atrial-natriuretic-factor and Heart-Diseases

Magnesium isoglycyrrhizinate (MgIG) is a magnesium salt of the 18-α glycyrrhizic acid stereoisomer that has exhibited hepato-protective effects and has anti-inflammatory, antioxidant, and antiviral activities. Here, we have investigated the effects and potential mechanisms of action of MgIG, with respect to myocardial fibrosis induced by isoproterenol (ISO) in mice. Mice were administered MgIG for 14days, with concurrent ISO dosing, and were sacrificed two weeks later. Lactate dehydrogenase (LDH) and creatine kinase (CK) concentrations were measured in the blood. Pathological changes in the myocardium were observed via light microscopy. In addition, the expression of the Bax and Bcl-2 genes, and the basic fibroblast growth factor (bFGF) protein were measured via an immunohistochemical method. The RNA expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), c-fos, and c-jun mRNA were quantified by reverse transcription-polymerase chain reaction (RT-PCR) in the myocardial tissue. The protein expression of toll-like receptor (TLR) 4, and nuclear factor kappa B (NF-κB) (p65) were measured using Western blot assays. Compared with the control group, the ISO group showed significant increases in bFGF, Bax, Bcl-2, TLR4, and NF-κB (p65) expressions, as well as increased serum levels of LDH and CK. MgIG had a protective effect on ISO-induced myocardial fibrosis, which might be ascribed, at least in part, to the inhibition of the TLR4/NF-κB (p65) signaling pathway.

Topics: Animals; Anti-Inflammatory Agents; Atrial Natriuretic Factor; bcl-2-Associated X Protein; Creatine Kinase; Disease Models, Animal; Fibroblast Growth Factor 2; Fibrosis; Heart Diseases; Humans; Hypertrophy; Isoproterenol; L-Lactate Dehydrogenase; Mice; Mice, Inbred Strains; Myocardium; Natriuretic Peptide, Brain; NF-kappa B; Proto-Oncogene Proteins c-bcl-2; Saponins; Toll-Like Receptor 4; Triterpenes

Corin is a transmembrane protease that activates atrial natriuretic peptide (ANP), an important hormone in regulating salt-water balance and blood pressure. This review focuses on the regulation of corin function and potential roles of corin defects in hypertensive, heart, and renal diseases.. Proprotein convertase subtilisin/kexin-6 has been identified as a primary enzyme that converts zymogen corin to an active protease. Genetic variants that impair corin intracellular trafficking, cell surface expression, and zymogen activation have been found in patients with hypertension, cardiac hypertrophy, and pre-eclampsia. Reduced corin expression has been detected in animal models of cardiomyopathies and in human failing hearts. Low levels of circulating soluble corin have been reported in patients with heart disease and stroke. Corin, ANP and natriuretic peptide receptor-A mRNAs, and proteins have been colocalized in human renal segments, suggesting a corin-ANP autocrine function in the kidney.. Corin is a key enzyme in the natriuretic peptide system. The latest findings indicate that corin-mediated ANP production may act in a tissue-specific manner to regulate cardiovascular and renal function. Corin defects may contribute to major diseases such as hypertension, heart failure, pre-eclampsia, and kidney disease.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Diseases; Humans; Hypertension; Kidney; Kidney Diseases; Pre-Eclampsia; Pregnancy; Proprotein Convertases; Receptors, Atrial Natriuretic Factor; Serine Endopeptidases

Polymorbid patients, diverse diagnostic and therapeutic options, more complex hospital structures, financial incentives, benchmarking, as well as perceptional and societal changes put pressure on medical doctors, specifically if medical errors surface. This is particularly true for the emergency department setting, where patients face delayed or erroneous initial diagnostic or therapeutic measures and costly hospital stays due to sub-optimal triage. A "biomarker" is any laboratory tool with the potential better to detect and characterise diseases, to simplify complex clinical algorithms and to improve clinical problem solving in routine care. They must be embedded in clinical algorithms to complement and not replace basic medical skills. Unselected ordering of laboratory tests and shortcomings in test performance and interpretation contribute to diagnostic errors. Test results may be ambiguous with false positive or false negative results and generate unnecessary harm and costs. Laboratory tests should only be ordered, if results have clinical consequences. In studies, we must move beyond the observational reporting and meta-analysing of diagnostic accuracies for biomarkers. Instead, specific cut-off ranges should be proposed and intervention studies conducted to prove outcome relevant impacts on patient care. The focus of this review is to exemplify the appropriate use of selected laboratory tests in the emergency setting for which randomised-controlled intervention studies have proven clinical benefit. Herein, we focus on initial patient triage and allocation of treatment opportunities in patients with cardiorespiratory diseases in the emergency department. The following five biomarkers will be discussed: proadrenomedullin for prognostic triage assessment and site-of-care decisions, cardiac troponin for acute myocardial infarction, natriuretic peptides for acute heart failure, D-dimers for venous thromboembolism, C-reactive protein as a marker of inflammation, and procalcitonin for antibiotic stewardship in infections of the respiratory tract and sepsis. For these markers we provide an overview on physiopathology, historical evolution of evidence, strengths and limitations for a rational implementation into clinical algorithms. We critically discuss results from key intervention trials that led to their use in clinical routine and potential future indications. The rational for the use of all these biomarkers, first, tackle diagnostic ambiguity and conse

Topics: Adrenomedullin; Algorithms; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Medicine; Fibrin Fibrinogen Degradation Products; Heart Diseases; Humans; Precision Medicine; Protein Precursors; Respiratory Tract Diseases; Switzerland; Triage; Troponin

Heart failure (HF) results from the impaired ability of heart to fill or pump out blood. HF is a common health problem with a multitude of causes and affects ~30 million people worldwide. Since ageing is a major risk factor for HF and as several treatment options are currently available to prolong the patients' survival, the number of affected patients is expected to grow. Even though traditional methods of assessment have been in use for managing HF, these are limited by time consuming and costly subjective interpretation and also by their invasive nature. Comparatively, biomarkers offer an objective and biologically relevant information that in conjunction with the patients' clinical findings provides optimal picture regarding the status of the HF patient and thus helps in diagnosis and prognosis. The current gold standard biomarkers for the diagnosis and prognosis of HF are B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP). Additional novel biomarkers (e.g., mid-regional pro atrial natriuretic peptide (MR-proANP), mid-regional pro adrenomedullin (MR-proADM), troponins, soluble ST2 (sST2), growth differentiation factor (GDF)-15 and galectin-3) can potentially identify different pathophysiological processes such as myocardial insult, inflammation and remodeling as the causes for the development and progression of HF. Different biomarkers of HF not only reflect the underlying mechanisms/pathways of HF and also its progression and also point specific therapy options. A multi-biomarker approach for personalized medical care is not too far fetched and such approach can greatly enhance diagnosis, prognostication, and therapy guidance for HF. In this review we describe the current status of HF biomarkers in clinical use and in laboratory research and the efforts aimed at the identification of novel biomarkers for HF.

Topics: Adrenomedullin; Animals; Atrial Natriuretic Factor; Biomarkers; Disease Progression; Galectin 3; Heart Diseases; Humans; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors

The mammalian heart expresses two closely related natriuretic peptide (NP) hormones, atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). The excretion of the NPs and the expression of their genes strongly respond to a variety of cardiovascular disorders. NPs act to increase natriuresis and decrease vascular resistance, thereby decreasing blood volume, systemic blood pressure and afterload. Plasma levels of BNP are used as diagnostic and prognostic markers for hypertrophy and heart failure (HF), and both ANF and BNP are widely used in biomedical research to assess the hypertrophic response in cell culture or the development of HF related diseases in animal models. Moreover, ANF and BNP are used as specific markers for the differentiating working myocardium in the developing heart, and the ANF promoter serves as platform to investigate gene regulatory networks during heart development and disease. However, despite decades of research, the mechanisms regulating the NP genes during development and disease are not well understood. Here we review current knowledge on the regulation of expression of the genes for ANF and BNP and their role as biomarkers, and give future directions to identify the in vivo regulatory mechanisms. This article is part of a Special Issue entitled: Heart failure pathogenesis and emerging diagnostic and therapeutic interventions.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Gene Expression Regulation; Heart; Heart Diseases; Humans; Natriuretic Peptide, Brain

Topics: Acute Coronary Syndrome; Acute Disease; Atrial Natriuretic Factor; Biomarkers; Critical Care; Dyspnea; Heart Diseases; Heart Failure; Humans; Immunoassay; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Pulmonary Embolism; Reference Values; Risk Assessment

As a continuation of "Postmortem Chemistry Update Part I," Part II deals with molecules linked to liver and cardiac functions, alcohol intake and alcohol misuse, myocardial ischemia, inflammation, sepsis, anaphylaxis, and hormonal disturbances. A very important array of new material concerning these situations had appeared in the forensic literature over the last two decades. Some molecules, such as procalcitonin and C-reactive protein, are currently researched in cases of suspected sepsis and inflammation, whereas many other analytes are not integrated into routine casework. As in part I, a literature review concerning a large panel of molecules of forensic interest is presented, as well as the results of our own observations, where possible.

Topics: Alcohol Drinking; Alcoholism; Anaphylaxis; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Forensic Pathology; Glucuronates; Heart Diseases; Heart Function Tests; Hormones; Humans; Inflammation; Liver; Liver Function Tests; Postmortem Changes; Protein Precursors; Sepsis; Sulfuric Acid Esters; Transferrin

The increasing importance of cardiac disease has generated an interest in improved screening strategies regarding preclinical cardiac abnormalities and employing measurement of circulating biomarkers. This review focuses on the utility of the B-type natriuretic peptides (NP) and the cardiac troponins (cTns) for this purpose.. Both the NPs and the cTns are closely related to cardiac structural and functional abnormalities that may progress to symptomatic heart disease, e.g., left ventricular (LV) hypertrophy, LV systolic and diastolic dysfunction. Both biomarkers provide incremental information to each other. However, biomarker results may be confounded by several non-cardiac conditions, and decision thresholds and recommendations on further clinical work-up are as yet not specified. Furthermore, cost issues will probably preclude widespread biomarker screening in general populations.. Measurement of the NPs or cTns is an attractive option for screening for cardiac abnormalities. This may be particularly effective in patients at higher risk for developing overt heart disease. Nevertheless, appropriate diagnostic and therapeutic responses to biomarker results need to be defined before routine screening can be recommended in the community setting.

Topics: Atrial Natriuretic Factor; Biomarkers; Heart Diseases; Humans; Mass Screening; Troponin

Cardiac biomarkers are used to identify cardiac disease in term and preterm infants. This review discusses the roles of natriuretic peptides and cardiac troponins. Natriuretic peptide levels are elevated during atrial strain (atrial natriuretic peptide (ANP)) or ventricular strain (B-type natriuretic peptide (BNP)). These markers correspond well with cardiac function and can be used to identify cardiac disease. Cardiac troponins are used to assess cardiomyocyte compromise. Affected cardiomyocytes release troponin into the bloodstream, resulting in elevated levels of cardiac troponin. Cardiac biomarkers are being increasingly incorporated into clinical trials as indicators of myocardial strain. Furthermore, cardiac biomarkers can possibly be used to guide therapy and improve outcome. Natriuretic peptides and cardiac troponins are potential tools in the diagnosis and treatment of neonatal disease that is complicated by circulatory compromise. However, clear reference ranges need to be set and validation needs to be carried out in a population of interest.

Topics: Atrial Natriuretic Factor; Biomarkers; Heart Diseases; Humans; Infant, Newborn; Myocytes, Cardiac; Natriuretic Peptide, Brain; Neonatology; Predictive Value of Tests; Prognosis; Troponin

Topics: Animals; Atrial Natriuretic Factor; Growth Differentiation Factor 15; Heart; Heart Diseases; Humans; Proteome; Proteomics

High blood concentration of the N-terminal cleavage product of the B-type natriuretic peptide (NT-proBNP) is strongly associated with cardiac dysfunction and is increasingly used for heart failure diagnosis. To identify genetic variants associated with NT-proBNP level, we performed a genome-wide association analysis in 1325 individuals from South Tyrol, Italy, and followed up the most significant results in 1746 individuals from two German population-based studies. A genome-wide significant signal in the MTHFR-CLCN6-NPPA-NPPB gene cluster was replicated, after correction for multiple testing (replication one-sided P-value = 8.4 × 10(-10)). A conditional regression analysis of 128 single-nucleotide polymorphisms in the region of interest identified novel variants in the CLCN6 gene as independently associated with NT-proBNP. In this locus, four haplotypes were associated with increased NT-proBNP levels (haplotype-specific combined P-values from 8.3 × 10(-03) to 9.3 × 10(-11)). The observed increase in the NT-proBNP level was proportional to the number of haplotype copies present (i.e. dosage effect), with an increase associated with two copies that varied between 20 and 100 pg/ml across populations. The identification of novel variants in the MTHFR-CLCN6-NPPA-NPPB cluster provides new insights into the biological mechanisms of cardiac dysfunction.

Topics: Adult; Aged; Atrial Natriuretic Factor; Chloride Channels; Chromosome Mapping; Chromosomes, Human, Pair 1; Female; Genome-Wide Association Study; Haplotypes; Heart Diseases; Humans; Likelihood Functions; Male; Markov Chains; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Models, Genetic; Multigene Family; Natriuretic Peptide, Brain; Polymorphism, Single Nucleotide; Protein Precursors; Regression Analysis

Cardiac biomarkers have well-established roles in acute coronary syndrome and congestive heart failure. In many instances, the detection of cardiac biomarkers may aid in the diagnosis and risk assessment of critically ill patients. Despite increasing interest in the use of cardiac biomarkers in noncardiac critical illness, no clear consensus exists on how and in which settings markers should be measured. This article briefly describes what constitutes an ideal biomarker and focuses on those that have been most well studied in critical illness, specifically troponin, the natriuretic peptides, and heart-type fatty acid-binding protein.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Critical Care; Critical Illness; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Heart Diseases; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Troponin

Pericardial fluid is a kind of serous fluid in pericardial cavity. Because blood undergoes postmortem changes such as autolysis and putrefaction, vitreous humor is limited,cerebrospinal fluid is easily mixed with blood, pericardial fluid, on the other hand, exists in a closed cavity and can be hardly contaminated by postmortem changes, and also is easily obtained. Pericardial fluid not only plays an important role in clinic practice, but also is widely applicable in forensic practice. This paper briefly presented the properties of pericardial fluid and its clinical significance. It reviewed biochemical changes in decedents died of heart diseases, drowning and asphyxia, and explored the significance in medico-legal investigation. Moreover, application of pericardial fluid in forensic serology, forensic toxicological analysis and other fields were also discussed. Pericardial fluid analysis may provide important information for determination of the cause of death with further investigation concerning forensic applicability of pericardial fluid.

Topics: Asphyxia; Atrial Natriuretic Factor; Biomarkers; Calcium; Drowning; Forensic Pathology; Heart Diseases; Humans; L-Lactate Dehydrogenase; Magnesium; Myocardium; Natriuretic Peptide, Brain; Pericardium; Postmortem Changes; Troponin I

Topics: Active Transport, Cell Nucleus; Animals; Atrial Natriuretic Factor; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Heart Diseases; Humans; Signal Transduction; Smad3 Protein; Transforming Growth Factor beta

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Brain; Diagnosis, Differential; Extracellular Fluid; Heart Diseases; Humans; Lung Diseases; Myocardium; Water

Natriuretic peptides (NPs) are released from the heart in response to pressure and volume overload. B-type natriuretic peptide (BNP) and N-terminal-proBNP have become important diagnostic tools for assessing patients who present acutely with dyspnea. The NP level reflects a compilation of systolic and diastolic function as well as right ventricular and valvular function. Studies suggest that using NPs in the emergency department can reduce the consumption of hospital resources and can lower costs by either eliminating the need for other, more expensive tests or by establishing an alternative diagnosis that does not require hospital stay. Caveats such as body mass index and renal function must be taken into account when analyzing NP levels. Natriuretic peptide levels have important prognostic value in multiple clinical settings, including in patients with stable coronary artery disease and with acute coronary syndromes. In patients with decompensated heart failure due to volume overload, a treatment-induced drop in wedge pressure is often accompanied by a rapid drop in NP levels. Knowing a patient's NP levels might thus assist with hemodynamic assessment and subsequent treatment titration. Monitoring NP levels in the outpatient setting might also improve patient care and outcomes.

Topics: Atrial Natriuretic Factor; Cardiovascular Diseases; Death, Sudden, Cardiac; Heart Diseases; Heart Failure; Hemodynamics; Humans; Kidney Failure, Chronic; Monitoring, Physiologic; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Obesity; Peptide Fragments; Prognosis; Pulmonary Edema; Pulmonary Embolism; Pulmonary Wedge Pressure; Renal Dialysis; Stroke; Weight Loss

Biochemical markers are available to detect cardiac involvement in many pediatric disease states and should be considered.. Analyses of three markers are readily available in clinical laboratories for improved diagnosis.. Increased workload of the heart has been associated with the release of biochemical markers (natriuretic peptides and cardiac enzymes) that indicate that a new genetic program has been activated and maladaptation is occurring in the atria, ventricles, or both. This review summarizes those that have been identified in fetal and pediatric practice. The expression of such markers is traced from early embryonic development to fetal life, to the neonate, to childhood, and then to adult life.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Biomarkers; Child; Graft Rejection; Heart Diseases; Humans; Infant; Infant, Newborn; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Renal Insufficiency; Sepsis; Troponin T

With the introduction of the first rapid, fully automated assay for N-terminal pro-B-type natriuretic peptide (Nt-proBNP) determination, clinical laboratories are now able to transfer a number of preliminary information derived from pilot research experiences to the context of clinical cardiology. Some confounding factors may, however, affect the interpretation of the Nt-proBNP test and its clinical value. The objective of this review is to highlight and discuss these potentially confounding variables.

Topics: Age Factors; Atrial Natriuretic Factor; Biomarkers; Epitopes; Heart Diseases; Humans; Immunoassay; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prognosis

Dystrophinopathies are due to mutations in the dystrophin gene on chromosome Xp21.1 and comprise the allelic entities Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) and X-linked dilative cardiomyopathy (XLDCM). In all three entities, the heart is affected to various degrees, depending on the stage of the disease and the type of the mutation (cardiac involvement, CI). The pathoanatomic evidence of CI in dystrophinopathies is the replacement of myocardium by connective tissue or fat. In DMD/BMD, the left ventricular posterobasal and lateral walls are most extensively affected, sparing the right ventricle and the atrium. Degree and dynamics of CI vary among the three entities. In DMD/BMD, CI usually remains subclinical in the early stages of the disease. Typical initial manifestations of CI in DMD/BMD are sinus tachycardia, tall R1 in V1, prominent Q in I, aVL, V6 or in II, III, and aVF, increased QT dispersion and possibly autonomic dysfunction. Initially, echocardiography is normal or shows regional wall motion abnormalities in areas of fibrosis. With spreading of fibrosis, left ventricular dysfunction and ventricular arrhythmias additionally occur. In the final stages of the disease, systolic function may lead to heart failure and sudden death. Subclinical or clinical CI is present in about 90% of the DMD/BMD patients but is the cause of death in only 20% of the DMD and 50% of the BMD patients. XLDCM is a rapidly progressive, almost exclusively myocardial disorder, starting in teenage males as heart failure due to dilative cardiomyopathy (CMP), leading to death from intractable heart failure within 1-2 years after diagnosis. Therapy of arrhythmias and CMP in all three disorders follows the established cardiological recommendations. Due to its protective effect, ACE inhibitors are recommended already at the early stages of the disease. Beta-blockers may be an additional option if indicated.

Topics: Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Diagnostic Imaging; Electrocardiography; Heart Conduction System; Heart Diseases; Humans; Muscular Dystrophies; Muscular Dystrophy, Duchenne; Myocardium; Natriuretic Peptide, Brain; Signal Processing, Computer-Assisted

This article will review the results of recent clinical studies relating to the pericardial fluid in patients with various heart diseases. In ischemic patients, several angiogenic growth factors are accumulated in a high concentration in pericardial fluid. These may contribute to the angiogenesis and arteriogenesis, which are self-protecting mechanisms of myocardial ischemia. In congestive heart failure, natriuretic peptides are released into the pericardial fluid in a higher concentration compared with plasma levels. This suggests that these peptides may act as autocrine and/or paracrine factors. Pericardial fluid from ischemic patients induces cell proliferation and apoptosis depending on the cell type. Intrapericardial drug administration may provide a reasonable therapeutic strategy for heart diseases. In conclusion, the analysis of pericardial fluid appears to be a logical approach for elucidation of the pathophysiology of the heart.

Topics: Angiogenesis Inducing Agents; Apoptosis; Atrial Natriuretic Factor; Heart; Heart Diseases; Humans; Natriuretic Peptide, Brain; Pericardial Effusion

The cardiac natriuretic peptides constitute a family of peptides that regulate fluid homeostasis as well as vascular tonus and growth. Following the fundamental establishment of the heart as an endocrine organ in the early 1980's, the cardiac natriuretic peptides have today been identified as potent biochemical tools in diverse aspects of clinical cardiology including as diagnostic, therapeutic and prognostic markers of cardiac dysfunction as well as potential drug targets. In man, Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are mainly synthesised and secreted by the failing heart, whereas the closely related C-type Natriuretic Peptide (CNP) appears to be a local factor secreted by the endothelium and hence is not considered as a cardiac natriuretic peptide. With the ongoing development of sensitive immunoassays, increased plasma concentrations of ANP and BNP peptides have been associated to a variety of cardiac diseases--but their clinical usefulness as biochemical markers in congestive heart failure is the most promising. In contrast to the large quantity of clinical research on cardiac-derived peptides, the basic understanding of the molecular heterogeneity of these peptides is however still insufficient. Since much clinical work on peptides derived from the proBNP precursor has been published recently, this mini-review will focus on these novel peptides and their potential applications in the clinical setting.

Topics: Amino Acid Sequence; Atrial Natriuretic Factor; Biomarkers; Heart Diseases; Heart Failure; Humans; Immunoassay; Molecular Sequence Data; Natriuretic Peptide, Brain; Protein Precursors

Topics: Animals; Atrial Natriuretic Factor; Heart; Heart Diseases; Lung; Lung Diseases; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Receptors, Peptide; Signal Transduction

Cardiac natriuretic peptide hormones (ANP and BNP) are synthesized and secreted by the heart, producing several biological effects, such as natriuresis, vasorelaxation, hypotension, and neuromodulation. Extensive studies conducted in both animals and humans have documented that cardiac natriuretic peptides (CNPs) are secreted into the circulatory system via the coronary sinus into the right atrium, and then rapidly degraded and removed from the blood by plasma proteases and specific clearance receptors. Usually, studies of CNPs kinetics have been carried out following an experimental protocol in which labeled or unlabeled hormone is administered (by constant infusion or bolus injection) and the corresponding concentration of the hormone is measured in peripheral venous blood. However, when a uniform intravascular concentration throughout artero-venous vessels is lacking due to the very rapid clearance of the substance being studied (such as CNPs), the classical compartmental or none compartmental approach may not be suitable for interpreting the experimental data. In this case, a more physiological circulatory model, which does not assume a uniform intravascular distribution of the hormone and comprises several anatomo-functional blocks arranged in a series and supplied by the same flow (cardiac output) should be adopted. Different experimental designs (infusion or bolus injection) as well as multiple sampling sites (aorta and pulmonary artery, inferior vena cava, femoral vein) were used in ANP kinetic studies. Using a circulatory approach, ANP has been demonstrated to be rapidly distributed and degraded; in healthy subjects about 50% of ANP secreted into the right atrium is extracted by the peripheral tissues during the first pass throughout the body. Since CNPs have important fluid-volume regulatory features, it has been postulated that they also play a key role in volume homeostasis in several pathophysiological states, such as congestive heart failure. Indeed, a markedly altered degradation and distribution of ANP in patients with cardiac failure who show a resistance to its natriuretic effects, even in those on the early stage of clinical disease, whose CNPs plasma levels are in the normal range, have been demonstrated. Recent studies indicate that some drugs, by inhibiting the degradation of CNPs by plasma proteases and can thus affect CNP kinetics, may be useful in the treatment of arterial hypertension and cardiac failure.

Topics: Animals; Atrial Natriuretic Factor; Heart; Heart Diseases; Humans; Myocardium; Natriuretic Peptide, Brain

Topics: Animals; Atrial Natriuretic Factor; Heart Diseases; Hemodynamics; Humans; Hypertension; Natriuretic Peptide, C-Type

Topics: Atrial Natriuretic Factor; Biomarkers; Heart Diseases; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins

Topics: Atrial Natriuretic Factor; Heart Diseases; Humans; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins

An accumulating body of experimental data supports the presence of a paracrine pathway for the modulation of myocardial function by cardiac endothelial cells. Cardioactive substances released by endothelial cells include nitric oxide, endothelin-1, prostanoids, adenylpurines, natriuretic peptides, and other agents that have so far only been characterised in bioassay studies. Endothelial cells also possess enzymatic activities, in particular ACE/kininase activity, which can alter local levels of angiotensin II and bradykinin. Many of the "endothelial" mediators can be produced by cardiac myocytes themselves, often under pathological conditions, suggesting a potential parallel autocrine pathway. Complex reciprocal relationships exist between individual mediators, which affect both their release and actions. Most studies to date have focused on the acute influence of these agents on contractile function; the longer-term modulation both of cardiac structure and function could be equally important. A notable feature of the action of several of the endothelial mediators is that they modify myocardial contractile behaviour predominantly through changes in myofilament properties rather than by altering cytosolic Ca2+ transients. This mode of action often results in a disproportionate effect on myocardial relaxation and diastolic tone. The opposing contractile effects and differing time-scales of action of agents such as nitric oxide and endothelin-1 are reminiscent of the interplay between these factors in the regulation of blood vessel tone. The endothelial paracrine pathway is likely to act in concert and to interact with other cardiovascular regulatory pathways, e.g., the Frank-Starling mechanism, neurohumoral influences, the effects of heart rate, coronary perfusion and load. A better understanding of its physiological and pathophysiological roles may lead to novel therapeutic strategies.

Topics: Animals; Atrial Natriuretic Factor; Endothelins; Endothelium, Vascular; Heart; Heart Diseases; Humans; Myocardial Contraction; Nitric Oxide; Rats; Renin-Angiotensin System

The cardiac natriuretic peptides (NP) -- atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) -- are polypeptide hormones produced by cardiocytes in the atria of mammals. ANF and BNP are continuously released from the heart, but appropriate mechanical or neuroendocrine stimuli increase their rate of release with or without a concomitant increase in synthesis. The results of our investigations lead us to propose that the endocrine response of the heart to pressure or volume load varies in relation to whether the challenge is acute, subacute or chronic. The acute response to stretch is based on a phenomenon referred to as "stretch-secretion coupling" which results in enhanced secretion of NP stored in the atria. NP release following stretch is made at the expense of a depletable NP pool with no apparent effect on synthesis. The stimulation of NP production that is seen during mineralcorticoid escape is referred to as "subacute" and is characterized by stimulation of atrial ANF and BNP gene transcription secondary to volume overload in which plasma ANF, but not plasma BNP, is significantly elevated. With chronic stimulation, as seen in DOCA-salt treatment at the hypertensive stage, activation of the cardiac fetal program in ventricle is seen together with a stimulation of ANF and BNP production in both atria and ventricles. However, the activation of NP gene expression in the atria is not necessarily associated with fetal isogene expression even though the ventricular hypertrophic process is characterized by the expression of fetal isogenes, including ANF and BNP, that are normally expressed in the fetal ventricle. It seems likely that the acute stimulation of NP release is based on an electromechanical coupling. However, protracted stimulation of release is seen in situations in which profound neuroendocrine changes have taken place, thus suggesting that the primary stimulus for chronically enhanced NP gene expression and NP release is based on changes in the hormonal environment of the atrial cardiocyte. It is concluded that the endocrine heart responds to changes in hemodynamic load with specific changes in translational, post-translational and storage processes for ANF and BNP following acute or chronic stimulation. As a result, plasma levels of ANF and BNP may be used as indicators of the degree of atrial hemodynamic overload and ventricular hypertrophy, respectively. It may be advanced that the endocrine heart differentiates and responds

Topics: Animals; Atrial Natriuretic Factor; Heart Diseases; Hemodynamics; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Stress, Mechanical; Transcription, Genetic

Topics: Amino Acid Sequence; Atrial Natriuretic Factor; Heart Diseases; Heart Failure; Humans; Hypertension; Molecular Sequence Data; Natriuretic Peptide, Brain; Protease Inhibitors

The original observation by de Bold et al. (1981) of a rapid, massive, and short-lasting diuretic and natriuretic effect following injection of rat atrial extracts into intact rats, led to the identification, isolation and purification of the atrial natriuretic factor (ANF). ANF is stored in atrial myocytes and released into the blood stream by atrial distension. Available data suggest that the mechanism of ANF-induced natriuresis involves either renal hemodynamic effects, such as the increase in glomerular filtration rate and reduction of medullary tonicity, or direct effect on sodium transport in the medullary collecting ducts. ANF induces relaxation of vascular smooth muscle, decreases blood pressure and cardiac output. All these effects displayed by ANF are associated to the an inhibition of aldosterone, renin and vasopressin release. Most of these actions are mediated by specific high affinity receptors, which are coupled to a particulate guanylate cyclase. Although ANF levels are increased in some disorders, such as severe heart failure, hypertension, chronic renal failure, the role of the peptide is uncertain. To better define the potential physiopathological role and the possible therapeutic implications of this new hormonal system in conditions of disturbed body fluid and sodium homeostasis, further experimental and clinical data must be awaited.

Topics: Atrial Natriuretic Factor; Gene Expression Regulation; Heart Atria; Heart Diseases; Humans; Hypertension; Kidney Diseases; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

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

Topics: Atrial Natriuretic Factor; Endocrine System Diseases; Heart Diseases; Humans; Hypertension; Kidney Failure, Chronic

The non-osmotic stimulation of release of arginine vasopressin (AVP) seems to be the main determinant of the impaired water excretion and hyponatraemia in patients with cardiac failure. This non-osmotic stimulation of AVP release could be secondary to a decrease in stroke volume to which the ventricular receptors respond by decreasing the vagal afferent input to the hypothalamus via the mid-brain. Improvement of cardiac stroke volume would then decrease AVP release and improve water excretion. In cardiac failure, the non-osmotic stimulation of AVP release is not clearly modulated by the renin-angiotensin system or by the atrial natriuretic peptide plasma concentration. Nevertheless, physiological concentrations of atrial natriuretic peptide could inhibit the renal epithelial water transport at the collecting duct level. Water-loading and osmotic-loading experiments in patients with cardiac failure indicated that the release of AVP is still under osmotic control and favoured the concept that volume depletion in general and cardiac failure in particular may lower the osmotic threshold and increase the osmotic sensitivity to vasopressin release. Experiments using a specific vasopressin antagonist rarely indicated a vasoconstrictor role for endogenous AVP in either experimental or clinical cardiac failure. Intrarenal factors also contributed to the impaired water excretion observed in patients with cardiac failure: increased central sympathetic efferent discharge and stimulation of the renin-angiotensin-aldosterone system would be expected as a consequence of the decreased effective arterial blood volume. These effects could then decrease maximal reabsorption of solute further impairing the ability of the kidney to excrete free water. The impaired water excretion is correlated with the severity of the cardiac deterioration and thus has prognostic implications.

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Heart Diseases; Humans; Hyponatremia; Kidney; Prognosis; Water-Electrolyte Imbalance

Topics: Animals; Atrial Natriuretic Factor; Endocrine Glands; Heart; Heart Diseases; Humans; Hypertension; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface; Second Messenger Systems

Topics: Atrial Natriuretic Factor; Heart Diseases; Humans

ANF is a newly discovered peptide hormone that has significant implications for critical care physicians. This hormone, released from the heart, is especially responsive to fluid challenges as well as to many of the drugs commonly used in the ICU, including pressor and anesthetic agents. It has potent arterial vasodilating effects in pharmacologic doses and may be an important natural vasodilating agent, especially in the renal vascular bed. In patients on dopamine, it may potentiate the renal vasodilating effect and may provide an effective therapy for developing acute renal failure. Children with congenital heart disease and patients with CHF have elevated levels that clearly alter the aldosterone-angiotensin II system and may help us to understand and treat these conditions more effectively. Additionally, ANF may be a marker for adequacy of treatment in these disease states. The potential uses for ANF include diuresis in patients with fluid overload and diuretic resistance, treatment of CHF, and as a short-acting vasodilator. In the ICU, many therapies affect cardiac pressures and volume regulation. Positive-pressure ventilation may decrease the release of ANF by decreasing venous return and thus contribute to water retention. Drugs used in the ICU may directly affect ANF levels and markedly affect the homeostasis of fluid and electrolyte balance. This hormone system interacts intimately with renin, angiotensin II, and aldosterone. These interactions may play a significant role in the development of essential hypertension. Although not addressed in this article, the treatment and understanding of essential hypertension may be significantly advanced by understanding these relationships. It is clear that ANF acts as a hormone with complex interactions between the heart, volume status, electrolyte balance, renin-angiotensin II-aldosterone, vasopressin, and vascular tone. Although currently no definitive picture exists for these complex interactions, this is an exciting new hormone with significant implications for patient management in the ICU. As research continues, the picture will become clearer and our understanding of this new hormone more precise.

Topics: Animals; Atrial Natriuretic Factor; Endocrine System Diseases; Heart Diseases; Humans; Kidney Diseases

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

Topics: Animals; Atrial Natriuretic Factor; Cardiovascular System; Glomerular Filtration Rate; Heart Diseases; Hemodynamics; Humans; Kidney Glomerulus; Kidney Tubules; Plasma Volume

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Heart Diseases; Humans; Kidney; Renin; Renin-Angiotensin System

Topics: Animals; Atrial Natriuretic Factor; Chemical Phenomena; Chemistry; Diuresis; Guinea Pigs; Heart Diseases; Humans; Kinetics; Mineralocorticoid Receptor Antagonists; Muscle Tonus; Muscle, Smooth; Natriuresis; Rats

Topics: Amino Acid Sequence; Animals; Atrial Natriuretic Factor; Blood Pressure; Diuresis; Dogs; Glomerular Filtration Rate; Heart Atria; Heart Diseases; Homeostasis; Humans; Hypothalamus; Kidney; Muscle Proteins; Natriuresis; Protein Precursors; Rats; Water-Electrolyte Balance

Topics: Atrial Natriuretic Factor; Heart; Heart Diseases; Humans; Microscopy, Electron; Myocardium; Parasympatholytics

Topics: Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Cyclic GMP; Diuretics; Glomerular Filtration Rate; Heart Diseases; Hemodynamics; Humans; Hypertension; Muscle, Smooth; Muscle, Smooth, Vascular; Renal Circulation; Renin-Angiotensin System

Human atrial natriuretic peptide (h-ANP) elicits biological effects such as natriuresis, diuresis, and vasodilation, and plays a role in regulating pulmonary circulation. We conducted this clinical study to define its role and elucidate its mechanisms.. Twelve consecutive adult patients scheduled to undergo cardiac surgery with cardiopulmonary bypass (CPB) were prospectively selected for this study. After the completion of surgery, h-ANP was infused from the right atrium through a Swan-Ganz (S-G) catheter. Blood samples for measurement of ANP and cyclic guanosine monophosphate (cGMP), the second messenger of ANP, were drawn from the pulmonary artery (PA) through the S-G catheter and from the left atrium (LA) through the left atrial pressure line, before and after the infusion of h-ANP. Hemodynamic values were measured at the same time.. After the h-ANP infusion, the plasma levels of ANP were significantly lower in the LA than in the PA, whereas the plasma levels of cGMP were significantly higher in the LA than in the PA. The infusion of h-ANP decreased the mean PA pressure significantly, and the systolic PA pressure remarkably.. The infusion of h-ANP after cardiac surgery stimulates the secretion of cGMP from the pulmonary vascular bed and dilates the PA, thereby decreasing the PA pressure.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Cyclic GMP; Female; Heart Diseases; Hemodynamics; Humans; Male; Middle Aged; Prospective Studies; Pulmonary Artery; Pulmonary Circulation; Vasodilator Agents

The purpose of this study was to investigate the efficacy of carperitide (human atrial natriuretic peptide [h-ANP]) in perioperative management in patients with renal dysfunction, especially its kidney-protecting effects.. The subjects were 18 patients who underwent elective cardiac surgery using cardiopulmonary bypass (CPB) with a preoperative serum creatinine (Cr) level of 1.2 mg/dl or more. The subjects were prospectively assigned to 2 groups: an h-ANP-treated group (Group H, n = 10) and a non-h-ANP-treated group (Group N, n = 8). At the beginning of surgery, h-ANP administration was initiated and continued for 5 days or more. The central dose was 0.02 microg/kg/min. The primary end point included the serum Cr level and creatinine clearance (Ccr).. In Group H, Cr level significantly decreased after surgery compared to the preoperative level. The Ccr values were significantly higher 2 and 3 days after surgery than the preoperative values. And the intraoperative urine volume significantly increased. In Group H, an increase in urinary N-acetyl-beta-D-glucosaminidase (NAG) level the day after surgery was significantly inhibited in comparison with Group N.. The results of this study suggest that in patients with renal dysfunction before cardiac surgery, continuous low-dose h-ANP therapy maintains renal function, preventing its deterioration.

Topics: Acetylglucosaminidase; Atrial Natriuretic Factor; Biomarkers; Blood Urea Nitrogen; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Creatinine; Fatty Acid-Binding Proteins; Heart Diseases; Humans; Infusions, Parenteral; Interleukin-6; Kidney Diseases; Perioperative Care; Prospective Studies; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Urodynamics

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

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

1. The cardiac natriuretic peptides, atrial natriuretic peptide and brain natriuretic peptide, are degraded via clearance receptors and the enzyme neutral endopeptidase (EC 3.4.24.11). We studied the regional plasma concentrations of these peptides and their response to acute neutral endopeptidase inhibition in a consecutive series of patients with a broad spectrum of severity of cardiac dysfunction who were undergoing diagnostic right and left heart catheterization (24 patients, mean age 62.6 years).2. Baseline blood samples were obtained for hormone analysis from femoral artery, femoral vein, renal vein, hepatic vein, superior vena cava, coronary sinus and pulmonary artery, and initial haemodynamic measurements were made. Twelve patients then received a neutral endopeptidase inhibitor (SCH 32615, 200 mg intravenously) and 12 received vehicle alone. The cardiac catheterization procedure was then completed and haemodynamic and hormone measurements were repeated.3.Haemodynamic status was similar at baseline in both groups, and at repeated measurement (post-procedure after placebo or active drugs) haemodynamic variables were not significantly different from baseline values. Plasma levels of atrial and brain natriuretic peptides exhibited an arteriovenous increment (344% and 124% respectively) across the heart (femoral artery to coronary sinus) and decrement (by 28-54% and 9-16% respectively) across all other tissue beds (P<0.05 for all) except the lung (no change). Final levels of atrial natriuretic peptide rose above initial levels at all sites in both groups (P<0.05) except coronary sinus levels in the vehicle group (no change). The increase was consistently greater in the inhibitor group at all sites (P<0.05 versus placebo). Levels of brain natriuretic peptide rose at all sites in the inhibitor group only (P<0.05). The transcardiac step-up in atrial natriuretic peptide was markedly augmented after the administration of neutral endopeptidase inhibitor. Other tissue gradients were not significantly altered by neutral endopeptidase inhibitor.4. Atrial and brain natriuretic peptides in plasma are degraded by a number of tissues, and respond differently to cardiac catheterization. Neutral endopeptidase has a significant role in determining plasma levels of natriuretic peptides, in part perhaps by influencing the amount of intact peptide reaching the circulation after secretion from the heart.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiac Catheterization; Dipeptides; Female; Femoral Artery; Femoral Vein; Heart Diseases; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neprilysin; Protease Inhibitors; Pulmonary Artery; Statistics, Nonparametric

Hypertonic-iso/hyperoncotic solutions have been the subject of numerous studies, mostly used in a fixed dosage (4 mL/kg bw or 250 mL). Nearly no study exists to prove whether this is the appropriate dosage especially in cardiac risk patients with accompanying diseases. We have compared preoperative volume loading with either 10% hydroxyethyl-starch/7.5% NaCl (HHT-HES) or 10% hydroxyethyl-starch/.9% NaCl (HES) in 50 mL bolus infusions. Volume loading was done with either HES or HHT-HES in 2 x 20 patients before aortic aneurysmectomy. The endpoint of stepwise infusion represented the highest cardiac index (CI) at the lowest possible wedge pressure (PCWP) (turning point of each individual Frank Starling relation). 167.5 mL (+/- 45.5 mL = 2.41 mL/kg bw) of HHT-HES and 440 mL (+/- 26.15 mL = 6.33 mL/kg bw) of HES were necessary. We observed a significant higher increase of the CI in the HHT-HES group. Significant increases of PCWP, pulmonary artery pressure, and central venous pressure occurred within the groups without any significant differences between the groups (p < .05). Results of the study showed: 1) The commonly used fixed dosage of 4 mL/kg bw of HHT-HES is too high in cardiac risk patients with slight hypovolemia. 2) HHT-HES should be given in an individual titration. 3) In the HHT-HES group we observed a positive inotropic effect (higher CI). 4) With the individual titration of HHT-HES no negative side effects occurred (especially no hypotension).

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Cardiac Output; Cyclic GMP; Drug Evaluation; Heart Diseases; Heart Rate; Hemodynamics; Humans; Hypertonic Solutions; Male; Middle Aged; Myocardial Infarction; Osmolar Concentration; Oxygen; Premedication; Pulmonary Wedge Pressure; Risk Factors; Sodium; Systole; Time Factors; Venous Pressure; Ventricular Function, Left; Ventricular Function, Right

The relationship between endogenous plasma concentrations of atrial natriuretic peptide and renin was examined in resting normal subjects and patients with cardiac impairment. To test the hypothesis that atrial natriuretic peptide inhibits renin secretion, intravenous infusions of atrial natriuretic peptide were administered to normal volunteers, patients with end-stage renal failure, and conscious dogs in both sodium-replete and sodium-depleted states. Plasma atrial natriuretic peptide and renin were inversely related in normal subjects (r = -0.52, n = 140, p less than 0.001), but a weak positive association between these two variables was observed in patients with cardiac impairment (r = 0.32, n = 60, p less than 0.02). Low doses of both 26- and 28-amino-acid human atrial natriuretic peptide (2 pmol/kg/minute for two hours) given to sodium-replete normal subjects halved plasma renin compared with time-matched placebo values (19 +/- 4 and 18 +/- 3 versus 36 +/- 8 microU/ml, p less than 0.001 for both). Incremental doses of synthetic atrial natriuretic peptide suppressed plasma renin below time-matched placebo values in both sodium-replete (maximal suppression 1.2 +/- 0.4 versus 8.6 +/- 1.4 microU/ml, p less than 0.001) and sodium-depleted (maximal suppression 18.9 +/- 4.9 versus 51 +/- 13 microU/ml, p less than 0.05) dogs. This effect was initially apparent at low doses of atrial natriuretic peptide (1 pmol/kg/minute), and renin suppression was maximal, in both states, with lesser doses of atrial natriuretic peptide than those at which maximal natriuresis was observed. Atrial natriuretic peptide administered to patients with end-stage renal failure (10 pmol/kg/minute for one hour) caused no change in plasma renin. These data confirm that atrial natriuretic peptide inhibits renin secretion in a dose-related manner and suggest that this action of the peptide is modified by both the baseline sodium status and renal function of the recipient.

Topics: Adult; Animals; Atrial Natriuretic Factor; Dogs; Heart Diseases; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renin; Sodium, Dietary

Ginkgolides are terpenoids peculiar to Ginkgo biloba, which have protective properties against cardiac diseases. This study aims to explore whether ginkgolide A (GA) could improve cardiac dysfunction of MI mice, and whether it could alleviate cardiac remodeling via binding to matrix metalloproteinase-9 (MMP9) to attenuate inflammation. Cardiac remodeling in mice induced by left coronary artery ligation were used in the in vivo model, and angiotensin (Ang) II-induced cardiac fibroblasts (NRCFs) and cardiomyocytes (NRCMs) isolated from neonatal rats were used in in vitro fibrosis and hypertrophy models, respectively. Cardiac dysfunction and fibrosis in MI mice were alleviated by GA treatment. Upregulations of collagen I (Col I), collagen III (Col III) and fibronectin in NRCFs, and enhanced levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and beta-myosin heavy chain (β-MHC) in NRCMs were inhibited by GA treatment. A total of 100 potential targets were found in 5 databases (TCMSP, BATMAN-TCM, PharmMapper, ETCM and SWISS Target). According to Protein Data Bank database GA could form hydrogen bonds between LYS65, GLU157, ASN17, ARG109, ARG106 of MMP9 protein, a target of GA. The regulatory role of GA in downregulating Col I, Col III, fibronectin in NRCFs, and enhancing levels of ANP, BNP and β-MHC in NRCMs were reversed by MMP9 overexpression, so as the downregulation of IL-1β, IL-6 and TNF-α in Ang II-induced NRCFs and NRCMs. GA could alleviate cardiac dysfunction and remodeling via binding to MMP9 to attenuate inflammation. Therefore, GA is a potential drug for cardiac remodeling therapy.

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; Cardiomegaly; Cardiotonic Agents; Fibronectins; Fibrosis; Ginkgolides; Heart Diseases; Inflammation; Lactones; Matrix Metalloproteinase 9; Mice; Myocardial Infarction; Myocytes, Cardiac; Rats; Ventricular Remodeling

Type 2 diabetes mellitus (T2DM) increases cardiac inflammation which promotes the development of cardiac fibrosis. We sought to determine the impact of circadian disruption on the induction of hyperglycaemia, inflammation and cardiac fibrosis.. Psammomys obesus (P. obesus) were exposed to neutral (12 h light:12 h dark) or short (5 h light:19 h dark) photoperiods and fed a low energy (LE) or high energy (HE) diet for 8 or 20 weeks. To determine daily rhythmicity, P. obesus were euthanised at 2, 8, 14, and 20 h after 'lights on'.. P. obesus exposed to a short photoperiod for 8 and 20 weeks had impaired glucose tolerance following oral glucose tolerance testing, compared to a neutral photoperiod exposure. This occurred with both LE and HE diets but was more pronounced with the HE diet. Short photoperiod exposure also increased myocardial perivascular fibrosis after 20 weeks on LE (51%, P < 0.05) and HE (44%, P < 0.05) diets, when compared to groups with neutral photoperiod exposure. Short photoperiod exposure caused elevations in mRNA levels of hypertrophy gene Nppa (atrial natriuretic peptide) and hypertrophy transcription factors Gata4 and Mef2c in myocardial tissue after 8 weeks.. Exposure to a short photoperiod causes impaired glucose tolerance in P. obesus that is exacerbated with HE diet and is accompanied by an induction in myocardial perivascular fibrosis.

Topics: Animals; Apoptosis; Atrial Natriuretic Factor; Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Type 2; Diet; Energy Intake; Fibrosis; Gene Expression Regulation; Gerbillinae; Glucose Tolerance Test; Heart Diseases; Light; Photoperiod; RNA, Messenger; Sarcoplasmic Reticulum Calcium-Transporting ATPases

Natriuretic Peptides (NP) are important in maintaining normal cardiac and metabolic status and have been used to predict cardiovascular events. Whether plasma concentrations of NP products within the normal range reflect cardio-metabolic health is unknown. Plasma NTproANP, NTproBNP and NTproCNP and their bioactive counterparts were measured in a random sample of 348 community dwellers aged 49-51 yr without heart disease and associations sought with established vascular risk factors, echocardiographic indices and a genetic variant previously linked with BNP. Stratified by sex, each of ten vascular risk factors were positively associated with NTproCNP whereas associations with NTproBNP and NTproANP were all negative. In both sexes, higher plasma NTproCNP was associated with higher arterial elastance, lower LV stroke volume and lower LV end diastolic volume. Exactly opposite associations were found with plasma NTproBNP or NTproANP. Sex specific differences were identified: positive association of NTproBNP with LV end systolic volume and the negative association with LV elastance were found only in males. The genetic variant rs198358 was independently associated with NTproBNP but not with NTproANP. In conclusion, higher NTproCNP is likely to be an adaptive response to impaired LV relaxation whereas genetic factors likely contribute to higher NTproBNP and improved cardio-metabolic health at midlife.

Topics: Atrial Natriuretic Factor; Cardiovascular System; Female; Heart Diseases; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Peptide Fragments; Risk Factors; Sex Characteristics

Tinnitus is recognized as a refractory disease, which is common in clinic, and always treated from the liver and kidney. We treat tinnitus mainly by heart based on syndrome differentiation. It often works well when the left

Topics: Atrial Natriuretic Factor; Audiometry, Pure-Tone; Auditory Threshold; Cochlea; Ear; Heart; Heart Diseases; Humans; Tinnitus

Topics: Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Atrial Remodeling; Biomarkers; Blood Pressure; Cardiomyopathy, Hypertrophic; Case-Control Studies; Catheter Ablation; Female; Heart Atria; Heart Diseases; Humans; Hypertension; Imaging, Three-Dimensional; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Veins; Tomography, X-Ray Computed; Troponin T; Vascular Remodeling

Studies on the use of atrial natriuretic peptide (ANP) as a biomarker for left atrial dilatation in horses have produced variable results. Few have been performed, and the results may have been influenced by ANP instability, differences in sampling protocol and changes in the assay over time. N-Terminal proANP (NT-proANP) is a more stable molecule and might be a good alternative for clinical use.. To compare ANP and NT-proANP in terms of the detection of left atrial dilatation and to determine the influence of sample storage at temperatures of -80 and -20°C.. Prospective clinical study.. Atrial natriuretic peptide and NT-proANP concentrations were compared between healthy horses (Group 1, n = 20), horses with mitral valve regurgitation and a normal atrial size (Group 2, n = 11) and horses with mitral valve regurgitation associated with left atrial dilatation (Group 3, n = 16). The ANP concentration was measured with an equine enzyme-linked immunosorbent assay and the NT-proANP concentration with an enzyme-linked immunosorbent assay developed for use in human patients. Samples were stored at -20 and -80°C and analysed within 7 months.. The NT-proANP concentrations were not significantly different between the groups. Horses in Group 3 had a significantly higher ANP concentration (median 366 pg/ml; interquartile range [IQR] 74-2000 pg/ml) compared with horses in Group 1 (median 31 pg/ml; IQR 31-333 pg/ml) or Group 2 (median 31 pg/ml; IQR 31-1152 pg/ml; P = 0.02). The ANP cut-off value for detection of left atrial dilatation was 52 pg/ml (sensitivity 81%; specificity 84%) for sample storage at -80°C, and 44 pg/ml (sensitivity 69%; specificity 84%) for storage at -20°C. A larger decrease in ANP (45 ± 126 pg/ml) than in NT-proANP (10 ± 31 pg/ml) was found associated with sample storage at -20 instead of -80°C.. Atrial natriuretic peptide, but not NT-proANP, can be used to detect left atrial dilatation in horses. Atrial natriuretic peptide is less stable than NT-proANP when samples are stored at -20°C. Atrial natriuretic peptide is a more suitable biomarker of left atrial dilatation in horses than NT-proANP.

Topics: Animals; Atrial Natriuretic Factor; Dilatation, Pathologic; Female; Heart Diseases; Horse Diseases; Horses; Male; Protein Precursors

Cardiac remodeling involves changes in heart shape, size, structure, and function after injury to the myocardium. The proinflammatory adaptor protein myeloid differentiation protein 88 (MyD88) contributes to cardiac remodeling. To investigate whether excessive MyD88 levels initiate spontaneous cardiac remodeling at the whole-organism level, we generated a transgenic MyD88 mouse model with a cardiac-specific promoter. MyD88 mice (male, 20-30 g, n=∼80) were born at the expected Mendelian ratio and demonstrated similar morphology of the heart and cardiomyocytes with that of wild-type controls. Although heart weight was unaffected, cardiac contractility of MyD88 hearts was mildly reduced, as shown by echocardiographic examination, compared with wild-type controls. Moreover, the cardiac dysfunction phenotype was associated with elevation of ANF and BNP expression. Collectively, our data provide novel evidence of the critical role of balanced MyD88 signaling in maintaining physiological function in the adult heart.

Topics: Animals; Atrial Natriuretic Factor; Blotting, Western; Echocardiography; Heart Diseases; Heart Failure; Male; Mice; Mice, Transgenic; Myeloid Differentiation Factor 88; Myocardial Contraction; Myocardium; Natriuretic Peptide, Brain; Organ Dysfunction Scores; Organ Size; Phenotype; Real-Time Polymerase Chain Reaction; Ventricular Remodeling

Pseudoinfarction is one of the most common electrocardiographic characteristics in cardiac light-chain (AL) amyloidosis. The aim of the present study was to analyze the prognostic significance of pseudoinfarction and define the relation between pseudoinfarction and clinical parameters in cardiac AL amyloidosis.. A total 110 consecutive patients who presented with a diagnosis of cardiac AL amyloidosis and without a positive history of coronary disease between 2010 and 2014 were enrolled. Patients were divided into two groups according to the presence (n=40) or absence (n=70) of pseudoinfarction on electrocardiography (ECG). Clinical parameters including laboratory tests, echocardiography, and follow-up were collected and analyzed.. Patients with pseudoinfarction had higher N-terminal pro-brain natriuretic peptide levels (9131pg/ml vs 4644pg/ml, p=0.02) and a worse New York Heart Association (NYHA) function (p<0.001). The pseudoinfarction group also had a larger left atrium size (44mm vs 41mm, p=0.03), a thicker ventricular wall (septum 14mm vs 13mm, p=0.005 and posterior wall 14mm vs 13mm, p=0.01), a lower left ventricular ejection fraction (50% vs 58%, p=0.013), and higher early-to-atrial transmitral flow velocity ratio (p=0.001). Also, the pseudoinfarction group was closely associated with a lower voltage (70% vs 38.6%, p=0.002), poor precordial R wave progression (78.4% vs 43.9%, p=0.001), lower Sokolow-Lyon index (13mm vs 9mm, p<0.001), and lower voltage to mass ratio (0.521 vs 0.442, p=0.028) on the ECG. After a median follow-up of 39 months, Kaplan-Meier survival analysis showed that lifetime was significantly shorter in the pseudoinfarction group (median 4 months vs 17 months, p<0.001). By adopting the multivariate Cox proportional model, NYHA heart failure III to IV and the presence of pseudoinfarction remained the only two independent prognostic determinants with death hazard ratio of 3.16 and 1.9, respectively.. The presence of pseudoinfarction on the ECG has a negative prognostic effect on AL patients with cardiac involvement.

Topics: Amyloidosis; Atrial Natriuretic Factor; Blood Flow Velocity; Echocardiography; Electrocardiography; Female; Heart Atria; Heart Diseases; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged; Multivariate Analysis; Prognosis; Protein Precursors; Stroke Volume

Proteinuria is a hallmark of chronic kidney disease (CKD) and cardiovascular disease (CVD), and a good predictor of clinical outcome. Selective endothelin A (ETA) receptor antagonist used with renin-angiotensin system (RAS) inhibitors prevents development of proteinuria in CKD. However, whether the improvement in proteinuria would have beneficial effects on CVD, independent of RAS inhibition, is not well understood. In this study, we investigated whether atrasentan, an ETA receptor antagonist, has renal and cardiovascular effects independent of RAS inhibition. Male Dahl salt sensitive (DSS) rats, at six weeks of age, received water with or without different doses of atrasentan and/or enalapril under high salt (HS) diet or normal diet (ND) for 6 weeks. At the end of 12th week, atrasentan at a moderate dose significantly attenuated proteinuria and serum creatinine without reducing mean arterial pressure (MAP), thereby preventing cardiac hypertrophy and improving cardiac function. ACE inhibitor enalapril at a dose that did not significantly lowered BP, attenuated cardiac hypertrophy while moderately improving cardiac function without reducing proteinuria and serum creatinine level. Nonetheless, combined therapy of atrasentan and enalapril that does not altering BP exerted additional cardioprotective effect. Based on these findings, we conclude that BP independent monotherapy of ETA receptor antagonist attenuates the progression of CKD and significantly mitigates CVD independent of RAS inhibition.

Topics: Animals; Atrasentan; Atrial Natriuretic Factor; Blood Pressure; Cardiomegaly; Disease Models, Animal; Echocardiography; Endothelin A Receptor Antagonists; Gene Expression; Heart Diseases; Hemodynamics; Hypertension; Hypertrophy; Kidney Function Tests; Male; Myocytes, Cardiac; Phenylephrine; Pyrrolidines; Rats; Receptor, Endothelin A; Renal Insufficiency, Chronic

Plasma atrial/A-type natriuretic peptide concentration (CpANP) was measured in horses presenting with various heart diseases to assess its potential diagnostic value.. Fifteen healthy horses (Group 1) and 60 horses with various heart diseases associated with normal chamber size and function (Group 2, n = 24), associated with abnormal left atrial (LA) size and/or function but normal left ventricle (LV) (Group 3, n = 19), or associated with both abnormal LA and LV size and/or function (Group 4, n = 17).. CpANP was measured by a commercially available radioimmunoassay. Echocardiographic measurements were compared between groups by one-way ANOVA and Holm-Sidak post-hoc test. Receiver operating characteristics (ROC) analyses were performed to identify the best cut-offs to distinguish between groups. Relations between echocardiographic measurements and biomarker concentrations were assessed with backward stepwise multiple linear regression.. CpANP increased from Group 1 to 4 and was significantly higher in horses with heart disease than in controls. CpANP was associated with maximum LA area and LV fractional area change. The ROC analyses showed good specificity but poor sensitivity to distinguish between healthy horses and horses with heart disease overall, and between healthy horses and horses with altered left-sided chamber dimensions and/or function.. CpANP is increased in horses with heart disease associated with altered left-sided chamber dimensions and/or function. However, its diagnostic value is compromised by poor sensitivity.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Female; Heart Diseases; Horse Diseases; Horses; Male

Equine atrial natriuretic peptide (ANP) plasma concentrations are correlated with left atrial size. However, species-specific assays are lacking and the results from human assays are poorly reproducible. A new methodology called processing independent analysis (PIA) that measures the total proANP product in plasma has proven to be successful in human medicine, but has never been used in horses. The aims were to establish an equine proANP reference interval by measurement of the total proANP product using PIA and to examine the proANP concentrations in horses with atrial dilatation. Sample stability was studied by comparison of storage at -80°C and -20°C. Plasma samples were obtained from 23 healthy horses, 12 horses with moderate or severe valvular regurgitation without atrial dilatation and 42 horses with valvular regurgitation and atrial dilatation. The proANP concentration was significantly (P<0.001) higher in horses with atrial dilatation (761.4 (442.1-1859.1) pmol/l) than in healthy horses (491.6 (429.5-765.9) pmol/l; P<0.001) or horses with cardiac disease but without atrial dilatation (544.4 (457.0-677.6) pmol/l). A cut-off value (573.8 pmol/l) for detection of atrial dilatation was calculated. Sample storage at -80°C did not differ from sample storage at -20°C. The measurement of total proANP in plasma detects atrial dilatation in horses and may be useful for clinical evaluation in equine medicine.

Topics: Animals; Atrial Natriuretic Factor; Case-Control Studies; Dilatation, Pathologic; Female; Heart Atria; Heart Diseases; Horse Diseases; Horses; Male; Reference Values

Measurement of atrial/A-type natriuretic peptide (ANP) concentrations may be of use for assessment of cardiac disease, and reliable data on the analytic performance of available assays are needed. To assess the suitability for clinical use of commercially available ANP assays, intra-assay and inter-assay coefficient of variation and dilution parallelism were calculated for three immunoassays (RIAPen, RIAPhoen, and an ELISAPen) using blood samples from healthy and diseased horses to cover a wide range of ANP concentrations. Further, agreement between assays was assessed using linear regression and Bland-Altman analyses. For all assays, precision was moderate but acceptable and dilution parallelism was good. All assays showed analytic performance similar to other immunoassays used in veterinary medicine. However, the results from the three assays were poorly comparable. Our study highlights the need for an optimised species-specific assay for equine samples.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Heart Diseases; Horse Diseases; Horses; Immunoassay; Linear Models; Reproducibility of Results

Studies of left atrial (LA) function, until the latter part of the 20th century, were mostly limited to experimental animal models and to studies related to clinical research in the cardiac catheterization laboratory. For this reason, LA function has received considerably less attention than left ventricular (LV) functions, even though evidence suggests that LA myopathy and failure may exist as an isolated entity, precede and/or coexist with LV myopathy. The introduction of echocardiography and Doppler echocardiography in clinical practice has contributed significantly to our understanding of LA function and its interrelationships with the LV, aorta, pulmonary artery and other parts of the cardiovascular system. In addition, LA with the secretion of atrial natriuretic peptides is playing an important role in cardiovascular and neurohumoral homeostasis. Today, it is well known that LA structural and functional abnormalities that are present in many diseases and disorders constitute a powerful prognostic indicator. As technology (echocardiography, magnetic resonance imaging, computed tomography and others) continues to evolve, it is expected that, in the near future, LA structure and function will be routinely used as LV function is used today.

Topics: Atrial Function, Left; Atrial Natriuretic Factor; Atrial Remodeling; Cardiac Imaging Techniques; Heart Atria; Heart Diseases; Humans

Anthracyclines are used to treat cancers during the second and third trimester of pregnancy. The chemotherapeutic effect of anthracyclines is associated with a dose- and time-dependent cardiotoxicity that is well described for infants and adults. However, data regarding fetal anthracycline-related cardiotoxicity after administration of chemotherapeutics during pregnancy are limited. In this study, we analyzed the acute effect of doxorubicin, an anthracycline derivative, on fetal and maternal rat myocardium. We injected 10 or 20 mg/kg i.v. doxorubicin to pregnant Wistar rats at day 18 of pregnancy; age-matched pregnant rats injected with physiologic saline served as controls. Maternal echocardiography and fetal Doppler scanning were performed before the injection and before sacrifice. Cesarean operation was performed at day 19 or 20, and maternal and fetal blood samples and heart biopsies were collected to measure apoptosis, the impact on cell proliferation, and structural cardiac damage. Acute maternal cardiotoxicity is associated with loss of body weight, moderately deteriorated left ventricular function, induction of apoptosis, and a decrease in cell turnover. Despite a 30% lower fetal body weight and elevated plasma B-type natriuretic peptide concentrations after doxorubicin administration, the fetal hearts had intact microstructure, an unaltered number of apoptotic cells, and preserved cell proliferation compared with controls. Our study suggests that acute treatment using anthracyclines during pregnancy impairs maternal cardiac function, whereas fetal hearts are protected.

Topics: Animals; Antibiotics, Antineoplastic; Apoptosis; Atrial Natriuretic Factor; Body Weight; Cell Proliferation; DNA Fragmentation; Doxorubicin; Echocardiography; Female; Fetal Heart; Heart Diseases; In Situ Nick-End Labeling; Injections, Intravenous; Maternal-Fetal Exchange; Myocardium; Myosins; Organ Size; Pregnancy; Rats; Rats, Wistar; RNA; Transcription, Genetic

We aimed to investigate whether atrial natriuretic peptide (ANP) attenuates angiotensin II (Ang II)-induced myocardial remodeling and to clarify the possible molecular mechanisms involved. Thirty-five 8-week-old male Wistar-Kyoto rats were divided into control, Ang II, Ang II + ANP, and ANP groups. The Ang II and Ang II + ANP rats received 1 μg/kg/min Ang II for 14 days. The Ang II + ANP and ANP rats also received 0.1 μg/kg/min ANP intravenously. The Ang II and Ang II + ANP rats showed comparable blood pressure. Left ventricular fractional shortening and ejection fraction were lower in the Ang II rats than in controls; these indices were higher (P < 0.001) in the Ang II + ANP rats than in the Ang II rats. In the Ang II rats, the peak velocity of mitral early inflow and its ratio to atrial contraction-related peak flow velocity were lower, and the deceleration time of mitral early inflow was significantly prolonged; these changes were decreased by ANP. Percent fibrosis was higher (P < 0.001) and average myocyte diameters greater (P < 0.01) in the Ang II rats than in controls. ANP decreased both myocardial fibrosis (P < 0.01) and myocyte hypertrophy (P < 0.01). Macrophage infiltration, expression of mRNA levels of collagen types I and III, monocyte chemotactic protein-1, and a profibrotic/proinflammatory molecule, tenascin-C (TN-C) were increased in the Ang II rats; ANP significantly decreased these changes. In vitro, Ang II increased expression of TN-C and endothelin-1 (ET-1) in cardiac fibroblasts, which were reduced by ANP. ET-1 upregulated TN-C expression via endothelin type A receptor. These results suggest that ANP may protect the heart from Ang II-induced remodeling by attenuating inflammation, at least partly through endothelin 1/endothelin receptor A cascade.

Topics: Angiotensin II; Animals; Anti-Inflammatory Agents; Atrial Natriuretic Factor; Cardiomegaly; Cells, Cultured; Disease Models, Animal; Endothelin-1; Fibrillar Collagens; Fibroblasts; Fibrosis; Heart Diseases; Inflammation; Inflammation Mediators; Infusions, Intravenous; Macrophages; Male; Mitral Valve; Myocardial Contraction; Myocardium; Rats; Rats, Inbred WKY; Receptor, Endothelin A; Signal Transduction; Stroke Volume; Time Factors; Ventricular Function, Left; Ventricular Remodeling

Atrial natriuretic peptide (ANP) is a cardiovascular biomarker that might be useful in assessing the severity of cardiac disease in horses. Plasma ANP concentrations (Cp(ANP)) were compared between horses with heart disease but normal chamber size and function (Group A; n=6), horses with heart disease associated with left atrial (LA) enlargement, LA dysfunction, and/or left ventricular (LV) enlargement (Group B; n=5), and horses with no clinically apparent cardiovascular disease (Group C; n=13). The median (min-max) for Cp(ANP) was significantly higher in Group B (53.5 (36.0-70.7) pg/mL), compared to Group A (12.5 (6.3-19.8) pg/mL) and Group C (13.4 (7.2-34.0) pg/mL). Backwards stepwise multiple linear regression showed that Cp(ANP) in horses with heart disease was related to LA dimensions, but not to LV size, LA function, and LV function. The results indicated that Cp(ANP) in horses might be useful in detecting LA enlargement and that Cp(ANP) could be related to the severity of cardiac disease. Larger prospective studies are necessary to confirm these results.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Female; Heart Diseases; Horse Diseases; Horses; Male; Pilot Projects; Ultrasonography

Topics: Animals; Atrial Natriuretic Factor; Female; Heart Diseases; Horse Diseases; Male

Various heart diseases present with sudden death; however, it is difficult to interpret the severity of or difference in respective preexisting and terminal cardiac dysfunction based on conventional morphology. The present study investigated the cardiac pathophysiology employing quantitative mRNA measurement of atrial and brain natriuretic peptides (ANP and BNP) in the myocardium as markers of cardiac strain, using autopsy materials consisting of acute ischemic heart disease (AIHD, n=40) with/without the pathology of apparent myocardial necrosis (n=19/21), recurrent myocardial infarction (RMI, n=19), chronic congestive heart disease (CHD, n=11) and right ventricular cardiomyopathy (RVC, n=5), as well as hemopericardium (HP, n=11) due to myocardial infarction (n=5) and aortic rupture (n=6), and acute pulmonary thromboembolism (PTE, n=5). Cardiac death groups showed higher ANP and/or BNP mRNA expressions in the left ventricle than acute fatal bleeding (sharp instrumental injury; n=15) and/or mechanical asphyxiation (strangulation; n=10). AIHD and RMI cases had similar ANP and BNP mRNA expressions in bilateral ventricular walls, but their bilateral atrial levels were lower in RMI. RVC showed higher mRNA expressions of posterior left ventricular BNP, and right ventricular and bilateral atrial ANP and BNP. HP cases had lower BNP mRNA expression in the right ventricular wall, but PTE showed lower ANP and BNP mRNA expressions in the left ventricular wall; however, these mRNA expressions at other sites were similar to those of AIHD. CHD presented findings similar to those of AIHD, but the pericardial BNP level was significantly increased. These observations indicate characteristic molecular biological responses of myocardial natriuretic peptides in individual heart diseases and suggest the possible application of molecular pathology to demonstrate cardiac dysfunction even after death.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Death, Sudden, Cardiac; Female; Forensic Pathology; Heart Atria; Heart Diseases; Heart Ventricles; Humans; Lung; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Organ Size; Pulmonary Embolism; RNA, Messenger

To determine whether measurement of plasma atrial natriuretic peptide (ANP) concentration could be used to identify heart disease in dogs and to assess disease severity in affected dogs.. Cross-sectional study.. 37 healthy dogs and 78 dogs with heart disease.. Dogs were divided into 5 groups on the basis of plasma ANP concentration: healthy, ANP-1 (< 50 pg/mL; n = 19), ANP-2 (50 to 100 pg/mL; 24), ANP-3 (101 to 200 pg/mL; 20), and ANP-4 (> 200 pg/mL; 15). All dogs underwent physical examination, echocardiography, thoracic radiography, and blood sampling before treatment.. Compared with healthy dogs, dogs with increased plasma ANP concentration had significant concomitant increases in heart rate, cardiothoracic ratio, vertebral heart score, fractional shortening, ratio of left atrial-to-aortic root diameter, and mitral early diastolic flow (E wave) velocity and a significant decrease in relative wall thickness. Use of plasma ANP concentration > 25 pg/mL to identify dogs with heart disease (International Small Animal Cardiac Health Council class > I) had a sensitivity of 91.0% and specificity of 94.7%. Use of plasma ANP concentration > 100 pg/mL to identify dogs with International Small Animal Cardiac Health Council class IIIb heart disease had a sensitivity of 81.0% and specificity of 81.1 %.. Results may provide reference values for plasma ANP concentration in dogs and suggest that plasma ANP concentration may help to distinguish dogs with cardiac disease from clinically normal dogs. Measurement of plasma ANP concentration may be a useful marker for predicting the severity of heart disease in dogs.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Dog Diseases; Dogs; Female; Heart Diseases; Male

Topics: Acute Coronary Syndrome; Americas; Atrial Natriuretic Factor; Biomarkers; Dyspnea; Early Diagnosis; Emergency Service, Hospital; Europe; Heart Diseases; Heart Failure; Humans; Hypertension, Pulmonary; Intensive Care Units; Japan; Myocardial Infarction; Natriuretic Peptide, Brain; Patient Discharge; Peptide Fragments; Practice Guidelines as Topic; Predictive Value of Tests; Prognosis; Survival Rate; Troponin; Ventricular Dysfunction, Left

Patients with liver cirrhosis suffer various degrees of cardiac dysfunction which may be crucial in determining the outcome of surgery. The aim of this study was to determine the role of natriuretic peptides on the assessment of cardiac dysfunction in patients with liver cirrhosis.. Prospective longitudinal study of 30 patients with hepatic cirrhosis. Severity of disease was assessed according to the Child-Turcotte-Pugh and Model for End Stage Liver Disease (MELD) scores. Cardiac function was assessed using endocrine markers [atrial natriuretic peptide-brain natriuretic peptide (BNP)] and isotopic ventriculography at baseline and after stimulation with dobutamine.. The ejection fraction was higher in patients with Child A+B and MELD less than 18 than in patients with advanced liver disease. A significant correlation between BNP plasma levels and MELD values was observed. Dobutamine induced a marked improvement in myocardial performance associated to a decrease in BNP levels. Multivariate analysis showed that BNP has prognostic value as a marker of cardiac ejection fraction. Patients whose baseline BNP concentrations were more than 70 pg/ml had an ejection fraction of around 45%.. This study has shown that increased baseline BNP concentrations may be regarded together with high Child and MELD scores, as the critical cardiac dysfunction threshold in cirrhotic patients.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Dobutamine; Female; Heart Diseases; Heart Rate; Humans; Liver Cirrhosis; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Radionuclide Ventriculography; Severity of Illness Index; Spain; Stroke Volume

Although renal dysfunction influences the threshold values of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in diagnosis of cardiac-related dyspnea (CRD), its effects on midregional pro-atrial natriuretic peptide (MR-proANP) threshold values are unknown. We evaluated the impact of renal function on MR-proANP concentrations and compared our results to those of BNP and NT-proBNP.. MR-proANP, BNP, and NT-proBNP concentrations were measured in blood samples collected routinely from dyspneic patients admitted to the emergency department. Patients were subdivided into tertiles based on their estimated glomerular filtration rate [eGFR, in mL · min(-1) · (1.73 m(2))(-1)]: tertiles 1 (<44.3), 2 (44.3-58.5), and 3 (≥58.6).. Of 378 patients studied, 69% (n = 260) had impaired renal function [<60 mL · min(-1) · (1.73 m(2))(-1)] and 30% (n = 114) had CRD. MR-proANP, BNP, and NT-proBNP concentrations were significantly increased in patients with impaired renal function. In each tertile, all peptides remained significantly increased in CRD patients by comparison with non-CRD patients. By ROC analysis, MR-proANP, BNP, and NT-proBNP threshold values for the diagnosis of CRD increased as eGFR decreased from tertile 3 to tertile 1. Areas under the ROC curve for all peptides were significantly lower in tertile 1. Using adapted thresholds, MR-proANP, BNP, and NT-proBNP remained independently predictive of CRD, even in tertile 1 patients.. Renal function influences optimum cutoff points of MR-proANP for the diagnosis of CRD. With use of an optimum threshold value adapted to the eGFR category, MR-proANP remains as effective as BNP and NT-proBNP in independently predicting a diagnosis of CRD in the emergency department.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Dyspnea; Emergency Service, Hospital; Female; Glomerular Filtration Rate; Heart Diseases; Humans; Kidney; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Female; Heart Diseases; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Pilot Projects; Predictive Value of Tests; Protein Precursors; Risk Factors; Stroke

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiac Surgical Procedures; Creatinine; Heart Diseases; Humans; Kidney; Kidney Diseases; Reproducibility of Results; Research Design; Treatment Outcome

Glucocorticoid is widely used as an anti-inflammatory drug in various diseases however excess of it often causes cardiovascular complications. The present study was undertaken to understand the molecular mechanism of glucocorticoid-induced cardiac dysfunction.. Rats were treated daily with synthetic glucocorticoid, dexamethasone with or without mifepristone or losartan up to 15 days. Hemodynamic parameters were measured by PV-loop method using Millar's instrument. Cardiac remodelling, fibrosis and oxidative stress were monitored after 15 days.. The systolic blood pressure was increased whereas the heart beat and cardiac output (n=6) were decreased by dexamethasone. Dexamethasone caused increase in the heart weight to body weight ratio (P<0.001, n=20), increased level of mRNA of atrial natriuretic peptide and an increased deposition of collagens in the extracellular matrix of the left ventricle which were inhibited by both mifepristone and losartan. The rate of oxygen consumption was decreased in association with increased levels of hypoxia inducible factor 1alpha, lipid peroxidation (P<0.01, n=3) and superoxide dismutase activity (P<0.01, n=3) in dexamethasone treated rat heart. All these changes were reversed by mifepristone and losartan.. The excess of glucocorticoid induces cardiac remodelling and pathophysiolgical changes of the myocardium via angiotensin II signalling pathway.

Topics: Angiotensin II; Animals; Anti-Inflammatory Agents; Atrial Natriuretic Factor; Collagen; Dexamethasone; Glucocorticoids; Heart Diseases; Hypoxia-Inducible Factor 1, alpha Subunit; Lipid Peroxidation; Male; Myocardium; Oxygen Consumption; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Signal Transduction; Superoxide Dismutase

Topics: Atrial Natriuretic Factor; Cyclic GMP; Heart Diseases; Humans; Receptors, Atrial Natriuretic Factor

Nppa, encoding atrial natriuretic factor, is expressed in fetal atrial and ventricular myocardium and is downregulated in the ventricles after birth. During hypertrophy and heart failure, Nppa expression is reactivated in the ventricles and serves as a highly conserved marker of heart disease. The Nppa promoter has become a frequently used model to study mechanisms of cardiac gene regulation. Nevertheless, the regulatory sequences that provide the correct developmental pattern and ventricular reactivation during cardiac disease remain to be defined. We found that proximal Nppa fragments ranging from 250 bp to 16 kbp provide robust reporter gene activity in the atria and correct repression in the atrioventricular canal and the nodes of the conduction system in vivo. However, depending on fragment size and site of integration into the genome of mice, the fetal ventricular activity was either absent or present in an incorrect pattern. Furthermore, these fragments did not provide ventricular reactivation in heart disease models. These results indicate that the proximal promoter does not provide a physiologically relevant model for ventricular gene activity. In contrast, 2 modified bacterial artificial chromosome clones with partially overlapping genomic Nppa sequences provided appropriate reactivation of the green fluorescent protein reporter during pressure overload-induced hypertrophy and heart failure in vivo. However, only 1 of these bacterial artificial chromosomes provided correct fetal ventricular green fluorescent protein activity. These results show that distinct distal regulatory sequences and divergent regulatory pathways control fetal ventricular activity and reactivation of Nppa during cardiac disease, respectively.

Topics: Animals; Atrial Natriuretic Factor; Atrioventricular Node; Disease Models, Animal; Gene Expression Regulation, Developmental; Heart Atria; Heart Diseases; Heart Ventricles; Male; Mice; Mice, Transgenic; Natriuretic Peptide, C-Type; Promoter Regions, Genetic; Protein Precursors

Topics: Atrial Natriuretic Factor; Child, Preschool; Heart Diseases; Humans; Infant; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type

To determine whether serum N-terminal pro-B-type natriuretic (NT-proBNP) concentration could be used to identify cardiac disease in dogs and to assess disease severity in affected dogs.. Cross-sectional study.. 119 dogs with mitral valve disease, 18 dogs with dilated cardiomyopathy, and 40 healthy control dogs.. Serum NT-proBNP concentration was measured with an ELISA validated for use in dogs. Results of physical examination, thoracic radiography, echocardiography, and serum biochemical analyses were recorded for dogs with cardiac disease.. Serum NT-proBNP concentration was significantly higher in dogs with cardiac disease than in control dogs, and a serum NT-proBNP concentration > 445 pmol/L could be used to discriminate dogs with cardiac disease from control dogs with a sensitivity of 83.2% and specificity of 90.0%. In dogs with cardiac disease, serum NT-proBNP concentration was correlated with heart rate, respiratory rate, echocardiographic heart size, and renal function. For dogs with cardiac disease, serum NT-proBNP concentration could be used to discriminate dogs with and without radiographic evidence of cardiomegaly and dogs with and without congestive heart failure.. Results suggested that serum NT-proBNP concentration may be a useful adjunct clinical test for diagnosing cardiac disease in dogs and assessing the severity of disease in dogs with cardiac disease.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathy, Dilated; Case-Control Studies; Diagnosis, Differential; Dog Diseases; Dogs; Enzyme-Linked Immunosorbent Assay; Female; Heart Diseases; Heart Valve Diseases; Male; Protein Precursors; Reproducibility of Results; Sensitivity and Specificity; Severity of Illness Index

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in the blood are clinical markers for the diagnosis of cardiac failure. This study was a comprehensive analysis of the postmortem pericardial levels of the natriuretic peptides in serial medico-legal autopsy cases (n=263, within 72 h postmortem) to assess their validity in investigating cardiac function. There was no significant relationship of pericardial ANP or BNP levels with postmortem time or the age of the subjects. The ANP and BNP levels showed negative correlations with the pericardial cardiac troponin T level. The ANP level was significantly elevated in drowning cases. Pericardial BNP and the BNP/ANP ratio were significantly higher for chronic congestive heart disease. However, asphyxiation, sharp instrument injury, hyperthermia, and fatal MA poisoning cases showed lower levels for both markers. These observations suggest that elevations in the postmortem pericardial ANP and BNP may mainly depend on acute atrial overload and subacute or chronic cardiac failure, respectively, and may be reduced by advanced myocardial damage.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Autopsy; Biomarkers; Cause of Death; Female; Heart Diseases; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pericardium; Radioimmunoassay; ROC Curve; Sensitivity and Specificity; Troponin T

Plasma brain natriuretic peptide (BNP) is elevated in asymptomatic patients with various cardiac abnormalities. We tested the hypothesis that measuring BNP is useful for detecting asymptomatic patients with cardiac abnormalities who are not identified by conventional health check-up programmes.. From 2001 to 2002, 6189 subjects (women 34.0%; mean age 56.6 years) underwent multiphasic health check-ups in our hospital, of which 4818 without cardiac abnormalities as revealed by the health check-up were enrolled in the present study. Their plasma concentrations of BNP were measured.. Plasma concentrations of BNP were higher than the normal reference upper limit of our hospital (21.3 pg mL(-1)) in 925 of the 4818 subjects. Echocardiography was performed in 471 subjects who were randomly selected from the 925 subjects with elevated BNP. Abnormal findings were detected in 174 subjects, comprising valvular heart disease in 83, systolic dysfunction in 10, diastolic dysfunction in 54, left ventricular hypertrophy in 41, left ventricular enlargement in 11, left atrial enlargement in 13 and paroxysmal atrial fibrillation in 3.. Since BNP measurement identifies additional subjects with cardiac abnormalities, it is useful for detecting asymptomatic cardiac abnormalities among apparently healthy subjects, and is suitable for use in high-quality mass screening.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Echocardiography; Female; Heart Diseases; Humans; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies

Insertion (I)/deletion (D) polymorphisms in the angiotensin-converting enzyme (ACE) gene have the potential to serve as a marker for an increased risk of cardiovascular events. Increased plasma levels of human atrial natriuretic polypeptide (ANP) and brain natriuretic polypeptide (BNP) are important indexes of cardiac function. The aim of this study was to examine possible relationships between I/D polymorphisms and the myocardial release of ANP and BNP in Japanese hemodialysis (HD) patients (n=131).. We studied 131 non-diabetic hemodialysis patients. The genotype of ACE gene was determined by polymerase chain reaction with a set of specific timers. ANP and BNP levels were measured before HD.. The plasma levels of ANP and BNP were significantly lower in the DD genotype group compared to those in the II group. Corresponding levels in the ID genotype group were intermediate between those in the DD and II groups. ACE polymorphism was associated with neither ejection fraction nor left ventricular mass/height index (LVMI), as evidenced by echocardiographic findings (n=107). Plasma levels of ANP were significantly correlated with left atrial diameter (LAD) in patients as a whole, but this correlation was only observed in the II genotype group, and not in the DD or ID groups. Plasma levels of BNP were significantly correlated with LAD, left ventricular end systolic diameter and LVMI in patients as a whole, but these correlations were seen only in the II genotype group.. The results suggest that the plasma levels of these natriuretic peptides should be evaluated on the basis of ACE polymorphism for assessing cardiac diseases due to volume overload in Japanese HD patients.

Topics: Atrial Natriuretic Factor; Female; Heart Diseases; Humans; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Renal Dialysis; Ultrasonography

Biomarkers are not established for cardiovascular phenotyping in mice. We compared the use of echocardiography with the determination of N-terminal propeptide of the atrial natriuretic peptide (Nt-proANP) and osteopontin (Opn). We measured plasma Nt-proANP and Opn levels in (1) the inbred strains C57BL/6, BALB/c, C3H/He, DBA/2, FVB/N, 129S1/Sv; (2) a surgical model of nonischemic myocardial infarction; and (3) delta-sarcoglycan (Sgcd) and calsarcin 1 [also known as myozenin 2 (Myoz2)] knockout models of cardiomyopathy. Left ventricular function was assessed as fractional shortening (FS) by echocardiography in conscious mice. Plasma Nt-proANP exhibited marked variability and ranged from 0.31 +/- 0.19 (C57BL/6 male mice) to 1.34 +/- 0.43 nmol/l (DBA/2 female mice), depending on sex, age, and genetic background. Opn was less variable than Nt-proANP and was decreased significantly in C3H/He and DBA/2 throughout the 16 wk of study. Nt-proANP increased temporarily in mice with myocardial injury. In contrast, Opn increased in both operated and sham-treated mice. Nt-proANP was inversely correlated with FS and distinguished controls from Sgcd and Myoz2 mutants with 100% sensitivity and 71% specificity. Opn was increased in Sgcd mutants, which exhibited only mildly reduced FS but marked myocardial degeneration and fibrosis. Both of these histologic features were absent in Myoz2 mutants. Nt-proANP is an early marker of cardiac disease and is suitable for age- and sex-matched comparisons between groups of transgenic and matched control mice. Opn is useful to detect inflammatory and degenerative myocardial disorders that may be missed by echocardiography.

Topics: Aging; Animals; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathies; Carrier Proteins; Disease Models, Animal; Female; Heart Diseases; Male; Mice; Mice, Inbred Strains; Mice, Knockout; Microfilament Proteins; Muscle Proteins; Osteopontin; Phenotype; Sarcoglycans; Species Specificity; Ventricular Remodeling

Nonenzymatic glycation that results in the production of early-glycation Amadori-modified proteins and advanced-glycation end products may be important in the pathogenesis of diabetic complications. However, the effects of early-glycated proteins, such as glycated serum albumin (Gly-BSA), are poorly defined. In this study, we investigated the effects of Gly-BSA on reactive oxygen species (ROS) production by cardiomyocytes.. Cultured neonatal rat cardiomyocytes were incubated with Gly-BSA or vehicle (bovine serum albumin [BSA]) for up to 48 hours. Gly-BSA dose-dependently increased in situ ROS production (whole-cell dichlorodihydrofluorescein fluorescence), with an optimum effect at 400 microg/mL after 24-hour incubation (152+/-10% versus BSA 100%; P<0.01). Treatment with the NADPH oxidase inhibitor apocynin, a Nox2 (gp91phox) antisense oligonucleotide (Nox2 AS), or the peptide gp91ds-tat significantly reduced Gly-BSA-induced ROS production at 24 hours (68.5+/-2.2%, 61.4+/-8.3%, and 53.2+/-5.4% reduction, respectively). NADPH-dependent activity in cell homogenates was also significantly increased by Gly-BSA at 24 hours (161+/-8% versus BSA) and was inhibited by diphenyleneiodonium, apocynin, NOX2AS, and the protein kinase C inhibitor bisindolylmaleimide I but not by a nitric oxide synthase inhibitor or mitochondrial inhibitors. Furthermore, bisindolylmaleimide I prevented Gly-BSA-stimulated Rac1 translocation, an essential step for NADPH oxidase activation. Gly-BSA-induced increases in ROS were associated with apocynin-inhibitable nuclear translocation of nuclear factor-kappaB and an increase in atrial natriuretic factor mRNA expression.. Gly-BSA stimulates cardiomyocyte ROS production through a protein kinase C-dependent activation of a Nox2-containing NADPH oxidase, which results in nuclear factor-kappaB activation and upregulation of atrial natriuretic factor mRNA. These findings suggest that early-glycated Amadori products may play a role in the development of diabetic heart disease.

Topics: Active Transport, Cell Nucleus; Animals; Atrial Natriuretic Factor; Cells, Cultured; Diabetes Complications; Glycoproteins; Heart Diseases; Humans; Membrane Glycoproteins; Myocytes, Cardiac; NADPH Oxidase 2; NADPH Oxidases; NF-kappa B; Rats; Reactive Oxygen Species; Serum Albumin, Bovine; Up-Regulation

The most energy-requiring organ in the body, the cardiac muscle, relies primarily on lipoprotein-derived fatty acids. Prenatal loss of cardiac lipoprotein lipase (LPL) leads to hypertriglyceridemia, but no cardiac dysfunction, in young mice. Cardiac specific loss of LPL in 8-wk-old mice was produced by a 2-wk tamoxifen treatment of MerCreMer (MCM)/Lpl(flox/flox) mice. LPL gene deletion was confirmed by PCR analysis, and LPL mRNA expression was reduced by approximately 70%. One week after tamoxifen was completed, triglyceride was increased with LPL deletion, 162 +/- 53 vs. 91 +/- 21 mg/dl, P < 0.01. Tamoxifen treatment of Lpl(flox/flox) mice did not cause a significant increase in triglyceride levels. Four weeks after tamoxifen, MCM/Lpl(flox/flox) mice had triglyceride levels of 190 +/- 27 mg/dl, similar to those of mice with prenatal LPL deletion. One week after the tamoxifen, MCM/Lpl(flox/flox), but not Lpl(flox/flox), mice had decreases in carnitine palmitoyl transferase I mRNA (18%) and pyruvate dehydrogenase kinase 4 mRNA (38%). These changes in gene expression became more robust with time. Acute loss of LPL decreased ejection fraction and increased mRNA levels for atrial natriuretic factor. Our studies show that acute loss of LPL can be produced and leads to rapid alteration in gene expression and cardiac dysfunction.

Topics: Animals; Atrial Natriuretic Factor; Carnitine O-Palmitoyltransferase; Cholesterol; Dyslipidemias; Echocardiography; Estrogen Antagonists; Fatty Acid Synthases; Gene Expression; Glucose; Heart Diseases; Integrases; Lipoprotein Lipase; Male; Mice; Mice, Knockout; Mice, Transgenic; Myocardium; PPAR gamma; Pyruvate Dehydrogenase Complex; RNA, Messenger; Tamoxifen; Triglycerides

Plasma N-terminal pro-brain natriuretic peptide (NTproBNP) is a sensitive marker for heart failure. This study tested whether the preoperative plasma level of NTproBNP could predict cardiac complications in patients undergoing non-cardiac surgery.. A total of 190 consecutive patients who underwent elective non-cardiac surgery that required general anaesthesia were studied. In addition to routine preoperative evaluation, a blood sample was taken for estimation of plasma NTproBNP concentration. Postoperative cardiac complications were defined as cardiac death, acute coronary syndrome, heart failure and haemodynamic compromise from cardiac arrhythmias.. Fifteen of the 190 patients had a cardiac complication: four had acute coronary syndrome and 13 had congestive heart failure. NTproBNP concentration was significantly higher in patients with a cardiac complication; a level greater than 450 ng/l was predictive of cardiac complications with a sensitivity of 100 per cent and a specificity of 82.9 per cent. Other factors associated with cardiac complications were a higher American Society of Anesthesiologists grade, age and clinical cardiac impairment, but in a multivariate analysis NTproBNP level was the only independent factor.. Preoperative plasma NTproBNP concentration may be an independent predictor of cardiac complications in patients undergoing non-cardiac surgery.

Topics: Atrial Natriuretic Factor; Biomarkers; Elective Surgical Procedures; Female; Heart Diseases; Humans; Male; Middle Aged; Multivariate Analysis; Postoperative Complications; Preoperative Care; Protein Precursors; Risk Factors

Aim of the study was to evaluate the role of atrial (ANP) and brain natriuretic peptides (BNP) as markers of preclinical cardiac disease in obesity.. We selected 26 obese (BMI > 29 kg m(-2)) never-treated hypertensives (24-h BP > 140 and/or 90 mmHg), 26 obese normotensives (24-h BP < 130/80 mmHg) and 25 lean (BMI < or = 25 kg m(-2)) never-treated hypertensives. Each subject underwent measurements of ANP and BNP plasma levels, 24-h ambulatory blood pressure (BP) monitoring, digitized M-mode and Doppler echocardiography.. Mean values of ANP and BNP were similar among the three groups. All the subjects had normal left ventricular (LV) systolic function. Within each group ANP levels were higher in patients with LV diastolic dysfunction than in patients with normal diastolic function, and BNP levels were higher in patients with LV hypertrophy and in patients with LV diastolic dysfunction. Within each group, ANP levels were inversely correlated with LV diastolic indices, whereas BNP levels were directly correlated with LV mass index and inversely correlated with LV diastolic indices. ANP and BNP levels were not correlated with other echocardiographic parameters, age, BMI or 24-h BP values.. In normotensive and hypertensive obese subjects the relationships of ANP and BNP levels with LV morpho-functional characteristics follow the same trend as in lean hypertensives, with ANP mainly influenced by diastolic dysfunction and BNP influenced by both LV hypertrophy and LV diastolic dysfunction. Therefore ANP and BNP can be considered useful markers of preclinical cardiac disease in obesity.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Female; Heart Diseases; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Ventricular Dysfunction, Left; Ventricular Function, Left

Patients with heart disease are at risk of developing congestive heart failure (CHF). Neurohormonal activation may make an important contribution.. In stable heart patients from primary care, to examine neuroendocrine markers of cardiac performance for the association to cardiac dysfunction, morbidity and mortality.. Plasma N-terminal atrial natriuretic peptide (N-ANP), catecholamines, 24-h ECG and blood pressure, serum urea and creatinine, echocardiography, chest X-ray and physical examination were performed. Death was recorded during 5 to 7 years of follow-up.. The study included 56 patients. Mean age was 71 years, 54% were men, 43% had clinical signs of CHF, 39 + 52 + 9% were in NYHA I + II + III, 34% had echocardiographic cardiac dysfunction, and 18 died during follow-up. N-ANP was related to all subtypes of cardiac dysfunction (p < 0.05). Catecholamines and premature ventricular captures (PVC) were related to valvular and systolic dysfunction, but heart rate variability and dipping blood pressure were not (p > 0.05). On multivariate analyses only, N-ANP and PVC were associated with clinical signs of CHF, echocardiographic cardiac dysfunction, and mortality (p < 0.05).. Plasma N-ANP was stronger than catecholamines and variables of 24-h monitoring (blood pressure and electrocardiogram) in predicting morbidity and mortality, thereby supporting the use of cardiac natriuretic peptides (i.e. N-ANP, BNP, or N-BNP) as the most valuable biomarker in community patients at risk of CHF.

Topics: Adult; Aged; Atrial Natriuretic Factor; Community Health Services; Epinephrine; Female; Heart Diseases; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Morbidity; Norepinephrine; Prognosis; Protein Precursors; Severity of Illness Index

N-terminal pro-B type natriuretic peptide (NTpBNP) is a potential marker of cardiac failure.. The Roche Elecsys(trade mark) 1010 and 2010 assays for NTpBNP were evaluated for precision, sample stability, and correlation between sample types and with other natriuretic peptides. Samples from 290 individuals aged 45-89 years with no cardiovascular risk factors, renal failure, electrocardiogram changes, evidence of structural abnormalities, or wall motion abnormalities on echocardiography and with an ejection fraction >50% were used to provide reference NTpBNP ranges.. The intra-assay imprecision was <10% across the analytical range and >3% at all concentrations analysed <30 ng/L. Inter-assay imprecision was 5.3-6.7% on the Elecsys 1010 and 4.4-5.0% on the Elecsys 2010, in the range 380-13000 ng/L. There was no statistically significant change in NTpBNP following storage in whole-blood samples at room temperature for 24 h before centrifugation; serum samples at room temperature for 7 days, at 4 degrees C for up to 11 days on clot-activation gel or 22 days separated from the gel. NTpBNP concentrations were stable throughout five freeze-thaw cycles. There was a close correlation between NTpBNP concentrations in matched serum, EDTA plasma and lithium-heparin plasma samples. NTpBNP and BNP were more closely associated than were N-terminal proatrial natriuretic peptide and NTpBNP. This association was stronger at lower concentrations. NTpBNP concentrations increased with age, with values higher in women than men.. NTpBNP is a stable molecule that can be measured easily and precisely using the Roche Elecsys 1010 or 2010 immunoassay analysers.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Female; Heart Diseases; Humans; Immunoassay; Male; Middle Aged; Peptide Fragments; Protein Precursors

Twenty-three dogs with heart failure were evaluated in a 12-month study by measuring baseline plasma atrial natriuretic peptide (ANP) concentrations. Ten dogs were classified as having mild to moderate cardiac disease (group 1) and 13 dogs were classified as having severe cardiac disease (group 2). The mean plasma ANP concentration for the group 1 dogs was 64 +/- 45 pg/mL and for the group 2 dogs, 328 +/- 122 pg/mL. The median survival time (1,095 d) for group 1 dogs was significantly greater (P < 0.05) than for group 2 dogs (58 d). A significantly (P < 0.05) greater median survival was noted for dogs with plasma ANP < 95 pg/mL (1095 d) compared with those with ANP > 95 pg/mL (58 d). Plasma ANP concentrations are a potential noninvasive predictor of survival in dogs with heart failure.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Dog Diseases; Dogs; Heart Diseases; Predictive Value of Tests; Prognosis; Prospective Studies; Radioimmunoassay; Survival Analysis

It is well known that plasma atrial natriuretic peptide (ANP) is an indicator of extracellular fluid volume expansion and that plasma ANP is considered to be a marker for setting the proper dry weight of HD patients. Although the plasma ANP is a prognostic predictor of cardiac death, the prognostic role of ANP in HD patients has yet to be elucidated. In this study, we investigated the prognostic role of ANP in HD patients.. Plasma ANP concentrations were measured in 105 HD patients after HD. Multiple regression analysis was performed to determine the major factors causing increased plasma ANP concentrations. Cardiac mortality was monitored for 24 months after baseline analysis, and the prognostic role of ANP was examined by Cox proportional hazards regression analysis.. Multiple regression analysis showed that cardiovascular disease (CD) and age were independent factors for elevated ANP (R2 = 0.298, p < 0.0001). During a 24-month follow-up period, cardiac death occurred in 11 patients. Kaplan- Meier survival estimates of patients from varying plasma ANP levels (<50 and >50 pg/ml) differed between the two groups (p < 0.0001). The group with the higher ANP level (>50 pg/ml) had the lower survival. When compared with patients with ANP <50, the hazard ratios for cardiac death of patients with ANP of >50 pg/ml were 32.0 (95% confidence interval (CI) 4.1 to 252.4). Univariate Cox proportional hazards model showed that ANP, left ventricular ejection fraction (LVEF), LVMI, age, serum albumin and C-reactive protein (CRP) were significantly associated with the risk of cardiac mortality. By stepwise multivariate Cox proportional hazards analysis, only ANP, LVMI and CRP remained powerful independent predictors of cardiac death. The relative risk ratios were 3.483 (95% CI 1.640-7.397) for ln ANP, 1.023 (1.008-1.038) for LVMI, and 1.379 (1.115-1.705) for CRP.. High plasma ANP level of post-HD were strongly associated with CD and age. Post-HD ANP level may be a reliable parameter for assessing the risk for cardiac death in HD patients by providing prognostic information independent of other variables previously reported.

Topics: Aged; Atrial Natriuretic Factor; Cardiovascular Diseases; Female; Follow-Up Studies; Heart Diseases; Humans; Male; Middle Aged; Prognosis; Regression Analysis; Renal Dialysis; Survival Analysis

The natriuretic peptides and their role in neurohumoral regulation of the cardiovascular system have become the focus of considerable interest from the scientific and clinical community in recent years. BNP in particular has been shown to be an important diagnostic and prognostic marker of use in a wide range of applications. As measurement techniques develop and are refined, routine evaluation of serum levels of these markers is expected to become more widespread. We have reviewed the biochemistry of the natriuretic peptide family, their role in cardiovascular pathophysiology and the evidence supporting their use in the clinical setting.

Topics: Atrial Natriuretic Factor; Biomarkers; Heart Diseases; Humans; Natriuretic Peptide, Brain

heart failure is primarily a disease of elderly people. Current guidelines suggest all patients with suspected heart failure should undergo objective assessment, usually by echocardiography. In the UK resources are limited and not all patients have access to echocardiography. The electrocardiogram is widely used as a pre-screening investigation. Recently the natriuretic peptides have been shown to correlate well with left ventricular function, and evidence is accumulating which suggests that B-type natriuretic peptide may have a role in detecting cardiovascular disease. Elderly patients attending day hospital often have non-specific cardiovascular symptoms. B-type natriuretic peptide measurement in parallel with conventional electrocardiogram, may offer a novel method of identifying those with significant cardiac disease, which may warrant treatment. This study assessed the role of B-type natriuretic peptide and electrocardiogram in the detection of cardiac disease in patients attending Day Hospital.. prospective cohort study of patients referred to Day Hospital with suspected cardiovascular disease.. this study prospectively evaluated 299 consecutive patients attending day hospital over a period of 13 months. Patients underwent clinical assessment, electrocardiography, echocardiography and natriuretic peptide measurement. Objective evidence of cardiac disease was based on electrocardiogram and echocardiographic findings.. Medicine for the Elderly Day Hospital, Royal Victoria Hospital, Dundee.. sensitivity, specificity, positive and negative predictive values of screening tests for left ventricular systolic dysfunction. Receiver-Operating-Characteristic curves for ability of B-type natriuretic peptide to detect cardiac disease (including left ventricular systolic dysfunction, valvular disease, atrial fibrillation and left ventricular hypertrophy). Mean B-type natriuretic peptide levels with 'incremental' levels of cardiovascular disease.. 299 patients (mean age 79; 65% female) completed the assessment. Ten percent of patients had left ventricular systolic dysfunction but 50% had objective evidence of cardiac disease. B-type natriuretic peptide was significantly elevated in patients with left ventricular systolic dysfunction, atrial fibrillation, left ventricular hypertrophy and valvular disease. Both B-type natriuretic peptide and the electrocardiogram were sensitive in detecting left ventricular systolic dysfunction but lacked specificity. Combining B-type natriuretic peptide with the electrocardiogram improved detection of left ventricular systolic dysfunction. B-type natriuretic peptide levels increased progressively as the number of different cardiac abnormalities increased.. B-type natriuretic peptide may be a useful marker for cardiac disease in patients attending Day Hospital. Half of the patients assessed had cardiac disease detected. Both the electrocardiogram and B-type natriuretic peptide were sensitive in the detection of left ventricular systolic dysfunction but lacked specificity. B-type natriuretic peptide was superior to the electrocardiogram in the detection of valvular disease. If used to pre-screen cardiovascular disease in Day Hospital patients, B-type natriuretic peptide and the electrocardiogram could reduce the need for echocardiography in some patients before implementing evidence-based treatments. B-type natriuretic peptide increases progressively as the number of different cardiac abnormalities increases and this may explain why B-type natriuretic peptide is of such prognostic value in older patients.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Electroencephalography; Female; Geriatric Assessment; Health Services for the Aged; Heart Diseases; Hospitalization; Humans; Male; Natriuretic Peptide, Brain; Prospective Studies

We have previously demonstrated that changes in myosin heavy chain (MHC) isoforms that occur in failing human hearts resemble the pattern produced in rodent myocardium in response to hypothyroidism. Because thyroid hormone status is usually within normal limits in these patients, we hypothesized that failing/hypertrophied human myocardium might have a defect in thyroid hormone signaling due to alterations in expression of thyroid hormone receptors (TRs).. To examine this hypothesis, we used RNase protection assay to measure mRNA levels of TRs in failing left ventricles that exhibited a fetal pattern of gene expression, ie, decreased expression of alpha-MHC with increased beta-MHC expression compared with left ventricles from age-matched controls. We detected expression of TR-alpha(1), -alpha(2), and -beta(1) isoforms in human left ventricles. In failing left ventricles, TR-alpha(1) was downregulated, whereas TR-alpha(2), a splice variant that does not bind thyroid hormone but inhibits responses to liganded TRs, was increased. Expression levels of TR-beta(1) did not differ significantly between the 2 groups. According to linear regression analysis, expression levels of TR-alpha(1) and -alpha(2) were positively and negatively correlated with those of alpha-MHC, respectively.. We conclude that decreases in TR-alpha(1) and increases in TR-alpha(2) may lead to local attenuation of thyroid hormone signaling in the failing human heart and that the resulting tissue-specific hypothyroidism is a candidate for the molecular mechanism that induces fetal gene expression in the failing human ventricle.

Topics: Adult; Atrial Natriuretic Factor; Female; Fetal Proteins; Gene Expression; Heart Diseases; Humans; Major Histocompatibility Complex; Male; Middle Aged; Receptors, Thyroid Hormone; RNA, Messenger; Signal Transduction

To investigate whether plasma concentrations of atrial natriuretic peptide (ANP) could be used to identify patients with radiation mediated cardiac dysfunction.. Circulating levels of ANP were measured in patients who have been irradiated on a large part of the heart (50-80%; Hodgkin's disease) or smaller part of the heart (20-30%; primary breast cancer). C-terminal ANP was determined by radioimmunoassay (RIA) using a commercial kit.. In this study ANP plasma levels of 121 patients (Hodgkin's disease, 73 patients; breast cancer, 48 patients) and 67 controls were examined. ANP plasma levels of both Hodgkin patients (28.8+/-2.2, P=0.003) and breast cancer patients (20.4+/-2.8 ng/l, P=0.01) were significantly elevated when compared to age-matched controls (13.5+/-1.2 ng/l). Both for the Hodgkin (R=0.42, P=0.05) and breast cancer group (R=0.50, P=0.09) a positive relation between ANP plasma values and age was found. However, no clear relation between ANP plasma levels and time post treatment could be demonstrated. Patients with clinical symptoms of cardiovascular disease (n=25) had significantly higher ANP plasma levels (P<0.001) compared to patients in the same treatment group without evidence of cardiac disease (50.2+/-7.5 vs. 23.3+/-1.3 ng/l, P<0.001, and 38.2+/-12.4 vs. 16.3+/-1.6 ng/l, P<0.001, for Hodgkin's disease and breast cancer, respectively). Eight patients suffered from essential hypertension (n=8), whereas the remaining group of 17 patients showed a variety of cardiac disorders (i.e. myocardial infarction, decreasing ventricular function, and atrial fibrillations). In 11 patients cardiac problems were manifest either before or within a few years after mediastinal therapy. In two patients treated for Hodgkin's disease, and in four patients treated for breast cancer cardiac problems became manifest a long time (>10 years) after radiotherapy. Probably in this group of patients cardiac problems are related to the therapy.. The present study indicates that ANP plasma levels could be used to identify patients with radiation induced cardiac dysfunction.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Breast Neoplasms; Cardiovascular Diseases; Female; Follow-Up Studies; Heart; Heart Diseases; Hodgkin Disease; Humans; Male; Mediastinum; Middle Aged; Radiation Injuries

The predictive value of plasma atrial natriuretic peptide (ANP) on the cardioversion outcome was evaluated in 46 hospitalized patients with recent-onset atrial fibrillation (AF). Cardioversion was successful in 42 (91%) patients, 7 (15%) of them regained sinus rhythm spontaneously. After 12 months, 14 (33%) cardioverted patients were in chronic AF. There were no differences in plasma ANP levels between groups where cardioversion failed, those who cardioverted but later developed chronic AF or those who remained in sinus rhythm. However, among patients who were on antiarrhythmic therapy, ANP levels obtained after cardioversion were lower in those who later remained in sinus rhythm. We conclude that lower ANP after cardioversion may be associated with increased chances of long-term preservation of sinus rhythm.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Atrial Natriuretic Factor; Electric Countershock; Electrocardiography; Heart Diseases; Humans; Male; Middle Aged; Prospective Studies

We examined whether measurement of the plasma BNP concentrations might be useful for the early diagnosis of the existence and severity of disease in patients with heart disease in daily clinical practice.. The plasma BNP and ANP concentrations in 415 patients with heart disease and hypertension and 65 control subjects were measured. Patients with heart disease had higher plasma BNP and ANP concentrations than did those with hypertension or control subjects. Among the etiology of cardiac diseases, specifically dilated cardiomyopathy and hypertrophic cardiomyopathy, was associated with the highest plasma BNP concentrations, whereas dilated cardiomyopathy was associated with the highest plasma ANP concentrations. Plasma BNP concentrations showed an increase as the severity of the heart disease, as graded according to the NYHA classification of cardiac function, increased. In both patients with heart disease and hypertension, the plasma BNP values were higher in those who had abnormalities in their echocardiogram and electrocardiogram as compared to those without any abnormalities. The plasma BNP levels also showed a significant correlation with left ventricular wall thickness and left ventricular mass. On the other hand, the plasma ANP levels showed significant correlations with left ventricular dimension. Receiver operative characteristic analysis revealed that plasma BNP levels showed substantially high sensitivity and specificity to detect the existence of heart diseases.. Measurements of the plasma BNP concentrations is useful to detect the existence of the diseases, and abnormalities of left ventricular function and hypertrophy in patients with heart disease in daily clinical practice.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Heart Diseases; Humans; Hypertension; Natriuretic Peptide, Brain; ROC Curve; Sensitivity and Specificity

Doxorubicin (Dox) is a potent anti-cancer agent with cardiotoxic side-effects but the mechanism of its cardiotoxicity and its effect on expression of the vasoactive atrial natriuretic peptide (ANP), an important marker for cardiac hypertrophy, are little understood. The present study examined Dox-induced changes in vivo in hearts of 6 mongrel dogs and 5 Sprague-Dawley rats and in vitro in cardiac cultures of neonatal rats. Quantitative RT-PCR analysis using gamma 32-p labeled primers for beta-actin, phospholamban (PLB) and ANP showed a selective 5-fold increase of ANP mRNA in Dox-treated dog hearts in comparison to controls. Similarly, northern analysis of GAPD, beta-actin, cardiac alpha-actin and ANP gave a selective 4.5-fold increase in ANP transcripts in Dox-treated rat hearts. On the other hand, there was a selective decrease (approximately 39%) of ANP transcripts in Dox-treated cardiac cultures relative to controls. Immunohistochemistry localized the ANP changes both in tissue sections and in cultures to the cardiomyocytes. The data clearly showed that Dox selectively increases ANP expression in dog and rat hearts in absence of cardiocyte hypertrophy but selectively decreases it in cardiac cultures. This differential effect of Dox on cardiocytes in vivo and in vitro should be a useful parameter for studies of transcriptional control of ANP expression.

Topics: Animals; Antineoplastic Agents; Atrial Natriuretic Factor; Blotting, Northern; Culture Techniques; Dogs; Doxorubicin; Fluorescent Antibody Technique; Gene Expression; Heart Atria; Heart Diseases; Immunohistochemistry; Male; Myocardium; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction

Left atrial/aorta ratio (LA/AO) by echocardiography and the plasma level of atrial natriuretic peptide (ANP) were measured in 32 dogs with left heart insufficiency. There was a significant correlation between plasma ANP concentration and LA/AO (r=0.66, p<0.001). The authors obtained the result that the degree of expansion of the left atrial diameter seemed to have a close relationship with plasma ANP concentration. Plasma ANP concentration decreased when the clinical signs of the patients improved. However, the LA/AO ratio after treatment did not decrease. From these findings, we concluded that plasma ANP concentration has the possibility to become a significant index in the diagnosis and prognosis of heart disease in dogs.

Topics: Animals; Aorta; Atrial Natriuretic Factor; Dog Diseases; Dogs; Echocardiography; Electrocardiography; Female; Heart Atria; Heart Diseases; Male; Radiography, Thoracic

Topics: Atrial Natriuretic Factor; Heart Diseases; Heart Transplantation; Humans; Natriuresis; Natriuretic Peptide, Brain; Predictive Value of Tests

Previous work has described short-term variation in the circulating plasma level of atrial natriuretic peptide (ANP), but the mechanism remains unknown. Our aim was to investigate the role of cardiac innervation in this variability.. Blood samples were obtained from the right atrium via a pulmonary artery flotation catheter every 2 min over a 90 min period. Seven patients who underwent cardiac transplantation by the standard biatrial technique (partial innervation) and ten patients who underwent transplantation by the bicaval technique (total denervation) were studied. ANP levels were measured by radioimmunoassay. The median ANP levels were somewhat higher in the biatrial group compared to the bicaval group [470 (150-1095) vs. 216 (100-605) pg. ml(-1); median (range); P = ns], and both were much higher than normal levels in the pulmonary artery (40 (24, 56) pg ml(-1); median and interquartile range). In both transplant groups circulating plasma ANP levels showed considerable variability. The median number of 'peaks' and 'troughs', as counted by visual inspection, were not significantly different between the two groups. Computer analysis identified 12-16 and 6-15 'pulses' in the biatrial and bicaval group, respectively. Further analysis revealed that pulse amplitude, height and area were significantly higher in the biatrial compared to the bicaval group.. It would appear that variability of circulating plasma levels of ANP is preserved despite complete or partial cardiac denervation, and so a neural mechanism does not appear to account for such variation.

Topics: Adult; Atrial Natriuretic Factor; Chronobiology Phenomena; Female; Heart Diseases; Heart Transplantation; Humans; Male; Middle Aged; Neural Pathways; Postoperative Period

Several peptides derived from the N-terminal sequence of pro-atrial natriuretic peptide (proANP) have been tested successfully as markers of heart disease. We have developed specific and sensitive competitive enzyme immunoassays for fragments [1-30] and [31-67] of proANP. Antisera were raised in sheep against synthetic peptides predicted to be highly immunogenic. Binding specificity was determined by epitope mapping. Microtiter plates were coated with antibody specific for the Fc region of sheep IgG to capture the affinity-purified specific anti-proANP antibodies in an oriented and reproducible form. Synthetic proANP calibrators or diluted samples were incubated simultaneously with biotinylated peptide and binding was quantitated using streptavidin-peroxidase and TMB. Immunoreactive proANP could be measured in diluted plasma, serum and urine. The detection limits of the proANP[1-30] and proANP[31-67] assays were 2.5 and 10 pmol/l respectively. The linearity of samples diluted beyond the recommended assay conditions was good. Recoveries of added standard peptides ranged from 102 to 112%. Circulating concentrations of immunoreactive proANP in 115 healthy subjects ranged from 0.11 to 0.47 nmol/l proANP[1-30] and 0.18 to 0.79 nmol/l proANP[31-67]. In patients with cardiac disease, proANP levels were increased significantly. The reference interval of proANP[31-67] in urine was 0.09 to 1.7 nmol/l, several-fold higher than proANP[1-30] (

Topics: Animals; Atrial Natriuretic Factor; Enzyme Stability; Enzyme-Linked Immunosorbent Assay; Epitope Mapping; Epitopes; Heart Diseases; Humans; Immunoenzyme Techniques; Protein Precursors; Sheep; Time Factors

Early diagnosis and treatment of heart failure lead to improved survival; pre-clinical detection would thus be beneficial. A non-invasive biochemical testing method would indeed be ideal to screen for the condition. In the present study, we sought to determine whether circulating levels of B-type natriuretic peptide (BNP) correlate with cardiac function in asymptomatic subjects. 294 consenting asymptomatic subjects were examined. BNP levels in elevated patients (> 18.4 pg / ml) showed significant correlation with echocardiographic parameters of the systolic and diastolic functions (EF r = -0.51, FS r = -0.50, E/A r = 0.42, p < 0.01). Moderate correlation with the CTR on chest X-ray was also seen (r = 0.23, p < 0.01). Multiple regression analysis showed numerous echocardiographic and hemodynamic parameters including those of systolic and diastolic function in addition to left ventricular wall thickness, blood pressure and serum creatinine levels to be significantly associated with raised BNP levels. Elevated BNP levels reflect cardiac function (both systolic and diastolic) in the asymptomatic population. Detection of cardiac dysfunction by the non-invasive biochemical test may prove useful in early pre-clinical diagnosis of heart failure.

Topics: Atrial Natriuretic Factor; Echocardiography; Electrocardiography; Female; Heart; Heart Diseases; Humans; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Radiography, Thoracic; Regression Analysis; Ventricular Function, Left

A homeodomain-containing transcription factor Csx/Nkx-2.5 is an important regulator of cardiogenesis in mammals. Three different mutants, Gln170ter (designated A) and Thr178Met (designated B) in the helix 2 of the homeodomain and Gln198ter mutation (designated C) just after homeodomain, have been reported to cause atrial septal defect with atrial ventricular block. We here examined the functions of these three mutants of Csx/Nkx-2.5. The atrial natriuretic peptide (ANP) promoter was activated by wild type Csx/Nkx-2.5 (WT, approximately 8-fold), B ( approximately 2-fold), and C ( approximately 6-fold) but not by A. When A, B, or C was cotransfected into COS-7 cells with the same amount of WT, WT-induced activation of the ANP promoter was attenuated by A and B (A > B), whereas C further enhanced the activation. Immunocytochemical analysis using anti-Myc tag antibody indicated that transfected Myc-tagged WT, B, and C were localized in the nucleus of both COS-7 cells and cardiomyocytes of neonatal rats, whereas A was distributed diffusely in the cytoplasm and nucleus in COS-7 cells. Electrophoretic mobility shift assay showed that Csx/Nkx-2.5-binding sequences were bound strongly by WT and C, weakly by B, but not by A. Immunoprecipitation and GST pull-down assay revealed that WT and all mutants interacted with GATA-4. The synergistic activation of the ANP promoter by WT and GATA-4 was further enhanced by C but was inhibited by A and B. In the cultured cardiomyocytes, overexpression of C but not WT, A, or B, induced apoptosis. These results suggest that although the three mutants induce the same cardiac phenotype, transactivation ability and DNA binding ability are different among the three mutants and that apoptosis may be a cause for C-induced cardiac defect.

Topics: Animals; Animals, Newborn; Apoptosis; Atrial Natriuretic Factor; Cell Nucleus; Cells, Cultured; COS Cells; Cytoplasm; DNA-Binding Proteins; Electrophoresis, Polyacrylamide Gel; GATA4 Transcription Factor; Gene Expression Regulation; Genes, Reporter; Glutathione Transferase; Heart Diseases; Heart Septal Defects, Atrial; Homeobox Protein Nkx-2.5; Homeodomain Proteins; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Microscopy, Fluorescence; Mutation; Myocardium; Nuclear Proteins; Phenotype; Plasmids; Precipitin Tests; Promoter Regions, Genetic; Protein Binding; Rats; Receptors, Purinergic P1; Serum Response Factor; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Transfection; Xenopus Proteins

Topics: Animals; Atrial Appendage; Atrial Natriuretic Factor; Disease Models, Animal; Dogs; Goats; Guinea Pigs; Heart Diseases; Hemodynamics; Humans; Hypertrophy; Sheep; Stroke; Thirst; Thrombosis

Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg/m(2). The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity.

Topics: Acute Disease; Adult; Aged; Antibiotics, Antineoplastic; Atrial Natriuretic Factor; Biomarkers; Cardiac Output, Low; Daunorubicin; Female; Heart Diseases; Heart Failure; Heart Function Tests; Humans; Leukemia; Male; Middle Aged; Natriuretic Peptide, Brain; Statistics, Nonparametric

Thirty adult patients with non-Hodgkin's lymphoma who were planned to receive up to 8-10 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) to a cumulative doxorubicin dose of 400-500 mg/m2 were studied to evaluate the value of serial plasma atrial natriuretic peptide (ANP), N-terminal pro-ANP (NT-proANP) and brain natriuretic peptide (BNP) measurements in the early detection of doxorubicin-induced left ventricular dysfunction. Plasma levels of natriuretic peptides were measured before every treatment course and 4 wk after the last one. Cardiac function was monitored with serial radionuclide ventriculography. Twenty-eight patients were evaluable for cardiotoxicity. Clinical heart failure developed in 2 patients (7%). Left ventricular ejection fraction (LVEF) decreased from 58.0+/-1.3% to 49.6+/-1.7% (p <0.001). Plasma levels of ANP increased from 16.4+/-1.3 pmol/l to 22.7+/-2.4 pmol/l (p= 0.002), NT-proANP from 288+/-22 to 380+/-42 pmol/l (p = 0.019) and BNP from 3.3+/-0.4 to 8.5+/-2.0 pmol/l (p = 0.020). There was a significant correlation between the increase in plasma ANP and the decrease in LVEF (r = -0.447, p = 0.029), and a trend towards significance between the increase in NT-proANP and the decrease in LVEF (r=-0.390, p=0.059). The decrease in LVEF started very early and could already be seen after the cumulative doxorubicin dose of 200 mg/m2, whereas the increase in plasma natriuretic peptides was not evident until the cumulative doxorubicin dose of 400 mg/m2. Our results show that neuroendocrine activation - increased concentrations of plasma natriuretic peptides - occurs when left ventricular function has reduced substantially and its compensatory capacity has been exceeded resulting in atrial and ventricular overload. Thus, serial natriuretic peptide measurements cannot be used in predicting the impairment of left ventricular function. On the other hand, our study suggests that natriuretic peptides are useful in the detection of subclinical left ventricular dysfunction in patients receiving doxorubicin therapy.

Topics: Adult; Aged; Antineoplastic Agents; Atrial Natriuretic Factor; Biomarkers; Doxorubicin; Female; Heart Diseases; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Ventricular Function, Left

A 47-year-old man with hypertensive heart disease and left heart failure due to left ventricular diastolic dysfunction was admitted to our hospital because of emergent hypertension. Chest radiography on admission showed slight cardiomegaly and mild pulmonary congestion with right pleural effusion Echocardiography showed concentric hypertrophy and normal contraction of the left ventricular wall Pulsed Doppler left ventricular inflow velocity wave and pulmonary venous flow velocity wave disclosed restrictive filling patterns. After Ca antagonist, nitrate, and diuretics were administered, blood pressure was normalized, and left ventricular inflow velocity wave showed the relaxation abnormality pattern and pulmonary venous flow velocity wave showed the normal pattern. Radioiodinated iodine-123 metaiodobenzyl guanidine (123I-MIBG) imaging in the state of normalized blood pressure showed decreased heart to mediastinum ratio and increased washout rate. Left heart catheterization and angiography revealed normal end-diastolic pressure and coronary arteries, but coronary flow reserve evaluated with Doppler flow wire and intracoronary adenosine triphosphate administration was impaired: Plasma level of atrial and brain natriuretic peptides, which were markedly elevated on admission, decreased with the improvement of heart failure. Doppler flow velocity patterns, plasma levels of atrial natriuretic peptide and brain natriuretic peptide, cardiac sympathetic nerve activity, and coronary flow reserve might be useful for evaluating the severity of left ventricular diastolic dysfunction in patients with hypertensive heart disease.

Topics: Atrial Natriuretic Factor; Calcium Channel Blockers; Coronary Circulation; Diastole; Diuretics; Echocardiography; Echocardiography, Doppler, Pulsed; Heart Diseases; Heart Failure; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nitrates; Radionuclide Imaging; Technetium Tc 99m Sestamibi; Ventricular Dysfunction, Left

In an attempt to identify and quantify the sites of atrial natriuretic peptide (ANP) degradation, a new tracer experiment has been developed. 125I-ANP was injected as a bolus just upstream from the right atrium, and blood was sampled from two different sites (pulmonary artery and aorta) in eight cardiac patients. Data were analyzed using a physiologically based circulatory model consisting of three blocks in series (right heart, lungs and left heart, and periphery) supplied by the same flow (cardiac output, measured by thermodilution); the extraction coefficients of the three blocks and of the whole body could be determined from the areas under tracer concentration curves in plasma (AUCs). The values for AUCs (means +/- SD) were 64.8 +/- 9.4 and 65.5 +/- 10.7% dose.l-1.min-1 for pulmonary artery and aorta curves, respectively; the area under the pulmonary artery curve could be subdivided into the area under the first-pass curve (30.6 +/- 4.7% dose. l-1.min-1) and the area under the recirculating curve (34.0 +/- 7.7% dose.l-1.min-1). The metabolic clearance rate of 125I-ANP, computed as dose divided by the area under the recirculating curve, was 3.1 +/- 0.7 l/min, and the whole body extraction was 47.6 +/- 6.6%. In our patients with myocardial dysfunction, neither right heart block nor lungs and left heart block significantly extracted ANP, and periphery block accounted for almost all removal of the hormone from the blood.

Topics: Adult; Atrial Natriuretic Factor; Female; Heart Diseases; Humans; Iodine Radioisotopes; Kinetics; Male; Middle Aged; Models, Cardiovascular; Radioactive Tracers

The present investigation was designed to determine the levels and circulating forms of peptides derived from Pro Atrial Natriuretic Peptide (ProANP) and to assess their usefulness as markers for severity of heart disease. A sensitive and specific "two-site" immunoradiometric assay (IRMA) for the measurement of C-terminal ProANP 99-126 (alpha ANP) and two radioimmunoassays (RIAs) for the measurement of N-terminal ProANP 31-67 and ProANP 79-98 were developed. Immunoassays were validated by measurement of circulating peptide concentrations in 15 normal volunteers and 44 patients with varying degrees of heart disease. Mean concentrations of immunoreactive (ir) alpha ANP, ProANP 79-98 and ProANP 31-67 in normal volunteers (n = 15) were 8.5 +/- 1.1, 143 +/- 16 and 587 +/- 83 pmoles/l, respectively, increasing in patients with mild heart disease (NYHA I to II; n = 22) to 17.1 +/- 2.1, 691 +/- 197 and 2160 +/- 540 pmoles/l with greatest increases being observed in patients with severe heart disease (NYHA III to IV; n = 22) of 103 +/- 23, 4550 +/- 590 and 10,600 +/- 1350 pmoles/l, respectively. RP-HPLC of pooled plasma revealed peaks corresponding to alpha ANP, beta ANP, ProANP 1-126, ProANP 1-98, ProANP 31-67 and ProANP 79-98, all apparently increased in heart disease. In conclusion, using a series of immunoassays, we observed the graded increase of alpha ANP, irProANP 31-67 and irProANP 79-98 with increasing severity of heart disease. All peptides proved useful markers, but only ProANP 79-98 levels were able to distinguish patients with mild heart disease (NYHA I) from normals. Finally, RP-HPLC analysis indicated that ProANPs 31-67 and 79-98 circulate as distinct entities, in addition to ProANP 1-98.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Chromatography, High Pressure Liquid; Diuretics; Enzyme Inhibitors; Heart Diseases; Humans; Middle Aged; Peptide Fragments; Protein Precursors; Radioimmunoassay

To investigate the relationship between left atrial function and secretion of atrial natriuretic peptide (ANP), we analyzed left ventricular inflow and pulmonary venous flow, left atrial dynamics, intracardiac pressures, and plasma ANP level in 92 patients with various cardiac diseases. From the apical four-chamber view, maximal left atrial volume and percent fractional change of the left atrial area during atrial systole (LA-%AC) were calculated. The ratio of peak early filling velocity to peak atrial systolic velocity (E/A) in the left ventricular inflow and the ratio of peak systolic velocity to peak diastolic velocity (S/D) in the pulmonary venous flow were measured with the pulsed Doppler method. A significant linear correlation was found between plasma ANP levels and pulmonary capillary wedge pressure. Significant linear correlations were also found between left ventricular end-diastolic pressure and both maximal left atrial volume and LA-%AC. Plasma ANP level was significantly correlated with maximal left atrial volume, LA-%AC, E/A, and S/D. A multivariate analysis revealed that only LA-%AC was significantly correlated with the plasma ANP level. These results suggest that left atrial systolic dysfunction associated with a left atrial afterload mismatch is closely related to the ANP secretion.

Topics: Aged; Atrial Function, Left; Atrial Natriuretic Factor; Echocardiography; Female; Heart Diseases; Humans; Male; Middle Aged; Pulmonary Wedge Pressure; Stroke Volume; Ventricular Function, Left

The aim of this study was to determine whether measurement of plasma levels of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) is an efficacious method to predict patients with heart disease irrespective of left ventricular function in a multiphasic health screening program. We have examined whether patients with various heart disease selected by physical examination, ECG, and chest X-rays can be identified by plasma levels of ANP and BNP. We examined 481 consecutive subjects who visited our checkup clinic for a multiphasic health screening test. By routine methods, among the 481 subjects, 13 were found to have some form of heart disease (old myocardial infarction, 2; cardiomyopathy, 2; valvular heart disease, 2; hypertensive heart disease, 5, and lone atrial fibrillation, 2). Sensitivity, specificity, and quintile analysis for identification of the patients with heart disease were determined by various cutoff levels of plasma ANP and BNP. Receiver operating characteristic (ROC) curves were constructed for the identification of these patients. A plasma BNP level of 40 pg/ml had a sensitivity of 85% and a specificity of 92% for heart disease detection. The area under the ROC curve for BNP was significantly greater than that for ANP (0.94 vs. 0.81; p < 0.001). A plasma BNP level of 13 pg/ml or less gave a 100% negative prediction value for heart disease. Plasma BNP concentration is a useful biochemical marker for the screening of asymptomatic patients with heart disease due to various etiologies from large population samples.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Diagnostic Errors; Female; Heart Diseases; Humans; Male; Middle Aged; Multiphasic Screening; Myocardial Contraction; Natriuretic Peptide, Brain; Predictive Value of Tests; Radioimmunoassay; ROC Curve

The aim was to examine the usefulness of plasma N-terminal proatrial natriuretic factor (N-terminal proANP) as a non-invasive marker of cardiac pressure in patients with normal to mildly elevated serum creatinine.. Blood samples were drawn at rest from 100 patients with cardiac disease undergoing diagnostic cardiac catheterization.. Using multivariate analysis, N-terminal proANP was independently related to mean pulmonary capillary wedge pressure (PCWP), mean right atrial pressure, serum creatinine (s-creatinine) and cardiac index. These indices accounted for about 50% of the variation in N-terminal proANP. All patients with N-terminal proANP < 1000 pmol/l had normal PCWP (< 13 mmHg). Areas under the receiver-operating characteristic (ROC) curves for N-terminal proANP for the detection of PCWP > or = 13, > or = 18 and > or = 24 mmHg were 0.903, 0.870 and 0.876, respectively.. These results suggest that analysis of plasma N-terminal proANP is a simple and powerful method for assessing cardiac pressure in patients with heart disease and normal and mildly elevated s-creatinine (< 165 micromol/l). The value of N-terminal proANP cannot, however, indiscriminately be used to assess cardiac haemodynamics. N-terminal proANP measurement is a useful screening parameter for identifying patients with normal cardiac pressures.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Cardiac Catheterization; Creatinine; Female; Heart Diseases; Hemodynamics; Humans; Male; Middle Aged; Multivariate Analysis; Protein Precursors; ROC Curve

Although a large number of studies have investigated the relationship between atrial natriuretic peptide (ANP) concentrations and circulatory abnormalities, it is presently unsettled as to whether this parameter provides valuable information in unselected patients with heart disease of different etiologies regardless of the presence of left ventricular dysfunction or heart failure.. The aim was to evaluate the correlation between ANP, hemodynamics and parameters of ventricular function in a large series of consecutive patients and to define the predictive value of ANP for the identification of specific circulatory abnormalities.. Cardiac catheterization was performed in 167 consecutive patients (62% males; mean age 62 yrs; range 18-85) and ANP serum levels were determined concomitantly by single antibody immune assay. Underlying etiology was: ischemic (67), valvular (72), idiopathic (12) and miscellaneous (16). Data management included: comparison of patients according to ANP values > or < 50% percentile of the cumulative distribution curve (i.e. 140 pg/ml); analysis of ANP concentrations according to the presence of normal or abnormal ventricular filling pressures; correlation between hemodynamic parameters and ANP concentrations; correlation of ANP with ventricular function in the whole population and in subgroups; calculation of sensitivity and specificity of ANP for the identification of abnormal filling pressures.. Mean ANP concentration was 181 +/- 139 pg/ml. Patients with ANP < 140 had significantly lower right-sided pressures but similar ventricular volumes and ejection fractions. By multivariate analysis, the single independent predictor of ANP was wedge pressure (p < 0.0001). Regarding etiology, severe mitral regurgitation was associated with the highest ANP levels (259 +/- 122 pg/ml), although the difference was not significant. The presence of abnormal left and right ventricular filling pressures was associated with significantly higher levels of ANP (p < 0.0001). A level of 125 pg/ml proved to be fairly sensitive (79%) but poorly specific (66%) for the detection of an abnormal wedge pressure. ANP was related to ventricular function only in the small subgroup of patients with dilated cardiomyopathy, where a significant negative correlation was found with both left ventricular (r = -0.72; p = 0.008) and right ventricular ejection fraction (-0.71; p = 0.01).. In unselected cardiac patients, ANP is confirmed to be a marker of left ventricular filling pressure in spite of poor specificity. Ventricular function appears to be related to ANP concentrations only in the subgroup of patients with pure heart-muscle disease.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Atrial Natriuretic Factor; Cardiac Catheterization; Coronary Angiography; Female; Heart Diseases; Hemodynamics; Humans; Logistic Models; Male; Middle Aged; Prospective Studies; Sensitivity and Specificity; Statistics, Nonparametric

Topics: Atrial Function; Atrial Natriuretic Factor; Heart Diseases; Humans

The arterial ketone body ratio (AKBR), an established clinical tool that reflects hepatic mitochondrial oxidation-reduction potential, predicts the outcome of patients with shock and multiple organ failure and the postoperative outcome in patients who have undergone major liver or heart surgery. The purpose of this study was to determine the prognostic significance of AKBR in patients with acute heart failure. The subjects of this study were 52 patients with acute heart failure. The following parameters were analyzed after Cox univariate hazard analysis was performed: AKBR, plasma norepinephrine, left ventricular ejection fraction, cardiac index, pulmonary arterial wedge pressure, sex, age, human atrial natriuretic peptide, endothelin-1, and cholesterol. The follow-up period was 30 weeks with cardiac death as the end point. Stepwise multivariate proportional hazard analysis revealed that AKBR was the most significant predictor of death, followed by norepinephrine and human atrial natriuretic peptide. Curve-fitting analysis revealed that the relationship between log (norepinephrine) and AKBR could best be described by two distinct lines, with their intersection at AKBR = 0.7 and norepinephrine = 418. With these results we conducted Kaplan-Meier analysis for AKBR > or = 0.7 and AKBR <0.7. The survival rate in patients with AKBR > or = 0.7 was 100%, whereas that in patients with AKBR <0.7 was 15% (p < 0.0001, log-rank analysis). These results indicate that AKBR is a novel independent predictor of death in heart failure.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Cardiac Output, Low; Female; Follow-Up Studies; Heart Diseases; Humans; Ketone Bodies; Male; Middle Aged; Norepinephrine; Prognosis; Proportional Hazards Models; Survival Analysis

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

This study was performed to elucidate the pathophysiological role of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in acute lung injury.. We sequentially measured plasma concentrations of immunoreactive BNP and ANP in 10 patients (mean age, 63 years (with acute lung injury and compared those with hemodynamic parameters and pulmonary functions.. Plasma concentrations of immunoreactive BNP and ANP were markedly elevated at entry into the study. Plasma BNP concentrations during the early course (3 days) showed significant (P < .01) positive correlations with systemic vascular resistance index (r = .708) and pulmonary vascular resistance index (r = .573), but a negative correlation with cardiac index (r = .608). Plasma ANP concentrations showed a significant (P < .05) positive correlation with pulmonary capillary wedge pressure (r = .398). Plasma BNP in 4 patients who died and 1 patient with acute renal failure remained elevated during the entire hospital length of stay (12 days).. These findings suggest that circulating BNP plays an important role in acute lung injury along with ANP as a compensatory mechanism for cardiac dysfunction accompanied by increased systemic vascular resistance index and pulmonary vascular resistance index. Circulating BNP may be a sensitive humoral marker for the degree of ventricular dysfunction associated with acute lung injury.

Topics: Acute Disease; Aged; Atrial Natriuretic Factor; Brain; Cardiac Output; Chromatography, Gel; Female; Heart Diseases; Heart Ventricles; Humans; Lung Injury; Male; Middle Aged; Natriuretic Agents; Plasma

Topics: Atrial Natriuretic Factor; Diastole; Forecasting; Heart Diseases; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Prognosis; Regression Analysis; Systole; Ventricular Dysfunction, Left

Neurohormonal activation is present and neurohormonal responses to dynamic exercise are altered in patients with congestive heart failure (CHF). The aim of this study was to determine if the responses of atrial natriuretic peptide (ANP) normalized for peak oxygen consumption (peak VO2) to exercise are augmented in patients with CHF. Ventilatory and ANP responses were assessed in 28 patients with CHF (NYHA classes II: 16, III: 12), 17 patients in NYHA class I, and 14 normal subjects during symptom-limited cardiopulmonary exercise testing. Plasma ANP was measured at rest and immediately after peak exercise. The increase in ANP was divided by peak VO2 and this ratio [ANP-Exercise Ratio: (peak ANP-rest ANP)/peak VO2] was compared among the 3 groups. Peak VO2 (Normal, NYHA I, CHF: 29.9 +/- 1.7, 24.0 +/- 1.3, 17.4 +/- 0.8 ml/min per kg), anaerobic threshold and peak work rate were lower in patients with CHF. The resting ANP level was significantly higher in patients with CHF (Normal, NYHA I, CHF: 35.4 +/- 4.6, 42.9 +/- 5.8, 80.8 +/- 12.9 pg/ml). The ANP level increased during exercise in all 3 groups, and patients with CHF had a significantly higher ANP level than normal subjects and NYHA class I patients (Normal, NYHA I, CHF: 65.3 +/- 10.7, 75.9 +/- 14.4, 141.6 +/- 20.1 pg/ml). The ANP-Exercise Ratio in patients with CHF was significantly higher than those in normal subjects and NYHA class I patients (Normal, NYHA I, CHF: 0.96 +/- 0.26, 1.32 +/- 0.38, 3.59 +/- 0.72). These data suggest that patients with CHF but not those in NYHA class I have an augmented ANP response, as reflected by both absolute ANP levels and by the exercise ratio, which was normalized by the peak exercise level.

Topics: Atrial Natriuretic Factor; Blood Pressure; Cerebral Ventricles; Female; Heart Diseases; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Oxygen Consumption; Physical Exertion; Respiration

The aim of the present study was to determine whether the level of plasma atrial natriuretic peptide (ANP), an indicator of atrial stretching, correlates with the formation of a thrombus in the left atrium during cardioembolic stroke with atrial fibrillation. Plasma concentrations of immunoreactive ANP and thrombin-antithrombin III complex (TAT) were measured in five age-matched groups including: 16 patients with acute cardioembolic stroke and atrial fibrillation (group 1), 26 patients with chronic cardioembolic stroke and atrial fibrillation (group 2), 27 patients with atrial fibrillation without previous stroke (group 3), 21 patients with acute lacunar stroke (group 4), and 27 healthy controls. The plasma ANP levels were higher in group 1, regardless of the stage, than those estimated at chronic stage in group 4 and in healthy controls. There were no stage-related differences between groups 1, 2 and 3. Plasma levels of ANP in group 2, a high risk group of cardioembolic stroke, were higher than in group 3, a low risk group. There was no correlation between plasma levels of ANP and mean blood pressure, pulse rate or plasma levels of TAT in any group. These results indicate that the determination of plasma ANP concentration is useful to distinguish a high risk patient from a low risk patient and also a cardioembolic stroke patient from a lacunar stroke patient. They also underscore the difficulties in recognizing left atrial thrombus formation by determining the plasma ANP concentration in cardioembolic stroke.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Atrial Natriuretic Factor; Case-Control Studies; Heart Diseases; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged

To elucidate a role of calcitonin gene-related peptide (CGRP) in anesthesia and surgery with cardiopulmonary bypass (CPB), we measured CGRP which is reported to be a marker for fluid overload, simultaneously with HANP (human atrial natriuretic hormone) in 12 patients during high dose fentanyl anesthesia (50-70 microgram. kg-1). Plasma concentration of CGRP increased to 3 times of the value during preanesthetic phase at 30 min after initiation of CPB. A 3-fold increase compared with control in CGRP occurred 30 min after initiation of CPB. A 3-fold increase in HANP also occurred just before termination of CPB. But, there was no correlation between plasma levels of CGRP and HANP. The changes in CGRP did not relate with those of pulmonary capillary wedge pressure. The results of the present study suggest that the mechanism for the increase is unclear, and CGRP could be influenced during cardiac or coronary artery surgery using CPB.

Topics: Adult; Aged; Anesthesia, General; Anesthetics, Intravenous; Atrial Natriuretic Factor; Calcitonin Gene-Related Peptide; Cardiopulmonary Bypass; Fentanyl; Heart Diseases; Humans; Intraoperative Period; Middle Aged

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

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

Plasma concentrations of atrial natriuretic peptide were measured in eight patients with cardiac disease but normal resting right atrial pressure, during cardiac catheterization. No patient had clinical evidence of overt heart failure. An increase in peptide concentrations was observed between the aorta or the peripheral vein and the pulmonary artery. A linear relation was found between peripheral vein and pulmonary artery peptide concentration. Mean pulmonary artery and capillary wedge pressure also correlated with the peptide levels. No correlation was observed between mean right atrial pressure and peptide concentration. These findings demonstrate that atrial natriuretic peptide release, even in the absence of cardiac failure, seems at least partly regulated by left atrial pressure. Finally, peripheral levels reflect the central concentrations of atrial natriuretic peptide.

Topics: Adult; Aged; Aged, 80 and over; Arginine Vasopressin; Atrial Function, Left; Atrial Natriuretic Factor; Catecholamines; Female; Heart Diseases; Hemodynamics; Humans; Male; Middle Aged; Radioimmunoassay; Renin-Angiotensin System

Topics: Atrial Natriuretic Factor; Blood Preservation; Cryopreservation; Heart Diseases; Humans; Hypertension; Kidney Diseases; Specimen Handling

Topics: Atrial Natriuretic Factor; Cyclic GMP; Heart Diseases; Humans

Topics: Atrial Natriuretic Factor; Heart Diseases; Heart Function Tests; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins

Circulating immunoreactive atrial natriuretic peptide, IrANP(99-126) and the N-terminal fragment of the prohormone, IrANP(1-98) were measured in two population samples from the general population of Gothenburg, Sweden. A group of 85-year olds (974 subjects) and a group of 40-year olds (191 subjects) were investigated in respect of cardiovascular, renal and metabolic disease. IrANP(99-126) and IrANP(1-98) were significantly higher in the 85-year olds compared to the 40-year olds, and were significantly increased in subjects with congestive heart failure, ischaemic heart disease, atrial fibrillation and renal dysfunction but not in subjects with hypertension. Eighty-five-year-old subjects who were on treatment with digitalis, beta-adrenergic-blockers, nitrates and diuretics had significantly increased IrANP(99-126) and IrANP(1-98). In multivariate analysis IrANP(99-126) concentrations were predictive for congestive heart failure, ischaemic heart disease, atrial fibrillation and treatment with beta-blockers and anti-depressant drugs. IrANP(1-98) was predictive for congestive heart failure, ischaemic heart disease, atrial fibrillation, diabetes mellitus, renal failure and drug treatment with beta-blockers and neuroleptics. We conclude that measurements of circulating concentrations of IrANP(99-126) and/or IrANP(1-98) may add valuable information in the diagnosis of congestive heart failure and ischaemic heart disease in an elderly population. It remains to be determined whether routine measurements of circulating IrANP (99-126) and IrANP(1-98) may be of value in predicting current cardiovascular disease for the individual patient.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Female; Heart Diseases; Humans; Kidney Diseases; Male; Metabolic Diseases; Peptide Fragments; Protein Precursors

The concentration of atrial natriuretic peptide was measured in order to evaluate its importance in patients suffering from a variety of cardiac diseases. There was a correlation between plasma concentrations of atrial natriuretic peptide and its "second messenger" cyclic guanosine monophosphate (cGMP) in all of the cases examined. We investigated the relationship between atrial natriuretic peptide and cGMP plasma concentrations during rest and exercise in comparison with the scintigraphically assessed left- and right-ventricular ejection fraction in patients with chronic heart disease (n = 20), and after orthotopic heart transplantation (n = 16); plasma concentrations were also measured in healthy controls (n = 14). Atrial natriuretic peptide and cGMP concentrations showed a similar correlation during rest and exercise with r = 0.74 and r = 0.81, respectively. With the exception of patients after heart transplantation, a significant negative correlation was seen between the left ventricular ejection fraction and atrial natriuretic peptide or cGMP plasma concentrations during rest conditions (r = 0.76 or 0.58, respectively). No correlation was apparent between plasma concentrations of atrial natriuretic peptide or cGMP and the left- or right ventricular ejection fraction during exercise. The concentrations of atrial natriuretic peptide and cGMP in plasma differed significantly between healthy controls and patients during rest and exercise. It is noteworthy that atrial natriuretic peptide and cGMP concentrations were markedly higher in patients after heart transplantation than in patients suffering from chronic heart disease. Our results indicate that plasma atrial natriuretic peptide and cGMP concentrations are sensitive markers of cardiac impairment.

Topics: Atrial Natriuretic Factor; Biomarkers; Cyclic GMP; Exercise; Heart Diseases; Heart Transplantation; Humans; Stroke Volume; Ventricular Function, Left; Ventricular Function, Right

1. The pericardial fluid of 20 open heart surgery patients with acquired heart disease was analysed for atrial natriuretic peptide by radioimmunoassay. 2. The concentration of atrial natriuretic peptide in the pericardial fluid was significantly higher than in the corresponding plasma (316.8 +/- 50.0 versus 121.7 +/- 29.1 pg/ml; P < 0.01) and was higher in patients with congestive heart failure than in those without heart failure (469.3 +/- 78.6 versus 181.8 +/- 26.7 pg/ml; P < 0.001). Pericardial and plasma atrial natriuretic peptide concentrations showed a significant positive correlation. Pericardial fluid and plasma samples were fractionated using both reverse-phase high-performance liquid chromatography and gel permeation chromatography. Each fraction was assayed for atrial natriuretic peptide by radioimmunoassay, revealing the presence of beta-atrial natriuretic peptide as well as alpha- and gamma-atrial natriuretic peptide. 3. The pericardial fluid concentration of cyclic GMP, the intracellular second messenger for atrial natriuretic peptide, was significantly higher in patients with congestive heart failure than in patients without heart failure.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cyclic GMP; Female; Heart Diseases; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Pericardium

To study the relationship between the plasma concentration of the atrial natriuretic peptide (ANP) and heart function and to discern the secretion pathway of ANP, we determined the peripheral plasma concentration of ANP in 18 heart patients and the intracardiac concentration of ANP in six heart patients during cardiac catheterization. All plasma was extracted through a Sep-Pak C18 cartridge by acid alcohol. The concentration of ANP was determined by a sensitive and specific radioimmunoassay method. We found that the plasma ANP concentration (pg/mL) in heart patients (ranging from 12 to 139, mean = 36.1 +/- 28.9) was statistically higher than that in normal adults (ranging from 8 to 20, mean = 12.4 +/- 3.3, n = 16; p less than 0.05). The ANP level in heart patients was inversely correlated with the left ventricular ejection fraction (r = -0.53, p less than 0.05) evaluated by radionuclide angiocardiography. The intracardiac level of ANP was 88 +/- 58 at the superior vena cava, 77 +/- 55 at the inferior vena cava, 124 +/- 68 at the right atrium, 98 +/- 64 at the right ventricle, 107 +/- 58 at the pulmonary artery, 98 +/- 52 at the left ventricle, 109 +/- 73 at the aorta and greater than 351 at the coronary sinus. In conclusion, ANP is mainly secreted via the coronary sinus into the atrial cavity. The peripheral plasma ANP concentration is higher in heart patients. It increases as the left ventricular ejection fraction decreases. Therefore, plasma ANP concentration may be a useful indicator for the assessment of cardiac function.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Coronary Circulation; Female; Heart Diseases; Humans; Male; Middle Aged

Three studies were performed: (1) a controlled investigation of alpha-human atrial natriuretic peptide (alpha-hANP) total body production and metabolic clearance rates using a bolus infusion technique (controls, patients 1 to 6); (2) a study of alpha-hANP kinetics in cardiac dysfunction patients using a constant infusion method (patients 7 to 14); and (3) a right heart catheterization study to determine the amount of alpha-hANP released into the circulation at the level of the right heart, estimated by the step-up in alpha-hANP concentration between the superior and inferior vena cava and the pulmonary artery, in the patients with left ventricular dysfunction. Baseline venous plasma alpha-hANP was 27.3 +/- 16.5 pg/ml in the controls (mean +/- SD; N = 6), 141.6 +/- 138.0 pg/ml in patients 1 to 6 (P less than 0.05 compared to controls), and 167.5 +/- 145.7 pg/ml in patients 7 to 14. Total body alpha-hANP production rate was markedly elevated in patients 1 to 6 compared to controls (0.45 +/- 0.36 vs. 0.11 +/- 0.06 micrograms/min, P less than 0.05) and was similar to that determined by the continuous infusion technique in patients 7 to 14 (0.62 +/- 0.44 micrograms/min, P = 0.49 compared to patients 1 to 6). alpha-hANP release into the right heart (0.17 +/- 0.11 micrograms/min), however, was significantly lower than total body production rate in the cardiac dysfunction patients, indicating that total body alpha-hANP secretion occurs from sites in addition to drainage into the right heart via the coronary sinus and anterior cardiac veins. Right atrial pressure correlated with the alpha-hANP released into the right heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiac Catheterization; Female; Heart Diseases; Humans; Infusions, Intravenous; Injections, Intravenous; Kinetics; Male; Middle Aged; Ventricular Function, Left

To assess the effects of atrial natriuretic factor (ANF) on cardiac function, synthetic human ANF was infused directly into the left main coronary artery of eight patients with congestive heart failure (CHF) and six subjects with normal left ventricular (LV) function (controls) who underwent cardiac catheterization. ANF infusion at the incremental rates of 60, 125, 400, and 800 ng/min induced a dose-related increase in plasma ANF concentrations in the coronary sinus, from 1,223 +/- 590 to 3,923 +/- 1,123 pg/ml in patients with CHF (p less than 0.01) and from 1,041 +/- 605 to 2,710 +/- 1,741 pg/ml in controls (p less than 0.01). Peripheral plasma ANF concentrations (femoral artery) increased from 538 +/- 278 to 752 +/- 262 pg/ml (p less than 0.01) in patients with CHF and from 193 +/- 63 to 401 +/- 147 pg/ml (p less than 0.01) in controls. The increase in peripheral or coronary sinus plasma ANF concentrations did not differ between patients with CHF and controls. At the three lowest ANF infusion rates, cardiac index (CI), systemic vascular resistance (SVR), and LV contractility assessed by peak positive dP/dt remained unchanged both in patients with CHF and in controls. At the highest ANF infusion rate, CI increased from 2.18 +/- 0.53 to 2.54 +/- 0.49 L/min/m2 (p less than 0.01) and SVR decreased from 14.6 +/- 3.6 to 12.8 +/- 4.5 mm Hg.min/L (p less than 0.01) in patients with CHF. There was no associated change in heart rate (HR), mean arterial blood pressure (MAP), cardiac filling pressures, or peak positive dP/dt.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiac Catheterization; Cardiac Output; Coronary Circulation; Coronary Vessels; Female; Heart Diseases; Heart Failure; Heart Ventricles; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Contraction; Vascular Resistance

Atrial natriuretic peptide (ANP), a cardiac hormone, is known to be located in the atrial specific granules, but its presence and localization in the ventricular muscle of the human heart has not been examined fully. Using a specific antibody to human ANP, we studied the conduction system and ventricular muscle with immunohistochemical and ultrastructural methods in 30 hearts obtained at autopsy. These included 12 normal and 18 diseased hearts. In the normal hearts, ANP-positive granules, which were regularly observed in the atrial myocytes, were found in small quantities in the cells of the penetrating and branching bundles in 4 of 12, and in the cells of the ventricular free walls in 2 of the 12 hearts. In the diseased hearts, the positivity increased significantly (P less than 0.05), being found in 13 of 18 (72.2%) conduction systems and 10 of 18 (55.6%) ventricular muscles. The granules were confirmed to be immunoreactive with ANP by ultrastructural examination. Furthermore, the presence of ANP mRNA in the conduction system as well as in the ventricular myocytes was demonstrated by Northern blot hybridization for which we used the complementary DNA of human ANP. Thus, a small quantity of ANP appears to be synthesized and stored in the conduction system and ventricles of some normal hearts. However, ANP was shown to be present in a larger percentage of the diseased hearts.

Topics: Aged; Atrial Natriuretic Factor; Blotting, Northern; Heart Conduction System; Heart Diseases; Heart Ventricles; Humans; Immunohistochemistry; Male; Microscopy, Immunoelectron; Muscles; Myocardium; Reference Values; RNA, Messenger; Tissue Distribution

The purpose of this study was to measure changes in serum atrial natriuretic factor concentrations immediately after heart operations in children under baseline conditions and in response to continuous infusion of dopamine (2.5 and 5.0 micrograms/kg/min). During control periods, levels of atrial natriuretic factor were elevated at 190 +/- 24 and 199 +/- 36 pg/ml. The cardiac index was 2.6 L/min/m2 and the renal plasma flow was decreased to 269 +/- 41 ml/min/1.73 m2, indicating a state of renal vasoconstriction (mean renal fraction of cardiac index of 10.0% +/- 1.0%). The mean sodium fractional reabsorption was 99.0% +/- 0.2%. During dopamine infusion, atrial natriuretic factor concentrations increased to 259 +/- 57 pg/ml and to 280 +/- 56 pg/ml, with dopamine 2.5 and 5.0 micrograms/kg/min, respectively (p = not significant), whereas left atrial pressure decreased from 11.7 +/- 0.9 mm Hg during the control period to 10.1 +/- 0.9 and to 9.9 +/- 1.0 mm Hg (p less than 0.05). No correlation was found between changes in left atrial pressure and atrial natriuretic factor levels. Dopamine at 5 micrograms/kg/min increased the cardiac index to 3.0 +/- 0.2 L/min/m2 (p less than 0.001) and the renal plasma flow to 406 +/- 61 ml/min 1.73 m2 (p less than 0.001), alleviating the renal vasoconstriction. The mean urinary sodium excretion increased to 0.33 +/- 0.08 mmol/kg/hr (p less than 0.01). The atrial natriuretic factor plasma concentrations were not related to the urinary sodium excretion, renal plasma flow, or glomerular filtration rate during the control period or during dopamine treatment. These data indicate that after heart operations in children, low urinary sodium excretion occurs despite high circulating atrial natriuretic factor levels. Atrial natriuretic factor concentrations were related neither to left atrial pressures nor to the renal changes induced by dopamine.

Topics: Adolescent; Atrial Natriuretic Factor; Child; Child, Preschool; Dopamine; Heart Diseases; Hemodynamics; Humans; Infant; Postoperative Period; Renal Circulation; Sodium

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

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

Due to the discovery and elaboration of alpha ANP, the heart can be considered a veritable endocrine gland involved in fluid and electrolyte homeostasis as well as blood pressure regulation. Nevertheless, the mechanisms regulating the synthesis and release of this new hormone are far from being understood. Heart-lung transplantation provides an interesting research model for evaluating the consequences of allograft denervation on alpha ANP synthesis and release, without the disadvantage of significantly increasing the overall atrial tissue mass, as observed in orthotopic heart transplantation. To appreciate better these consequences, we studied the changes in alpha ANP release following heart-lung transplantation. Five patients were included in the study. It began during the immediate postoperative period and went on to the 8th postoperative day. Alpha ANP levels were determined using radioimmunoassay. The postoperative course was characterized by a rapid significant increase in hormone levels as of the 6th postoperative day (45.6 +/- 5.5 fmol/ml). These findings were comparable to those found in a previous study involving orthotopic heart transplantation alone. Thus, the heart-lung group was also capable of high levels of alpha ANP release from the onset. However, this rapidly increasing release was not found to be correlated with the changes in hemodynamic parameters observed postoperatively (blood and cardiac filling pressures). Moreover, we observed no episodes of rejection which might explain the increased release of this hormone. Finally, the fact that increased alpha ANP release occurs despite a smaller increase in the overall tissue mass is more than noteworthy. In conclusion, as we found in our initial study involving heart transplant recipients, the sustained high levels of alpha ANP observed following heart-lung transplantation are in favour of a possible modulating role played by cardiac innervation on the release of this hormone.

Topics: Adult; Analysis of Variance; Atrial Natriuretic Factor; Denervation; Female; Heart Diseases; Heart-Lung Transplantation; Hemodynamics; Humans; Male; Postoperative Period; Time Factors

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Female; Heart Atria; Heart Diseases; Humans; Male; Middle Aged

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

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

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

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

The regulation of atrial natriuretic peptide (ANP) synthesis within cardiac atrial myocytes was investigated in 8 patients undergoing cardiac surgery (valve replacement or coronary bypass graft). Hemodynamic data were obtained during cardiac catheterization and venous plasma samples for ANP were withdrawn prior to surgery. Probes for determination of tissue ANP levels and ANPmRNA concentrations were taken from the right atrium. Both plasma ANP (r = 0.75; P less than .05) and ANPmRNA (r = 0.86; P less than .01) were closely related to mean pulmonary artery pressure. ANPmRNA was also related to plasma ANP (r = 0.60; P less than .07). However, no significant relationships were obtained between either plasma ANP or ANPmRNA and right atrial ANP concentrations. These data suggest that right atrial ANP synthesis is regulated by cardiac filling pressures and possibly by plasma ANP levels, independent from corresponding ANP tissue concentrations.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Atria; Heart Diseases; Humans; Male; Middle Aged; RNA, Messenger

Several reports have demonstrated a close correlation between plasma atrial natriuretic peptide (ANP) concentration and atrial pressure in stable heart diseases. However, few studies have investigated whether plasma ANP concentration is a noninvasive indicator of hemodynamic parameters during the treatment of heart failure. Thus, we have studied the relationship between peripheral plasma ANP concentration and concurrent hemodynamic variables during the treatment of heart failure, and, in order to determine whether secretion of ANP is stimulated in this disease condition, we compared the plasma ANP concentration in the pulmonary artery with that in the peripheral veins. Studies were performed in each of 9 patients with acute heart failure due to myocardial infarction (Group A) or chronic heart failure (Group B), who were matched as closely as possible for treatment, age, sex and cardiac output. In group A, no significant correlation was found between plasma ANP levels and any measured hemodynamic variables. In group B, peripheral plasma ANP concentrations were significantly correlated with left atrial pressure (r = 0.82, p less than 0.01), but not with right atrial pressure (r = 0.56, p greater than 0.05). Furthermore, in group B ANP levels in pulmonary arterial plasma were consistently higher than those in peripheral venous plasma, whereas in group A the opposite was observed in expired cases. These results suggest that measurement of peripheral plasma ANP is a useful noninvasive method for estimating left atrial pressure during the treatment of chronic heart failure. However, plasma ANP concentration may not be a valid means of estimating hemodynamic parameters in acute heart failure due to myocardial infarction. In such cases, the increased secretion of ANP was not obvious, and there may be other factors, in addition to atrial pressure, that regulate cardiac secretion of ANP.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Blood Pressure; Female; Heart; Heart Atria; Heart Diseases; Hemodynamics; Humans; Least-Squares Analysis; Male; Middle Aged; Myocardial Infarction; Pulmonary Artery; Veins

An electron microscopic immunocytochemical study of left ventricular myocardium was carried out in 16 patients with heart disease of various etiologies in order to characterize the secretory granules arising in the ventricular muscle cells. The electron-dense granules observed in the ventricular muscle cells were demonstrated only in 3 patients with dilated cardiomyopathy and chronic congestive heart failure. They were scattered throughout the cytoplasm of the ventricular muscle cells at paranuclear, interfibrillar and subsarcolemmal areas, and tended to be most numerous in the vicinity of the Golgi apparatus. These granules were often found to be bound by limiting membranes of homogeneous electron density. Protein A-gold electron microscopic immunocytochemistry with anti-alpha-human atrial natriuretic polypeptide resulted in specific staining of the granules. These findings, taken together indicate that the secretory granules containing atrial natriuretic polypeptide (ANP) exist in the ventricular muscle cells in a particular category of patients with dilated cardiomyopathy and chronic congestive heart failure. Thus, it is suggested that human ventricular muscle cells have retained the genetic ability to form specific ANP-containing granules in certain clinical disorders.

Topics: Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Cytoplasmic Granules; Female; Heart Diseases; Heart Failure; Heart Septal Defects, Atrial; Heart Ventricles; Humans; Immunohistochemistry; Male; Microscopy, Electron; Microscopy, Immunoelectron; Middle Aged; Myocardium

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

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

We used new commercially available direct radioimmunoassay to measure human atrial natriuretic peptide (h-ANP) in plasma from 48 individuals who were being evaluated for left and right ventricular function. For 13 healthy individuals with normal ventricular function these concentrations ranged up to 54 ng/L. Measurements of h-ANP clearly differentiated between normal subjects, patients with coronary artery disease, and patients who had undergone orthotopic heart transplantation (ANOVA P less than 0.0001, significant differences between all groups)--all showing normal ventricular function at rest. There was a strong negative correlation (r = -0.64, P less than 0.001) between left ventricular ejection fraction and h-ANP concentrations in plasma of patients with proven coronary artery disease, patients with cardiomyopathy, and healthy individuals. Results by the present method and methods involving extraction of the sample correlated well. Evidently the direct assay of h-ANP in plasma yields information that could be used to help evaluate heart disorders and other pathophysiological conditions causing increased h-ANP concentrations in plasma.

Topics: Adult; Atrial Natriuretic Factor; Heart Diseases; Heart Transplantation; Heart Ventricles; Humans; Middle Aged; Radioimmunoassay; Stroke Volume

Immunoreactive atrial natriuretic peptide (irANP) has been measured in 24 patients of various cardiac diseases by radioimmunoassay. According to the TCM, these patients were divided into 4 groups: cardiac energy deficiency mild (A) and severe (B) groups; simple cardiac deficiency (C); and the control (D). The New York Heart Association (NYHA) classification of cardiac function in 5 cases of group A were all degree IV; in 6 cases of group B were 2 of degree IV and 4 of degree III; in 6 cases of group C were 1 of degree III, 3 of degree II and 2 of degree I; and in 6 cases of group D were all degree I. The results of chest X-ray and echocardiogram suggested that the classification of cardiac function was objective. The quantity of irANP in group A-D and NYHA IV-I decreased gradually and was correlated with left ventricular ejection fraction (r = -0.87, P less than 0.01). The average amounts of irANP in the different TCM groups A-D were at the equivalent levels in the groups NYHA IV-I. Meanwhile it was found that the cardiac energy deficiency patients had abnormality in some parameters of hemorrheology, but no correlation with irANP. It suggested that the diagnosis of cardiac deficiency by TCM was correlated with the different degree of NYHA in the sense of biochemical index of irANP. The irANP might be considered as one of the objective signs of the cardiac energy deficiency, which also might represent the severity of the disease.

Topics: Atrial Natriuretic Factor; Female; Heart Diseases; Humans; Male; Medicine, Chinese Traditional

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

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

The relation of plasma levels of atrial natriuretic peptide (ANP) to those of cyclic 3', 5'-guanosine monophosphate (cGMP) was studied in 43 patients with various heart diseases. Plasma levels of both ANP and cGMP were significantly (p less than 0.001) elevated in 34 patients with chronic heart diseases, and a significant positive correlation was observed between the two variables (r = 0.706, p less than 0.01). Clinical improvement of congestive heart failure resulted in a concomitant decrease in plasma ANP and cGMP levels in 6 patients. In 3 patients with paroxysmal atrial fibrillation, plasma levels of ANP and cGMP increased markedly during arrhythmia. These results indicate that increased circulating ANP may stimulate cGMP production in target cells, which in turn raises plasma levels of cGMP in humans.

Topics: Aged; Atrial Natriuretic Factor; Cyclic GMP; Female; Heart Diseases; Heart Failure; Humans; Male; Middle Aged

To elucidate the posttranslational processing of gamma-human atrial natriuretic polypeptide (human atrial natriuretic factor-[1-126]), which is a prohormone of alpha-human atrial natriuretic polypeptide (human atrial natriuretic factor-[99-126]), and the secretion of gamma-human atrial natriuretic polypeptide-derived peptides from the heart, we established a radioimmunoassay specific for the N-terminal sequence of gamma-human atrial natriuretic polypeptide, gamma-human atrial natriuretic polypeptide-(1-25), as well as a radioimmunoassay for alpha-human atrial natriuretic polypeptide. With the aid of the radioimmunoassays for gamma-human atrial natriuretic polypeptide-(1-25) and for alpha-human atrial natriuretic polypeptide, we detected 290 +/- 35.6 pg/ml of gamma-human atrial natriuretic polypeptide-(1-25)-like immunoreactivity in plasma from healthy humans, while the simultaneously determined plasma alpha-human atrial natriuretic polypeptide-like immunoreactivity level was 20.9 +/- 2.8 pg/ml. Correlation between the two values was significant. High performance gel permeation chromatographic analysis revealed that the plasma gamma-human atrial natriuretic polypeptide-(1-25)-like immunoreactivity was composed of a component (molecular weight, 10,000) without alpha-human atrial natriuretic polypeptide-like immunoreactivity, while the plasma alpha-human atrial natriuretic polypeptide-like immunoreactivity was composed of alpha-human atrial natriuretic polypeptide with a molecular weight of 3000. In patients with heart diseases, the plasma gamma-human atrial natriuretic polypeptide-(1-25)-like immunoreactivity level showed a concomitant and graded increase, with the plasma alpha-human atrial natriuretic polypeptide-like immunoreactivity level in agreement with the severity of the disease. There were significant positive correlations between the two immunoreactivity levels and right or left atrial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Atrial Natriuretic Factor; Female; Heart Diseases; Humans; Male; Natriuresis; Peptide Fragments; Protein Precursors; Protein Processing, Post-Translational; Radioimmunoassay

Plasma levels of immunoreactive atrial natriuretic peptide (ANP) were estimated in 69 elderly patients over 60 years of age (mean 76.4 years) with or without heart diseases and in ten young, healthy volunteers (mean 33.0 years) to evaluate the clinical significance of ANP in the elderly. Plasma ANP levels in nine patients without heart diseases were significantly (P less than .01) higher than in the ten young, healthy subjects (mean +/- SD, 46.0 +/- 22.0 vs 22.1 +/- 6.3 pg/mL) and a significant positive correlation was observed between ANP level and age in these subjects (r = 0.60, P less than 0.01). Plasma ANP levels in 60 patients with heart diseases (158.4 +/- 158.5 pg/mL) were significantly (P less than 0.05) greater than in nine patients without heart diseases. Plasma ANP levels in patients with congestive heart failure or atrial fibrillation were 285.8 +/- 185.2 or 223.0 +/- 185.9 pg/mL, respectively; each of these values was significantly (P less than 0.01) higher than in patients without heart diseases. In three patients with paroxysmal atrial fibrillation, plasma ANP levels during atrial fibrillation were three times greater than when atrial fibrillation returned to normal sinus rhythm (377.3 +/- 78.5 vs 101.1 +/- 68.5 pg/mL). These results indicate that plasma ANP levels increase with advancing age, and that increased ANP levels are associated with various heart diseases in elderly subjects, possibly through stretch of the atrial wall.

Topics: Adult; Aged; Aged, 80 and over; Aging; Atrial Natriuretic Factor; Female; Heart Diseases; Humans; Hypertension; Male; Middle Aged

Topics: Atrial Natriuretic Factor; Heart Diseases; Humans; Myocardium

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiac Catheterization; Dogs; Female; Heart Diseases; Humans; Male; Middle Aged; Pulmonary Artery

Out of 32 patients (f = 10, m = 22; mean age: 46 +/- 3 years) with untreated essential (primary) hypertension (WHO-classification I-III) and without clinical signs of congestive heart failure or chronic renal failure, 19 showed plasma-ANP base levels above the normal range (greater than 100 pg/ml; normal range: 50 +/- 10 pg/ml). While high sodium loading caused an increase of plasma ANP levels and a concomitant decrease of plasma renin and aldosterone concentrations, low sodium loading caused the opposite pattern of ANP and renin/aldosterone secretion. Some patients with essential hypertension with highly elevated plasma ANP levels (10-20-fold above the normal range) showed an only moderate decrease of ANP and a slight increase of renin under a low sodium diet. Plasma ANP levels were significantly correlated with the heart volume (r = 0.54; p less than 0.05; radiologically determined), the electrocardiographic signs of left ventricular hypertrophy (Sokolow-Lyon index; r = 0.62; p less than 0.05) and with the left atrial diameter (r = 0.34; p less than 0.05; determined by 2-D-echocardiography). We speculate that high levels of plasma ANP in patients with essential hypertension might be interpreted as a compensatory mechanism either for an insufficient excretion of sodium or for myocardial dysfunction.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Catecholamines; Female; Heart Diseases; Humans; Hydrocortisone; Hypertension; Male; Middle Aged; Reference Values; Renin; Sodium

Using RIAs for the N- and C-terminal fragments of the human atrial natriuretic polypeptide (ANP) precursor gamma ANP, that is gamma ANP-(1-25), and alpha ANP [gamma ANP-(99-126)], we studied the secretion of gamma ANP-derived peptides from the heart in normal subjects and patients with heart disease, chronic renal failure, and cirrhosis. We detected gamma ANP-(1-25)-like immunoreactivity (-LI) in plasma from normal subjects (n = 17) in considerable amounts [mean, 510 +/- 62 (+/- SE) pg/mL (174 +/- 21 pmol/L)]; the mean plasma alpha ANP-LI level at the same time in these subjects was 32.8 +/- 4.4 pg/mL (10.7 +/- 1.4 pmol/L). Gel permeation chromatographic analysis of plasma samples from normal subjects and patients with heart disease and chronic renal failure revealed two major components; one was alpha ANP, and the other was the 10K N-terminal gamma ANP fragment (N-peptide) resulting from the removal of alpha ANP (3K) from gamma ANP (13K). In addition, gamma ANP (13K), which possessed both gamma ANP-(1-25)-LI and alpha ANP-LI, and beta ANP, an antiparallel dimer of alpha ANP, were detected in some patients as minor components. A significant positive correlation between plasma levels of the N-terminal gamma ANP fragment and alpha ANP (P less than 0.01) and almost equal step-ups in the coronary sinus plasma levels of the N-terminal gamma ANP fragment and alpha ANP suggest that they are cosecreted in equimolar amounts. The high molar ratio of plasma gamma ANP-(1-25)-LI to alpha ANP-LI (17.4 +/- 1.4) in normal subjects and the significantly higher ratio in patients with chronic renal failure (36.9 +/- 7.1; P less than 0.01) suggest the slower clearance of the N-terminal gamma ANP fragment than alpha ANP and a role for the kidney in its degradation. Since the molar ratio of plasma gamma ANP-(1-25)-LI to alpha ANP-LI in patients with cirrhosis (20.7 +/- 2.7) was similar to that in normal subjects, it is unlikely that the N-terminal gamma ANP fragment is metabolized by the liver. In patients with heart disease, plasma gamma ANP-(1-25)-LI and alpha ANP-LI levels were higher in those with cardiac decompensation and were positively correlated with right atrial pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure, indicating cosecretion of the N-terminal gamma ANP fragment and alpha ANP in response to atrial stretch.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adult; Aged; Atrial Natriuretic Factor; Chromatography, Gel; Chromatography, High Pressure Liquid; Female; Heart Diseases; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Male; Middle Aged; Peptide Fragments; Radioimmunoassay

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiopulmonary Bypass; Female; Heart Diseases; Humans; Intraoperative Period; Male; Middle Aged; Postoperative Period; Water-Electrolyte Balance

In nonimmunologic hydrops fetalis associated with heart anomaly, plasma human atrial natriuretic peptide (hANP) values in umbilical venous blood were significantly higher than those in normal infants. These findings indicate that significant release of hANP from atria is induced by the decompensatory state of the fetal heart.

Topics: Atrial Natriuretic Factor; Female; Fetal Blood; Fetal Diseases; Fetal Heart; Heart Diseases; Humans; Hydrops Fetalis; Pregnancy; Prenatal Diagnosis

Topics: Animals; Atrial Natriuretic Factor; Brain; Heart Diseases; Humans; Myocardium; Tissue Distribution

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Blood Pressure; Child; Child, Preschool; Echocardiography; Female; Heart Diseases; Humans; Infant; Male; Middle Aged; Pulmonary Artery; Stroke Volume; Ultrasonography

Simultaneous measurements of plasma atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (GMP) concentrations were performed in children with various forms of cardiac diseases (n = 22) and in control children (n = 29). In healthy children, plasma ANP and cyclic GMP levels ranged between 2.4 and 98.0 (mean 45.8) pg/mL and 0.2 to 2.8 (mean 1.40) pmol/mL, respectively. In children with cardiac diseases, plasma ANP (26.0 to 499.7 [mean 188.7] pg/mL) and cyclic GMP (0.2 to 6.0 [mean 2.9] pmol/mL) levels were significantly higher than in control children (both P less than .0001). There was a linear correlation between the two values in children with cardiac diseases (P less than .01). Because the effects of ANP to target tissues are mediated by cyclic GMP, cyclic GMP appears to be a marker for the cellular responses to ANP. The increased cyclic GMP levels in children with cardiac diseases indicate that ANP exerts its effects on target organs also in states of chronically enhanced ANP levels.

Topics: Adolescent; Atrial Natriuretic Factor; Child; Child, Preschool; Cyclic GMP; Heart Defects, Congenital; Heart Diseases; Humans; Infant; Reference Values

The sequence of atrial natriuretic factor (ANF) has been determined, as well as the complete structure of the rat and human complementary DNA and gene. ANF and ANF messenger RNA are present not only in atria but also in ventricles. The circulating form of ANF has been identified as the C-terminal of the molecule, ANF (Ser 99-Tyr 126). The isolated secretory granules of rat atrial cardiocytes contain only pro-ANF (Asn 1-Tyr 126). An enzyme (IRCM-SP1) has been isolated from heart atria and ventricles. This enzyme is highly specific in cleaving ANF (Asn 1-Tyr 126), to yield ANF (103-126), (102-126), and (99-126). In target cells, ANF produces a rise in cyclic guanosine 3',5'-monophosphate (cGMP) due to activation of particulate guanylate cyclase, and inhibition of adenylate cyclase leading in some cases to a decrease in cyclic adenosine 3',5'-monophosphate (cAMP). ANF produces relaxation of rabbit and rat aortic strips, inhibits steroidogenesis in both zona glomerulosa and zona fasciculata cells, and inhibits the release of arginine vasopressin from the isolated rat hypothalamohypophysial preparation in vitro but decreases AVP release in vivo only at pharmacological doses. In all forms of experimental hypertension, plasma levels of ANF are increased and, at some time periods, atrial levels are also decreased. The ventricular levels of immunoreactive ANF are also increased in renal hypertension. Infusion of ANF by minipumps decreases the blood pressure near control levels in several models of experimental hypertension. In cardiomyopathic hamsters with heart failure, the atrial levels of immunoreactive ANF are decreased while the plasma and ventricular levels are increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Function; Atrial Natriuretic Factor; Chromosome Mapping; Cytoplasmic Granules; DNA; Genes; Heart Diseases; Humans; Hypertension; Kidney; Rats; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

In children with various forms of cardiac diseases (aged 2 months to 16 years) significantly higher plasma atrial natriuretic peptide (ANP; range 36-680, median 247 pg/ml) and cyclic 3'5'-guanosine monophosphate (cGMP; range 0.2-46, median 8.2 pmol/ml) levels were found than in control children (p less than 0.0001). In control children (aged 4 months to 17 years) plasma ANP and cGMP levels were measured in the range of 2.4-98 pg/ml and of 0.2-2.8 pmol/ml, respectively. There was a linear correlation between the two parameters in children with cardiac diseases (r = 0.62, p less than 0.01). Children with elevated mean right atrial pressure (i.e., greater than 6 mm Hg) showed significantly higher plasma ANP levels than children with normal atrial pressure (p less than 0.01). However, there was only a weak linear correlation between mean right atrial pressure and plasma ANP levels (r = 0.48, p less than 0.01). Plasma ANP levels from right atrium, pulmonary artery, left atrium and left ventricle were significantly higher than those from vena cava (p less than 0.05). Analysis of ANP-like immunoreactive material by high performance liquid chromatography suggested that alpha-ANP is the major form of circulating ANP in blood of children with cardiac diseases.

Topics: Adolescent; Atrial Function; Atrial Natriuretic Factor; Child; Child, Preschool; Chromatography, High Pressure Liquid; Cyclic GMP; Heart Defects, Congenital; Heart Diseases; Hemodynamics; Humans; Infant; Pressure

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Female; Heart Atria; Heart Diseases; Humans; Male; Middle Aged; Pressure

Molecular forms of atrial natriuretic polypeptides circulating in human plasma were analyzed by chromatographic separation, coupled with radioimmunoassay. Analyses were done with human plasma samples taken from 24 human subjects, divided into groups of healthy volunteers, patients with renal disease, and patients with heart disease, with 8 subjects in each group. Although alpha-hANP was found as a major circulating form in most of the plasma specimens (16 cases), beta-hANP accompanied by alpha-hANP was found in 6 cases including 2 healthy volunteers. In addition, hANP-immunoreactive macromolecule, which is likely a bound form of hANP, was found to some extent in all the specimens tested. Diversity of human plasma in ANP molecular distribution was discussed in connection with a radioimmunoassay for plasma ANP.

Topics: Atrial Natriuretic Factor; Cross Reactions; Heart Diseases; Humans; Kidney Diseases; Molecular Weight

A sensitive and specific procedure for the measurement of atrial natriuretic peptide (ANP) in human plasma by radioreceptor assay, using bovine adrenal membranes treated with Triton-X-100, is described. Plasma levels (mean +/- SEM) of ANP in healthy subjects on a normal sodium intake were 8.4 +/- 1.4 pg/ml and could be modified by changes in sodium intake with increases in sodium intake being associated with higher levels. Mean plasma ANP was approximately 2-fold higher in patients with essential hypertension and 4-fold higher in patients with cardiac or renal disease. The values obtained were comparable in magnitude to those obtained by radioimmunoassay and there was a strong correlation (r = 0.94; p less than 0.001) between the values obtained by radioimmuno- and radioreceptor-assay. These results suggest that circulating ANP corresponds to the biologically active peptide and point to an important role of the atrial peptides in the control of sodium balance.

Topics: Adult; Aged; Atrial Natriuretic Factor; Female; Heart Diseases; Humans; Hypertension; Kidney Diseases; Male; Middle Aged; Radioimmunoassay; Radioligand Assay; Reference Values; Sodium

Plasma atrial natriuretic peptide (ANP) concentrations were measured by both direct radio-immunoassay and with pre-extraction of the peptide from plasma using C18 reverse phase columns. Peptide concentrations were measured in normal subjects (including a group of eight volunteers who received an intravenous infusion of 0.9% NaCl solution), patients with renal failure (including a group with end-stage disease undergoing renal dialysis) and patients with a spectrum of cardiac dysfunction. The overall correlation of results from direct and extracted assay methods was good. However, absolute values from extracted assays were significantly lower than from parallel direct assays. This discrepancy was due to interference from platelets and from another, as yet unidentified, plasma component demonstrated by gel filtration experiments. Extraction of the peptide from plasma by C18 columns largely eliminated these sources of interference and was particularly important for accurate measurement of peptide concentrations within the normal range. Plasma peptide concentrations were elevated in cardiac and renal failure, fell with renal dialysis and rose in normal subjects challenged with an intravenous isotonic fluid load. These findings suggest that ANP participates in the regulation of body fluid volumes and arterial pressure.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Buffers; Chromatography, Gel; Chromatography, High Pressure Liquid; Female; Heart Diseases; Humans; Kidney Failure, Chronic; Male; Middle Aged; Radioimmunoassay

Because anecdotal reports suggest that concentrations of atrial natriuretic peptide are raised during tachycardias, plasma immunoreactive atrial natriuretic peptide concentrations were measured in 34 consecutive patients when tachycardia was diagnosed and again five and 15 minutes after conversion to sinus rhythm. Plasma atrial natriuretic peptide concentrations were raised in all but four patients, and were higher in patients with known heart disease than in those without. The concentrations were higher with ventricular tachycardia than with atrial fibrillation or supraventricular tachycardia, and in acute versus chronic tachycardia. There was only a weak positive relation between ventricular rate and atrial natriuretic peptide (r = 0.31); but there was a closer inverse correlation between atrial natriuretic peptide and systolic arterial pressure (r = -0.60). Conversion to sinus rhythm was associated with a definite fall in plasma atrial natriuretic peptide concentrations. Despite very high baseline concentrations of atrial natriuretic peptide only two patients reported polyuria. It is likely that atrial pressure rather than ventricular rate determines atrial natriuretic peptide release during tachycardia. Despite the absence of polyuria in all but two patients in this study atrial peptides could still contribute to, or cause, the polyuria of tachycardias.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Blood Pressure; Electric Countershock; Female; Heart Diseases; Heart Ventricles; Humans; Male; Middle Aged; Tachycardia; Time Factors

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

Topics: Atrial Natriuretic Factor; Brain Chemistry; Heart Diseases; Hemodynamics; Hormones; Humans; Neuropeptides

Plasma concentrations of immunoreactive alpha-human atrial natriuretic polypeptide (i alpha-hANP) and cyclic guanosine monophosphate (cGMP) were measured in 70 patients with heart disease. Plasma concentrations of i alpha-hANP were directly related to the severity of heart disease (F = 29.61, p less than 0.001). Plasma concentrations of i alpha-hANP were well correlated with pulmonary capillary wedge pressure (PCWP; r = 0.64, p less than 0.001), mean pulmonary arterial pressure (PAP; r = 0.62, p less than 0.001), and mean right atrial pressure (RAP; r = 0.75, p less than 0.001). Plasma concentrations of cGMP were also directly related to the severity of heart disease (F = 13.61, p less than 0.001) and highly correlated with plasma concentrations of i alpha-hANP (r = 0.73, p less than 0.001). Plasma concentrations of cGMP were also closely correlated with PCWP (r = 0.69, p less than 0.001), mean PAP (r = 0.61, p less than 0.001), and mean RAP (r = 0.60, p less than 0.001). The i alpha-hANP concentrations of plasma samples obtained from the coronary sinus were approximately fourfold higher than those of samples obtained from the pulmonary artery, whereas cGMP concentrations were comparable in plasma samples obtained from either site. Elevation of cGMP concentrations following intravenous infusion of synthetic alpha-hANP was comparable in plasma samples obtained from the coronary sinus and the pulmonary artery. These findings suggest that elevated plasma concentrations of i alpha-hANP in cardiac patients result from an increase in the secretion of ANPs, which is probably accelerated by elevation of right or left atrial pressure, and that plasma concentrations of cGMP reflect circulating levels of alpha-hANP.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cyclic AMP; Female; Heart Diseases; Humans; Male; Middle Aged; Osmolar Concentration; Radioimmunoassay

Atrial natriuretic factor (ANF) acts through specific receptors at its target tissues. Receptor-occupancy by ANF induces activation of particulate guanylate cyclase, increased cyclic GMP formation and also inhibition of adenylate cyclase which results in a decrease of cyclic AMP formation. These second messenger systems appear to mediate the effects of ANF in target tissues. Following receptor-mediated activation of particulate guanylate cyclase, cyclic GMP is extruded from the cells, which leads to elevated cyclic GMP levels in plasma and urine in man, whereas cyclic AMP levels remain unchanged. Since cyclic GMP has a much longer half-life than ANF, it is more sensitive as a marker for ANF release than ANF itself, which has a half-life of just a few minutes. Since cyclic GMP is excreted into urine, determinations of urine cyclic GMP can also allow conclusions about the ANF system when blood sampling is impractical. Thus, cyclic GMP and not cyclic AMP is a sensitive biological marker for ANF.

Topics: Adenylyl Cyclases; Animals; Atrial Natriuretic Factor; Cyclic GMP; Enzyme Activation; Guanylate Cyclase; Heart Diseases; Humans; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

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

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

Topics: Amyloidosis; Atrial Natriuretic Factor; Heart Diseases; Humans; Immunoenzyme Techniques

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

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

Regional plasma alpha human atrial natriuretic peptide concentrations were measured, and their relation to intracardiac pressures assessed, in an unselected series of 45 patients undergoing diagnostic cardiac catheterisation. Arteriovenous gradients in plasma concentrations of alpha human atrial natriuretic peptide were consistent with its cardiac secretion and its clearance by the liver and kidneys. Plasma concentrations of the peptide in the pulmonary artery, aorta, and superior vena cava correlated closely with the mean right atrial and pulmonary arterial pressures, and similar, though weaker, positive relations were seen with the left ventricular end diastolic and pulmonary artery wedge pressures. Concentrations of both atrial natriuretic peptide and renin showed significant inverse relations with serum sodium concentrations. Plasma concentrations of alpha human atrial natriuretic peptide are an additional objective indicator of the severity of haemodynamic compromise in patients with cardiac impairment.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Diseases; Heart Rate; Humans; Male; Middle Aged; Pulmonary Wedge Pressure; Renin

In an attempt to clarify the mechanisms regulating the release of atrial natriuretic peptide (ANP) in man, ANP levels in pulmonary arterial plasma determined by RIA were correlated to hemodynamic variables in 17 patients with heart disease who underwent cardiac catheterization and angiocardiography. In addition, plasma ANP levels in various blood vessels were determined in 7 patients with heart disease and in 7 normal subjects to determine the source and the site of removal of circulating ANP. A significantly positive correlation was found between plasma ANP levels and mean pulmonary arterial wedge pressure, while the correlation between plasma ANP levels and mean right atrial pressure was not significant. After the injection of contrast medium, both mean right arterial pressure and plasma ANP levels increased, and a significant positive correlation was found between the two variables. When ANP levels in plasma collected from various blood vessels were compared, the highest levels were found in the coronary sinus. Plasma ANP levels in the renal vein were the lowest and were 50% of the levels in the aorta. Plasma ANP levels in the superior vena cava and internal jugular vein were higher than that in the antecubital vein. Analysis of immunoreactive ANP in pooled plasma by high performance liquid chromatography revealed that the retention time of the main ANP peak coincided with that of synthetic human alpha ANP. These results indicate that circulating ANP mainly originates from the heart, the kidney rapidly takes up a significant amount of ANP from the circulation, and an increase in both left and right atrial pressure triggers ANP release in man.

Topics: Adolescent; Adult; Aged; Atrial Function; Atrial Natriuretic Factor; Female; Heart Diseases; Humans; Male; Middle Aged; Pressure; Pulmonary Wedge Pressure

A direct radioimmunoassay for the rapid and accurate detection of human ANP from unextracted plasma is described. The sensitivity was approximately 50 pg/ml, respectively 2.5 pg/tube, the intra-assay variation 4%, and the inter-assay variation less than 12%. Rat ANP (1-28, 5-25, 5-27 and 5-28), oxydized and reduced hANP as well as plasma samples from various patients run in parallel to the 1-28 hANP standard curve. These findings imply, that the antibody primarily recognizes the mid-region (amino acids 6-25) of the intact ANP, that the C-terminal portion further increases the immunoreactivity, and that circulating plasma hANP is reliably measured. Plasma hANP ranged from 50-166 pg/ml (mean +/- SD: 98.3 +/- 44.6) in healthy individuals, there was no significant difference between samples were drawn in upright or lying position, the apparent half-life of injected hANP was 5.65 minutes. Patients with liver cirrhosis revealed significantly higher hANP levels of 244.5 +/- 173.5 pg/ml. Patients with various forms of cardiac disease had hANP concentrations ranging from 50 to 1744 pg/ml, depending at least partially on the right atrial pressure. No difference was observed if the samples were drawn from either right or left intracardial locations. Our findings with this system demonstrate that hANP is reliably measured even without prior extraction.

Topics: Antibody Specificity; Atrial Natriuretic Factor; Blood Pressure; Half-Life; Heart Diseases; Humans; Liver Cirrhosis; Radioimmunoassay

Topics: Anuria; Atrial Natriuretic Factor; Heart Diseases; Heart Failure; Humans; Hypertension; Male; Middle Aged; Oliguria

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

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

An age-related dependence of plasma ANP levels was studied in 163 healthy children (94 boys, 69 girls) between the ages of day 1 and 16 yr. In neonates during the first 2-4 days of life, significantly higher plasma ANP plasma levels (range 129-356 pg/ml, mean 227) were found compared with older infants and children (p less than 0.001). Beyond the neonatal period through adolescence no significant difference in ANP concentrations could be found between the various age groups. Plasma ANP levels ranged between 2 and 109 pg/ml (mean 47) for all age groups after the newborn period. ANP levels were also determined in 15 adult volunteers and in arterial and venous cord blood of 16 healthy newborns, and concentrations were similar to those found in children. In addition, plasma ANP levels were measured in 40 children with various cardiac diseases; 22 of 40 patients exhibited ANP levels above the upper normal range seen in control children. Of these 22 patients all except two children revealed clinical signs of heart failure. In contrast 15 of 17 children without heart failure showed plasma ANP levels within the range of control children. ANP plasma levels ranged between 93 and 967 pg/ml (mean 284) in patients with heart failure and between 15 and 118 pg/ml (mean 57) in patients without heart failure, respectively. Increased ANP levels in neonates and cardiac patients may result from increased atrial distention and reflect a compensatory mechanism to improve cardiac function by reducing pre- and afterload.

Topics: Adolescent; Aging; Atrial Natriuretic Factor; Child; Child, Preschool; Female; Heart Diseases; Humans; Infant; Infant, Newborn; Male; Radioimmunoassay

To study the factors controlling the release of atrial natriuretic factor (ANF), we analyzed the peripheral plasma ANF concentration in 34 patients with heart disease who underwent cardiac catheterization. A significant positive correlation between plasma ANF concentration and pulmonary arterial pressure (systolic, r = 0.87; diastolic, r = 0.75; mean, r = 0.85; each p less than 0.001) was found in all the patients examined. There were significant positive correlations between plasma ANF concentration and systolic right ventricular pressure (r = 0.86, p less than 0.001), pulmonary capillary wedge pressure (r = 0.50, p less than 0.01) and mean right atrial pressure (r = 0.39, p less than 0.05). A weak but significant negative correlation was found between plasma ANF concentration and stroke volume index (r = -0.43, p less than 0.05). The correlation coefficient between plasma ANF concentration and mean pulmonary arterial pressure was significantly stronger than those between plasma ANF concentration and pulmonary capillary wedge pressure, and between plasma ANF concentration and mean right atrial pressure (p less than 0.05 and p less than 0.01, respectively). In 10 patients with mitral valvular disease, significant correlations with plasma ANF concentration were also found for pulmonary arterial pressure (systolic, r = 0.80; diastolic, r = 0.82; mean, r = 0.82; each p less than 0.01). These findings suggest that pulmonary arterial pressure may play an important role in the mechanism of release of ANF from atrial cardiocytes.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Atria; Heart Diseases; Humans; Male; Middle Aged; Pulmonary Artery; Sensory Receptor Cells

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Dogs; Heart Diseases; Heart Rate; Heart Ventricles; Hemodynamics; Regional Blood Flow

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

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