTproBNP as markers for the severity of heart failure, the present data do not support the concept that plasma levels of RLX are related to the severity of myocardial dysfunction and that systemic RLX acts as a compensatory vasodilatatory response hormone in ischemic heart disease.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Cardiac Catheterization; Exercise; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Relaxin

B-type natriuretic peptide (BNP) is a peptide hormone of myocardial origin with significant cardioprotective properties. Patients with myocardial ischemia present with high levels of BNP in plasma and elevated expression in the myocardium. However, the molecular mechanisms of BNP induction in the ischemic myocardium are not well understood. The aim of the investigation was to assess whether myocardial hypoxia induces the production of BNP in human ventricular myocytes. To test the hypothesis that reduced oxygen tension can directly stimulate BNP gene expression and release in the absence of hemodynamic or neurohormonal stimuli, we used an in vitro model system of cultured human ventricular myocytes (AC16 cells). Cells were cultured under normoxic (21% O(2)) or hypoxic (5% O(2)) conditions for up to 48 h. The accumulation of BNP, atrial natriuretic peptide (ANP), and vascular endothelial growth factor (VEGF) was then measured. Hypoxia stimulated the protein release of BNP and VEGF but not ANP. In concordance, the increased mRNA levels of BNP and VEGF but not ANP were found on culturing AC16 cells under hypoxic conditions. The analysis of the transcriptional activity of the hypoxia-inducible factor 1 (HIF-1) in nuclear extracts showed that HIF-1 activity was induced under hypoxic conditions. Finally, the treatment of AC16 cells with the HIF-1 inhibitor rotenone in hypoxia inhibited BNP and VEGF release. In conclusion, these data indicate that hypoxia induces the synthesis and secretion of BNP in human ventricular myocytes, likely through HIF-1-enhanced transcriptional activity.

Topics: Atrial Natriuretic Factor; Cell Line; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Myocardial Ischemia; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oxygen; RNA, Messenger; Vascular Endothelial Growth Factor A

The purpose of this study was to investigate the effect of resveratrol, a polyphenol present in grapes and red wine, on ventricular remodeling after myocardial infarction (MI) in rats. After permanent ligation of the left anterior descending artery, surviving rats were randomly allocated to three groups and treated with 1 mg/kg/day resveratrol (R-1 group), 0.1 mg/kg/day resveratrol (R-0.1 group), or vehicles (control group) administered by intraperitoneal injection once daily for four weeks. We examined the effects of resveratrol by echocardiography, hemodynamic studies, histologic examinations, and real-time quantitative polymerase chain reaction. The R-1 group had significantly increased fractional shortening of the left ventricle, ameliorated left ventricular dilatation, reduced left ventricular end-diastolic pressure, and reduced infarct size. In contrast, the R-0.1 group experienced no beneficial effects on myocardial infarction. The R-1 group also had significantly attenuated expression of myocardial atrial natriuretic peptide and transforming growth factor-beta1 mRNAs. This study indicates that resveratrol is a potent cardioprotective agent in MI rats. Its cardioprotective effects may be due to a reduction of atrial natriuretic peptide and transforming growth factor-beta1, which are known to protect the heart from detrimental remodeling.

Topics: Animals; Antioxidants; Atrial Natriuretic Factor; Collagen Type I; Echocardiography; Hemodynamics; Male; Mice; Myocardial Ischemia; Random Allocation; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Transforming Growth Factor beta1; Ventricular Remodeling

It is known that many heart diseases are accompanied by a significant increase in the level of atrial natriuretic peptide (ANP), a regulator of cardiovascular homeostasis, in the pericardial fluid. Cellular sources of ANP in pericardial cavity remain uncertain. By EM immunocytochemistry, we have examined the presence and localization of ANP in rat and human pericardium. ANP-immunoreactive material was revealed in granules of mast cells (MCs) situated in connective tissue of the pericardium. MCs have an oval form and measure about 6.5 x 12.5 and 9.1 x 13.6 microm in the rat and human pericardium, respectively. Density of MC population makes up about 50 and 10 cells/mm2 in the rat and human pericardium, respectively. Our data suggest possible participation of the pericardial MCs in endocrine function of pericardium and in control of the ANP level in pericardial cavity.

Topics: Adult; Aged; Animals; Atrial Natriuretic Factor; Biopsy; Homeostasis; Humans; Immunohistochemistry; Mast Cells; Microscopy, Electron; Middle Aged; Myocardial Ischemia; Pericardium; Rats

There is controversy whether new biomarkers are able to identify myocardial ischemia in the absence of myonecrosis.. We measured NT-pro BNP, NT-pro ANP, ischemia-modified albumin (IMA) and placental growth factor (PlGF) in patients undergoing nuclear stress testing for suspected ischemic heart disease. A thallium scan was used for detection of reversible myocardial ischemia and cardiac troponin T (cTnT) for exclusion of stress-induced myonecrosis. Of 195 patients, 24 with reversible and 62 with no perfusion defect were included in the analysis. Plasma levels were measured before, 18 min and 4 h after stress testing.. Of the 86 patients, 52 received an exercise stress and 34 dipyridamol. New myonecrosis indicated by cTnT could be excluded in all patients. Plasma levels of NT-pro BNP and NT-pro ANP before testing were significantly higher in patients who later developed reversible perfusion defects (NT-pro BNP 139.00 (58.25/367.01) pg/mL vs 327.45 (120.50/972.85) pg/mL, p<0.05; NT-pro ANP 732.5 (470.0/1220.0) pg/mL vs 1470.0 (694.0/1910.0) pg/mL, p<0.05). Plasma levels of NT-pro BNP, NT-pro ANP and PIGF did not change significantly after stress testing, IMA levels rose significantly after 4 h in patients with and without reversible perfusion defects.. The elevation of NTpro BNP and NT-pro ANP at baseline may represent the cumulative effect of repeated bouts of myocardial ischemia. A single brief episode of provoked ischemia does not cause a significant increase of the measured biomarkers beside from IMA after exercise stress test potentially indicating skeletal muscle ischemia.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Dipyridamole; Exercise Test; Female; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Placenta Growth Factor; Predictive Value of Tests; Pregnancy Proteins; Protein Precursors; Radionuclide Imaging; Research Design; Sensitivity and Specificity; Serum Albumin; Severity of Illness Index; Troponin T; Vasodilator Agents

Bone marrow cells implantation (BMI) has been reported to efficiently improve ischemic heart disease. However, BMI strategies are generally invasive. To establish a BMI strategy for ischemic heart disease, we performed implantation of autologous cryopreserved mononuclear cells (MNCs) from bone marrow (BM) retrogradely into the myocardium via the coronary vein in pigs with acute myocardial infarction (AMI) and old myocardial infarction (OMI).. BM cells were harvested from the pigs' fumurs. MNCs were collected by centrifugation and were cryopreserved. Anterior myocardial infarction was induced by occlusion of the midportion of the left anterior descending coronary artery without surgical intervention. Frozen BM cells were quickly thawed and injected retrogradely via the coronary vein into the myocardium through a single balloon infusion catheter 6 h and 2 weeks after the induction of infarction. Four weeks after implantation, coronary arteriograms were obtained, cardiac function was analyzed with the use of a conductance catheter, and histopathologic analysis was performed with a confocal laser microscope. Plasma levels of natriuretic peptides and angiogenic growth factors were measured after BMI.. Flow cytometric analysis revealed that 90% of cryopreserved BM cells were viable in vitro. Labeled BM cells were entirely distributed around in the infarcted area of maycardium in pigs. BMI increased collateral neovascuralization in infarcted hearts. BMI significantly improved cardiac function in AMI with BMI and OMI with BMI groups. BMI also increased the formation of microcapillary arteries in infarcted hearts. Levels of natriuretic peptides were significantly decreased, and levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2) were significantly increased after BMI. Confocal laser microscopy revealed the presence of proliferative and activated myocardial cells in infarcted hearts after BMI.. The retrograde infusion of cryopreserved BM cells into myocardium efficiently induced angiogenesis and improved cardiac function in pigs with AMI or OMI. These results suggest that the present strategy of BMI will be safe and feasible as an angiogenic cell therapy for ischemic heart disease.

Topics: Animals; Atrial Natriuretic Factor; Bone Marrow Cells; Bone Marrow Transplantation; Coronary Vessels; Cryopreservation; Fibroblast Growth Factor 2; Injections; Male; Myocardial Infarction; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Neovascularization, Physiologic; Swine; Vascular Endothelial Growth Factor A

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Biomarkers; Coronary Restenosis; Coronary Stenosis; Half-Life; Humans; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Outpatients; Protein Precursors; Systole; Ventricular Function, Left

The heart undergoes repair and initiates protective mechanisms via ventricular unloading. We examined the presence of 2 markers in pre-unloaded and post-unloaded human cardiac tissue that are important indicators of cardiac failure, tumor necrosis factor-alpha and inducible nitric oxide synthase. We also measured 2 nuclear transcription factors, NFkappaB50 and NFkappaB65, comparing quantities and localizations to determine if mechanical unloading reduced their presence, as these markers are also thought to be indicators of impending heart failure. Amounts and localizations in patients that had been diagnosed with either ischemic or non-ischemic cardiomyopathy were compared after mechanical unloading with a left ventricular assist device. To establish that unloading had been achieved, levels of atrial natriuretic protein were determined.. Core biopsies were harvested at assist device implantation and removal. Fluorescence deconvolution microscopy image reconstructions of fluorescence probes were correlated with data obtained by western Blot and electrobility shift assays.. Statistically significant differences in localization and amounts of tumor necrosis factor and nitric oxide synthase were seen between pre- and post-assist device samples. Amounts of tumor necrosis factor and nitric oxide synthase in ischemic tissue were increased at the time of assist device removal, but decreased in dilated or idiomyopathic samples. Ventricular unloading resulted in reduced levels of natriuretic protein, with the greatest reduction being seen in ischemic tissue. Both NFkappaB50 and NFkappaB65 increased in ischemic tissue, but only NFkappaB50 in non-ischemic samples.. Changes in localization of the factors and altered levels of cytokine and nitric oxide synthase indicate that the heart switches to a "protective and repair" mode, and mechanical unloading allows this transition to occur. Observed changes were dependent on the etiology of the disease.

Topics: Atrial Natriuretic Factor; Biomarkers; Biopsy; Blotting, Western; Cardiomyopathy, Dilated; Device Removal; Electrophoresis; Heart Ventricles; Heart-Assist Devices; Humans; Microscopy, Fluorescence; Myocardial Ischemia; Myocardium; Nitric Oxide Synthase; Severity of Illness Index; Tumor Necrosis Factor-alpha

Because of its unique storage and release mechanisms allowing a very rapid response to haemodynamic changes, pro-atrial natriuretic peptide (proANP) may be a helpful cardiac marker in the detection of myocardial ischaemia.. A total of 260 consecutive patients with suspected myocardial ischaemia referred for rest/ergometry myocardial perfusion single-photon emission computed tomography (SPECT) were enrolled. Levels of plasma proANP were determined before and 1 min after maximal exercise.. Baseline proANP and peak exercise proANP were significantly higher in patients with myocardial ischaemia as compared to those without ischaemia (median, 82 [IQR, 57-112] vs. 67 [IQR, 50-106] pmol L(-1), P = 0.007; and 89 [IQR, 65-121] vs. 78 [IQR, 57-116] pmol L(-1), P = 0.033). The area under the ROC curve for baseline proANP was 0.597 (95% CI, 0.527-0.667), as compared to 0.577 (95% CI, 0.507-0.648) for peak exercise proANP. Exercise-induced changes in proANP were similar in patients with and without myocardial ischaemia, and showed no correlation with the extent of myocardial ischaemia.. Baseline proANP and peak exercise proANP are significantly higher in patients with myocardial ischaemia. However, because of considerable overlap in proANP levels between patients with and without myocardial ischaemia, neither measurement seems helpful in the detection of myocardial ischaemia in clinical practice.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Coronary Angiography; Coronary Stenosis; Exercise; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Prospective Studies; ROC Curve; Stroke Volume; Tomography, Emission-Computed, Single-Photon

1. As a result of its enormous surface area and necessary thinness for gas exchange, the alveolocapillary barrier is vulnerable to mechanical disruption from raised pulmonary microvascular pressure (Pmv). 2. Because surfactant protein-B (SP-B) leaks into the blood stream from the alveoli in response to alveolocapillary barrier damage and exercise leads to increased Pmv, we sought to determine whether exercise results in increased plasma SP-B. Moreover, in the setting of exercise-induced left ventricular dysfunction, the consequent increase in left heart filling pressure and, therefore, P(mv) would be expected to further increase plasma SP-B levels. 3. Twenty consecutive subjects referred for treadmill exercise stress echocardiography (ESE) had venous blood sampled immediately before and after ESE for batch atrial natriuretic peptide (ANP) and SP-B assay. Echocardiographic measures of pulmonary haemodynamics (pulmonary artery flow acceleration time (pafAT) and right ventricular outflow tract velocity time integral (rVTI)) were also taken pre- and post-exercise. 4. Although circulating ANP levels increased following exercise (P < 0.001), there was no change in circulating SP-B levels in the entire cohort. 5. Ten subjects had a positive ESE for ventricular dysfunction. Although circulating ANP was increased post-exercise in both the negative and positive ESE groups (P < 0.05 and P < 0.01, respectively), circulating SP-B only increased post-exercise in the positive ESE group (P < 0.05). Echocardiographic parameters supported an increment in P(mv) in the cohort with exercise-induced left ventricular dysfunction because this group had an increase in pafAT (P < 0.05; reflecting pulmonary artery pressure) and no change in rVTI. 6. Physical exertion associated with a Bruce protocol ESE is insufficient to increase circulating SP-B, despite evidence of increased left atrial and pulmonary vascular pressure. However, in the setting of exercise-induced myocardial dysfunction, there is a detectable increase in circulating SP-B. 7. The exaggerated increase in pulmonary vascular pressure in exercise-induced myocardial dysfunction may result in increased SP-B leakage from the alveoli into the circulation by altering the integrity of the alveolocapillary barrier to protein.

Topics: Atrial Natriuretic Factor; Exercise; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Pulmonary Surfactant-Associated Protein B; Ventricular Dysfunction, Left

The aim of the present study was to investigate the putative role of endothelin (ET) in mediating ischemia/hypoxia-induced ANP release utilizing exogenous ET-1 or ET receptor antagonists (BQ-123 or Bosentan). Isolated rat hearts with non-distended atria were perfused using a Langendorff apparatus and heart rate maintained constant via atrial pacing. Global ischemia was induced either by direct reduction in perfusion or by infusion of exogenous ET-1 (5 x 10(-10) M) for 30 minutes. Perfusion with the ET receptor antagonists, BQ-123 (10(-6) M) or Bosentan (10(-5) M) was initiated 10 minutes before onset of ischemia. Moderate or severe ischemia was induced by reduction (52-61% and 70-82%, respectively) in perfusate flow. Thirty minutes of ischemia/hypoxia (5% O2) was followed by 30 minutes of reperfusion/re-oxygenation. Both moderate and severe ischemia increased ANP release. BQ-123 and Bosentan did not affect basal or ischemia-induced ANP release. Exogenous ET-1 perfusion induced a late increase in ANP release (P < 0.01) that did not exceed the increase in ANP release associated with equivalent direct flow reduction. Hypoxia induced an 8-fold increase in ANP release rate. The ANP release rate returned toward basal levels after re-oxygenation. Bosentan, but not BQ-123, significantly attenuated (P < 0.01) hypoxia-induced ANP release. In conclusion, in this system, ANP release is stimulated by moderate (or severe) ischemia and severe hypoxia independent of change in atrial distension; endogenous ET does not mediate basal and ischemia-induced ANP release; and hypoxia-induced ANP release is partially modulated via interaction with endogenous ET.

Topics: Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Bosentan; Endothelin Receptor Antagonists; Endothelins; Heart; Hypoxia; Male; Myocardial Ischemia; Peptides, Cyclic; Radioimmunoassay; Rats; Sulfonamides

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

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

Angiogenic gene therapy in angina pectoris has been disappointing so far. Reasons might be that the administered genes already are overexpressed in ischemic myocardium, or that atrial and brain natriuretic peptides (ANP and BNP) are overexpressed, as they have anti-angiogenic effects. Five stable angina pectoris patients without heart failure were studied. Left ventricular biopsies were taken during coronary by-pass surgery from a region with stress-inducible ischemia and from a normal region. Both ANP and BNP but not vascular endothelial growth factor (VEGF) and VEGF-receptor 1 and 2 were overexpressed in ischemic regions compared to non-ischemic regions as measured by real-time PCR. The expression of 15 other angiogenic genes measured by oligonucleotide arrays was not consistently increased in ischemic regions. The overexpression of ANP and BNP suggests an anti-angiogenic effect in ischemic heart disease. The lack of overexpression of angiogenic genes supports the concept of therapeutic overexpression of these genes.

Topics: Aged; Angina Pectoris; Atrial Natriuretic Factor; Female; Gene Expression Regulation; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Oligonucleotide Array Sequence Analysis; Tissue Distribution; Vascular Endothelial Growth Factor A

Left ventricular aneurysm repair (LVR) reduces LV wall stress and improves LV function. However, as we reported previously, the initial improvement of LVR was short-term because of LV remodeling but could be maintained longer with postoperative use of an angiotensin-converting enzyme (ACE) inhibitor. Atrial natriuretic peptide (ANP) has been used to treat patients with heart failure by natriuretic and vasodilatory actions. Recent reports have suggested that ANP inhibits the rennin-angiotensin system. In this study, the effects of ANP after LVR were evaluated.. Rats that had an LV aneurysm 4 weeks after left anterior descending artery ligation underwent LVR by plicating the LV aneurysm and were randomized into 2 groups: LVR+A group was intravenously administrated with 10 microg/h of carperitide, recombinant alpha-hANP, by osmotic-pump for 4 weeks, and the LVR group was given normal saline. Echocardiography revealed better LV remodeling and function in LVR+A group than in LVR group. Four weeks after LVR, left ventricular end diastolic pressure (LVEDP) and Tau were significantly lower in LVR+A group (LVEDP: 10+/-4 in LVR+A group versus 18+/-6 mm Hg in LVR group, Tau: 13+/-2 versus 17+/-2ms). End-systolic elastance (Ees) was higher in LVR+A group (Ees: 0.34+/-0.2 versus 0.19+/-0.11 mm Hg/microL). The levels of myocardial ACE activity in LVR+A group was significantly lower than in LVR group. The mRNA expressions of brain natriuretic peptide and transforming growth factor beta1 inducing fibrosis significantly decreased in LV myocardium in LVR+A group. Histologically, myocardial fibrosis was significantly reduced in LVR+A group.. Intravenous administration of ANP had beneficial effects on LV remodeling, function, and fibrosis after LVR. ANP could be a useful intravenous infusion drug for postoperative management after LV repair surgery.

Topics: Animals; Atrial Natriuretic Factor; Calcium-Transporting ATPases; Drug Evaluation, Preclinical; Fibrosis; Gene Expression Profiling; Heart Aneurysm; Humans; Hypertrophy, Left Ventricular; Infusion Pumps, Implantable; Infusions, Intravenous; Ligation; Male; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Peptidyl-Dipeptidase A; Random Allocation; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Renin-Angiotensin System; RNA, Messenger; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Single-Blind Method; Transforming Growth Factor beta; Transforming Growth Factor beta1; Ventricular Remodeling

The aim of this study was to determine the effect of transient myocardial ischemia on circulating natriuretic peptide levels.. Natriuretic peptides are released by the heart in response to wall stress. We hypothesized that transient myocardial ischemia would cause acute changes in circulating natriuretic peptide levels.. B-type natriuretic peptide (BNP), N-terminal fragment of BNP pro-hormone (NT-pro-BNP), and N-terminal fragment of atrial natriuretic peptide pro-hormone (NT-pro-ANP) levels were measured in 112 patients before, immediately after, and 4 h after exercise testing with nuclear perfusion imaging.. Baseline levels of BNP were associated with the subsequent severity of provoked ischemia, with median levels of 43, 62, and 101 pg/ml in patients with none, mild-to-moderate, and severe inducible ischemia, respectively (p = 0.03). Immediately after exercise, the median increase in BNP was 14.2 pg/ml in patients with mild-to-moderate ischemia (p = 0.0005) and 23.7 pg/ml in those with severe ischemia (p = 0.017). In contrast, BNP levels only rose by 2.3 pg/ml in those who did not develop ischemia (p = 0.31). A similar relationship was seen between baseline NT-pro-BNP levels and inducible ischemia, but the changes in response to ischemia were less pronounced. NT-pro-ANP levels rose with exercise in both ischemic and non-ischemic patients. When added to traditional clinical predictors of ischemia, a post-stress test BNP >or=80 pg/ml remained a strong and independent predictor of inducible myocardial ischemia (odds ratio 3.0, p = 0.025).. Transient myocardial ischemia was associated with an immediate rise in circulating BNP levels, and the magnitude of rise was proportional to the severity of ischemia. These findings demonstrate an important link between the severity of an acute ischemic insult and the circulating levels of BNP.

Topics: Atrial Natriuretic Factor; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Natriuretic Peptides; Nerve Tissue Proteins; Peptide Fragments; Predictive Value of Tests; Protein Precursors; Radionuclide Imaging; Sensitivity and Specificity; Severity of Illness Index

Atrial natriuretic peptide (ANP) is a cardiac peptide, the transcription of which is up-regulated in the ischaemic ventricle. However, the molecular mechanism of ANP induction is unclear. This study demonstrated that ANP mRNA expression in rat ventricular myocardium is induced in an early phase of ischaemia, preceded by hypoxia-inducible factor-1 (HIF-1) alpha expression. The ANP gene was also induced by hypoxia or HIF-1 inducers such as CoCl2 and desferrioxamine in H9c2 and neonatal cardiomyocytes. The 2307 bp 5'-flanking region of the rat ANP gene was cloned and fused to the luciferase gene. Evidence of the promoter activity was only apparent in the myocytes and was induced by hypoxia and HIF-1 inducers. The overexpression of HIF-1alpha markedly enhanced ANP promoter activity, and a dominant-negative isoform completely suppressed it. We demonstrated that the promoter regions are essential for hypoxic ANP induction. One promoter region, containing the HIF-1-binding sequence, is regulated directly by HIF-1. The other region is also activated by HIF-1 despite having no HIF-1-binding sequence. These results suggest that HIF-1 enhances the transactivation of the ANP gene in hypoxic myocytes, implying that stimulation of the ANP promoter by HIF-1 may in fact be responsible for the induction of the ANP gene in ischaemic ventricular myocardium.

Topics: Animals; Atrial Natriuretic Factor; Base Sequence; Blotting, Western; Cells, Cultured; DNA Primers; DNA-Binding Proteins; Electrophoretic Mobility Shift Assay; Gene Expression Regulation; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Myocardial Ischemia; Myocardium; Nuclear Proteins; Promoter Regions, Genetic; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factors; United States

Topics: Atrial Natriuretic Factor; Biomarkers; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Prognosis; Ventricular Remodeling

Implantation of a left ventricular assist device (LVAD) in the failing human heart initiates structural and functional changes termed reverse remodeling. Mechanical unloading improves cardiac adrenergic responsiveness and lipid metabolism, processes regulated by caveolar function. We tested the hypothesis that mechanical unloading alters the expression of caveolins and these changes are linked to altered expression of markers of reverse remodeling.. Paired human myocardial samples were obtained from patients who received an LVAD as a bridge to cardiac transplantation. Transcript levels were measured using real-time Q-RT-PCR in RNA prepared from 34 pairs of formalin-fixed myocardial tissue blocks. Caveolin-1 and -3 protein levels were determined from frozen tissue (n=5) by Western blots. Caveolin-3 localization was demonstrated by immunohistochemistry.. Caveolin-1 protein levels were upregulated in all LVAD-patients after mechanical unloading (P=0.002). Caveolin-1 mRNA was increased in 76% of the patients (n=34, P<0.001). Larger induction of caveolin-1 was associated with greater suppression of ANF. Caveolin-3 transcript levels increased in 82% of the cohort, along with a 2.5-fold induction of caveolin-2. Sarcolemmal caveolin-3 staining was increased after LVAD-support, although no change in total caveolin-3 protein was detected. The mRNA levels of the caveolin-associated CD36 also increased with unloading. Patients with ischemic cardiomyopathy showed greater induction of CD36 (P<0.05) than non-ischemic cases, as well as highly correlated changes in the expression of caveolin isoforms.. Mechanical unloading induces the expression of caveolins and CD36. The induction of caveolin-1 and the reciprocal suppression of ANF suggest that the changes in the expression of both genes are linked to decreased hemodynamic load. Enhanced caveolin expression during mechanical unloading of failing human hearts may be a part of the reverse remodeling of lipid metabolism, nitric oxide production and adrenergic signaling.

Topics: Adult; Atrial Natriuretic Factor; Blotting, Western; Caveolin 1; Caveolin 2; Caveolin 3; Caveolins; CD36 Antigens; Cluster Analysis; Heart Failure; Heart-Assist Devices; Humans; Immunohistochemistry; Middle Aged; Myocardial Ischemia; Myocardium; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Carperitide, a synthetic alpha-human atrial natriuretic peptide (ANP) is a newly developed drug for the treatment of heart failure. However, effects of carperitide on susceptibility to ischemia reperfusion injury are left to be determined. Isolated rat hearts were subjected to Langendorff perfusion. Six hearts received 0.1 microM of carperitide for 10 min, 6 hearts received 1 mM of a NO synthetase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) for 5 min before the infusion of carperitide, 6 hearts received 0.02 microM of a PKC synthetase inhibitor chelerythrine chloride for 5 min before the infusion of carperitide, 6 hearts received 100 microM of a selective mitochondrial ATP-sensitive potassium (KATP) channel blocker 5-dehydroxydecanoate (5HD) before the infusion of carperitide, 6 hearts received 10 microM of a soluble guanylate cyclase inhibitor methylene blue for 5 min before the infusion of carperitide, and 6 hearts served as a control with no drug infusion. All hearts were then subjected to 20 min of global ischemia followed by 120 min of reperfusion. Left ventricular pressures and coronary flow were measured throughout the experiment and infarct size was detected at the end of experiment. Both plasma and tissue cGMP levels were also determined. The results showed: (1) Carperitide significantly reduced infarct size compared to control (26.1 +/- 2.8 vs. 42.7 +/- 2.3%, carperitide vs. control, p < 0.05). This effect was reversed by L-NAME, chelerythrine and 5HD, but not methylene blue. (2) Plasma cGMP levels were increased in carperitide-treated group. This effect was reversed by L-NAME (0.16 +/- 0.03 vs. 1.04 +/- 0.09* vs. 0.28 +/- 0.02 nmol/L, control vs. carperitide vs. L-NAME, *p < 0.01 vs. control). We conclude that preischemic infusion of carperitide exerts cardioprotective effects possibly through NO-PKC dependent pathway followed by mitochondrial KATP channel activation.

Topics: Adenosine Triphosphate; Alkaloids; Animals; Atrial Natriuretic Factor; Benzophenanthridines; Cyclic GMP; Enzyme Inhibitors; Heart; Ischemia; Ischemic Preconditioning, Myocardial; Methylene Blue; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocardium; NG-Nitroarginine Methyl Ester; Nitric Oxide; Phenanthridines; Potassium Channel Blockers; Potassium Channels; Protein Kinase C; Rats; Reperfusion; Time Factors; Tissue Distribution

The purpose of this study was to investigate the impact of successful heart transplantation in patients with refractory heart failure receiving bridging therapy on sequential plasma levels of big endothelin, norepinephrine, atrial natriuretic peptide and aldosterone.. Fourteen patients (2 women, 12 men) accepted for heart transplantation were studied. All had severe chronic heart failure refractory to optimized oral therapy with angiotensin-converting enzyme inhibitors and furosemide, were in New York Heart Association functional Class IV, and had a left ventricular ejection fraction of <15%, Right heart catheterization was performed in all patients (cardiac index 1.9 +/- 0.1 liters/min. m(2), pulmonary capillary wedge pressure 30 +/- 2 mmHg, systemic vascular resistance index 2,827 +/- 253 dyn. s/cm(5). m(2)). As bridging therapy, patients received either prostaglandin E(1), prostaglandin E(1) and dobutamine or dobutamine alone as a continuous infusion. Neurohumoral variables were measured prior to bridging therapy and 3.5 months before and 7 and 10 months after successful heart transplantation.. Big endothelin, norepinephrine and atrial natriuretic peptide plasma levels decreased from 7.4 +/- 2.9 fmol/ml, 1112 +/- 686 pg/ml and 366 +/- 312 pg/ml to 6.0 +/- 4.5 fmol/ml, 720 +/- 503 pg/ml and 198 +/- 160 pg/ml, respectively, after bridging therapy, and further to 2.1 +/- 0.9 fmol/ml (p < 0.00001 vs baseline), 527 +/- 31 pg/ml (p < 0.02 vs baseline) and 115 +/- 70 pg/ml (p < 0.03 vs baseline), respectively, after cardiac transplantation. Aldosterone plasma levels decreased from 242 +/- 220 pg/ml to 183 +/- 142 pg/ml during bridging therapy and increased after heart transplantation to 252 +/- 189 pg/ml. Plasma creatinine levels increased from 1.2 +/- 0.4 mg/dl at baseline to 1.4 +/- 0.2 mg/dl after transplantation (NS).. The study suggests that excessive overproduction of big endothelin, atrial natriuretic peptide and norepinephrine is predominantly related to pump failure and, after cardiac transplantation, a moderate spillover of big endothelin persists. Its specific origin, however, remains to be elucidated. Furthermore, our data suggest a protective effect of prostaglandin E(1) on kidney function after heart transplantation.

Topics: Aged; Aldosterone; Atrial Natriuretic Factor; Austria; Biomarkers; Blood Urea Nitrogen; Creatinine; Endothelins; Female; Heart Failure; Heart Transplantation; Humans; Intraoperative Care; Male; Middle Aged; Myocardial Ischemia; Norepinephrine; Postoperative Care; Pulmonary Wedge Pressure; Treatment Outcome; Vascular Resistance

There is epidemiologic evidence that the prognosis of patients with nonischemic heart failure is better than that for patients with ischemic heart failure. In addition, studies have revealed that patients with ischemic heart failure show a poorer response to medical therapy. However, the pathophysiologic difference between ischemic and nonischemic heart disease is unclear. To clarify this point, we measured atrial natriuretic peptide, brain natriuretic peptide, angiotensin II, endothelin (ET)-1. interleukin-1beta interleukin-6. tumor necrosis factor (TNF)-alpha soluble TNF receptor I, and soluble TNF receptor II concentrations in plasma and pericardial fluid in patients with ischemic or nonischemic heart disease undergoing cardiac surgery. The pericardial ET-1 concentration in patients with ischemic heart disease was statistically greater than that in patients with nonischemic heart disease (about 1.5-fold), although no difference was found in the plasma ET-1 concentration. These findings suggest that the production and secretion of ET-1 from the myocardium in patients with ischemic heart disease are augmented to a greater extent than in patients with nonischemic heart disease. This result may lead to a greater understanding of the pathophysiology of ischemic heart disease.

Topics: Angiotensin II; Atrial Natriuretic Factor; Endothelin-1; Growth Substances; Humans; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Pericardial Effusion; Prognosis; Receptors, Tumor Necrosis Factor

Left ventricle (LV) hypertrophy is associated with an increased risk of sudden death, which may be due in part to a greater vulnerability to severe ventricular arrhythmias. Our objectives were to determine (i) whether pressure overload-induced LV hypertrophy increases susceptibility to ischemia- and/or reperfusion-induced ventricular fibrillation (VF), and (ii) whether any increased susceptibility is mediated by changes intrinsic to the hypertrophied myocardium. LV pressure overload was induced in rats by abdominal aortic constriction (AC), while controls received sham-operations (SH). Three weeks after the operation, LV weight was 44 +/- 3% greater in AC rats than in SH rats although right ventricle (RV) weights were similar. At this time, isolated hearts (n = 12/group) were subjected to dual coronary perfusion. Alter 15 minutes of aerobic perfusion, either the left or right coronary bed (supplying predominantly LV or RV tissue, respectively) was subjected to 7 minutes of zero-flow ischemia and either 5 minutes of reperfusion (reperfusion study) or 40 minutes of sustained ischemia (ischemia study). AC rats exhibited greater susceptibility than SH rats to both ischemia- and reperfusion-induced ventricular fibrillation, but only when the hypertrophied LV was subjected to ischemia. The increased susceptibility to arrhythmias was not entirely due to a larger ischemic zone, indicating that intrinsic changes within hypertrophied myocarium played a role in arrhythmogenesis.

Topics: Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Blood Pressure; Coronary Circulation; Disease Susceptibility; Heart Rate; Hypertrophy, Left Ventricular; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Random Allocation; Rats; Rats, Wistar; RNA, Messenger; Ventricular Pressure

Pericardial fluid (PF) contains several vasoactive agents in higher concentrations than venous plasma (VP). However, with human atrial natriuretic peptide (ANP) controversial data have been reported in earlier studies performed on a limited number of patients (less than 20). The present study was designed to characterize the ANP levels in human PF and cardiac tissues, and to ascertain whether myocardial ischemic state is a major factor in determining ANP production of the human heart. In a total of 316 consecutive patients undergoing open heart surgery ANP levels in VP, PF, atrial and ventricular tissues were measured by radioimmunoassay and analyzed by high-performance liquid chromatography (HPLC). The data are presented as median and 25th-75th percentiles. Our results showed ANP concentration [ANP] of PF significantly exceeded that of VP and [ANP] in the atrial tissue was significantly higher than in the ventricular tissue (p < 0.001). In patients without myocardial ischemia (valvular heart disease) [ANP] in the PF was 258.3 (189.9-342.5) pg/ml, in the VP 28.4 (11.7-57.6) pg/ml and 151.7 (78.4-447.6) ng/mg in the atrial, 0.4 (0.2-1.6) ng/mg in the ventricular tissue. The corresponding values for patients with coronary artery disease were 208.1 (153.8-318.9) pg/ml in the PF, 19.8 (9.4-27.9) pg/ml in the VP, 129.6 (66.5-455.0) ng/mg in the atrial and 1.0 (0.1-1.8) ng/mg in the ventricular tissue. The ventricular tissue levels correlated to the atrial tissue levels (r = 0.317; p < 0.05). Great difference (p < 0.001) was found in the atrial tissue levels between females [414.6 (119.7-734.4) ng/mg] and males [105.4 (65.3-204.2) ng/mg]. In HPLC analysis the majority of the pericardial fluid and tissue ir-ANP coeluted with human ANP [99-126]. In conclusion, [ANP] in PF of cardiosurgical patients is higher by an order of magnitude than in VP. Intrapericardial ANP may reflect the peptide concentration in the myocardial interstitium and may represent a paracrine regulatory mechanism, which seems independent of ANP-induced putative antiischemic influences.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Chromatography, High Pressure Liquid; Female; Heart Atria; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Ischemia; Pericardial Effusion; Radioimmunoassay

Atrial natriuretic peptide (ANP) release is increased in patients with ischaemic left ventricular dysfunction. A beneficial effect of naloxone on recovery from myocardial stunning was shown previously. The aim of this study was to investigate the effects of naloxone on ANP release during regional myocardial ischaemia and stunning in awake dogs.. Ten dogs were chronically instrumented for measurement of heart rate, left atrial, aortic, and left ventricular pressure (LVP), LV dP x dtmax/min(-1), and myocardial wall-thickening fraction. An occluder around the left anterior descending artery (LAD) allowed induction of reversible ischaemia in the LAD-perfused myocardium. Each dog underwent two ischaemic episodes (randomized crossover fashion; separate days): 10 min of LAD occlusion (1) after application of naloxone (63 microg kg(-1)), and (2) without naloxone. ANP levels were measured at baseline (BL) and at predetermined time points until complete recovery of myocardial stunning occurred.. LAD ischaemia-induced release of ANP (peak level: 182 (30) vs 27 (7) pg ml(-1) BL) only in the control group without naloxone. Between 1 and 180 min of reperfusion, ANP levels were significantly higher only in the control group (P<0.05).. Pre-ischaemic application of naloxone prevents this ischaemia-induced ANP-release in conscious dogs.

Topics: Animals; Atrial Natriuretic Factor; Blood Flow Velocity; Cross-Over Studies; Dogs; Female; Hemodynamics; Male; Myocardial Ischemia; Myocardial Stunning; Naloxone; Narcotic Antagonists; Natriuretic Peptide, Brain

We measured plasma atrial/brain natriuretic peptide (ANP/BNP) levels at rest and during exercise and correlated the results with various clinical findings, particularly with myocardial ischemia, in asymptomatic hypertrophic cardiomyopathy (HCM).. In patients with HCM, ANP and BNP levels are elevated and exercise-induced myocardial ischemia is common. However, it has not yet been elucidated how these levels at rest and their change with dynamic exercise are related to ischemia.. Levels of ANP and BNP were measured at rest and at peak exercise during (99m)Tc-tetrofosmin scintigraphy in 31 asymptomatic patients with non-obstructive HCM and in 10 control subjects.. Levels of ANP and BNP at rest and the change of ANP and BNP levels (PG/ML) from rest to exercise were significantly greater in HCM than in control subjects (ANP: rest, 53.2 +/- 31.8 vs. 11.6 +/- 6.1; exercise, 114.5 +/- 74.8 vs. 28.3 +/- 23.4. BNP: rest, 156.7 +/- 104.1 vs. 9.8 +/- 9.6; exercise, 201.6 +/- 131.5 vs. 13.2 +/- 14.5). Septal perforator compression (SPC) and exercise-induced ischemia were observed, respectively, in 20 (64.5%) and in 19 (61.3%) patients with HCM. The increment of ANP during exercise was similar between HCM subgroups with or without inducible ischemia. However, BNP levels at rest and BNP increments during exercise were significantly greater in the HCM subgroup with inducible ischemia than in the subgroup without (rest, 190.5 +/- 116.2 vs. 103.1 +/- 48.3; exercise, 250.5 +/- 142.2 vs. 124.2 +/- 58.6). Multiple logistic regression analysis revealed that SPC and BNP levels at rest were independently associated with exercise-induced ischemia.. Measurement of plasma BNP levels at rest may be useful in predicting silent myocardial ischemia in HCM.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiomyopathy, Hypertrophic; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Predictive Value of Tests; Reference Values

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

Acute myocardial infarction (AMI) remains the leading cause of death in developed countries. Although reperfusion of coronary arteries reduces mortality, it is associated with tissue injury. Endothelial P-selectin-mediated infiltration of neutrophils plays a key role in reperfusion injury. However, the mechanism of the P-selectin induction is not known. Here we show that infarct size after ischemia/reperfusion was significantly smaller in mice lacking guanylyl cyclase-A (GC-A), a natriuretic peptide receptor. The decrease was accompanied by decreases in neutrophil infiltration in coronary endothelial P-selectin expression. Pretreatment with HS-142-1, a GC-A antagonist, also decreased infarct size and P-selectin induction in wild-type mice. In cultured endothelial cells, activation of GC-A augmented H2O2-induced P-selectin expression. Furthermore, ischemia/reperfusion-induced activation of NF-kappaB, a transcription factor that is known to promote P-selectin expression, is suppressed in GC-A-deficient mice. These results suggest that inhibition of GC-A alleviates ischemia/reperfusion injury through suppression of NF-kappaB-mediated P-selectin induction. This novel, GC-A-mediated mechanism of ischemia/reperfusion injury may provide the basis for applying GC-A blockade in the clinical treatment of reperfusion injury.

Topics: Animals; Atrial Natriuretic Factor; Binding Sites, Antibody; Blotting, Western; Evans Blue; Guanylate Cyclase; Heart Ventricles; Mice; Mice, Inbred C57BL; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Natriuretic Peptide, Brain; Neutrophils; NF-kappa B; P-Selectin; Peroxidase; Polysaccharides; Receptors, Atrial Natriuretic Factor; Signal Transduction; Time Factors; Up-Regulation

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

The pharmacologic profiles of nicorandil in the cardiovascular system have been characterized by K-channel opening and nitrate activities. However, the effects of nicorandil on acute heart failure have yet to be elucidated. To investigate the effects of nicorandil under such pathophysiologic conditions, we administered nicorandil intravenously to dogs with acute ischemic heart failure induced by coronary embolization and compared the results with those induced by cromakalim and nitroglycerin. The heart failure in this experiment was demonstrated by a reduction of mean blood pressure (MBP) from 143+/-3 to 129+/-2 mm Hg (p < 0.01); cardiac output (CO) from 2.18+/-0.10 to 1.06+/-0.05 L/min (p < 0.01); stroke volume (SV) from 12.7+/-0.6 to 6.8+/-0.3 ml/min (p < 0.01); Vmax, an index of the contractility of the left ventricle, from 105.5+/-4.4 to 49.9+/-1.8 1/s (p < 0.01), and an increase in right atrial pressure (RAP) from 2.9+/-0.3 to 5.3+/-0.3 mm Hg (p < 0.01); left ventricular end-diastolic pressure (LVEDP) from 2.5+/-0.4 to 26.0+/-1.4 mm Hg (p < 0.01); and T, time constant of left ventricular relaxation, from 38.3+/-0.8 to 62.4+/-2.8 ms (p < 0.01). Furthermore, plasma renin activity (PRA) and plasma atrial natriuretic peptide (ANP) increased (from 1.72+/-0.29 to 5.03+/-0.68 ng AngI/ml/h, p < 0.01; from 103.9+/-5.8 to 411.5+/-29.4 pg/ml, p < 0.01, respectively), whereas brain natriuretic peptide (BNP) remained unchanged (from 23.1+/-2.2 to 26.9+/-1.4 pg/ml). Nicorandil (10-40 microg/kg/min, i.v. infusion for 20 min for each dosing) or cromakalim (0.25-1 microg/kg/min) decreased MBP, systemic vascular resistance (SVR), RAP, and LVEDP, and increased CO, SV, and Vmax. However, the reduction of RAP in cromakalim was significantly smaller than those of nicorandil and nitroglycerin in comparison at similar hypotensive doses. Nitroglycerin (2.5-10 microg/kg/min) decreased MBP, RAP, and LVEDP, and increased Vmax but did not change CO or SV. Increased plasma ANP levels, an index of cardiac filling pressure after induction of acute ischemic heart failure, were decreased significantly by cromakalim and tended to decrease by nicorandil or nitroglycerin. Plasma BNP levels and PRA were not influenced by any of these drugs. These results suggest that nicorandil produces the reduction of both preload and afterload followed by an improvement of cardiac contractility in this model. The increase in CO may be mediated mainly by the drug's K-channel opening activities and the

Topics: Acute Disease; Animals; Atrial Natriuretic Factor; Cardiac Output, Low; Cromakalim; Dogs; Embolization, Therapeutic; Female; Hemodynamics; Hormones; Male; Microspheres; Myocardial Ischemia; Natriuretic Peptide, Brain; Nicorandil; Nitroglycerin; Potassium Channels; Renin; Vasodilator Agents

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

A number of observations indicate that myocardial glucose utilization is increased late during post-ischemic reperfusion. The present study was designed to examine whether transient ischemia elicits altered expression of glucose transporters GLUT-1 and GLUT-4. In rats, the left anterior descending coronary artery was occluded for 20 min followed by reperfusion for 1, 3 or 7 days. Regional myocardial uptake and phosphorylation of glucose was determined based on myocardial accumulation of 2-deoxy-D-[2, 6-3H]glucose-6-phosphate. In hearts from fasted rats, after 3 days of reperfusion, myocardial uptake and phosphorylation of glucose was 48% higher in the reperfused region compared to a remote control region. No regional difference in myocardial glucose uptake and phosphorylation was detectable in hearts from fed rats. After 1 day of reperfusion, expression of myocardial glucose transporter GLUT-1 mRNA was increased to 195+/-24% (mean+/-SEM) of the value measured in the remote region and the expression of GLUT-4 mRNA was decreased to 58+/-7%. After 3 days of reperfusion both mRNA and protein of GLUT-1 were higher in the reperfused region, averaging 133+/-23% and 249+/-36%, respectively. The corresponding values for GLUT-4 mRNA and protein were 77+/-7% and 62+/-6%, respectively. The results indicate that a short period of ischemia alters the expression of glucose transporter isoforms GLUT-1 and GLUT-4. Observed changes may be involved in the mechanisms underlying late changes of substrate metabolism during reperfusion.

Topics: Acute Disease; Animals; Atrial Natriuretic Factor; Blood Glucose; Deoxyglucose; Fatty Acids; Genetic Code; Glucose Transporter Type 1; Glucose Transporter Type 4; Insulin; Male; Monosaccharide Transport Proteins; Muscle Proteins; Myocardial Ischemia; Myocardial Reperfusion; Phosphorylation; Rats; Rats, Wistar; RNA, Messenger

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

Echocardioscopy in M- and B-modes with measurement of routine parameters of central hemodynamics and thickness of carotid intimal-medial segment as well as radioimmunoassay of plasma concentrations of atrial natriuretic peptide (ANUP) were performed in 159 patients aged 42-63 years (17 healthy subjects and 142 patients with cardiac failure associated with ischemic heart disease and sinus rhythm, without history of myocardial infarction). The results were indicative of possible use of ANUP as a marker of initial cardiac insufficiency and a corrector of the disease prognosis.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Cardiac Output; Carotid Arteries; Echocardiography; Heart Atria; Heart Failure; Humans; Middle Aged; Myocardial Contraction; Myocardial Ischemia; Prognosis; Radioimmunoassay; Ventricular Dysfunction, Left

Newly discovered circulating peptides, N-terminal pro-brain natriuretic peptide (N-BNP) and adrenomedullin (ADM), were examined for prediction of cardiac function and prognosis and compared with previously reported markers in 121 patients with myocardial infarction.. The association between radionuclide left ventricular ejection fraction (LVEF) and N-BNP at 2 to 4 days (r=-.63, P<.0001) and 3 to 5 months (r=-.58, P<.0001) after infarction was comparable to that for C-terminal BNP and far stronger than for ADM (r=-.26, P<.01), N-terminal atrial natriuretic peptide (N-ANP), C-terminal ANP, cGMP, or plasma catecholamine concentrations. For prediction of death over 24 months of follow-up, an early postinfarction N-BNP level > or = 160 pmol/L had sensitivity, specificity, positive predictive value, and negative predictive values of 91%, 72%, 39%, and 97%, respectively, and was superior to any other neurohormone measured and to LVEF. Only 1 of 21 deaths occurred in a patient with an N-BNP level below the group median (Kaplan-Meier survival analysis, P<.00001). For prediction of heart failure (left ventricular failure), plasma N-BNP > or = 145 pmol/L had sensitivity (85%) and negative predictive value (91%) comparable to the other cardiac peptides and was superior to ADM, plasma catecholamines, and LVEF. By multivariate analysis, N-BNP but not ADM provided predictive information for death and left ventricular failure independent of patient age, sex, LVEF, levels of other hormones, and previous history of heart failure, myocardial infarction, hypertension, or diabetes.. Plasma N-BNP measured 2 to 4 days after myocardial infarction independently predicted left ventricular function and 2-year survival. Stratification of patients into low- and high-risk groups can be facilitated by plasma N-BNP or BNP measurements, and one of these could reasonably be included in the routine clinical workup of patients after myocardial infarction.

Topics: Adrenomedullin; Atrial Natriuretic Factor; Biomarkers; Cyclic GMP; Epinephrine; Female; Heart; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Norepinephrine; Peptides; Predictive Value of Tests; Prognosis; Radionuclide Imaging; Regression Analysis; Sensitivity and Specificity; Survival Rate; Ventricular Function, Left

Effects were studied of diltiazem on parameters characterizing cardiohemodynamics, peripheral bloodflow, condition of atrial natriuretic peptide (ANUP), of cyclic nucleotides (cGMP), the renin-angiotensin system in patients with various manifestations of stenocardia. An inhibitory action of diltiazem on ANUP and cGMP secretion in a VEM-test was recordable but changes were not significant at the height of the drug action in rest. Improvement in myocardial contractility after the course treatment with the drug was accompanied by reduction in blood plasma levels of ANUP and cGMP. It is suggested that changes in ANUP concentration might be traced to improvement in the anginal course and to the drug effects such as lowering of myocardial oxygen demand, of pre- and afterload, improvement in the indices for myocardial contractility.

Topics: Adult; Aged; Angina Pectoris; Angina, Unstable; Atrial Natriuretic Factor; Calcium Channel Blockers; Diltiazem; Exercise Tolerance; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Neurotransmitter Agents; Renin-Angiotensin System

The aim of this study was to test the hypothesis that plasma endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) concentrations in patients with ischemic heart disease are related either to myocardial ischemia or left ventricular (LV) dysfunction during dobutamine stress echocardiography. Plasma concentrations of ET-1 and ANP were measured in three patient groups. Group I (n = 21) patients had normal stress echocardiography and a resting LV ejection fraction (LVEF) of 40% or more. Group II (n = 32) had positive stress echocardiography and a resting LVEF of more than 40%. Group III (n = 18) had positive stress echocardiography with a resting LVEF of less than 40%. All three groups were subjected to thallium 201 scintigraphy and coronary angiography studies. The resting LV end-diastolic pressure was significantly higher in groups II and III than in Group I. The LVEF decreased significantly in group III compared to groups I and II. In the resting state, groups II and III had higher ET-1 concentrations than Group I (p = 0.021 and p = 0.039, respectively). The plasma ANP concentration was higher in group III than in groups I and II (p = 0.005 and p = 0.054, respectively). During peak dobutamine infusion, the ET-1 concentration dropped 8.7% from the baseline in group I, 10.2% in group II, and 10.5% in group III. The ANP concentrations were increased in all three groups but only the increase in Group II reached statistical significance. In conclusion, in patients with suspected ischemic heart disease, the concentrations of ET-1 and ANP may predict significant anatomic and functional coronary artery disease. However, ET-1 does not play a pathophysiologic role during an ischemic attack.

Topics: Adult; Aged; Atrial Natriuretic Factor; Coronary Angiography; Dobutamine; Echocardiography; Endothelin-1; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Tomography, Emission-Computed, Single-Photon

In a model of acute ischaemic left ventricular failure in pigs, we compared the plasma levels and cardiac secretion of the three atrial peptides, atrial natriuretic factor (ANF), N-terminal proatrial natriuretic factor (N-terminal proANF) and brain natriuretic peptide (BNP). Acute ischaemic left ventricular failure was induced by embolization of the left coronary artery with plastic microspheres. Thereafter, treatment was given by an intravenous injection of the angiotensin II receptor (AT1) antagonist losartan. Effects of failure induction and treatment were documented by measurement of haemodynamic parameters and plasma concentrations of catecholamines, plasma renin activity, angiotensin II and aldosterone. Acute left ventricular failure was accompanied by significant increases in cardiac secretion and plasma levels of all three atrial peptides, which was considerably more pronounced for ANF and N-terminal proANF than for BNP. Treatment with losartan resulted in significant decreases in plasma ANF and N-terminal proANF, whereas BNP did not change. These findings indicate that ANF and N-terminal proANF may be better suited than BNP as markers of cardiac preload during the development and treatment of acute heart failure.

Topics: Acute Disease; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Animals; Atrial Natriuretic Factor; Biomarkers; Disease Models, Animal; Embolism; Female; Heart; Heart Failure; Losartan; Male; Microspheres; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Protein Precursors; Swine

To ascertain whether atrial natriuretic peptides could be used as prospective and independent predictors of total mortality in an elderly population.. Atrial natriuretic peptides, ANP(1-98) and ANP(99-126), were measured in 541 subjects from the 85-year-old population of Gothenburg, Sweden. Before the study cardiovascular disorders such as congestive heart failure, ischaemic heart disease, hypertension and atrial fibrillation were defined. Total mortality was recorded during the prospective 60-month follow-up period.. Individuals aged 85 years from the population of Gothenburg, Sweden, were visited once at home and made one visit to Vasa Hospital.. Sixty-month mortality in relation to circulating concentrations of atrial natriuretic peptides.. Circulating concentrations of ANP(1-98) and ANP(99-126) were significantly correlated with 60-month mortality in the total study population (ANP(1-98), P < 0.001: ANP(99-126), P < 0.01). In subjects with cardiovascular disorders, 60-month mortality was significantly correlated with increased concentrations of ANP(1-98) (P < 0.01) and ANP(99-126) (P < 0.05). In subjects with no defined cardiovascular disorder, 60-month mortality was significantly correlated with increased ANP(1-98) concentrations (P < 0.01).. In the elderly population, atrial peptides predict mortality in subjects with defined cardiovascular disorders as well as in the total population and may predict future cardiovascular disorder.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Atrial Natriuretic Factor; Heart Diseases; Heart Failure; Humans; Hypertension; Myocardial Ischemia; Survival Rate

The aim of the study was to investigate the release of natriuretic peptides during myocardial ischaemia and reperfusion associated with cardioplegic cardiac arrest. Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations were measured in paired arterial, central venous and coronary sinus blood samples in 19 patients undergoing elective coronary artery bypass grafting before aortic crossclamping and 1, 5, 10 and 20 min after aortic declamping. Peak myocardial BNP release after aortic declamping was significantly higher than baseline values before aortic crossclamping. Both peak and cumulative BNP release during reperfusion correlated significantly with the severity of ischaemia, as assessed by myocardial lactate production. In 3 patients with perioperative myocardial ischaemia, cumulative and peak myocardial BNP release after aortic unclamping was markedly higher than in the remaining 16 uneventful patients. Myocardial ANP release during reperfusion was not significantly different from baseline values before aortic crossclamping. In conclusion, our data demonstrate a significantly enhanced myocardial BNP release early during reperfusion of the human heart after global ischaemia associated with cardioplegic cardiac arrest.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Coronary Artery Bypass; Extracorporeal Circulation; Female; Heart Arrest, Induced; Humans; Lactic Acid; Male; Middle Aged; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Troponin; Troponin T

In order to clarify the different secretion profiles of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in response to acute hemodynamic change by volume expansion, we measured plasma ANP and BNP levels after intravenous isotonic saline infusion for 3 min at a rate of 3 ml/kg body weight/min in 15 patients with ischemic heart disease. Plasma ANP and BNP levels before the volume loading were 30.7 +/- 16.7 and 19.4 +/- 24.6 pg/ml, respectively. Five and 10 minutes after infusion, plasma ANP levels rose significantly to 43.5 +/- 20.7 and to 46.0 +/- 22.5 pg/ml, respectively (p < 0.01), and plasma BNP levels rose significantly to 27.3 +/- 30.8 and 24.8 +/- 23.2 pg/ ml, respectively (p < 0.01). The BNP/ANP ratio was not affected by volume loading. The maximum increments of plasma ANP level correlated significantly with those of the mean pulmonary capillary wedge pressure (mPCWP, r = 0.78, p < 0.01) or left ventricular end-diastolic pressure (LVEDP, r = 0.86, p < 0.01). However, there were no significant correlations between the maximum increments of plasma BNP levels and those of mPCWP or LVEDP. Plasma ANP level can be a useful parameter for atrial pressure even if the hemodynamic state change rapidly. However, in an early phase of ventricular overload BNP secretion is not increased sufficiently despite the raised LVEDP, and plasma BNP level may not always reflect ventricular hemodynamics.

Topics: Atrial Natriuretic Factor; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Sodium Chloride

Congestive heart failure results in biatrial stretch, which stimulates myocyte release of atrial natriuretic factor (1-126). The N-terminal fragment, proatrial natriuretic factor(1-98), (proANF), is released on an equimolar basis with the C-terminal (99-126) active hormone and may be assayed simply because of prolonged in vitro stability. Proatrial natriuretic factor has been shown to be predictive of clinical status in patients with congestive heart failure. This retrospective analysis was undertaken to evaluate the relationship between N-terminal atrial natriuretic factor(1-98) and survival in patients with stable congestive heart failure.. Proatrial natriuretic factor was sampled from 316 patients (mean age, 68 (+/-) 11 years; 71% men) recruited from an outpatient heart failure clinic. The mean ejection fraction was 34 (+/-) 13%. Seventy-three deaths were registered during the period of data collection (42 months). Deaths per proANF quartile (n = 79) were as follows: 2 (2.5%) in quartile I. 13 (16.5%) in quartile II, 21 (26.6%) in quartile III, and 37 (46.8%) in quartile IV. The odds ratio estimates for death adjusted for age and sex were 7.6, 13.9, and 33.9 for the second, third, and fourth quartiles, respectively. Survival curves constructed according to proANF quartiles demonstrate significant differences in mortality rates. The correlation with death was greater for proANF as compared with left ventricular end-diastolic diameter (P < .001), systolic pulmonary artery pressure (P < .005), or ejection fraction (P < .05).. These data indicate that the concentration of proANF is related to prognosis in patients with heart failure and that moderate elevation is associated with markedly decreased survival. Analysis should be of practical value in the assessment of prognosis in this heterogeneous population.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Predictive Value of Tests; Prognosis; Protein Precursors; Retrospective Studies; Survival Analysis

We tested the hypothesis that neurohormonal and immunological activation differs in ischemic and idiopathic dilated cardiomyopathy since recent intervention trials indicate that ischemic cardiomyopathy seems to carry a worse prognosis than idiopathic cardiomyopathy of comparable clinical severity.. In ten patients with ischemic cardiomyopathy undergoing spiroergometric evaluation venous levels of norepinephrine, epinephrine, renin, angiotensin, atrial natriuretic peptide as well as soluble interleukin-2-receptor were determined before, during and 10 min after exercise. Results were compared to sixteen patients with idiopathic cardiomyopathy with similar peak oxygen uptake (13.3+/-3 vs. 13.6+/-3 ml/kg/min; P=ns).. In ischemic patients, norepinephrine, angiotensin, and interleukin-2 receptor levels were significantly higher before, during and after exercise. Interleukin-2-receptor levels correlated with angiotensin.. We conclude that in ischemic as compared to idiopathic cardiomyopathy, a more pronounced activation of the sympathetic, renin-angiotensin and T-cell immune system is present at rest, during and after exercise. These data may contribute to explain differences in response to intervention and in prognosis. They warrant further investigation.

Topics: Adult; Aged; Angiotensin II; Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Epinephrine; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Norepinephrine; Pilot Projects; Receptors, Interleukin-2; Regression Analysis; Renin; Renin-Angiotensin System; Statistics, Nonparametric; Sympathetic Nervous System; T-Lymphocytes

Recently, we developed a goat model of chronic atrial fibrillation (AF). Due to AF, the atrial effective refractory period (AERP) shortened and its physiological rate adaptation inversed, whereas the rate and stability of AF increased. The goal of the present study was to evaluate the role of (1) the autonomic nervous system, (2) ischemia, (3) stretch, (4) atrial natriuretic factor (ANF), and (5) rapid atrial pacing in this process of electrical remodeling.. Twenty-five goats were chronically instrumented with multiple epicardial atrial electrodes. Infusion of atropine (1.0 mg/kg; n=6) or propranolol (0.6 mg/kg; n=6) did not abolish the AF-induced shortening of AERP or interval (AFI). Blockade of K+(ATP) channels by glibenclamide (10 micromol/kg; n=6) slightly increased the AFI from 95+/-4 to 101+/-5 ms, but AFI remained considerably shorter than during acute AF (145 ms). Glibenclamide had no significant effect on AERP after electrical cardioversion of AF (69+/-14 versus 75+/-15 ms). Volume loading by 0.5 to 1.0 L of Hemaccel (n=12) did not shorten AERP. The median plasma level of ANF increased from 42 to 99 pg/mL after 1 to 4 weeks of AF (n=6), but ANF infusion (0.1 to 3.1 microg/min, n=4) did not shorten AERP. Rapid atrial pacing (24 to 48 hours; n=10) progressively shortened AERP from 134+/-10 to 105+/-6 ms and inversed its physiological rate adaptation.. Electrical remodeling by AF is not mediated by changes in autonomic tone, ischemia, stretch, or ANF. The high rate of electrical activation itself provides the stimulus for the AF-induced changes in AERP.

Topics: Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Function; Atrial Natriuretic Factor; Atropine; Cardiac Pacing, Artificial; Dilatation; Electrophysiology; Glyburide; Goats; Heart; Myocardial Ischemia; Neurotransmitter Agents; Physical Stimulation; Propranolol; Refractory Period, Electrophysiological

A specific and sensitive radioimmunoassay (RIA) for the N-terminal fragment of proatrial natriuretic peptide (NproANP) was developed. Antiserum raised in rabbits against a mixture enriched with prohormone was 100% cross-reactive with human proANP(1-30). Plasma concentrations of proANP(1-30) and ANP immunoreactivities (ir-) were simultaneously measured in healthy subjects and patients with congestive heart failure (CHF; 26 dilated cardiomyopathy and 5 ischemic heart disease). High plasma levels of both ir-proANP(1-30) and ir-ANP were detected in CHF patients. Circulating ir-ANP levels were elevated in New York Heart Association functional Classes II and III patients but not in Class I patients. However, plasma levels of ir-proANP(1-30) were higher in asymptomatic patients than in healthy subjects, and markedly increased in patients of Classes II and III. Analysis of ir-proANP(1-30) by gel filtration chromatography or reverse-phase high pressure liquid chromatography revealed a 10 kDa peptide circulating as a distinct entity. These findings indicate that: (i) the most probable form of NproANP in human plasma is a 10 kDa peptide and (ii) in CHF patients the rise in plasma ir-proANP(1-30) levels is more pronounced than the variation in plasma ir-ANP. Thus, NproANP plasma levels may prove to be a more sensitive marker of left ventricular dysfunction than ANP.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Chromatography, Gel; Chromatography, High Pressure Liquid; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Protein Precursors; Radioimmunoassay

This study was designed to examine the plasma levels of B-type or brain natriuretic peptide (BNP), as well as A-type or atrial natriuretic peptide (ANP) in patients with unstable angina as compared with those in patients with stable exertional angina and control subjects. We measured the plasma levels of BNP and ANP in 33 patients with unstable angina, 20 patients with stable exertional angina, and 20 control subjects. The plasma levels of BNP were significantly increased in patients with unstable angina compared with those in patients with stable exertional angina and control subjects, respectively (39.5 +/- 29.4 pg/ml vs 15.1 +/- 8.0 pg/ml; p < 0.01 and 39.5 +/- 29.4 pg/ml vs 10.3 +/- 6.4 pg/ml; p < 0.01, respectively). On the other hand, there was no significant difference in the plasma levels of ANP among the three groups. Furthermore, in patients with unstable angina, the plasma levels of BNP decreased significantly after the medical treatment (from 39.5 +/- 29.4 pg/ml to 15.8 +/- 11.0 pg/ ml; p < 0.01), whereas the plasma levels of ANP did not change. We conclude that the plasma levels of BNP are increased in the majority of patients with unstable angina and that the increased levels decrease toward normal after treatment.

Topics: Adult; Aged; Angina Pectoris; Angina, Unstable; Atrial Natriuretic Factor; Cardiovascular Agents; Echocardiography; Electrocardiography; Electrocardiography, Ambulatory; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Physical Exertion

The aim of this investigation was to test whether the administration of atrial natriuretic peptide (ANP) has cardioprotective effects against ischaemic and reperfusion injury.. Thoracotomized dogs underwent a 30 min left circumflex coronary artery occlusion and 60 min of reperfusion (control group; n = 16). The ANP group (n = 9) received a 20 micrograms bolus injection of synthetic alpha human ANP (SUN 4936) followed by infusion at a dose of 0.1 microgram/kg/min from the beginning of coronary occlusion to the end of the procedure.. Administration of exogenous ANP increased plasma ANP immediately and maintained levels at 3000 pg/ml, resulting in an 8-fold increase in plasma cyclic guanosine monophosphate (cGMP) levels. Plasma ANP and plasma cGMP levels did not change at all in controls. There were no significant differences in haemodynamic parameters during ischaemia and reperfusion between the groups. In the ANP group, the prevalence and frequency of ventricular extrasystoles within 10 min after reperfusion decreased markedly [ANP 22% vs. control 100%, P < 0.01, and ANP 1 (1) vs. control 92 (50), P < 0.05, respectively]. No dog in the ANP group had ventricular fibrillation (VF), but the incidence of VF was not statistically significant between the groups [ANP 0% vs. control 25%]. ATP content in the inner layers of the ischaemic myocardium in the ANP group was higher than in controls (P < 0.05) [1.92 (0.28) vs. 1.18 (0.13) mumol/g wet weight]. There was no significant difference in the content of myocardial tissue angiotensin II between the groups.. These data show that the infusion of ANP has cardioprotective effects on myocardial ischaemia and reperfusion in this model. These beneficial effects are probably due to direct effects through cGMP rather than haemodynamic changes.

Topics: Angiotensin II; Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cyclic GMP; Dogs; Female; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium

Topics: Adult; Analysis of Variance; Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Cardiac Catheterization; Coronary Vessels; Diastole; Female; Femoral Vein; Humans; Male; Middle Aged; Myocardial Ischemia; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular 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

The separate effects of hypoxia and ischemia on atrial natriuretic peptide (ANP) release were evaluated in Langendorff-perfused rabbit hearts. Heart rate, coronary flow, and atrial and ventricular volumes were kept constant. Hypoxia was induced for 20 min at room temperature in seven hearts and at 37 degrees C in a second group of seven hearts. A third group of eight hearts was subjected to global ischemia for 20 min by reducing coronary flow to 1 ml/min at room temperature. All hearts were reoxygenated/reperfused at 37 degrees C for 30 min. Hypoxia at 37 degrees C induced a significant increase in ANP release. In contrast, both room temperature hypoxia and ischemia were characterized by a significant decrease in ANP release, despite hemodynamic alterations similar to those recorded during hypoxia at 37 degrees C. Both reoxygenation and reperfusion induced a prompt reversal of the changes of ANP release observed during the period of oxygen deprivation. These data demonstrate that decreased oxygen availability and reduced coronary flow are not the primary factors affecting release of ANP during ischemia and that alterations of myocardial temperature may play a major role in this phenomenon.

Topics: Animals; Atrial Natriuretic Factor; Coronary Circulation; Heart; Heart Rate; Hemodynamics; Hypoxia; In Vitro Techniques; Myocardial Ischemia; Myocardial Reperfusion; Rabbits; Temperature; Time Factors

To assess whether infarct size, ischemic area and/or survival correlates with circulating atrial natriuretic peptides (long acting sodium stimulator, vessel dilator, or atrial natriuretic factor), these peptides were measured in a canine model of acute myocardial infarction. Elevations in the circulating concentrations of atrial natriuretic factor, vessel dilator, and long acting sodium stimulator were significant (P < 0.05) within 6 min of coronary occlusion of the left anterior descending coronary artery. The percentage of ischemic myocardium ranged from 20 to 67% with a mean of 37 +/- 17%. The area of infarction ranged from 1 to 13% with the infarcted area of non-survivors being twice that of survivors. Both the ischemic and infarcted areas correlated (P < 0.05) with the circulating concentrations of these atrial natriuretic peptides. Survival correlated also with the circulating plasma concentrations of vessel dilator, atrial natriuretic factor and long acting sodium stimulator (P < 0.05). When these circulating concentrations were evaluated, however, by determining their area under their respective concentrations curves and expressing each as the log area under plasma concentration-time curve (area under the curve) per kg of weight (Y = 58.48X-23.62; r = 0.825; P = 0.0009), vessel dilator was the only atrial natriuretic peptide that correlated with survival.

Topics: Animals; Atrial Natriuretic Factor; Confidence Intervals; Dogs; Hemodynamics; Linear Models; Male; Myocardial Infarction; Myocardial Ischemia; Radioimmunoassay

The immediate and longer term variability of selected vasoactive- and volume-regulating neurohormones were measured in patients entering a substudy of the Studies of Left Ventricular Dysfunction--a randomized clinical trial in patients with left ventricular ejection fraction < or = 35%. The variability of these hormones has not been determined in a large cohort of patients. Immediate (short-term) variability was assessed by systematically comparing levels after 15 and 30 minutes of supine rest at the initial visit, and longer term variability was assessed by comparing 30-minute supine rest values at the initial visit with corresponding values taken at 30 minutes after 16 to 24 days of stable therapy. Initial values obtained at the first visit after 30-minute supine rest for all 209 patients were (mean +/- SEM) 512 +/- 21 pg/ml pg/ml for plasma norepinephrine, 1.9 +/- 0.2 ng/ml/hr for plasma renin activity, 3.0 +/- 0.1 pg/ml for plasma arginine vasopressin, and 129 +/- 5.3 pg/ml for plasma atrial natriuretic peptide. All variables were moderately increased relative to established normal values. There was a small but significant decrease from 15- to 30-minute supine posture in all neurohormones, except arginine vasopressin. In the presence of stable background therapy, no significant differences were found between measurements obtained after 30 minutes supine rest at the initial visit and 16 to 24 days later. Spearman correlation coefficients corresponding to immediate and longer term variability were high (range 0.55 to 0.79) (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Arginine Vasopressin; Atrial Natriuretic Factor; Biomarkers; Disease Progression; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Norepinephrine; Randomized Controlled Trials as Topic; Renin; Supine Position; Ventricular Dysfunction, Left

Plasma renin activity (PRA), angiotensin II (ATII), aldosterone (ALD) and atrial natriuretic factor (ANF) were determined in 30 patients with high altitude myocardial hypoxidosis (HAMH) with radioimmunoassay and the data were compared with those of 40 healthy subjects and 26 patients with high altitude chronic cardiopathy (HACC). All of them have been in Lasa, a place with an altitude of 3,658 meter, for a long time. The results showed that PRA and plasma ATII increased significantly (P < 0.05-0.01) and plasma ANF decreased significantly (P < 0.01) in patients with HACC and were higher than those in the control. It is suggested that disturbance of these biologically active substances might play a role in the development of HAMH.

Topics: Adolescent; Adult; Altitude Sickness; Atrial Natriuretic Factor; Blood Gas Analysis; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Renin-Angiotensin System

We assess hemodynamic, vascular, and hormonal effects of endothelin-1 (ET-1) at pathophysiologic levels on normal and ischemic myocardium. Thirty conscious chronically instrumented dogs were studied before, during, and after a 10-min coronary artery occlusion (CAO) performed either during ET-1 infusion (2.5 ng/kg.min, n = 15) or during placebo infusion (n = 15). ET-1 infusion produced an increase in plasma ET-1 (from 1.3 +/- 0.1 to 11.5 +/- 1.1 pM, p < 0.0001) during CAO (pathophysiologic value). Left anterior descending artery (LAD) blood flow (measured by Doppler flow probe) decreased similarly during CAO with ET-1 or placebo (p = 0.0001, NS, ET-1 vs. placebo). Both endocardial and epicardial blood flows in ischemic regions also decreased (p = 0.0001) during CAO but were threefold greater with ET-1 than with placebo (endocardium 42 +/- 7 vs. 14 +/- 2 ml/min/100 g, p = 0.003). No significant difference in myocardial blood flows between groups was observed in control regions. CAO produced increases (p < 0.005) in heart rate (HR), mean aortic pressure (AOP), and ventricular pressures but no change in atrial pressures. The changes in these parameters were comparable in the ET-1 and placebo groups. Despite the greater residual flow during CAO, however, ET-1 decreased the function of the ischemic zone during reperfusion as assessed by systolic shortening (p < 0.05). Atrial natriuretic factor (ANF), unchanged during CAO with placebo, increased from 38.3 +/- 6.1 to 53.3 +/- 10 pM with ET-1 (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Blood Urea Nitrogen; Catecholamines; Coronary Circulation; Creatinine; Dogs; Endothelins; Hemodynamics; Microspheres; Myocardial Contraction; Myocardial Ischemia; Potassium; Regional Blood Flow; Renal Circulation

Keeping pre-transplant patients alive while waiting for a suitable donor to be found is still a major challenge. New pharmacological agents which can provide improved hemodynamics are urgently needed in patients with severe heart failure who are on the waiting list for cardiac transplantation. Intravenous enoximone therapy (an initial 0.5 mg/kg bolus, then 1.25-5.0 mcg/kg/min infusion) was administered to 18 transplant candidates with heart failure progression despite optimal drug regimen including digoxin, diuretics, and ACE-inhibitors. Complete hemodynamic, echocardiographic, and neurohumoral studies were performed before and 24 h after intravenous enoximone infusion. Enoximone infusion increased cardiac index (1.78 +/- 0.45 l/min/qm vs. 3.04 +/- 0.83 l/min/qm; p < 0.001) and stroke volume index (22.33 +/- 9.45 ml/qm vs. 32.28 +/- 7.29 ml/qm; p < 0.05) and decreased wedge pressure (24.1 +/- 11.98 mmHg vs. 17.78 +/- 8.76 mmHg; p < 0.05) and systemic vascular resistance (1700.8 +/- 555.8 dyn x s x cm-5 vs. 952.8 +/- 384.0 dyn x s x cm-5; p < 0.001). Heart rate and mean arterial pressure were unchanged. Left ventricular ejection time (225.1 +/- 26.9 ms vs. 242.2 +/- 25.8 ms; p < 0.05) was increased, whereas other echocardiographic parameters were unchanged (left ventricular end-diastolic dimension, left ventricular end-systolic dimension, fractional shortening, early diastolic relaxation parameter Te). Plasma neurohumoral parameters did not change (aldosterone, epinephrine, renin, atrial natriuretic factor) except for a significant drop of norepinephrine (936.7 +/- 443.2 pg/ml vs. 522.4 +/- 287.6 pg/ml; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Combined Modality Therapy; Dose-Response Relationship, Drug; Echocardiography; Enoximone; Epinephrine; Female; Heart Failure; Heart Transplantation; Hemodynamics; Hormones; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Ischemia; Norepinephrine; Renin; Stroke Volume

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Diastole; Female; Heart Failure; Humans; Linear Models; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Ventricular Function, Left

We studied the effects of short-term global ischemia and reperfusion on ANP secretion from Langendorff-perfused rat hearts compared with isolated ventricles. Effects of regional ischemia, with or without increased atrial pressure, were examined in Langendorff-perfused and working heart models. Five minutes of global ischemia were associated with elevated levels of atrial natriuretic peptide (ANP) in the coronary effluent immediately and for approximately 10 min after resumption of reperfusion, resulting in a net hormone excess of 23 +/- 5 ng/g wet wt. The ventricles produced on the average 11% ANP compared with the whole heart, and their contribution of to postischemic ANP overflow was approximately proportional to their basal production. In Langendorff-perfused hearts, regional ischemia increased the concentration of ANP in the coronary effluent 51 +/- 11%, whereas the secretion rate (per minute) decreased 18 +/- 5%. In the presence of atrial distension in the working heart model, a trend for increase in ANP secretion was apparent. We conclude that global ischemia, even of brief duration, has an independent stimulatory effect on ANP release, the ischemic atrium being responsible for most of the excess. Regional ischemia, when not accompanied by atrial distention, reduces the ANP secretion rate during the ischemic period. Heart failure secondary to ischemia stimulates ANP secretion, but this response seems to be both delayed and attenuated compared with atrial stretch alone.

Topics: Animals; Atrial Natriuretic Factor; Coronary Vessels; Heart; Heart Rate; Heart Ventricles; In Vitro Techniques; Male; Myocardial Ischemia; Myocardial Reperfusion; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Regression Analysis; Time Factors

The aim was to investigate (1) the relationship between atrial natriuretic factor (ANF) release and the extent of ischaemia-hypoxia, and (2) the potential role of eicosanoids in ANF release during global ischaemia, particularly the cyclo-oxygenase derivatives (prostaglandins) and the lipoxygenase derivatives (leukotrienes).. Using an isolated perfused, spontaneously beating rat heart, global ischaemia was achieved by the reduction of perfusion flow rate relative to basal flow rate. ANF was measured by radioimmunoassay.. A decrease in perfusion flow rate by 75-80% to a final value of 2-2.5 ml.min-1.g-1 heart (n = 6) caused a gradual but sustained increase of ANF release which reached a plateau after 12 min, attaining a peak value of 89.9 (SEM 26.6)% over baseline. A decrease in perfusion flow rate by 55-60% (n = 5) also resulted in an increased ANF secretion, with a peak of 125.6(23.2)% over baseline at 14 min. A decrease in perfusion flow rate by 25-30% to a final value of 5-6.75 ml.min-1.g-1 heart (n = 4) showed no change in ANF release. The mean basal value of ANF release was 8.23(2.39) ng.min-1.g-1 heart (n = 26). In a separate series of experiments using a reduction of 55-60% in perfusion flow rate but with the addition to the perfusion medium of the specific cyclo-oxygenase inhibitor meclofenamate 10 microM (n = 5) or the lipoxygenase inhibitor nordihydroguaiaretic acid 10 microM (n = 5), no increase in ANF release occurred during the period of global ischaemia. Neither inhibitor affected ANF release during basal perfusion rates (7-9 ml.min-1.g-1 heart).. ANF released in response to global ischaemia is likely to be mediated by prostanoids generated via the cyclo-oxygenase pathway and leukotrienes generated via the lipoxygenase pathway. Both pathways may provide important paracrine/autacoid regulatory roles for the protection of the heart during ischaemia by stimulating ANF release, with the subsequent beneficial effects of the peptide on peripheral tissues, ultimately leading to a reduction in load on the heart.

Topics: Animals; Atrial Natriuretic Factor; Disease Models, Animal; Diterpenes; Eicosanoids; Ginkgolides; Heart Rate; Lactones; Male; Masoprocol; Meclofenamic Acid; Myocardial Contraction; Myocardial Ischemia; Myocardium; Perfusion; Platelet Activating Factor; Rats; Rats, Inbred Strains; Secretory Rate

Secretion of immunoreactive atrial natriuretic factors (ANF) after injury by ischaemia-reperfusion and toxic oxygen metabolites (TOM) was investigated in the following groups of Langendorff-perfused rat hearts: 1.1., control perfusion; 1.2., hearts perfused with H2O2 (200 mumol l-1) as a TOM-generating agent for 10 min, followed by recovery for 30 min; 1.3., thiourea (10 mmol l-1), a hydroxyl radical scavenger, was given together with H2O2; 2.1., control perfusion; 2.2., ischaemia (37 degrees C) for 20 min followed by reperfusion for 40 min. Ischaemia-reperfusion and TOM temporarily decreased left ventricular developed pressure and increased left ventricular end-diastolic pressure. The cardiac effects of H2O2 were inhibited by thiourea. Coronary flow (CF) was increased by TOM and decreased by ischaemia-reperfusion. Immunoreactive ANF was measured sequentially in the coronary effluent by radioimmunoassay. Basal secretion of immunoreactive ANF for all groups pooled was 0.45 +/- 0.02 pmol min-1 (mean +/- SEM), and did not change significantly with time in any group. In conclusion, ischaemia-reperfusion and TOM do not influence secretion of immunoreactive ANF.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Coronary Circulation; Free Radicals; Hydrogen Peroxide; In Vitro Techniques; Male; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Rats; Rats, Wistar

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

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

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: Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; Humans; Myocardial Ischemia; Pulmonary Wedge Pressure

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

Eighteen anaesthetized open chest cats were subjected to 10, 30, or 50 min occlusion of the left anterior descending coronary artery (LAD). Heart rate, left ventricular end-diastolic (LVEDP) and systolic pressure (LVSP), and dp/dt were continuously recorded during the experiments. Prior to LAD-occlusion, and just before termination of the experiments, blood samples were collected from the left femoral artery for measurements of atrial natriuretic factor (ANF), catecholamines, electrolytes, urea, and creatinine. Simultaneously, biopsies were collected from the right auricular wall. The tissue was embedded in Lowicryl K4M, and ultrathin sections were incubated with anti-ANF antibodies and secondary antibodies conjugated to gold particles. The density of ANF-containing atrial-specific granules labelled with gold particles was morphometrically calculated. LVEDP increased significantly in all three time groups, and when pooling the pre- and postocclusion values, there was an increase from 5.1 +/- 0.4 to 10.3 +/- 1.2 mmHg (p < 0.05). The noradrenaline level increased from 0.93 +/- 0.18 to 2.34 +/- 0.75 nmol l-1 (p < 0.05) after LAD-occlusion. Similarly, the mean plasma level of ANF in the 18 cats increased from 57.6 +/- 11.9 to 98.9 +/- 22.6 pmol l-1 (p < 0.05). Atrial granular density appeared to decline after 10 min of occlusion (from 0.141 +/- 0.017 to 0.127 +/- 0.022 granules-1 microns 2 sarcoplasm), and after 30 min there was a significant decrease (0.080 +/- 0.012 granules/microns 2, p < 0.05). However, after 50 min occlusion the granular density was almost restored (0.133 +/- 0.017 granules/microns 2). Plasma ANF showed a positive linear correlation to LVEDP and to the noradrenaline level.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Cats; Femoral Artery; Heart Atria; Heart Rate; Hemodynamics; Immunohistochemistry; Myocardial Ischemia; Norepinephrine; Pressure; Ventricular Function, Left

Radiation of the precordial region with ultrasound at 880 kHz, 0.4 W/cm2 for 12 minutes was examined for its impact on blood levels of thyrotropin, tri-iodothyronine, thyroxine, atrial natriuretic factor, cyclic nucleotides (cAMP and cHMP) in 70 patients with Functional Classes II-III exercise-induced angina. The radiation was found to lead to elevated plasma levels of atrial natriuretic factor, cHMP and inhibited plasma cAMP in patients with coronary heart disease as compared to the control group.

Topics: Adult; Atrial Natriuretic Factor; Humans; Male; Middle Aged; Myocardial Ischemia; Nucleotides, Cyclic; Pituitary Gland; Thorax; Thyroid Gland; Thyroid Hormones; Thyrotropin; Ultrasonic Therapy