atrial-natriuretic-factor and Arrhythmias--Cardiac

Coronary heart disease (CHD) is the leading cause of death and disability in Europe. For patients presenting with an acute ST-segment elevation myocardial infarction (STEMI), timely myocardial reperfusion using either thrombolytic therapy or primary percutaneous coronary intervention (PPCI) is the most effective therapy for limiting myocardial infarct (MI) size, preserving left-ventricular systolic function and reducing the onset of heart failure. Despite this, the morbidity and mortality of STEMI patients remain significant, and novel therapeutic interventions are required to improve clinical outcomes in this patient group. Paradoxically, the process of myocardial reperfusion can itself induce cardiomyocyte death-a phenomenon which has been termed 'myocardial reperfusion injury' (RI), the irreversible consequences of which include microvascular obstruction and myocardial infarction. Unfortunately, there is currently no effective therapy for preventing myocardial RI in STEMI patients making it an important residual target for cardioprotection. Previous attempts to translate cardioprotective therapies (antioxidants, calcium-channel blockers, and anti-inflammatory agents) for reducing RI into the clinic, have been unsuccessful. An improved understanding of the pathophysiological mechanisms underlying RI has resulted in the identification of several promising mechanical (ischaemic post-conditioning, remote ischaemic pre-conditioning, therapeutic hypothermia, and hyperoxaemia), and pharmacological (atrial natriuretic peptide, cyclosporin-A, and exenatide) therapeutic strategies, for preventing myocardial RI, many of which have shown promise in initial proof-of-principle clinical studies. In this article, we review the pathophysiology underlying myocardial RI, and highlight the potential therapeutic interventions which may be used in the future to prevent RI and improve clinical outcomes in patients with CHD.

Topics: Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Blood Glucose; Calcium; Cardiotonic Agents; Cell Death; Coronary Occlusion; Disease Models, Animal; Hemorrhage; Humans; Hydrogen-Ion Concentration; Hyperbaric Oxygenation; Hypothermia, Induced; Ischemic Postconditioning; Microvessels; Mitochondria, Heart; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Myocardial Contraction; Myocardial Infarction; Myocardial Reperfusion Injury; Myocarditis; Myocytes, Cardiac; Nitric Oxide; Oxidative Stress; Percutaneous Coronary Intervention

Topics: Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Biomarkers; Humans; Natriuretic Peptide, Brain; Severity of Illness Index

Topics: Acute Kidney Injury; Animals; Arrhythmias, Cardiac; Ascites; Atrial Natriuretic Factor; Cardiovascular Diseases; Cerebrovascular Disorders; Heart Failure; Humans; Hypertension; Hyperthyroidism; Hypothyroidism; Kidney; Liver Cirrhosis; Myocardial Infarction; Sodium; Thyroxine

Duchenne's progressive muscular dystrophy (DMD) is a genetic muscle disorder that causes degeneration and atrophy of the systemic and cardiac muscle. The disease is manifested early in childhood, and most of patients die by age 20 years of respiratory failure or heart failure. The cardiac involvement in DMD is characterized pathologically by degeneration and fibrosis of the myocardium, centering around the posterolateral wall of the left ventricle. Functionally, an abnormal electrocardiogram, valve motion, wall thickness, and wall motion are observed. Furthermore, abnormalities in plasma levels of atrial natriuretic peptide and autonomic function are also demonstrated. In this review, the cardiac involvements in DMD in the following aspects are described: 1) Electrocardiogram; a) high-frequency notches on the QRS complexes, b) amplitude of QRS complexes, c) late potential, d) arrhythmias, e) heart rate variability, f) a 10-year follow-up study, 2) Echocardiographic findings, 3) Hemodynamic findings, 4) Atrial natriuretic peptide.

Topics: Arrhythmias, Cardiac; Atrial Natriuretic Factor; Echocardiography; Electrocardiography; Fibrosis; Follow-Up Studies; Heart Rate; Humans; Mitral Valve Prolapse; Muscular Dystrophies; Myocardial Contraction; Myocardium; Vectorcardiography

Topics: Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Humans; Kidney; Myocardial Infarction; Neurosecretory Systems; Peptidyl-Dipeptidase A; Prognosis; Rats; Renin-Angiotensin System; Vasoconstriction

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

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

The prognostic importance of levels of urinary excretion of cyclic GMP (cGMPu), the second messenger of the atrial natriuretic factor (ANF) was studied in different cardiac pathologies in 31 patients (19 males and 12 females, average age 66 +/- 15 years) and compared with 31 control subjects of the same age (+/- 4 years) and sex. In the control group, the average cGMPu was 0.35 +/- 0.17 mumoles/24 hours/m2, and, with respect to urinary creatinine, increased with age (r = 0.54, p = 0.002). In the 16 patients with cardiac failure, the cGMPu was very high (1.03 +/- 0.59 mumoles/24 hours/m2, p less than 0.001) without any significant correlation with NYHA functional class although it fell after treatment. After myocardial infarction (8 cases including 3 with cardiac failure), the cGMPu was also high (0.49 +/- 0.33 mumoles/24 hours/m2) but it did not differ significantly from the control values in the 9 atrial arrhythmias without cardiac failure. The cGPMu was related to the cardiothoracic ratio but not to any blood gas parameter or echocardiographic measurement. In conclusion, the cGMPu is more stable and easier to measure than the ANF. It would seem to be a sensitive marker of cardiac failure complicating the most common cardiac pathologies observed in clinical practice.

Topics: Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cyclic GMP; Female; Heart Atria; Heart Diseases; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction

Having outlined the principal physiological and pathological aspects of the atrial natriuretic factor (ANF) on the basis of data found in the literature, the authors report the results of their research on variations of ANF plasma level during hyperkinetic atrial arrhythmia, acute myocardial infarction with and without complications as well as hypotensive and renal effects of synthetic ANF in congestive heart failure. Regardless of the cause of hyperkinetic atrial arrhythmia, high ANF levels were normalized or significantly reduced after the return to sinus rhythm whereas with the sole reduction of ventricular rate ANF remained raised. In uncomplicated myocardial infarction ANF level was raised to an extent inversely proportional to the ejection fraction. In cardiogenic shock, ANF values were high and correlated to the high central venous pressure and heart rate. On the contrary, in the hypotensive bradycardia syndrome ANF values were normal even when the syndrome had occurred in the acute stage of infarction. In congestive heart failure, ANF administration had contradictory effects in that diuresis was induced by lower doses, and hypotension by higher ones.

Topics: Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Heart Failure; Humans; Myocardial Infarction; Research; Shock, Cardiogenic; Stroke Volume

This review updates some recent advances of a new and exciting developments in basic and clinical cardiology: a) the role, in the congestive heart failure (CHF), of the neurohormonal systems (NHS) which act to maintain circulatory homeostatic equilibrium, and b) the therapeutic implications of such a role. Six NHS, acting in CHF, have presently been identified: three of them induce vasoconstriction and sodium retention (sympathetic nervous systems, renin-angiotensin-aldosterone system and arginine-vasopressine system); the remaining three offset or balance the former ones, acting, therefore as "counterregulators" (prostaglandins--PGE2 and PGI2--, dopaminergic system and atrial natriuretic factor). Each one of these NHS influences the "compensatory" mechanisms of heart failure, acting on the target-organs both by direct effects and by interaction with other NHS; consequently, in heart failure, all the NHS are stimulated with the respective increase in the plasma levels of their agents. In asymptomatic stages of ventricular dysfunction the stimulation of the vasodilator-and-natriuretic systems appears to be predominant and able to maintain circulatory equilibrium. However, as the heart dysfunction increases and becomes symptomatic, the vasoconstrictor and sodium-retaining forces appear to predominate; this phenomenon becomes increasingly apparent as the functional class becomes more advanced. The hyperstimulation of these last systems has an extremely important role in the pathophysiology and clinical manifestations of congestive heart failure, as well as in its prognosis. Therefore, the attempts to correct these neurohormonal imbalance in patients with heart failure has a sound rational basis, not only to improve the symptoms and the exercise capacity but also to increase the survival of these patients. At the present time, amongst the potential pharmacological interventions acting on NHS in CHF, the blockade of the SRA system with ACE-inhibitors is generally accepted as the most feasible, the safer and the most effective therapeutic tool. In fact, its application has broadened from an earlier use in severe CHF to other symptomatic stages of cardiac failure, including the milder forms. In addition, preliminary data strongly suggest its unique usefulness in asymptomatic phases of ventricular dysfunction. Looking back at the medical therapy of heart failure, it can be concluded that we are starting a new era. Throughout 200 years (since the introduction of d

Topics: Angiotensin-Converting Enzyme Inhibitors; Arginine Vasopressin; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Heart Failure; Humans; Hyponatremia; Kidney; Neurotransmitter Agents; Prognosis; Prostaglandins; Receptors, Dopamine; Renin-Angiotensin System; Sympathetic Nervous System

Atrial natriuretic factor (ANF) is a cardiac peptide hormone whose detection led to the discovery of a new natriuretic vasomotor relaxant hormonal system where the heart plays the role of an endocrine gland. Atrial distension represents the main stimulus for the release of ANF. Its cardiovascular effects consist primarily of hypotension related to its relaxant properties, a decrease in cardiac output and a negative inotropic effect. The close relations between ANF and the heart implicate this hormone as a major factor in all cardiovascular disorders, and in particular in congestive heart failure where its plasma concentration represents an index of hemodynamic and functional disease severity. Hemodynamic changes related to valvular heart disease, whether of the mitral or aortic valve, as well as dysrhythmias have a significant effect on release of ANF. Thus, it is now well recognized that ANF, released by the heart, is implicated in the pathophysiology of cardiovascular disorders.

Topics: Arrhythmias, Cardiac; Atrial Natriuretic Factor; Heart Diseases; Heart Valve Diseases; Humans; Kidney

The demonstration by De Bold, in 1981, that atrial extracts are able to produce a dramatic hypotensive and natriuretic effect led, within 5 years, to the identification and biosynthesis by genetic biotechnology of a new hormone: the atrial natriuretic polypeptidic factor or cardionatrin which is stored in the atrial granules previously described by Kisch. The secretion of this hormone is stimulated by distension of both right and left atria, and this explains why it plays a key role in cardiovascular homeostasis. Cardionatrin acts mainly as an antagonist of two pressive systems: the renin-angiotensin-aldosterone system and the adrenergic system. It acts by stimulating receptors which induce an increase of cyclic guanosine monophosphate and a decrease of cyclic adenosine monophosphate. Its natriuretic effect is explained not only by an increase in glomerular filtration rate but also by an increased secretion of papillar interstitial fluid into the collecting ducts.

Topics: Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Hemodynamics; Homeostasis; Humans

The mechanisms of L-carnitine action and ergogenic pleiotropic effects of drugs, which play important role in sports medicine are described. Results of a comparative, parallel-group randomized clinical trial of L-carnitine (Elkar, PikFarma) in young athletes (football players, walkers) are reported. Elkar increases the body adaptation to physical stress and has a pronounced therapeutic effect in athletes with stress-induced cardiomyopathy by reducing the representation of potentially dangerous arrhythmia (sinus bradycardia less than 2 - 5 centile, 2nd degree atrioventricular block type II, T-wave inversion in more than 2 leads, and/or ST segment depression) and severity of benign ECG disturbances and hemodynamic changes, and decreasing the concentration of biochemical markers of myocardial damage (troponin, natriuretic peptide, creatine phosphokinase MB fraction) and cortisol. In general, Elkar contributed to a significant reduction in symptoms of cardiac remodeling in 75% of patients and had a weak effect in 25% of patents. It is concluded that the use of Elkar in playing sports and sports coaching quality of endurance is appropriate, especially in terms of myocardial remodeling.

Topics: Adaptation, Physiological; Administration, Oral; Adolescent; Arrhythmias, Cardiac; Athletes; Atrial Natriuretic Factor; Atrioventricular Block; Biomarkers; Cardiotonic Agents; Carnitine; Child; Creatine Kinase; Female; Humans; Hydrocortisone; Male; Physical Endurance; Physical Fitness; Soccer; Stress, Physiological; Troponin T; Walking

We studied low-dose human atrial natriuretic peptide (hANP) infusion therapy during cardiac surgery and reported the cardiac and renal protective effects. The efficacy of a bolus injection of hANP (the "hANP shot") simultaneously with induction of cardioplegia has been proven in animal experiments. In the present study the clinical effects of this "hANP shot" were examined.. The subjects were 67 patients undergoing Coronary artery bypass grafting. At the time of inducing cardioplegia, 1 group received a simultaneous bolus injection of 100 μg of hANP (hANP group) and the other group received an injection of physiological saline (placebo group). The primary endpoints were (1) operative mortality and complications, and (2) the creatine kinase isoenzyme MB (CPK-MB), troponin-I, and human heart fatty acid binding protein (H-FABP) levels. The secondary endpoints were (1) the incidence of arrhythmia, and levels of (2) atrial and B-type natriuretic peptides, and cyclic guanosine monophosphate (cGMP), and (3) renin, angiotensin II, and aldosterone. Postoperative CPK-MB, troponin-I, and H-FABP levels were significantly lower in the hANP group than in the placebo group. Postoperative arrhythmia was significantly less frequent in the hANP group than in the placebo group.. It is possible to achieve cardioprotective effects based on the safety of the "hANP shot", as well as from biomarkers of ischemia and results related to arrhythmia. The "hANP shot" should also be evaluated as a safer and new cardioprotective method for cardiac surgery.

Topics: Aged; Aldosterone; Angiotensin II; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cardiotonic Agents; Coronary Artery Bypass; Creatine Kinase, MB Form; Cyclic GMP; Dose-Response Relationship, Drug; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Female; Heart Arrest, Induced; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Postoperative Complications; Renin; Troponin I

Low-dose continuous human atrial natriuretic peptide (hANP) administration during cardiac surgery has been reported on previously. In the present study, the efficacy of the therapy during emergent coronary artery bypass grafting (CABG) for acute coronary syndrome (ACS) is investigated.. One hundred and twenty-four patients patients undergoing emergent CABG for ACS were divided into 2 groups; a group receiving administration of hANP (hANP group) and a group not receiving hANP infusion (non-hANP group). The postoperative peak levels of creatine kinase-MB were significantly lower in the hANP group as compared with those in the non-hANP group. The incidence of postoperative arrhythmias was also significantly lower in the hANP group as compared with that in the non-hANP group. The postoperative brain natriuretic peptide was significantly lower in the hANP group as compared with that in the non-hANP group until 1 year after the operation. The free-rate of cardiac events after the operation was also significantly higher in the hANP group as compared with that in the non-hANP group.. It is therefore considered that hANP might not only be effective for overcoming some major shortcomings of cardiopulmonary bypass, but also might be effective to attenuate ischemia-reperfusion injury, protect the myocardium, have an anti-arrhythmic effect, and suppress left ventricular remodeling.

Topics: Acute Coronary Syndrome; Aged; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cardiopulmonary Bypass; Coronary Artery Bypass; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Myocardial Reperfusion Injury; Natriuretic Peptide, Brain; Ventricular Remodeling

The aim of the present study was to evaluate the efficacy of alpha-human atrial natriuretic peptide (hANP) in cardiac surgery under cardiopulmonary bypass (CPB).. A prospective randomized study was conducted with 150 patients who underwent scheduled coronary artery bypass grafting to compare a group of patients receiving 0.02 microg x kg(-1) x min(-1) of hANP from the initiation of CPB with a group not receiving hANP. Hemodynamics, levels of atrial and brain natriuretic peptides (BNP), angiotensin-II and aldosterone, renin activity, and left ventricular (LV) function were examined. The hANP group showed significantly lower renin activity and lower levels of angiotensin-II and aldosterone during the early postoperative period, compared with the non-hANP group. The incidence of postoperative ventricular arrhythmia and the postoperative peak level of creatine kinase-MB were significantly lower in the hANP group. BNP at 1 month after surgery and measures of LV function were also significantly lower in the hANP group.. Low-dose continuous infusion of hANP during cardiac surgery not only had a compensatory effect for the imperfections of CPB during the early postoperative period but also an inhibitory effect on postoperative LV remodeling and a reduction in ischemia/reperfusion injury. hANP should be part of the postoperative care for cardiac surgery.

Topics: Aged; Aldosterone; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Blood Pressure; Cardiopulmonary Bypass; Coronary Artery Disease; Creatine Kinase, MB Form; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Natriuretic Peptide, Brain; Postoperative Period; Renin; Reperfusion Injury; Ventricular Function, Left; Ventricular Remodeling

Metabolic syndrome (MetS) is a cluster of factors that increase the risk of developing diabetes, stroke, and heart failure. The pathophysiology of injury by ischemia/reperfusion (I/R) is highly complex and the inflammatory condition plays an important role by increasing matrix remodeling and cardiac apoptosis. Natriuretic peptides (NPs) are cardiac hormones with numerous beneficial effects mainly mediated by a cell surface receptor named atrial natriuretic peptide receptor (ANPr). Although NPs are powerful clinical markers of cardiac failure, their role in I/R is still controversial. Peroxisome proliferator-activated receptor α agonists exert cardiovascular therapeutic actions; however, their effect on the NPs' signaling pathway has not been extensively studied. Our study provides important insight into the regulation of both ANP and ANPr in the hearts of MetS rats and their association with the inflammatory conditions caused by damage from I/R. Moreover, we show that pre-treatment with clofibrate was able to decrease the inflammatory response that, in turn, decreases myocardial fibrosis, the expression of metalloprotease 2 and apoptosis. Treatment with clofibrate is also associated with a decrease in ANP and ANPr expression.

Topics: Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Clofibrate; Inflammation; Ischemia; Metabolic Syndrome; Natriuretic Peptides; PPAR alpha; Rats; Receptors, Atrial Natriuretic Factor; Reperfusion Injury

Two siblings presented with cardiomyopathy, hypertension, arrhythmia, and fibrosis of the left atrium. Each had a homozygous null variant in

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Natriuretic Factor; Cardiomyopathies; Fibrosis; Heart Atria; Humans; Hypertension; Natriuretic Peptide, Brain; Serine Endopeptidases; Siblings

The CHKB gene encodes choline kinase β, which catalyzes the first step in the biosynthetic pathway for the major phospholipid phosphatidylcholine. Homozygous loss-of-function variants in human CHKB are associated with a congenital muscular dystrophy. Dilated cardiomyopathy is present in some CHKB patients and can cause heart failure and death. Mechanisms underlying a cardiac phenotype due to decreased CHKB levels are not well characterized. We determined that there is cardiac hypertrophy in Chkb

Topics: Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Choline Kinase; Disease Models, Animal; Heart Failure; Humans; Mice; Phosphatidylcholines

We evaluated the significance of perinatal plasma natriuretic peptide (NP) levels in neonates with congenital heart defects (CHDs) or arrhythmias and determined whether measurement of perinatal plasma NP levels and echocardiographic assessment in utero could predict heart failure after birth.. The study was conducted between 2012 and 2016 to evaluate the correlation of perinatal atrial NP (ANP) and brain NP (BNP) levels at birth with the modified Ross score after birth and the cardiovascular profile (CVP) score before birth.. A total of 122 singletons with CHDs or arrhythmias and 27 controls were analyzed. Neonatal blood sampling was performed at a median of 0.7 h (range, 0.1-1.5) after birth. The neonatal plasma ANP and BNP levels shortly after birth were significantly higher than those in the umbilical artery (UA) plasma. The ANP and BNP levels in UA and neonatal blood were correlated with the modified Ross score. The neonatal plasma ANP and BNP levels and the modified Ross scores were inversely correlated with the CVP score in neonates with CHDs or arrhythmias. The area under the receiver operating characteristic curve of UA ANP levels for predicting neonatal heart failure was highest among those for the CVP score, perinatal plasma ANP and BNP levels, and their combinations.. The plasma ANP and BNP levels increased markedly shortly after birth. Assessment of the UA plasma ANP level at birth and the CVP score in utero may be utilized to predict neonatal heart failure.

Topics: Arrhythmias, Cardiac; Atrial Natriuretic Factor; Female; Heart Defects, Congenital; Heart Failure; Humans; Infant, Newborn; Natriuretic Peptide, Brain; Natriuretic Peptides; Pregnancy; Vasodilator Agents

The cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are important regulators of cardiovascular physiology, with reduced natriuretic peptide (NP) activity linked to multiple human cardiovascular diseases. We hypothesized that deficiency of either ANP or BNP would lead to similar changes in left ventricular structure and function given their shared receptor affinities.. We directly compared murine models deficient of ANP or BNP in the same genetic backgrounds (C57BL6/J) and environments. We evaluated control, ANP-deficient (Nppa-/-) or BNP-deficient (Nppb-/-) mice under unstressed conditions and multiple forms of pathological myocardial stress. Survival, myocardial structure, function and electrophysiology, tissue histology, and biochemical analyses were evaluated in the groups. In vitro validation of our findings was performed using human-derived induced pluripotent stem cell cardiomyocytes (iPS-CMs). In the unstressed state, both ANP- and BNP-deficient mice displayed mild ventricular hypertrophy which did not increase up to 1 year of life. NP-deficient mice exposed to acute myocardial stress secondary to thoracic aortic constriction (TAC) had similar pathological myocardial remodelling but a significant increase in sudden death. We discovered that the NP-deficient mice are more susceptible to stress-induced ventricular arrhythmias using both in vivo and ex vivo models. Mechanistically, deficiency of either ANP or BNP led to reduced myocardial cGMP levels and reduced phosphorylation of the cAMP response element-binding protein (CREBS133) transcriptional regulator. Selective CREB inhibition sensitized wild-type hearts to stress-induced ventricular arrhythmias. ANP and BNP regulate cardiomyocyte CREBS133 phosphorylation through a cGMP-dependent protein kinase 1 (PKG1) and p38 mitogen-activated protein kinase (p38 MAPK) signalling cascade.. Our data show that ANP and BNP act in a non-redundant fashion to maintain myocardial cGMP levels to regulate cardiomyocyte p38 MAPK and CREB activity. Cardiac natriuretic peptide deficiency leads to a reduction in CREB signalling which sensitizes the heart to stress-induced ventricular arrhythmias.

Topics: Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cyclic GMP; Mice; Myocytes, Cardiac; Natriuretic Peptide, Brain; Natriuretic Peptides; p38 Mitogen-Activated Protein Kinases; Vasodilator Agents

Left atrial appendage (LAA) closure decreases atrial natriuretic peptide (ANP) levels, which indirectly increases the risk of arrhythmogenicity. We aimed to determine the effect of a combined angiotensin receptor-neprilysin inhibitor (ARNi) on arrhythmogenicity following LAA closure in an animal model.. Twenty-four rabbits were randomized into four groups: (1) control, (2) LAA closure (LAAC), (3) heart failure (HF)-LAAC, and (4) HF-LAAC with sacubitril/valsartan (+ARNi). HF models were developed in the HF-LAAC and HF-LAAC+ARNi groups. Epicardial LAA exclusion was performed in the LAAC, HF-LAAC, and HF-LAAC+ARNi groups. ANP levels were measured. An electrophysiological study was performed. The myocardium was harvested for histopathological analysis.. The ANP level decreased in the LAAC group (785 ± 103 pg/mL, p = 0.03), failed to increase in the HF-LAAC group (917 ± 172 pg/mL, p = 0.3), and increased in the HF-LAAC+ARNi group (1524 ± 126 pg/mL, p < 0.01) compared to that in the control group (1014 ± 56 pg/mL). The atrial effective refractory period (ERP) was prolonged in the HF-LAAC group and restored to baseline in the HF-LAAC+ARNi group. Ventricular ERP was the longest in the HF-LAAC group. The atrial fibrillation window of vulnerability (AF WOV) was elevated in the LAAC, HF-LAAC, and HF-LAAC+ARNi groups, with the latter group having lower AF WOV than the two former groups. Ventricular fibrillation (VF) inducibility was the highest in the HF-LAAC group (51 ± 5%, p < 0.001), followed by the LAAC group (30 ± 4%, p = 0.006) and the HF-LAAC+ARNi group (25 ± 5%, p = 0.11) when compared to the control group (18 ± 4%). Atrial and ventricular fibrosis were noted in all groups except the control group.. LAA closure decreased ANP, which in turn increased AF and VF inducibility. Atrial and ventricular arrhythmogenicity was suppressed by ARNi.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Animals; Arrhythmias, Cardiac; Atrial Appendage; Atrial Natriuretic Factor; Biphenyl Compounds; Drug Combinations; Heart Atria; Models, Animal; Neprilysin; Rabbits; Septal Occluder Device; Treatment Outcome; Valsartan

Natriuretic peptides (NPs) play a pivotal role in maintaining fetal circulation; however, little is known about their metabolism. The aim of the present study was to elucidate the metabolism of plasma NPs in the fetoplacental circulation.. Plasma NP concentrations in maternal vein and umbilical artery (UA) and vein (UV) samples from fetuses with congenital heart defect (n = 86) or arrhythmia (n = 31) and controls (n = 127) were analyzed.. Levels of plasma atrial NP (ANP) and brain NP (BNP) showed good correlation between UV versus UA samples (p < 0.01). In all three fetus groups, the regression coefficients between UV and UA plasma ANP levels were close to 0.5, while those between UV and UA plasma BNP levels were close to 1. The molecular forms of immunoreactive ANP in UA plasma showed a single peak corresponding to mature ANP, while those of immunoreactive BNP in UA plasma showed two major peaks and several minor peaks corresponding to mature BNP-32 and its partially digested peptides, as well as glycosylated and non-glycosylated BNP precursors (proBNP). No correlation was found between fetuses and mothers in terms of either plasma ANP or BNP levels.. The mother and fetus independently secrete and metabolize both ANP and BNP. Fetal plasma ANP consists exclusively of the mature form, and the placenta and umbilical vessels are possible major sites of ANP metabolism. In contrast, fetal plasma BNP consists predominantly of the precursor forms, which may contribute to protecting BNP from metabolism in the fetoplacental circulation.

Topics: Arrhythmias, Cardiac; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Female; Gene Expression; Heart Defects, Congenital; Humans; Infant, Newborn; Male; Natriuretic Peptide, Brain; Placenta; Placental Circulation; Pregnancy; Prospective Studies; Receptors, Atrial Natriuretic Factor; Umbilical Arteries; Umbilical Veins

The arrhythmogenesis of ventricular myocardial ischemia has been extensively studied, but models of atrial ischemia in humans are lacking. This study aimed at describing the electrophysiological alterations induced by acute atrial ischemia secondary to atrial coronary branch occlusion during elective coronary angioplasty.. Clinical data, 12-lead ECG, 12-hour Holter recordings, coronary angiography, and serial plasma levels of high-sensitivity troponin T and midregional proatrial natriuretic peptide were prospectively analyzed in 109 patients undergoing elective angioplasty of right or circumflex coronary arteries. Atrial coronary branches were identified and after the procedure patients were allocated into two groups: atrial branch occlusion (ABO, n=17) and atrial branch patency (non-ABO, n=92). In comparison with the non-ABO, patients with ABO showed: (1) higher incidence of periprocedural myocardial infarction (20% versus 53%, P=0.01); (2) more frequent intra-atrial conduction delay (19% versus 46%, P=0.03); (3) more marked PR segment deviation in the Holter recordings; and (4) higher incidence of atrial tachycardia (15% versus 41%, P=0.02) and atrial fibrillation (0% versus 12%, P=0.03). After adjustment by a propensity score, ABO was an independent predictor of periprocedural infarction (odds ratio, 3.4; 95% confidence interval, 1.01-11.6, P<0.05) and atrial arrhythmias (odds ratio, 5.1; 95% confidence interval, 1.2-20.5, P=0.02).. Selective atrial coronary artery occlusion during elective percutaneous transluminal coronary angioplasty is associated with myocardial ischemic damage, atrial arrhythmias, and intra-atrial conduction delay. Our data suggest that atrial ischemic episodes might be considered as a potential cause of atrial fibrillation in patients with chronic coronary artery disease.

Topics: Action Potentials; Aged; Angioplasty, Balloon, Coronary; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Biomarkers; Chi-Square Distribution; Constriction, Pathologic; Coronary Angiography; Coronary Circulation; Coronary Occlusion; Coronary Vessels; Electrocardiography, Ambulatory; Female; Heart Atria; Heart Conduction System; Heart Rate; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Propensity Score; Prospective Studies; Risk Factors; Time Factors; Troponin T

To evaluate the influence of mating behavior on cardiac function, changes in heart rate (HR), electrocardiogram (ECG), hematocrit (Hct) and serum concentration of alpha-atrial natriuretic peptide (alpha-ANP) were evaluated in 10 clinically sound Thoroughbred stallions before and after mating behavior. The stallions were submitted twice to experimental pseudomating in the same month in 2009 and 2010. Measurements and blood samples were collected at a stable before mating (baseline) and at a covering yard before and after mating. ECG was recorded by a Holter-ECG system. Arrhythmias were detected in 5 stallions before or after mating behavior. Minimum HR (HRmin), maximum HR (HRmax) and HR recorded when the stallions entered into yard (HRent) and ejaculated (HRejc) were 34.2 ± 3.7, 168.9 ± 14.2, 141.8 ± 35.3 and 142.6 ± 27.3 beats/min, respectively. Time from entrance into the yard to ejaculation (mating time; MT) ranged from 30 to 2,103 sec and was highly correlated with HRent (r=-0.82) and the time required for attaining HRmax after entrance into the yard (dT HRmax) (r=0.87). Hct and serum alpha-ANP concentration significantly increased after ejaculation (60.0 ± 3.2%, P<0.0001, and 1.54 ± 0.61 ng/ml, P=0.0353) compared with the baselines values (46.9 ± 4.4%, 1.40 ± 0.60 ng/ml). HRent and Hct were significantly higher in the stallions with an MT of less than 5 min (n=5) compared with those (n=5) with an MT of more than 5 min (P=0.0324 and P=0.0082). Mating behavior increases the workload of the heart in Thoroughbred stallions.

Topics: Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Electrocardiography; Heart; Heart Rate; Hematocrit; Horses; Humans; Male; Regression Analysis; Sexual Behavior, Animal

Topics: Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cardiotonic Agents; Coronary Artery Bypass; Female; Heart Arrest, Induced; Humans; Male; Postoperative Complications

We sought to determine the physiologic actions and potential therapeutic applications of mutant atrial natriuretic peptide (mANP).. The cardiac hormone atrial natriuretic peptide (ANP) is a 28-amino acid (AA) peptide that consists of a 17-AA ring structure together with a 6-AA N-terminus and a 5-AA C-terminus. In a targeted scan for sequence variants within the human ANP gene, a mutation was identified that results in a 40-AA peptide consisting of native ANP((1-28)) and a C-terminal extension of 12 AA. We have termed this peptide mutant ANP.. In vitro 3',5'-cyclic guanosine monophosphate (cGMP) activation in response to mANP was studied in cultured human cardiac fibroblasts known to express natriuretic peptide receptor A. The cardiorenal and neurohumoral properties of mANP compared with ANP were assessed in vivo in normal dogs.. We observed an incremental in vitro cGMP dose response with increasing concentrations of mANP. In vivo with high-dose mANP (33 pmol/kg/min), we observed significantly greater plasma cGMP activation, diuretic, natriuretic, glomerular filtration rate enhancing, renin-angiotensin-aldosterone system inhibiting, cardiac unloading, and blood pressure lowering properties when compared with native ANP. Low-dose mANP (2 pmol/kg/min) has natriuretic and diuretic properties without altering systemic hemodynamics compared with no natriuretic or diuretic response with low-dose native ANP.. These studies establish that mANP activates cGMP in vitro and exerts greater and more sustained natriuretic, diuretic, glomerular filtration rate, and renal blood flow enhancing actions than native ANP in vivo.

Topics: Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Blood Pressure; Cell Culture Techniques; Cyclic GMP; Dogs; Fibroblasts; Glomerular Filtration Rate; Humans; Mutant Proteins; Mutation; Myocardium; Renin-Angiotensin System

Cardiac hypertrophy is associated with ventricular arrhythmias and sudden death. The molecular mechanisms that predispose the hypertrophied heart to arrhythmias are not well understood. In mice, deletion of the gene coding for the atrial natriuretic peptide receptor, guanylyl cyclase A (GC-A-/-), causes arterial hypertension, cardiac hypertrophy and sudden death. We used this mouse model to study molecular mechanisms of arrhythmias in the hypertrophied heart. Right and left ventricular monophasic action potential durations (APD) were recorded in isolated, Langendorff-perfused hearts during pacing from the right atrium and ventricle. The atrioventricular (AV) node was ablated to provoke bradycardia. Intracellular Ca(2+) transients were measured in isolated INDO-1 loaded ventricular myocytes. Cardiac expression of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) was analyzed by western blotting. Polymorphic ventricular arrhythmias (pVT) occurred spontaneously after mechanical AV block in 20/45 hearts from 12-month-old GC-A-/- mice (P < 0.05), but neither in age-matched GC-A+/+ hearts nor in hearts from 3-month-old mice of either genotype. Triggered activity preceded pVT. APD were prolonged and systolic Ca(i)(2+) levels were increased in GC-A-/- hearts independently of age. In 12-month-old GC-A-/- hearts only, dispersion of APD and expression levels of CaMKII were increased. CaMKII expression was particularly increased in hearts with pVT. Direct inhibition of CaMKII activation by KN93 (0.5 or 2 microM) or inhibition of Ca(2+)/calmodulin-dependent activation of CaMKII by W-7 (25 microM) suppressed pVT in GC-A-/- hearts (P < 0.05) while prolonging APD. The combination of increased CaMKII activity and altered action potential characteristics facilitates ventricular arrhythmias in hypertrophic GC-A-/- hearts.

Topics: Action Potentials; Aging; Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Calcium; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases; Electrophysiology; Enzyme Activation; Enzyme Inhibitors; Gene Expression Regulation, Enzymologic; Guanylate Cyclase; Heart Ventricles; Kinetics; Mice; Mice, Knockout; Receptors, Atrial Natriuretic Factor; Time Factors

The relationship between atrial stretching and changes in cell excitability is well documented. Once stretched, human atrial myocytes (HuAM) release atrial natriuretic peptide (hANP). Receptors for hANP (NPR) are coupled to a guanylyl cyclase (GC) activity, and are present on HuAM, but the electrophysiological effects of hANP are largely unknown. We investigated the effect of hANP on If, the hyperpolarization-activated current present in HuAM, and the underlying intracellular pathway.. HuAM were isolated from atrial appendages and utilized for patch-clamp recording.. hANP caused a significant and concentration dependent shift of the midpoint activation potential (DeltaVh) toward less negative potentials of 6.9 +/- 1.0 mV at 0.1 nM; 13.0 +/- 2.6 mV at 1 nM and 15.3 +/- 2.2 mV at 10 nM (p < 0.001 for all); a parallel increase of If rate of activation occurred. The effect of hANP was completely blocked by isatin, a potent antagonist of NPR (p < 0.01 vs. hANP). In the presence of the inhibitors of guanylyl cyclase (ODQ and LY83583), hANP caused a significantly smaller DeltaVh (p < 0.01 vs. hANP for both). 8Br-cGMP mimicked the effect of hANP, both in the presence and absence of KT5823, a selective inhibitor of Protein kinase G. Pretreatment with pertussis toxin (PTX) did not change the effect of hANP, thus excluding a major role for the coupling of NPR with the Gi-Proteins system. Pretreating cells with cyclopentyladenosine (CPA), an A1-adenosine receptor agonist, completely blocked hANP effect. Adding hANP to maximal serotonin concentration produced an additive response.. Our data demonstrate for the first time that ANP is able to increase If, likely through a modulation of intracellular cGMP and cAMP levels. This effect could have implications in the relationship between stretch and arrhythmogenesis in the human atrium.

Topics: Adenosine; Adult; Aged; Aged, 80 and over; Aminoquinolines; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Calcium Channels; Carbazoles; Cyclic GMP-Dependent Protein Kinases; Dose-Response Relationship, Drug; Female; Guanylate Cyclase; Heart Atria; Humans; Indoles; Isatin; Male; Middle Aged; Myocytes, Cardiac; Patch-Clamp Techniques; Purinergic P1 Receptor Agonists; Receptors, Atrial Natriuretic Factor; Serotonin; Signal Transduction

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

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

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

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

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

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

The mechanism(s) responsible for the release of brain natriuretic peptide (BNP), a cardiac hormone of ventricular origin, are still not completely understood. We measured plasma atrial natriuretic peptide (ANP) and BNP in 15 subjects (10 men, mean age 67 +/- 3 years) with a dual chamber pacemaker and unimpaired heart function during ventricular pacing, which is known to induce an increase in atrial pressure and plasma ANP concentration. Under ECG monitoring, all subjects received sequential atrioventricular pacing for 30 minutes and ventricular pacing for 30 minutes, at the same rate of 80 beats/min. Arterial pressure and plasma BNP and ANP levels were measured every 10 minutes throughout the study. Ventricular pacing led to atrioventricular dissociation in eight subjects and to retrograde ventriculo-atrial conduction in seven. Arterial pressure remained unchanged in all subjects. In the group with atrioventricular dissociation, plasma ANP increased from 10.14 +/- 0.58 to 16.72 +/- 0.92 fmol/mL at the 60th minute (P < 0.0001), whereas plasma BNP did not change at all (from 1.26 +/- 0.07 to 1.16 +/- 0.09 fmol/mL). In the group with retrograde conduction, plasma ANP concentration doubled (from 10.95 +/- 1.66 to 21.40 +/- 1.51 fmol/mL, P < 0.0001), BNP increased 1.5-fold (from 1.16 +/- 0.06 to 1.64 +/- 0.14 fmol/mL, P < 0.001), and the ANP:BNP ratio augmented from 10:1 to 13.4:1. These results indicate that the release of ANP and BNP is regulated by different mechanisms, supporting the view that there is a dual natriuretic peptide system, comprising ANP from the atria and BNP from the ventricles.

Topics: Aged; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Atrioventricular Node; Blood Pressure; Cardiac Pacing, Artificial; Electrocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Pacemaker, Artificial; Ventricular Function

The aim of the study was to investigate the plasma concentration of atrial natriuretic peptide (ANP) in acute myocardial infarction (AMI), its association with age, sex, essential hypertension, infarct localization, complications of AMI, infarct size, left atrial and ventricular chamber sizes and therapy of AMI. I studied 40 pts (9 female, 31 male, mean 56.9 + 10 years) with first AMI up to 6 hours onset the first symptoms (mean 2.4 + 1.2 hours). The ANP concentration was measured at the time of admission to the hospital (ANP 0) and at time 4, 8, 16, 24, 48, 72 hours after admission (ANP mean). Arrhythmias was assessed by 24 hour ecg Holter monitoring. Infarct size was assessed by serial CK-MB measurement in first 72 hours of AMI. Contractility disturbances and left atrial and ventricular chamber sizes was assessed by echocardiography. The average plasma concentration of ANP was significantly elevated (28.1 +/- 4.3 fmol/ml). The mean ANP concentration was significantly higher in pts with essential hypertension than in pts without hypertension (36.1 + 7.7 vs 21.7 + 4.2 fmol/ml). The ANP concentration in pts with inferior myocardial infarction was significantly higher than in pts with anterior myocardial infarction (32.1 + 6.1. vs 20.9 + 4.1 fmol/ml). The ANP mean in pts with complications of AMI (congestive heart failure, arrhythmias, reinfarction, death) was significantly higher than in pts without complications (49.5 + 13.3 vs 21.6 + 7.1 fmol/ml). I observed positive correlation between plasma ANP and left atrial chamber sizes (r = 0.59) and diastolic ventricular dimension (r = 0.56).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Biomarkers; Electrocardiography, Ambulatory; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Recurrence; Treatment Outcome

In a longitudinal study comprising a total of 18 patients, the paradoxical time course of hANP plasma levels, i.e. the reproducibility of the low levels previously reported in cases of extreme cardiac insufficiency after administration of amiodarone, was investigated over a period of 9 months. At the same time, the effect of the degree of cardiac insufficiency and arrhythmia on the secretion of hANP was observed. The patients had been admitted to hospital because of the diagnoses "cardiac insufficiency secondary to cardiomyopathy" or "Grade IVb arrhythmia according to Lown's classification". During in-patient treatment, antiarrhythmic therapy was commenced in all patients. Clinical examinations and determinations of humoral parameters during therapy showed a substantial number of patients, who exhibited no increase in hANP levels despite massive cardiac decompensation. As far as drug therapy of patients with severe arrhythmias secondary to congestive (dilated) cardiomyopathy is concerned, amiodarone has proved to be the drug of choice in combination with digitalis, ACE inhibitors and diuretics. There is a close correlation between the degree of cardiac insufficiency and plasma hANP levels.

Topics: Aged; Aldosterone; Amiodarone; Arginine Vasopressin; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Captopril; Cardiomyopathy, Dilated; Drug Therapy, Combination; Electrocardiography, Ambulatory; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Longitudinal Studies; Male; Middle Aged

Persistent atrial standstill is a very rare pathophysiologic condition whose diagnosis is established when both electrical and mechanical silence of the atria are confirmed. To test the hypothesis that secretion of atrial natriuretic peptide is disturbed in patients with persistent atrial standstill, the response of atrial natriuretic peptide secretion and other neurohormonal factors during exercise was investigated in three patients with a rate-responsive ventricular demand (VVI) pacemaker implanted for confirmed persistent atrial standstill. The results were compared with those observed in eight normal subjects and patients with a rate-responsive VVI (Group A) or atrial demand (AAI) (Group B) pacemaker implanted for confirmed sick sinus syndrome. Patients in Group A displayed significant elevation of alpha-human atrial natriuretic peptide secretion both before and during exercise (122.5 +/- 14.8 and 207.5 +/- 8.3 pg/ml, respectively) compared with those in Group B (55 +/- 14.1 and 116.4 +/- 51.5 pg/ml, respectively) and the normal subjects (18.9 +/- 9.8 and 30.8 +/- 19.2 pg/ml, respectively). This indicated development of a nonphysiologic increase in atrial volume or pressure overload, or both, in rate-responsive VVI pacing because of lack of atrioventricular synchrony. However, patients with persistent atrial standstill had undetectable (less than 10 pg/ml) or almost undetectable secretion of atrial natriuretic peptide as well as lower levels of cyclic guanosine monophosphate in the circulation both before and during exercise. Changes in plasma catecholamines during exercise were similar in patients with persistent atrial standstill compared with the other groups. This study indicates that "endocrinologic silence" accompanies electrical and mechanical silence of the atria, which may constitute a third diagnostic clue to persistent atrial standstill.

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Function; Atrial Natriuretic Factor; Cyclic AMP; Cyclic GMP; Electrocardiography; Epinephrine; Exercise; Exercise Test; Female; Heart Atria; Humans; Male; Middle Aged; Norepinephrine; Pacemaker, Artificial; Sick Sinus Syndrome

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Heart; Heart Atria; Humans; Male; Middle Aged

Recently two peptides consisting of amino acids (AA) 1-30 and 31-67 of the N-terminus of the 126 AA prohormone of atrial natriuretic factor (pro ANF) as well as atrial natriuretic factor (ANF, AA 99-126; C-terminus) were found to have vasodilatory and natriuretic properties. These peptides as well as ANF circulate in man as part of the N-terminus of the prohormone. To determine if the polyuria, associated with both ventricular and supraventricular arrhythmias, is associated with increased circulating concentrations of the N-terminus and C-terminus of the ANF prohormone, 20 individuals with spontaneous arrhythmias, including ten persons with atrial fibrillation, six with paroxysmal supraventricular tachycardia, and four with ventricular tachycardia, were evaluated before and after conversion to sinus rhythm. In all 20 patients, the circulating concentrations of the whole N-terminus (ie, AA 1-98), the midportion of the N-terminus (pro ANF 31-67) that circulates as a distinct 3900 molecular weight peptide after being proteolytically cleaved from the N-terminus, and the C-terminus were significantly higher (p less than 0.001) than their concentration in 54 persons with sinus rhythm. With conversion to sinus rhythm, the plasma C-terminus concentration of these 20 arrhythmia patients decreased to the level of persons with sinus rhythm within 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Natriuretic Factor; Female; Heart Rate; Humans; Male; Middle Aged; Molecular Weight; Radioimmunoassay; Tachycardia; Tachycardia, Supraventricular

Transgenic mice expressing atrial natriuretic factor-SV40 T-antigen fusion genes (ANF-TAG) developed cardiac tumors asymmetrically in the right atrium. Features associated with cardiac failure, including increased plasma creatine kinase activity (MM and MB) and ventricular dysrhythmias, also were associated with atrial tumor growth. These atrial tumors were able to grow at histocompatible sites (subcutaneously in syngeneic animals) for protracted periods of time yielding a series of transplantable atrial tumor lineages. The transplantable tumors displayed several cardiac-specific characteristics, such as endogenous electrical activity and expression of cardiac-specific proteins. These transplantable atrial tumors constitute a novel experimental resource for developing cell lines which display an adult cardiac phenotype.

Topics: Animals; Antigens, Polyomavirus Transforming; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cloning, Molecular; Electrocardiography; Female; Heart; Heart Atria; Heart Neoplasms; Mice; Mice, Transgenic; Neoplasm Transplantation; Oncogenes

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

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

Topics: Aged; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Forearm; Hemodynamics; Humans; Male; Middle Aged; Regional Blood Flow

Topics: Adult; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Female; Hemodynamics; Humans; Male

Transgenic mice that carry fusions between the transcriptional regulatory sequences of atrial natriuretic factor (a hormone intimately involved in the regulation of blood pressure) and those encoding SV40 T antigen (an oncoprotein) were generated. Although both atria express the fusion gene, the pathological response to T antigen is asymmetrical. The right atrium undergoes a several hundredfold increase in mass while the left atrium remains relatively normal in size. Hyperplasia is accompanied by a progressive increase in both the frequency and severity of abnormalities in the atrial conduction system, which ultimately result in death.

Topics: Animals; Antigens, Polyomavirus Transforming; Arrhythmias, Cardiac; Atrial Natriuretic Factor; DNA, Recombinant; Electrocardiography; Electrophysiology; Genes, Regulator; Heart Atria; Heart Conduction System; Heart Neoplasms; Hyperplasia; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Transgenic; Oncogenes; Promoter Regions, Genetic

There is ample evidence from animal models indicating that secretion of atrial natriuretic factor (ANF) can be induced by an increase in atrial contraction frequency or atrial distension. The influence of these stimulatory signals on ANF secretion in humans has not been fully elucidated. We assessed the responses to graded right atrial pacing in 28 patients (aged 33 to 70 years) at rates of 100, 125, and 150 beats/min on right atrial pressure, left atrial size (by two-dimensional echocardiography in 9 of 28 patients), and circulating plasma ANF levels. At pacing rates of 125 and 150 beats/min, ANF levels increased from a baseline value of 64 +/- 9 fmol/ml (mean +/- SEM) to 89 +/- 13 fmol/ml (pp less than 0.05) and to 132 +/- 17 fmol/ml, respectively (p less than 0.001). Right atrial pressure increased from a baseline value of 4.1 +/- 0.7 mm Hg to 4.5 +/- 0.6 mm Hg at a pacing rate of 125 beats/min (p less than 0.05) and to 6.1 +/- 0.8 mm Hg at a pacing rate of 150 beats/min (p less than 0.001). Left atrial dimension increased from a baseline value of 44.5 +/- 3 mm to 49.5 +/- 3 mm at a pacing rate of 125 beats/min (p less than 0.05) and increased further to 52.5 +/- 3 mm at a pacing rate of 150 beats/min (p less than 0.001). No significant changes in atrial pressure or size or in plasma ANF were observed at a pacing rate of 100 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Blood Pressure; Cardiac Pacing, Artificial; Heart Atria; Humans; Male; Middle Aged; Pressure

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

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

In an attempt to clarify the clinical significance of atrial natriuretic peptide (ANP) in man, plasma levels of immunoreactive ANP were studied in patients with heart diseases and in those with chronic renal failure. When ANP concentrations in pulmonary arterial plasma were compared with hemodynamic variables in patients with heart diseases who underwent cardiac catheterization, a significant positive correlation was found between plasma ANP levels and mean pulmonary capillary wedge pressure, while plasma ANP levels were not significantly correlated to mean right atrial pressure (MRAP). After the injection of contrast medium, both MRAP and plasma ANP levels increased and a significant positive correlation was observed between two variables. Plasma levels of ANP were elevated in patients with congestive heart failure according to the severity. In addition, patients associated with atrial fibrillation showed significantly higher plasma ANP levels than those on sinus rhythm. In patients with paroxysmal atrial arrhythmias, plasma ANP levels increased markedly during paroxysms. Patients with chronic renal failure had elevated plasma ANP levels, which fell after hemodialysis. These results suggest that both left and right atrial tissue can secrete ANP as a result of stretching of the cardiocytes in man and that plasma ANP levels are elevated in patients with congestive heart failure and in those with chronic renal failure by increased atrial pressure due to volume expansion. Abnormal atrial contraction per se, in addition, may stimulate ANP secretion.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Atrial Natriuretic Factor; Cardiac Catheterization; Female; Heart Diseases; Heart Failure; Humans; Kidney Failure, Chronic; Male; Middle Aged; Pulmonary Wedge Pressure; Renal Dialysis

In order to study the effect of atrial tachycardia on the release of atrial natriuretic peptide (ANP), AVP, and methionine enkephalin (M-Enk), plasma concentrations of these peptides in the right ventricle were determined in patients with various arrhythmias (N = 10) during cardiac catheterization and incremental atrial pacing. Each pacing (100 per min, the maximum rate for 1:1 atrioventricular conduction, and 200 per min) lasted 4 to 5 min. Plasma ANP was significantly increased from 53.1 +/- 12.2 in the resting condition to 168.9 +/- 59.9 pmol/l at a pacing rate of 200 beats per min (P less than 0.05); plasma AVP tended to decrease, but not significantly, and plasma M-Enk did not change at all. Pulse pressure in the right atrium (PPRA) and mean right atrial pressure (MRAP) tended to increase during the pacing, and at the rate of 200 beats per min PPRA was significantly higher than at the rate of 100 beats per min. Mean arterial blood pressure, plasma osmolality, and plasma sodium and potassium concentrations did not change significantly. There were significant correlations between plasma ANP and PPRA, MRAP and heart rate. These results indicate that atrial pacing stimulates ANP release with a rise in right atrial pressure, but does not influence M-Enk and AVP releases.

Topics: Adult; Aged; Arginine Vasopressin; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cardiac Catheterization; Enkephalin, Methionine; Female; Hemodynamics; Humans; Male; Middle Aged; Pacemaker, Artificial

Radio-immunoassay of atrial natriuretic peptide (ANP) and infusions of alpha-human ANP (alpha-hANP) have been used to study the secretion, metabolism, regulation and actions of ANP in man. Plasma immunoreactive ANP (irANP) was twice as high in arterial blood as in simultaneously sampled venous plasma from the femoral, hepatic and renal vein, but no arteriovenous difference was found across the lung. Analysis of plasma extracts by high performance liquid chromatography confirmed that alpha-hANP-like material was a major component in coronary sinus and peripheral arterial and venous plasma. In normal subjects, venous plasma irANP was increased by both acute and chronic sodium loads, and by exercise. The cardiac secretion of irANP, and peripheral venous levels, were markedly increased by atrial pacing in four patients investigated for arrhythmia. Plasma irANP concentrations were elevated in many patients with circulatory disorders, including chronic renal failure, congestive heart failure and during spontaneous tachyarrhythmias. Constant 60-min intravenous infusions of alpha-hANP increased urinary sodium excretion in normal subjects, under conditions of both high- and low-sodium intake, and selectively reduced plasma aldosterone concentrations. These effects were observed at the venous levels of plasma irANP found in some patients with circulatory disease. Taken together, the present studies suggest that ANP has important endocrine functions in human health and disease.

Topics: Aldosterone; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Chromatography, High Pressure Liquid; Female; Heart Failure; Humans; Hyperaldosteronism; Kidney Failure, Chronic; Natriuresis; Physical Exertion; Pregnancy; Radioimmunoassay

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Female; Heart Atria; Humans; Male; Middle Aged; Muscle Proteins; Polyuria