pituitrin and Heart-Failure

This is a literature review of the use of aquaretic in patients with acute decompensated heart failure (ADHF), including the physiologic function of vasopressin and its mechanism of action in heart failure patients, and aquaretic drugs with their respective risks and benefits.Vasopressin is one of several hormones that can cause hyponatremia and worsen congestion in ADHF patients. Aquaretics are a class of drugs that have an antagonistic effect on vasopressin receptors, especially V2R. Aquaretics use in ADHF patients can provide relief for congestive symptoms with no serious adverse effects. In-depth additional understanding regarding aquaretics may be useful for clinical judgments in treating ADHF patients.

Topics: Acute Disease; Heart Failure; Humans; Receptors, Vasopressin; Vasopressins

The automatism of cardiac pacemaker cells, which is tuned, is regulated by the autonomic nervous system (ANS) and multiple endocrine and paracrine factors, including cardiovascular peptides. The cardiovascular peptides (CPs) form a group of essential paracrine factors affecting the function of the heart and vessels. They may also be produced in other organs and penetrate to the heart via systemic circulation. The present review draws attention to the role of vasopressin (AVP) and some other cardiovascular peptides (angiotensins, oxytocin, cytokines) in the regulation of the cardiovascular system in health and cardiovascular diseases, especially in post-infarct heart failure, hypertension and cerebrovascular strokes. Vasopressin is synthesized mostly by the neuroendocrine cells of the hypothalamus. There is also evidence that it may be produced in the heart and lungs. The secretion of AVP and other CPs is markedly influenced by changes in blood volume and pressure, as well as by other disturbances, frequently occurring in cardiovascular diseases (hypoxia, pain, stress, inflammation). Myocardial infarction, hypertension and cardiovascular shock are associated with an increased secretion of AVP and altered responsiveness of the cardiovascular system to its action. The majority of experimental studies show that the administration of vasopressin during ventricular fibrillation and cardiac arrest improves resuscitation, however, the clinical studies do not present consisting results. Vasopressin cooperates with the autonomic nervous system (ANS), angiotensins, oxytocin and cytokines in the regulation of the cardiovascular system and its interaction with these regulators is altered during heart failure and hypertension. It is likely that the differences in interactions of AVP with ANS and other CPs have a significant impact on the responsiveness of the cardiovascular system to vasopressin in specific cardiovascular disorders.

Topics: Angiotensins; Arginine Vasopressin; Cardiovascular Diseases; Cardiovascular System; Cytokines; Heart Failure; Humans; Hypertension; Lung; Oxytocin; Vasopressins

Pulmonary hypertension (PH), an often unrelenting disease that carries with it significant morbidity and mortality, affects not only the pulmonary vasculature but, in turn, the right ventricle as well. The survival of patients with PH is closely related to the right ventricular function. Therefore, having an understanding of how to manage right ventricular failure (RVF) and acute pulmonary hypertensive crises is imperative for clinicians who encounter these patients. This review addresses the management of these patients in detail, addressing: (a) the pathophysiology of RVF, (b) intensive care monitoring of these patients in the intensive care unit, (c) imaging of the right ventricle, (d) intubation and mechanical ventilation, (e) inotrope and vasopressor selection, (f) pulmonary vasodilator use, (g) interventional and surgical procedures for the acutely failing right ventricle, and (h) mechanical support for RVF.

Topics: Biomarkers; Capnography; Central Venous Pressure; Critical Care; Echocardiography; Epinephrine; Epoprostenol; Extracorporeal Membrane Oxygenation; Heart Failure; Heart Ventricles; Humans; Hypertension, Pulmonary; Iloprost; Intensive Care Units; Milrinone; Nitric Oxide; Radiography, Thoracic; Respiration, Artificial; Spectroscopy, Near-Infrared; Vasodilator Agents; Vasopressins; Ventricular Dysfunction, Right; Ventricular Function, Right

Angiotensin II (ANG II) and vasopressin (VP) interact in several physiological mechanisms, playing a role in arterial hypertension and congestive heart failure. Aim and Methods of Search: To overview the primary mechanism involved in the regulation of cardiovascular function, PubMed/Medline was searched, and authors selected original articles and reviews written in English.. Angiotensin II (ANG II) and vasopressin (VP) are involved in several physiological mechanisms. ANG II stimulates VP release via angiotensin receptor 1. ANG II and VP stimulate aldosterone synthesis and secretion and enhance its action at the renal collecting duct level. VP is also involved in the cardiovascular reflex control of the sympathetic nervous system (SNS). Also, VP potentiates vasoconstriction and cardiac contractility, enhancing the effect of ANG II on sympathetic tone and arterial pressure. On the other hand, ANG II and VP act antagonistically in regulating baroreflex control of the SNS. There is evidence that high VP plasma levels increase baroreflex sympatho-inhibitory responses, and the arterial baroreflex response is shifted to lower pressure. This cardiovascular reflex control is mediated mainly in the brain, specifically in the circumventricular organ area postrema (AP). The modulation of cardiovascular reflex control induced by VP is abolished after lesions of the AP. VP modulation of baroreflex function is also under the control of α2-adrenergic pathway arising from the nucleus of the solitary tract (NTS) and synapsing on VP-ergic neurons of supraoptic and paraventricular nuclei. Presynaptic α2-adrenergic stimulation within the NTS inhibits VP release induced by hypovolemia and the effects of VP and AP on baroreflex control of SNS, thus showing baroreceptor afferent inputs are processed within the NTS and contribute to the increased baroreflex sympatho-inhibitory responses.. In patients with congestive heart failure (CHF), plasma VP levels are elevated, inducing an up-regulation of aquaporin 2 water channel expression in renal collecting duct (CD) cells provoking exaggerated water retention and dilutional hyponatremia. Antagonists of VP and ANG II receptors reduce edema, body weight, and dyspnea in CHF patients.. Hormonal imbalance between ANG II, VP, and SNS may induce hypertension and impaired water-electrolyte balance in cardiovascular diseases.

Topics: Angiotensin II; Animals; Cardiovascular Physiological Phenomena; Cardiovascular System; Heart Failure; Humans; Hypertension; Receptor Cross-Talk; Reflex, Abnormal; Sympathetic Nervous System; Vasopressins

Pregnancy and early life create specific psychosomatic challenges for the mother and child, such as changes in hemodynamics, resetting of the water-electrolyte balance, hypoxia, pain, and stress, that all play an important role in the regulation of the release of oxytocin and vasopressin. Both of these hormones regulate the water-electrolyte balance and cardiovascular functions, maturation of the cardiovascular system, and cardiovascular responses to stress. These aspects may be of particular importance in a state of emergency, such as hypertension in the mother or severe heart failure in the child. In this review, we draw attention to a broad spectrum of actions exerted by oxytocin and vasopressin in the pregnant mother and the offspring during early life. To this end, we discuss the following topics:

Topics: Animals; Female; Heart Failure; Humans; Infant, Newborn; Oxytocin; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Vasopressins; Water-Electrolyte Balance

Our knowledge of the pathophysiology of heart failure (HF) underwent profound changes during the 1980s. Once thought to be of exclusively structural origin, HF began to be seen as the consequence of hormonal imbalance. A number of seminal studies were published in that decade focusing on the impact of neurohormonal activation in HF. Presently, eight neurohormonal systems are known to have a key role in HF development: four stimulate vasoconstriction and sodium/water retention (the sympathetic nervous system, the renin-angiotensin-aldosterone system [RAAS], endothelin, and the vasopressin-arginine system), while the other four stimulate vasodilation and natriuresis (the prostaglandin system, nitric oxide, the dopaminergic system, and the natriuretic peptide system [NPS]). These systems are strongly interconnected and are subject to intricate regulation, functioning together in a delicate homeostasis. Disruption of this homeostasis is characteristic of HF. This review explores the historical development of knowledge on the impact of the neurohormonal systems on HF pathophysiology, from the first studies to current understanding. In addition, the therapeutic potential of each of these systems is discussed, and currently used neurohormonal antagonists are characterized. Special emphasis is given to the latest drug approved for use in HF with reduced ejection fraction, sacubitril/valsartan. This drug combines two different molecules, acting on two different systems (RAAS and NPS) simultaneously.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Drug Combinations; Heart Failure; Humans; Neurosecretory Systems; Renin-Angiotensin System; Sympathetic Nervous System; Tetrazoles; Valsartan; Vasopressins

Modulating neurohormonal imbalance is the cornerstone of successful therapy in patients with chronic heart failure with reduced ejection fraction (HFrEF). Plasma arginine vasopressin (AVP) levels are elevated in HFrEF and may contribute to disease progression by excess signaling at either the V1a or V2 receptors. The effects of V1a receptor antagonism are almost completely unexplored, but V1a signaling is closely related to that for angiotensin II and blocking that receptor deserves further study. Interfering with V2 signaling causes free water diuresis and improves congestion without worsening renal function when added to loop diuretics but alone did not improve outcomes when carried into the post-acute phase in one large study. Outcomes in chronic HFrEF are quite good while outcomes in acute HF remain poor. Therefore, further study of V2 or combined V1/V2 blockade of the effects of AVP would most likely yield positive results in patients with acute HF, perhaps especially as alternative, not adjunctive therapy to loop diuretics.

Topics: Antidiuretic Hormone Receptor Antagonists; Chronic Disease; Disease Progression; Female; Heart Failure; Humans; Male; Neurophysins; Protein Precursors; Receptors, Vasopressin; Sodium Potassium Chloride Symporter Inhibitors; Stroke Volume; Vasopressins

The nonapeptide hypothalamic hormone vasopressin (VP), exerts important effects on cardiovascular system via its receptors V1, V2 and V3. Patients with congestive heart failure (CHF) present elevated plasma VP levels. Aim of this paper is to review the role of vasopressin in CHF.. We analyzed the best of published literature dealing with the role of VP in patients affected by CHF, identifying keywords and MeSH terms in Pubmed and then searching them. The last search was performed on August 2017.. Scientific articles dealing with the relationship between VP and CHF show that circulating high VP levels found in CHF despite an exaggerated increase in circulatory blood volume can contribute to CHF exacerbation. In particular, the stimulation of V1R induces vascular constriction responsible for increased systemic vascular resistance and afterload, and, in addition, coronary vasoconstriction with consequent reduced coronary circulation and cardiac contractility, whereas the stimulation of V2R induces free water reabsorption and this is responsible of preload increase and congestion of pulmonary vascular bed with edema and hyponatremia, markers of advanced CHF.. VP can play an important role among the derangements of the endocrine system in CHF even being a possible target in the treatment of this condition. Vaptans, antagonists of VP receptors, in fact, are able to increase urine output and plasma sodium levels without the increased risk of arrhythmic death induced by diuretics, even though, further studies are needed to establish a possible role of these drugs in the treatment of CHF.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Cardiovascular Agents; Cardiovascular System; Heart Failure; Hemodynamics; Humans; Hypothalamus; Receptors, Vasopressin; Signal Transduction; Up-Regulation; Vasopressins

Despite the introduction of multiple new pharmacological agents over the past three decades in the field of heart failure (HF), overall prognosis remains poor. Hyponatremia is prevalent in HF patients and has been suggested as a contributor to poor response to standard therapy. Elevated levels of arginine vasopressin (AVP), a peptide hormone produced in the hypothalamus, play a role in development of hyponatremia, and AVP and its surrogate, copeptin, are related to changes in osmolality, hemodynamics, neuro-hormones as well as in overall outcome in HF patients. Of current pharmacological interest are the selective and non-selective vasopressin receptor antagonists (VRAs), which inhibit vasoconstriction and cardiac remodeling mediated by the V

Topics: Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Benzazepines; Glycopeptides; Heart Failure; Hemodynamics; Humans; Hyponatremia; Receptors, Vasopressin; Tolvaptan; Vasopressins

The left atrium plays an important role in the maintenance of cardiovascular and neurohumoral homeostasis in heart failure. However, with progressive left ventricular dysfunction, left atrial (LA) dilation and mechanical failure develop, which frequently culminate in atrial fibrillation. Moreover, LA mechanical failure is accompanied by LA endocrine failure [deficient atrial natriuretic peptide (ANP) processing-synthesis/development of ANP resistance) and LA regulatory failure (dominance of sympathetic nervous system excitatory mechanisms, excessive vasopressin release) contributing to neurohumoral overactivity, vasoconstriction, and volume overload (global LA failure). The purpose of the present review is to describe the characteristics and emphasize the clinical significance of global LA failure in patients with heart failure.

Topics: Atrial Fibrillation; Atrial Function, Left; Atrial Natriuretic Factor; Heart Atria; Heart Failure; Humans; Sympathetic Nervous System; Vasoconstriction; Vasopressins; Ventricular Dysfunction, Left

Acute decompensated heart failure (ADHF) is associated with substantial morbidity and mortality, and represents a considerable financial burden to society. Historically, few prospective, randomized, double-blinded trials have investigated the optimal management of ADHF, and most guideline recommendations are based primarily on expert opinion. However, in the last decade, a considerable amount of research has added to the understanding of the management of ADHF in both patients with fluid overload and low cardiac output. In addition, as mechanical circulatory support devices and heart transplantation continue to evolve, significant advances have also been made with regard to the proper selection of patients for advanced surgical options. Finally, several novel pharmacologic agents have shown promise in early trials and may represent the next steps in ADHF management. Although advances have been made over the past decade, many questions remain.

Topics: Acute Disease; Diuretics; Dopamine; Heart Failure; Heart Transplantation; Humans; Natriuretic Peptide, Brain; Nitroprusside; Ultrafiltration; Vasodilator Agents; Vasopressins

Congestion is the most important contributor to morbidity and mortality in heart failure. In patients without congestion, maintaining a neutral sodium balance is imperative to prevent evolving volume overload. Adequate use of neurohumoral blockers, in combination with dietary sodium restriction, is essential and may preclude the need for maintenance diuretic therapy. If volume overload still prevails, loop diuretics remain the mainstay treatment to reduce excessive extracellular volume. However, combinational drug therapy might offer a more attractive alternative to achieve a balanced natriuresis, instead of further uptitration of loop diuretics. Importantly, elevated cardiac filling pressures may be caused by volume misdistribution and impaired venous capacitance, rather than absolute volume overload. Vasodilator therapy to unload the heart, increase venous capacitance, and lower arterial impedance might be interesting in such cases. This review offers a practical approach into current and potential future pharmacologic therapies for managing congestion, focusing on combinational and targeted therapy.

Topics: Cardiovascular Agents; Drug Therapy, Combination; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Natriuresis; Sodium Potassium Chloride Symporter Inhibitors; Vasodilator Agents; Vasopressins

Hyponatremia is a known complication in patients with heart failure (HF). HF patients with severe congestion, hyponatremia, and renal insufficiency are difficult to manage and may have worse outcomes. A main cause of hyponatremia is inappropriately elevated level of plasma arginine vasopressin (AVP), which causes water retention at the collecting duct. AVP antagonists have thus been developed to increase aquaresis and serum sodium levels in patients with euvolemic and hypervolemic hyponatremia. Although tolvaptan, an AVP-2 receptor antagonist, did not show outcomes benefit in patients with decompensated HF, prospective studies are ongoing to evaluate its optimal role in targeted HF patients.

Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Clinical Trials as Topic; Heart Failure; Humans; Hyponatremia; Prospective Studies; Tolvaptan; Vasopressins

Water excretion is regulated in large part through the regulation of osmotic water permeability of the renal collecting duct epithelium. Water permeability is controlled by vasopressin through regulation of the water channel, aquaporin-2 (AQP2). Two processes contribute: (1) regulation of AQP2 trafficking to the apical plasma membrane; and (2) regulation of the total amount of the AQP2 protein in the cells. Regulation of AQP2 abundance is defective in several water-balance disorders, including many polyuric disorders and the syndrome of inappropriate antidiuresis. Here we review vasopressin signaling in the renal collecting duct that is relevant to the two modes of water permeability regulation.

Topics: Animals; Aquaporin 2; beta Catenin; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Heart Failure; Humans; Inappropriate ADH Syndrome; Kidney Tubules, Collecting; Liver Cirrhosis; Mice; Myosin-Light-Chain Kinase; Nephrotic Syndrome; Permeability; Phosphoproteins; Phosphorylation; Polyuria; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-jun; Rats; Signal Transduction; Transcription Factor AP-1; Transcription Factors; Vasopressins

Most patients with heart failure (HF) already have or develop renal dysfunction; this might contribute to their poor outcome. Current treatment for HF can also contribute to worsen renal function. High furosemide doses are traditionally associated with worsening renal function (WRF), but patients with fluid overload may benefit of aggressive fluid removal. Unfortunately, promising therapies like vasopressin antagonists and adenosine antagonists have not been demonstrated to improve outcomes. Likewise, correction of low renal blood flow through dopamine, inotropic agents, or vasodilators does not seem to be associated with a clear benefit. However, transient WRF associated with acute HF treatment may not necessarily portend a poor prognosis. In this review, we focus on the strategies to detect renal dysfunction in acute HF, the underlying pathophysiological mechanisms, and the potential treatments.

Topics: Acute Disease; Adenosine; Biomarkers; Cardiotonic Agents; Diuretics; Dopamine; Heart Failure; Humans; Kidney; Kidney Diseases; Mineralocorticoid Receptor Antagonists; Prognosis; Vasodilator Agents; Vasopressins

Topics: Adrenomedullin; Chronic Disease; Endothelins; Heart Failure; Hemodynamics; Humans; Natriuretic Peptides; Renin-Angiotensin System; Sympathetic Nervous System; Vasopressins

Current treatment of acute decompensated heart failure (ADHF) has not reduced the significant morbidity or mortality associated with this disease, and has promoted drug development aimed at neurohormonal targets. Hypervolemic hyponatremia, which is linked to the nonosmotic release of arginine vasopressin, is associated with a poor prognosis in patients with heart failure (HF). Vasopressin acts on V(2) and V(1a) receptors to cause water retention and vasoconstriction, respectively. Clinical trials have demonstrated that vasopressin receptor antagonists (VRAs) are effective in treating hypervolemic hyponatremia in ADHF without a negative impact on renal function. The small hemodynamic benefit seen with VRA use appeared to result from V(2)-receptor antagonist-induced increase in urine output rather than from a vasodilatory drug effect. VRA use in ADHF trials was associated with minimal symptomatic improvement and no impact on morbidity or mortality. At present, clinical trial evidence does not support the routine use of VRAs in ADHF. Given the favorable renal profile of VRAs, studies on the possible benefit of VRAs in ADHF patients with renal insufficiency and diuretic resistance appear warranted.

Topics: Acute Disease; Animals; Antidiuretic Hormone Receptor Antagonists; Benzamides; Benzazepines; Clinical Trials as Topic; Heart Failure; Hemodynamics; Humans; Hyponatremia; Prognosis; Pyrroles; Tolvaptan; Vasoconstriction; Vasopressins

Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Diuretics; Edema, Cardiac; Heart Failure; Humans; Receptors, Vasopressin; Tolvaptan; Vasopressins

Topics: Benzazepines; Cardiomyopathy, Dilated; Diuretics; Heart Failure; Humans; Tolvaptan; Vasopressins

It is now becoming clear that two major systems namely the sympathetic nervous system and the renin-angiotensin system are activated in response to ischemic injury; these result in the elevation of plasma catecholamines and angiotensin II during the development of myocardial infarction as well as congestive heart failure. Although plasma levels of several other hormones including aldosterone, endothelin, vasopressin, natriuretic peptides, growth factors and inflammatory cytokines are also increased in heart failure, their relationship with changes in catecholamine and/or angiotensin levels as well as their significance for the induction of congestive heart failure are poorly understood. In this article we have examined the evidence regarding the role of endothelin and vasopressin in the pathogenesis of cardiac hypertrophy and congestive heart failure in addition to evaluating the significance of their antagonism by using their receptor blockade for treatment of congestive heart failure. Endothelin appears to maintain blood pressure by its vasoconstricting action whereas vasopressin primarily produces similar effect by retention of body fluid. Myocardium is also known to express both ET-A and ET-B receptors in addition to V1 and V2 receptors for vasopressin, which have been shown to induce cardiac remodeling. Out of various ET-1 receptor antagonists, which are available, a non-selective endothelin receptor antagonist, bosentan, as well as an ET-A receptor antagonist, BQ-123, seem most promising for the treatment of congestive heart failure. Likewise, vasopressin antagonists such as a non-selective antagonist, conivaptan, as well as V2 selective antagonist, tolvaptan, may prove highly valuable for the therapy of this condition. Since most of the existing interventions are helpful in treating patients with congestive heart failure only partially, there appears to be a real challenge for developing some combination therapy for the treatment of congestive heart failure.

Topics: Angiotensin II; Animals; Antidiuretic Agents; Antihypertensive Agents; Benzazepines; Biomarkers; Bosentan; Catecholamines; Drug Therapy, Combination; Endothelin-1; Heart Failure; Humans; Peptides, Cyclic; Renin-Angiotensin System; Sulfonamides; Sympathetic Nervous System; Tolvaptan; Treatment Outcome; Vasopressins

Concomitant anemia, heart failure, and renal disease can be seen in a large proportion of patients with heart failure. The purpose of this review is to discuss the current definitions and mechanisms involved in this pathophysiological relationship, as well as the potential management and treatment options available for these patients.. Dysfunctional heart can promote the dysfunction of the kidneys through a variety of pathophysiological mechanism, the reciprocal holds true as well. Heart failure has been considered as the most common type of cardiovascular complication seen in patients with renal failure. Central to this relationship lies anemia, which can be the result or the cause of either heart or kidney disease.. Cardiorenal syndrome is a complex condition, which requires the collaboration and resources from cardiology, cardiac surgery, nephrology, and critical care. Of great importance is recognizing the presence of cardiorenal syndrome and appreciating the impact it can play on treatment options and survival.

Topics: Adenosine; Anemia; Chronic Disease; Diuretics; Heart Failure; Hemofiltration; Humans; Kidney Failure, Chronic; Prognosis; Renin-Angiotensin System; Risk Factors; Vasodilator Agents; Vasopressins

Hospitalization for heart failure is a major health problem with high in-hospital and postdischarge mortality and morbidity. Non-potassium-sparing diuretics (NPSDs) still remain the cornerstone of therapy for fluid management in heart failure despite the lack of large randomized trials evaluating their safety and optimal dosing regimens in both the acute and chronic setting. Recent retrospective data suggest increased mortality and re-hospitalization rates in a wide spectrum of heart failure patients receiving NPSDs, particularly at high doses. Electrolyte abnormalities, hypotension, activation of neurohormones, and worsening renal function may all be responsible for the observed poor outcomes. Although NPSD will continue to be important agents to promptly resolve signs and symptoms of heart failure, alternative therapies such as vasopressine antagonists and adenosine blocking agents or techniques like veno-venous ultrafiltration have been developed in an effort to reduce NPSD exposure and minimize their side effects. Until other new agents become available, it is probably prudent to combine NPSD with aldosterone blocking agents that are known to improve outcomes.

Topics: Adenosine; Cardiovascular Diseases; Heart Failure; Hemofiltration; Hormone Antagonists; Humans; Kidney Diseases; Risk Assessment; Risk Factors; Sodium Potassium Chloride Symporter Inhibitors; Time Factors; Treatment Outcome; Vasopressins; Water-Electrolyte Balance

To evaluate acute hemodynamic, short-term, and long-term effects of vasopressin antagonists in patients with heart failure (HF).. Searches of the PubMed database (1966-February 2010) were conducted. Search terms included AVP receptor antagonist, CHF, tolvaptan, conivaptan, lixivaptan, HF, and hyponatremia. Manufacturers' prescribing information, manufacturer Web site searches, and searches made on www.clinicaltrials.gov were also included.. All clinical trials identified from the reference search and data sources were reviewed. Articles were included if they were relevant to short-term and long-term outcomes of patients with HF who were treated with vasopressin antagonists.. Trials of conivaptan, tolvaptan, and lixivaptan were evaluated. The evidence indicates that all agents increase urine output >10 mL/h, and conivaptan and tolvaptan decrease pulmonary capillary wedge pressure (-2.6 +/- 0.7, -5.4 +/- 0.7, and -4.6 +/- 0.7 mm Hg for placebo, conivaptan 20 mg, and conivaptan 40 mg, respectively; -5.67 +/- 4.58 to -6.38 +/- 4.12 mmHg for tolvaptan, and -4.16 +/- 4.57 mm Hg for placebo) in patients with HF. Both of these changes occur without inducing electrolyte abnormalities or renal dysfunction. Trials with conivaptan in acute HF have not demonstrated a benefit in cardiac index, mean arterial pressure, or vascular resistance. Data from clinical trials indicate that tolvaptan may decrease dyspnea (p < 0.05) and pedal edema (p < 0.001). To date, no large-scale trials of any agent have demonstrated an improvement in left ventricular systolic function, rehospitalization, worsening HF, or death.. Vasopressin antagonists cannot be considered routine pharmacotherapy for HF. Further, conivaptan should not be used for the treatment of acute HF. There is not enough literature to advocate for or against the use of lixivaptan in patients with HF. Tolvaptan may be considered for the treatment of hyponatremia.

Topics: Azepines; Benzamides; Benzazepines; Heart Failure; Humans; Hyponatremia; Neurotransmitter Agents; Pyrroles; Tolvaptan; Vasopressins

Acute heart failure (AHF) is a frequent medical condition associated with a poor prognosis. Based on systolic blood pressure at presentation, patients with AHF can be classified into 5 clinical profiles enabling a more targeted use of standard medications including diuretics, vasodilators and inotropes. The most recent guidelines underline the importance of a rapid management and the favorable impact of heart failure programs, which reduce morbidity and mortality after an admission for AHF. New therapeutic perspectives include ultrafiltration, vasopressin and adenosine antagonists, relaxin and new inotropes such as istaroxime.

Topics: Acute Disease; Adenosine; Algorithms; Cardiotonic Agents; Diuretics; Drug Therapy, Combination; Etiocholanolone; Heart Failure; Hemodiafiltration; Humans; Oxygen Inhalation Therapy; Practice Guidelines as Topic; Prognosis; Relaxin; Risk Factors; Treatment Outcome; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

Arginine vasopressin (AVP or antidiuretic hormone) is one of the key hormones in the human body responsible for a variety of cardiovascular and renal functions. It has so far escaped introduction into the routine clinical laboratory due to technical difficulties and preanalytical errors. Copeptin, the C-terminal part of the AVP precursor peptide, was found to be a stable and sensitive surrogate marker for AVP release. Copeptin behaves in a similar manner to mature AVP in the circulation, with respect to osmotic stimuli and hypotension. During the past years, copeptin measurement has been shown to be of interest in a variety of clinical indications, including cardiovascular diseases such as heart failure, myocardial infarction, and stroke. This review summarizes the recent progress on the diagnostic use of copeptin in cardiovascular and renal diseases and discusses the potential use of copeptin measurement in the context of therapeutic interventions with vasopressin receptor antagonists.

Topics: Arginine Vasopressin; Biomarkers; Blood Volume; Cardiovascular Diseases; Cardiovascular System; Glycopeptides; Heart Failure; Humans; Kidney; Kidney Diseases; Myocardial Infarction; Prognosis; ROC Curve; Shock, Cardiogenic; Stroke; Vasopressins

Early in the management of acute illness, it is critically important that volume status is accurately estimated. If inappropriate therapy is given because of errors in volume assessment, acute mortality rates are increased. Unfortunately, as the gold standard of radioisotopic volume measurement is costly and time-consuming, in the acute care environment clinicians are forced to rely on less accurate measures. In this manuscript, the authors review the currently available techniques of volume assessment for patients presenting with acute illness. In addition to discussing the accuracy of the history, physical examination, and radiography, acoustic cardiography and bedside ultrasonography are presented.

Topics: Blood Volume; Body Fluids; Cardiography, Impedance; Dyspnea; Heart Auscultation; Heart Failure; Humans; Natriuretic Peptides; Physical Exertion; Radiography, Thoracic; Vasopressins; Vital Signs; Water-Electrolyte Balance

Hyponatremia is the most prevalent electrolyte disorder in hospitalized patients. Vasopressin plays an important role in the pathogenesis of this disorder through its action on the vasopressin type 2 receptor (V(2)R), leading to electrolyte-free water reabsorption. Multiple vasopressin receptor antagonists have recently been developed that differ in their specificity for V(2)R and V(1)R. These agents have applications in diseases that can result in hypervolemic and euvolemic hyponatremia, such as the syndrome of inappropriate antidiuretic hormone secretion, congestive heart failure and cirrhosis. V(2)R antagonists have demonstrated promise in the short-term correction of hyponatremia, although the long-term survival benefits of these drugs are less clear. This review discusses the physiology of vasopressin in hyponatremia, the clinical implications of the disorder and examples of individual therapeutics used in treatment strategies.

Topics: Animals; Antidiuretic Agents; Antidiuretic Hormone Receptor Antagonists; Clinical Trials as Topic; Heart Failure; Humans; Hyponatremia; Inappropriate ADH Syndrome; Liver Cirrhosis; Receptors, Vasopressin; Vasopressins

The non-peptide vasopressin antagonists (VPA), called vaptans, were developed in the 1990s to antagonize both the pressor and antidiuretic effects of vasopressin. There are three subtypes of VPA receptors: V1a, V1b and V2. V1a receptors are widely distributed in the body, mainly the blood vessels and myocardium. The V1b receptors are located mainly in the anterior pituitary gland and play a role in ACTH release. V2 receptors are located in the collecting tubular renal cells. Both V1a and V1b receptors act through the intracellular phosphoinositol signalling pathway, Ca(++) being the second messenger. V2 receptors work through AMPc generation, which promotes aquaporin 2 (AQP2) trafficking and allows water to enter the cell. The vaptans act competitively at the AVP receptor. The most important are mozavaptan, lixivaptan, satavaptan and tolvaptan, all of which are selective V2 antagonists and are administered through the oral route. In contrast, conivaptan is a dual V1 and V2 antagonist administered through the endovenous route. The main characteristics of vaptans are their effect on free water elimination without affecting electrolyte excretion. There are several studies on the effects of these drugs in hypervolemic hyponatremia (heart failure, hepatic cirrhosis) as well as in normovolemic hyponatremia (inappropriate secretion of ADH [SIADH]). Current studies show that the vaptans are effective and well tolerated, although knowledge of these drugs remains limited. There are no studies of the use of vaptans in severe hyponatremia. Osmotic demyelination syndrome due to excessively rapid correction of hyponatremia has not been described.

Topics: Adult; Antidiuretic Hormone Receptor Antagonists; Aquaporin 2; Benzamides; Benzazepines; Calcium Signaling; Clinical Trials as Topic; Cyclic AMP; Double-Blind Method; Drug Therapy, Combination; Heart Failure; Humans; Hyponatremia; Inappropriate ADH Syndrome; Kidney Tubules, Collecting; Liver Cirrhosis; Morpholines; Multicenter Studies as Topic; Neoplasms; Pituitary Gland, Anterior; Pyrroles; Randomized Controlled Trials as Topic; Receptors, Vasopressin; Second Messenger Systems; Spiro Compounds; Tolvaptan; Vasopressins

Hyponatremia is the most common electrolyte abnormality found in hospitalized patients with heart failure. It may occur in patients who have hypovolemic, hypervolemic, or euvolemic state. It is usually not corrected by available therapies. It is a major predictor of prognosis, and correction of hyponatremia can be effectively accomplished by vasopressin antagonists. However, it still remains to be seen whether the normalization of serum sodium with vasopressin antagonists will also lead to an improved long-term prognosis.

Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Heart Failure; Humans; Hyponatremia; Prognosis; Sodium; Tolvaptan; Treatment Outcome; Vasopressins

Topics: Animals; Aquaporin 2; Aquaporins; Endocytosis; Exocytosis; Heart Failure; Humans; Kidney; Kidney Concentrating Ability; Liver Cirrhosis; Phosphorylation; Protein Transport; Signal Transduction; Urologic Diseases; Vasopressins; Water; Water-Electrolyte Balance; Water-Electrolyte Imbalance

The pathogenesis of cardiac failure involves activation of the neurohumoral axis including stimulation of the sympathetic nervous system, the renin-angiotensin-aldosterone, and nonosmotic vasopressin systems. While these responses are critical in maintaining arterial pressure, they are associated with renal vasoconstriction, as well as sodium and water retention. In advanced circumstances, renal dysfunction and hyponatremia occur with cardiac failure. Even a modest rise in serum creatinine related to diminished renal function in heart failure patients is associated with increased risk for cardiovascular morbidity and mortality. Similarly, increased thirst and the nonosmotic stimulation of vasopressin in advanced cardiac failure leads to hyponatremia, which is also a major risk factor for mortality. Currently, V2 vasopressin receptor antagonists have been shown to correct hyponatremia in cardiac failure. One such agent, conivaptan, also is a V1 receptor antagonist which could theoretically benefit heart failure patients by decreasing cardiac afterload and remodeling. The effect of V2 receptor antagonists to correct hyponatremia in heart failure patients appears to be quite safe. However, to date no effect on mortality has been demonstrated.

Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Heart Failure; Humans; Hyponatremia; Kidney; Kidney Diseases; Vasopressins

Heart failure (HF) is still one of the most important causes of morbidity and mortality worldwide. Neurohormonal changes appear to play an important role in the development and continuation of HF. Among the mediators responsible for these changes, antidiuretic hormone (ADH) is probably the least known. However, elevated concentrations of ADH are frequently found in this syndrome and have prognostic value in addition to known biomarkers. Recent experimental studies and clinical trials have aroused interest in the possible benefits of ADH receptor antagonists. This article reviews the pathophysiological mechanisms of ADH in HF and the latest advances in ADH antagonism in the therapeutic management of HF.

Topics: Heart Failure; Humans; Vasopressins

The tools available to physicians for the treatment of hyponatremia, the most common of electrolyte disorders, are limited by lack of effectiveness, compliance difficulties, and toxicity problems. For this reason the development of novel oral antagonists of vasopressin provide a new approach to the management of these disorders. Since vasopressin plays a central role in the pathogenesis of most hyponatremic disorders, the inhibition of binding of the hormone to its receptors is likely to provide a most reliable and reproducible response leading to increases in free water excretion. This article reviews many of the studies that have been undertaken with this new class of agents, both in hypovolemic and hypervolemic settings.

Topics: Body Water; Heart Failure; Humans; Hyponatremia; Vasopressins

Topics: Arginine Vasopressin; Heart Failure; Humans; Hyponatremia; Receptors, Vasopressin; Vasopressins

The majority of patients with acute decompensated heart failure are admitted with symptoms of congestion. The classic symptoms of "congestive" heart failure reflect fluid overload, that is, orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema; these symptoms can be so dramatic that it is not surprising that patients seek hospitalization. Activation of the renin angiotensin system coupled with sympathetic hyperactivity results in marked sodium retention and high filling pressures that ultimately bring about these congestive symptoms. The treatment goal of patients hospitalized with volume overload and high filling pressures is to improve symptoms by normalizing the filling pressure and volume status without worsening renal function. The current use of diuretics, vasodilators, and ultrafiltration, as well as potential future use of investigational agents such as oral vasopressin antagonists and adenosine A1-receptor antagonists, is surrounded by the important issues of when to stop intravenous therapy in hospitalized patients and the exact mechanism by which the filling pressures are normalized. New data from evidence-based clinical trials and optimal strategies for monitoring fluid overload will help define this issue and ultimately reduce mortality in these patients.

Topics: Acute Disease; Adenosine A1 Receptor Antagonists; Diuretics; Evidence-Based Medicine; Heart Failure; Hospitals; Humans; Medication Therapy Management; Patient Care Management; Practice Guidelines as Topic; Renin-Angiotensin System; Ultrafiltration; Vasodilator Agents; Vasopressins

Heart failure is one of the leading causes of hospitalizations in the United States. Concomitant and significant renal dysfunction is common in patients with heart failure. Increasingly, the syndrome of heart failure is one of cardiorenal failure, in which concomitant cardiac and renal dysfunctions exist, with each accelerating the progression of the other. One fourth of patients hospitalized for the treatment of acute decompensated heart failure will experience significant worsening of renal function, which is associated with worse outcomes. It remains unclear whether worsening renal function specifically contributes to poor outcomes or whether it is merely a marker of advanced cardiac and renal dysfunction. Diuretic resistance, with or without worsening renal function, is also common in acute decompensated heart failure, although the definition of diuretic resistance, its prevalence, and prognostic implications are less well defined. The term cardiorenal syndrome has been variably associated with cardiorenal failure, worsening renal function, and diuretic resistance but is more comprehensively defined as a state of advanced cardiorenal dysregulation manifest by one or all of these specific features. The pathophysiology of the cardiorenal syndrome is poorly understood and likely involves interrelated hemodynamic and neurohormonal mechanisms. When conventional therapy for acute decompensated heart failure fails, mechanical fluid removal via ultrafiltration, hemofiltration, or hemodialysis may be needed for refractory volume overload. While ultrafiltration can address diuretic resistance, whether ultrafiltration prevents worsening renal function or improves outcomes in patients with cardiorenal syndrome remains unclear. Evidence regarding the potential renal-preserving effects of nesiritide is mixed, and further studies on the efficacy and safety of different doses of nesiritide in heart failure therapy are warranted. Newer therapeutic agents, including vasopressin antagonists and adenosine antagonists, hold promise for the future, and clinical trials of these agents are underway.

Topics: Acute Disease; Adenosine; Cardiotonic Agents; Dopamine; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Insufficiency; Risk Factors; Sodium Potassium Chloride Symporter Inhibitors; Ultrafiltration; Vasopressins

Therapy of heart failure is more difficult when renal function is impaired. Here, we outline the effects on kidney function of the autacoid, adenosine, which forms the basis for adenosine A(1) receptor (A(1)R) antagonists as treatment for decompensated heart failure. A(1)R antagonists induce a eukaliuretic natriuresis and diuresis by blocking A(1)R-mediated NaCl reabsorption in the proximal tubule and the collecting duct. Normally, suppressing proximal reabsorption will lower glomerular filtration rate (GFR) through the tubuloglomerular feedback mechanism (TGF). But the TGF response, itself, is mediated by A(1)R in the preglomerular arteriole, so blocking A(1)R allows natriuresis to proceed while GFR remains constant or increases. The influence of A(1)R over vascular resistance in the kidney is augmented by angiotensin II while A(1)R activation directly suppresses renin secretion. These interactions could modulate the overall impact of A(1)R blockade on kidney function in patients taking angiotensin II blockers. A(1)R blockers may increase the energy utilized for transport in the semi-hypoxic medullary thick ascending limb, an effect that could be prevented with loop diuretics. Finally, while the vasodilatory effect of A(1)R blockade could protect against renal ischaemia, A(1)R blockade may act on non-resident cells to exacerbate reperfusion injury, where ischaemia to occur. Despite these uncertainties, the available data on A(1)R antagonist therapy in patients with decompensated heart failure are promising and warrant confirmation in further studies.

Topics: Adenosine; Animals; Heart Failure; Humans; Kidney; Kidney Tubules, Collecting; Kidney Tubules, Proximal; Receptors, Purinergic P1; Reperfusion Injury; Vasoconstriction; Vasopressins; Xanthines

As vasopressin receptors are found in many different tissues, vasopressin antagonists may benefit the treatment of numerous disorders. Effects of vasopressin via V1(a) and V2 receptors are closely implicated in a variety of water-retaining diseases and cardiovascular diseases, including heart failure, hyponatremia, hypertension, renal diseases, syndrome of inappropriate antidiuretic hormone secretion, cirrhosis, and ocular hypertension. Furthermore, V1(a) vasopressin antagonists might be useful in cerebral ischemia and stroke, Raynaud's disease, dysmenorrhoea and tocolytic treatment. V1(b) selective vasopressin antagonists are discussed in terms of their usefulness in the treatment of emotional and psychiatric disorders. The vaptans are vasopressin receptor antagonists with V1(a) (relcovaptan) or V2 (tolvaptan, lixivaptan, satavaptan) selectivity or non-selective activity (conivaptan). Conivaptan is the first vaptan which has been approved by the FDA for the treatment of euvolemic hyponatremia. For further indications such as congenital heart failure, studies are going on.

Topics: Antidiuretic Agents; Antidiuretic Hormone Receptor Antagonists; Heart Failure; Humans; Hyponatremia; Vasopressins

Vasopressin antagonists have been studied in a variety of clinical settings, including patients with acute and chronic heart failure. The clinical trials published to date have sought to describe the clinical and physiologic effects of these agents in an effort to prove clinical efficacy and safety. A variety of agents with varying effects on V2 and V1a vasopressin receptor subtype have been studied. They have been shown to reduce bodyweight and improve serum sodium without worsening renal function. They may also decrease the need for loop diuretic use and may be particularly useful in patients with hyponatremia in the setting of volume overload. Further studies are underway that are powered to assess for morbidity and mortality benefits. The beneficial effects have been well documented but, until outcomes are understood more fully, the use of these agents should be limited to currently approved indications. In the USA, this includes only the treatment of euvolemic hyponatremia.

Topics: Antidiuretic Hormone Receptor Antagonists; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Heart Failure; Humans; Hyponatremia; Male; Randomized Controlled Trials as Topic; Receptors, Vasopressin; Risk Factors; Severity of Illness Index; Survival Rate; Treatment Outcome; Vasopressins

In chronic heart failure (CHF), persistent autonomic derangement and neurohumoral activation cause structural end-organ damage, decrease exercise capacity, and reduce quality of life. Beneficial effects of pharmacotherapy and of exercise training in CHF have been documented at various functional and structural levels. However, pharmacologic treatment can not yet reduce autonomic derangement and neurohumoral activation in CHF to a minimum. Various studies suggest that exercise training is effective in this respect.. After reviewing the available evidence we conclude that exercise training increases baroreflex sensitivity and heart rate variability, and reduces sympathetic outflow, plasma levels of catecholamines, angiotensin II, vasopressin, and brain natriuretic peptides at rest.. Exercise training has direct and reflex sympathoinhibitory beneficial effects in CHF. The mechanism by which exercise training normalizes autonomic derangement and neurohumoral activation is to elucidate for further development of CHF-related training programs aimed at maximizing efficacy while minimizing workload.

Topics: Arginine; Autonomic Nervous System Diseases; Baroreflex; Catecholamines; Chronic Disease; Endothelins; Exercise Therapy; Heart Failure; Heart Rate; Humans; Natriuretic Peptide, Brain; Neurotransmitter Agents; Renin-Angiotensin System; Treatment Outcome; Vasopressins

In a national heart failure registry, hyponatremia (serum sodium < 130 mEq/L) was initially reported in 5% of patients and considered a risk factor for increased morbidity and mortality. In a chronic heart failure study, serum sodium level on admission predicted an increased length of stay for cardiovascular causes and increased mortality within 60 days of discharge. Hyponatremia in patients with congestive heart failure (CHF) is associated with a higher mortality rate. Also, by monitoring and increasing serum sodium levels during hospitalization for CHF, patient outcomes may improve. This review describes the pathophysiology of hyponatremia in relation to CHF, including the mechanism of action of vasopressin receptors in the kidney, and assesses the preclinical and clinical trials of vasopressin receptor antagonists--agents recently developed to treat hyponatremia. In hospitalized patients with CHF, hyponatremia plays a major role in poor outcomes. Vasopressin receptor antagonists have been shown to be safe and effective in clinical trials in patients with hyponatremia.

Topics: Arginine Vasopressin; Azepines; Benzamides; Benzazepines; Chronic Disease; Clinical Trials as Topic; Diuretics; Heart Failure; Humans; Hyponatremia; Models, Biological; Pyrroles; Registries; Renin-Angiotensin System; Sodium; Tolvaptan; Treatment Outcome; Vasopressins

Mild hyponatremia is common in patients hospitalized for worsening heart failure, and it is a major predictor of post-discharge mortality and morbidity irrespective of left ventricular ejection fraction. Recent data also suggest that standard therapy for heart failure does not improve or normalize serum sodium concentration during hospitalization. There are conclusive data that vasopressin antagonists improve or normalize serum sodium in this patient population. However, it is not known if this improvement or normalization in serum sodium is associated with an improvement in post-discharge outcomes. Future trials with vasopressin antagonists in patients hospitalized with worsening heart failure and hyponatremia are in order.

Topics: Heart Failure; Humans; Hyponatremia; Sodium; Survival Rate; Treatment Outcome; Vasopressins

The first non-peptide vasopressin receptor antagonist (VRA) was recently approved by the United States Food and Drug Administration, and several others are now in late stages of clinical development. Phase 3 trials indicate that these agents predictably reduce urine osmolality, increase electrolyte-free water excretion, and raise serum sodium concentration. They are likely to become a mainstay of treatment of euvolemic and hypervolemic hyponatremia. Although tachyphylaxis to the hydro-osmotic effect of these agents does not appear to occur, their use is accompanied by an increase in thirst, and they do not always eliminate altogether the need for water restriction during treatment of hyponatremia. Experience with use of these agents for treatment of acute, severe, life-threatening hyponatremia as well as chronic hyponatremia is limited. Further studies are needed to determine how they are best used in these situations, but the risk of overly rapid correction of hyponatremia seems low. Results of long-term trials to determine the ability of VRAs to reduce morbidity or mortality in congestive heart failure or to slow the progression of polycystic kidney disease are awaited with great interest.

Topics: Antidiuretic Hormone Receptor Antagonists; Azepines; Benzamides; Benzazepines; Clinical Trials as Topic; Diabetes Insipidus, Nephrogenic; Fibrosis; Heart Failure; Humans; Hyponatremia; Osmolar Concentration; Polycystic Kidney Diseases; Pyrroles; Receptors, Vasopressin; Sodium; Tolvaptan; United States; United States Food and Drug Administration; Vasopressins

Increased arginine vasopressin (AVP) secretion in heart failure may lead to vasoconstriction, left ventricular remodeling, and water retention-actions that promote afterload, preload, and hyponatremia and thereby cause disease progression. Interfering with AVP-mediated signaling pharmacologically may be beneficial in heart failure. Selective antagonism of the vasopressin 2 (V2) receptor may facilitate a safe diuresis and normalize low serum sodium levels, as demonstrated in preliminary clinical trials. Pure V2 antagonism, however, may stimulate AVP secretion and enhance V1a signaling, while pure V1a receptor antagonism may lead to unwanted V2 stimulation and secondary water retention and volume expansion. Combined V1a and V2 receptor antagonism could potentially prove advantageous as a therapy for heart failure by acting synergistically to facilitate diuresis and improve hemodynamics.

Topics: Antidiuretic Hormone Receptor Antagonists; Aquaporin 2; Arginine Vasopressin; Disease Progression; Heart Failure; Humans; Hyponatremia; Treatment Outcome; Vasopressins

This article discusses the pathophysiology of sodium and water retention in edematous disorders with a particular focus on cardiac failure, cirrhosis, and pregnancy. The body fluid volume hypothesis, which emphasizes the dominant role of arterial baroreceptors in renal sodium and water excretion, is reviewed. With arterial underfilling, either due to a decrease in cardiac output or peripheral arterial vasodilation, the normal central inhibition of the sympathetic nervous system activity and baroreceptor-mediated, nonosmotic arginine vasopressin (AVP) release is attenuated. The resultant increase in renal adrenergic activity stimulates the renin-angiotensin-aldosterone system. Although the resultant increase in systemic vascular resistance compensates for the primary arterial underfilling, this activation of the neurohumoral axis results in diminished sodium and water delivery to the renal collecting duct sites of aldosterone, AVP, and natriuretic peptide action. This diminished distal sodium and water delivery will be discussed as an important factor in the failure to escape from the sodium-retaining effects of aldosterone, the resistance to the natriuretic and diuretic effects of natriuretic peptides, and the diminished maximal solute-free water excretion in patients with edema. The role of the nonosmotic AVP release in water retention and hypo-osmolality/hyponatremia has been demonstrated in patients and experimental animals by administering nonpeptide, orally active vasopressin V2 receptor antagonists. These agents have been found to increase solute-free water excretion in patients with water-retaining, hyponatremic edema as well as in experimental animals.

Topics: Aldosterone; Body Water; Edema; Female; Heart Failure; Humans; Hyponatremia; Liver Cirrhosis; Pregnancy; Pregnancy Complications; Renin-Angiotensin System; Vasodilation; Vasopressins

Cardiovascular failure in critically ill patients carries a high mortality. Identification and treatment of the underlying etiology simultaneously with prompt therapy are indicated to avoid the consequences of prolonged shock. Physicians should assess patients using all available clinical, radiologic, and laboratory data to avoid the pitfalls associated with use of single measures of regional or global perfusion. Continued evidence of inadequate perfusion despite fluid resuscitation warrants consideration of placement of a pulmonary artery catheter or pharmacologic support of the cardiovascular system. Finally, the dynamic nature of physiology in critically ill patients requires constant patient reassessment and flexibility in treatment to tailor therapy individually as the pathologic state evolves.

Topics: Algorithms; Blood Vessels; Catheterization, Swan-Ganz; Glucocorticoids; Heart; Heart Conduction System; Heart Diseases; Heart Failure; Humans; Myocardial Infarction; Oxygen Consumption; Shock, Cardiogenic; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

Renal insufficiency is becoming an increasingly common and devastating comorbidity in both acute and chronic heart failure settings. Part of the problem is due to the lack of insight into the underlying pathophysiology of salt and water balance leading to the congestive states. This review summarizes our current understanding regarding the cause and consequences of renal insufficiency in patients with heart failure, and addresses some of the limitations of current therapeutic strategies. Based on these limitations, this paper will explore the ongoing efforts to develop novel drug therapeutics to prevent or ameliorate renal impairment in patients with heart failure. These include natriuretic peptides and other vasodilators, adenosine receptor antagonists, and vasopressin receptor antagonists all currently undergoing late-stage clinical trials.

Topics: Adenosine; Angiotensin-Converting Enzyme Inhibitors; Antidiuretic Agents; Diuretics; Drug Therapy, Combination; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptides; Neurotransmitter Agents; Prognosis; Renal Insufficiency; Treatment Outcome; Vasodilator Agents; Vasopressins

Growing number of studies reveal that the brain neural network plays significant role in the short-term and long-term regulation of the cardiovascular functions. The neurons involved in the complex neurogenic control of the cardiovascular system use classical neurotransmitters and nonconventional mediators such as peptides (angiotensin II, vasopressin, natriuretic peptides, endothelins, opioids, cytokines), steroids, ouabain-like factors and gaseous compounds. Among them the neuropeptides form a group of substances arising significant interest. Thanks to wide distribution of peptidergic neurons in the central nervous system, location of peptide receptors on neurons and glial cells, versatile but frequently overlapping mechanisms of activation of the intracellular processes the neuropeptides play significant role in short-term and long-term regulation of excitability and remodeling of the neurons. In several instances they modulate effects of the classical transmitting systems involved in regulation blood pressure, heart rate, water-electrolyte balance, metabolism, stress, pain, mood and memory. Prolonged activation or inhibition of specific neuropeptide pathways frequently results in long-lasting disorders of several regulatory systems. In this review this is exemplified by overactivity of angiotensin II, vasopressin and cytokines in the brain during hypertension, heart failure and stress. Multifarious actions of angiotensin II and vasopressin, and their mutual interaction with cytokines make of these neuropeptides excellent candidates for the compounds responsible for long-term resetting of the central cardiovascular control, and forming a link between the cardiovascular diseases, stress and mood disorders.

Topics: Angiotensin II; Brain; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Cytokines; Heart Failure; Humans; Hypertension; Nerve Net; Neuropeptides; Neurosecretory Systems; Stress, Psychological; Vasopressins

Vasopressin receptor antagonists are a new class of drugs that address the problems of fluid retention, hyponatremia, and renal dysfunction in heart failure. Elevated vasopressin levels in heart failure cause myocardial fibrosis, hypertrophy and vasoconstriction by activating the V1a receptors, as well as water retention and hyponatremia by activating V2 receptors. Antagonism of V1a receptors alone is of little benefit. In contrast, antagonism of V2 receptors results in increased free water excretion and increased sodium concentration. Vasopressin receptor antagonists may be viewed as the first new class of agents with predominantly aquaretic effects, in contrast to the natriuretic effects of loop diuretics. The predominant action of vasopressin receptor antagonists is water excretion, without depletion of other electrolytes, and less neurohormonal stimulation compared with loop diuretics. Classified as neurohormonal antagonists, vasopressin receptor antagonists acutely may improve congestion and hyponatremia, while chronically preventing progression of left ventricular dysfunction. Several compounds have been evaluated in late-stage clinical trial programs, and at least one may be used as an adjunct to standard medical therapy, combining aquaresis for congestion with neurohormonal antagonism for morbidity and mortality. We reviewed recent patents dealing with heart failure, hyponatremia, anti-diuretic hormone, and vasopressin antagonists.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Azepines; Benzamides; Benzazepines; Heart Failure; Humans; Pyrroles; Receptors, Vasopressin; Tolvaptan; Vasopressins

Heart failure represents a major public health problem in the industrialized countries and despite of optimal medical treatment its mortality remains high. The history of its management reflects growth and changes in our understanding of its pathophysiology. In the past, pharmacological treatment of heart failure was aimed only at relieving edema and improving hemodynamics. Today, however, a major aim of treatment is to antagonize the sympathetic nervous system and renin-angiotensin-aldosterone system, to avert harmful effects of neurohormonal activation on the myocardium and peripheral vessels. Currently, the major pharmacological treatments for heart failure are diuretics, ACE inhibitors, beta-blockers and (in NYHA classes III-IV) aldosterone antagonists. Some patients may also require specific treatment with additional drugs (e.g. anti-arrhythmia agents, anticoagulants, or vasodilators) or procedures such as coronary revascularization, or implantable devices such as pacemakers and implantable cardioverter defibrillators, or resynchronization devices. Patients with end-stage heart failure may require cardiac transplantation or ventricular assist devices. This review is summarized the recent practical drug therapy of heart failure and the results of the newer clinical trial.

Topics: Adrenergic beta-Antagonists; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Defibrillators, Implantable; Digitalis Glycosides; Diuretics; Endothelin Receptor Antagonists; Erythropoietin; Heart Failure; Heart-Assist Devices; Humans; Hungary; Immunologic Factors; Mineralocorticoid Receptor Antagonists; Pacemaker, Artificial; Peptide Hydrolases; Primary Prevention; Risk Factors; Severity of Illness Index; Vasopressins

Vasopressin antagonists are a class of neurohormonal antagonists with applications in both the short-term and long-term management of patients with acute decompensated heart failure (ADHF). The pharmacologic effects of vasopressin antagonists include changes in fluid balance and hemodynamics that may improve symptoms and outcomes in patients hospitalized with ADHF. With chronic therapy, vasopressin antagonists offer the potential to improve outcomes through a variety of mechanisms, including more effective treatment of congestion, preservation or improvement of renal function, or a reduction in the use of concomitant loop diuretic therapy. Several vasopressin antagonists are currently in advanced clinical trials for the treatment of ADHF, chronic stable heart failure, and hyponatremia.

Topics: Acute Disease; Antidiuretic Hormone Receptor Antagonists; Azepines; Benzamides; Benzazepines; Heart Failure; Humans; Pyrroles; Stroke Volume; Tolvaptan; Treatment Outcome; Vasoconstriction; Vasopressins

Treatment of chronic heart failure (HF) is based on interference with the renin-angiotensin-aldosterone system and the adrenergic nervous system. Diuretics are used in volume-expanded patients. Insights from clinical trials and registries establish the need to consider correcting both cardiac loading conditions and nonload-related biological factors if HF therapy is to be optimized. Arginine vasopressin (AVP) represents a potentially attractive target for therapy in both acute and chronic HF. Excessive AVP secretion could contribute to both systolic and diastolic wall stress via V1a- and V2-mediated effects on the peripheral vasculature and on water retention. Arginine vasopressin also may directly and adversely affect myocardial function due to the effect of V1a activation on myocardial contractility and cell growth. Last, AVP may contribute to hyponatremia, a powerful predictor of poor outcome in HF. The development of effective nonpeptide antagonists to both the V1a and V2 receptors for AVP now allows for testing the hypotheses that interfering with AVP-mediated signaling could be beneficial in HF. This review summarizes the theoretical rationale for further development of such therapy, reviews the status of current compounds under development, and suggests key issues that need to be addressed as these agents undergo further clinical testing.

Topics: Animals; Drug Therapy, Combination; Heart Failure; Humans; Vasopressins

Topics: Adrenergic Fibers; Endothelins; Heart Failure; Humans; Natriuretic Peptides; Neurotransmitter Agents; Renin-Angiotensin System; Vasopressins

Topics: Antidiuretic Hormone Receptor Antagonists; Cytokines; Drug Evaluation; Endothelin Receptor Antagonists; Endothelins; Heart Failure; Humans; Immunologic Factors; Interleukin-6; Neurotransmitter Agents; Receptors, Cytokine; Receptors, Endothelin; Receptors, Vasopressin; Treatment Outcome; Tumor Necrosis Factor-alpha; Vasopressins

Acute decompensated heart failure represents a major, growing health problem in the developed world. However, until recently, relatively little research has been performed in this field to provide a basis for rational treatment strategies. The purpose of this review is to discuss the current approach and the potential future strategies for treatment of patients with acute decompensated heart failure.. Recent data have confirmed the heterogeneous nature of patients admitted with acute decompensated heart failure, and the limitations of the current therapeutic regimens with diuretics, intravenous vasodilators (ie, nitroglycerin, nitroprusside), and intravenous inotropes (ie, dobutamine, milrinone). A new vasodilator, nesiritide, has been demonstrated to improve hemodynamics and symptoms at 3 hours compared with nitroglycerin, and has been added to the therapeutic armamentarium in the United States. However, none of these agents has been shown to influence patient outcomes favorably. Given the high readmission rates, morbidity, and mortality of acute decompensated heart failure, other newer approaches, such as antagonists to a number of neurohumoral targets (ie, endothelin [tezosentan], vasopressin [conivaptan, tolvaptan], and adenosine) and non-cAMP-mediated inotropy (ie, levosimendan), are currently under investigation and showing promise.. Acute decompensated heart failure presents a challenging therapeutic problem for clinicians. Although they readily correct the hemodynamic abnormalities, current treatment strategies have significant limitations and have not been shown to improve morbidity or mortality. A number of new agents are under investigation with the goal of improving patient outcomes.

Topics: Acute Disease; Adenosine; Cardiotonic Agents; Catheterization, Swan-Ganz; Dobutamine; Drug Therapy; Endothelins; Forecasting; Heart Failure; Humans; Milrinone; Natriuretic Peptide, Brain; Vasopressins

Topics: Angiotensin-Converting Enzyme Inhibitors; Arginine; Chronic Disease; Diagnosis, Differential; Diuretics; Drug Therapy, Combination; Endothelin-1; Heart Failure; Humans; Hypertension; Prognosis; Renin-Angiotensin System; Vasopressins

Vasopressin is an endogenous peptide hormone with the antidiuretic and vasoactive action. Its mechanisms of action on vasal smooth muscles and kidney collective tubules are well known. This hormone also plays a role in the central nervous system and influences smooth muscles of the gastrointestinal tract. The recent research results indicated much more extensive effects of endogenous vasopressin action on the circulation than appeared from the water-electrolyte balance regulation only. The use of this hormone is actually an alternative for catecholamine in treatment of the shock. This paper presents short review of vasopressin action, actual clinical use and perspectives in use of vasopressin antagonists in the heart failure.

Topics: Central Nervous System; Gastrointestinal Tract; Heart Failure; Humans; Muscle, Smooth; Shock; Vasopressins

Topics: Apoptosis; Calcium; Genetic Therapy; Heart Failure; Humans; Myocardial Contraction; Myocardium; Receptors, Adrenergic, beta; Vasopressins

In this review, we will focus on the central neural mechanisms that couple osmotic perturbations to changes in sympathetic nerve discharge, and the possible impact these actions have in cardiovascular diseases such as arterial hypertension and congestive heart failure.. Changes in extracellular fluid osmolality lead to specific regulatory responses in defence of body fluid and cardiovascular homeostasis. Systemic hyperosmolality is well known to stimulate thirst and the release of antidiuretic hormone. These responses are largely due to osmosensing neurones in the forebrain lamina terminalis and hypothalamus and are critical elements in a control system that operates to restore body fluid osmolality. An equally important, but less characterized, target of central osmoregulatory processes is the sympathetic nervous system.. Understanding the neurobiology of sympathetic responses to changes in osmolality has important implications for body fluid and cardiovascular physiology. By stabilizing osmolality, vascular volume is preserved and thereby relatively normal levels of cardiac output and arterial pressure are maintained.

Topics: Animals; Blood Pressure; Dogs; Extracellular Space; Heart Failure; Humans; Hypertension; Intracellular Fluid; Kidney; Osmolar Concentration; Prosencephalon; Rats; Sodium Chloride; Sympathetic Nervous System; Vasopressins; Water-Electrolyte Balance

Vasopressin, or antidiuretic hormone, is a peptide hormone that is released from the posterior pituitary gland in response to changes in blood pressure and plasma osmolality. The main pathophysiological states associated with high plasma vasopressin concentrations are cirrhosis, cardiac failure and syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Pharmacological treatments for disorders of excess vasopressin secretion have been limited. However, oral bio-available selective and non-selective V(1) and V(2) receptor antagonists have recently become available for clinical use. Water retention in cirrhosis is a common problem, leading to ascites, peripheral oedema and hyponatraemia. Raised plasma vasopressin concentrations and decreased delivery of glomerular filtrate are believed to be the most important factors in the development of water retention. V(2) receptor antagonists are aquaretic agents that promote water excretion and improve hyponatraemia. Their potential role in cirrhosis has been examined in a number of recent studies that have shown increased free water clearance and serum sodium concentrations with few adverse effects. V(2) receptor antagonists represent a novel and promising new class of agent that may have major clinical utility in the treatment of patients with liver cirrhosis.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Azepines; Benzamides; Benzazepines; Controlled Clinical Trials as Topic; Diuretics; Heart Failure; Homeostasis; Humans; Inappropriate ADH Syndrome; Liver Cirrhosis; Models, Animal; Morpholines; Piperidines; Pyrroles; Quinolones; Rats; Spiro Compounds; Vasopressins

Topics: Angiotensin-Converting Enzyme Inhibitors; Aquaporin 2; Aquaporin 6; Aquaporins; Heart Failure; Humans; Kidney; Kidney Diseases; Natriuretic Peptide, Brain; Vasopressins

In recent times, there have been many developments in therapies for acute heart failure, in contrast to the preceding 20 years. These have been mainly fueled by new and expanding knowledge about the pathophysiology of heart failure, which has allowed for insight into potential therapeutic strategies. This review will examine the key emerging therapies for acute heart failure, in light of available pathophysiological and clinical evidence.

Topics: Antidiuretic Hormone Receptor Antagonists; Heart Failure; Humans; Hydrazones; Natriuretic Agents; Natriuretic Peptide, Brain; Pyridazines; Pyridines; Simendan; Tetrazoles; Treatment Outcome; Vasodilator Agents; Vasopressins

Heart failure is characterized by sodium and fluid retention, sympathetic overactivation, parasympathetic withdrawal, vasoconstrictor activation and cytokine elevation. New therapies for heart failure attempt to control neurohormonal activation and limit progressive left ventricular dysfunction. Nesiritide (human B-type natriuretic peptide) is a recently approved new vasodilator that has been given to almost 1000 patients in numerous clinical investigations, it belongs to a new class of heart failure drugs known as natriuretic peptides. Nesiritide decreases pulmonary capillary wedge pressure, systemic vascular resistance, mean right atrial pressure and pulmonary artery pressure, while improving cardiac index, stroke volume and heart failure symptoms. Many endothelin receptor antagonists are in various stages of development. Early clinical studies have demonstrated beneficial cardiovascular hemodynamic effects. Other new drugs for heart failure also include calcium sensitizers, neutral endopeptidase and vasopeptidase inhibitors, aldosteron receptor antagonists, vasopressin antagonists and cytokine inhibitors. All are being actively investigated and many show significant promise as beneficial therapies in the treatment of heart failure.

Topics: Calcium Channels; Cytokines; Endothelin Receptor Antagonists; Enzyme Inhibitors; Heart Failure; Humans; Natriuretic Peptide, Brain; Neprilysin; Phosphoric Diester Hydrolases; Systole; Vasopressins

Neurohormonal activation plays a significant role in left ventricular remodeling and progression of heart failure. Treatment strategies that antagonize the RAS and sympathetic nervous system can attenuate the left ventricular remodeling process. Natriuretic peptides, specifically BNP, are a marker of left ventricular dysfunction. With the progressive increase in the incidence and prevalence of heart failure, treatment approaches must focus on the underlying cause as well as on blocking the neurohormonal activation that leads to the remodeling process.

Topics: Aldosterone; Disease Progression; Heart Failure; Humans; Natriuretic Peptides; Neurotransmitter Agents; Norepinephrine; Renin-Angiotensin System; Vasopressins; Ventricular Remodeling

Heart failure is characterized by sodium and fluid retention, sympathetic overactivity, parasympathetic withdrawal, vasoconstrictor activation and cytokine elevation. New therapies for heart failure attempt to control neurohormonal activation and limit progressive left ventricular dysfunction. Nesiritide (human B-type natriuretic peptide) is a recently approved new vasodilator that has been given to almost 1,000 patients in numerous clinical investigations; it belongs to a new class of heart failure drugs known as natriuretic peptides. Nesiritide decreases pulmonary capillary wedge pressure, systemic vascular resistance, mean right atrial pressure and pulmonary artery pressure, while improving cardiac index, stroke volume and heart failure symptoms. Many endothelin receptor antagonists are in various stages of development. Early clinical studies have demonstrated beneficial cardiovascular hemodynamic effects. Other new drugs for heart failure also include calcium sensitizers, neutral endopeptidase and vasopeptidase inhibitors, aldosterone receptor antagonists, vasopressin antagonists and cytokine inhibitors. All are being actively investigated and many show significant promise as beneficial therapies in the treatment of heart failure.

Topics: Animals; Calcium Signaling; Cytokines; Endothelin Receptor Antagonists; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Natriuretic Agents; Phosphodiesterase Inhibitors; Protease Inhibitors; Vasopressins

The kidneys play the crucial role in the maintenance of the body fluid volume homeostasis. Several hypotheses have been introduced to explain sodium and water retention leading to edematous states in such pathologic conditions as congestive heart failure (CHF) and cirrhosis. We have suggested a unifying arterial underfilling hypothesis, explaining the development of edema in these conditions. Arterial underfilling, caused by decreased cardiac output or peripheral arterial vasodilation, leads to activation of the sympathetic nervous system, renin-angiotensin-aldosterone system, and nonosmotic vasopressin release. This review discusses the pathophysiologic mechanisms resulting in renal sodium and water retention, impaired mineralocorticoid escape, and resistance to atrial natriuretic peptide in patients with CHF and cirrhosis. Furthermore, the basis of current therapies in these disorders is discussed, including beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, aldosterone antagonists, and diuretics in CHF and cirrhosis, as well as new approaches to treatment of water retention with vasopressin V(2) receptor antagonists.

Topics: Body Water; Heart Failure; Homeostasis; Humans; Liver Cirrhosis; Renin-Angiotensin System; Sodium; Sympathetic Nervous System; Vasopressins

Topics: Atrial Natriuretic Factor; Heart Failure; Humans; Natriuresis; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Peptides; Sodium; Vasoconstriction; Vasopressins

Disorders of the serum sodium concentration (hypo- and hypernatremia) are amongst the most frequent electrolyte disorders in clinical medicine. They are attributable to disturbance of to water metabolism. Hyponatremia is almost always a condition of water excess while hypernatremia is due water deficiency. Physiological normonatremia (normal plasma osmolality) is maintained by an integrated system involving regulated water intake via thirst and control of water excretion via antidiuretic hormone secretion. Therefore hypo- and hypernatremia should be analyzed in terms of dysregulated ADH secretion, fluid intake and renal water excretion. Hyponatremia is usually a disorder of vasopressin excess, due to 'non-osmotic' vasopressin release. The latter may occur in two different settings: (I) SIADH, (II) baroreceptor mediated vasopressin secretion (cardiac failure, liver cirrhosis). This entities are easy to distinguish in clinical practice. SIADH is associated with striking lower plasma concentrations of urate, creatinine and urea. In SIADH the blood pressure is normal and there is no edema. In contrast in the hyponatremia of liver cirrhosis and heart failure the plasma measurements indicated are usually slightly elevated, the blood pressure is low and there is edema. The typical patient with hypernatremia is old and has no thirst sensation. Hypo- or hypernatremia may cause major neurologic symptoms. These symptoms are more related to the rate of change in the serum sodium concentration than to the absolute level of a hypo- or hypernatremia reached. The traditional treatment for hyponatremia used to be water restriction. However V2-Vasopressin-Antagonists may provide a better treatment modality in the future. Hypernatremia is treated by slow rehydratation.

Topics: Diagnosis, Differential; Drinking; Fluid Therapy; Heart Failure; Humans; Hypernatremia; Hyponatremia; Inappropriate ADH Syndrome; Liver Cirrhosis; Vasopressins

Neurohumoral systems activated in heart failure are reviewed in relation to prognostic and diagnostic information. Plasma levels of noradrenaline, renin, vasopressin, endothelin-1, ANP, BNP, and TNF-alpha are all elevated in heart failure. Most of these factors correlate with the prognosis, but only a minor part seems to possess additional, independent information when other information that is normally available in such patients is taken into account. At present, the diagnosis of heart failure cannot be made on only one blood sample. However, neuroendocrine markers seem: 1) to have a role in the diagnosis and classification of heart failure, 2) to be useful in providing a "neuroendocrine profile", which elucidates different aspects of heart failure, and 3) to be of probable value in the choice and titration of medical treatment for the individual patient in the future.

Topics: Atrial Natriuretic Factor; Endothelin-1; Heart Failure; Humans; Norepinephrine; Prognosis; Tumor Necrosis Factor-alpha; Vasopressins

Pathogenic mechanisms of chronic systolic heart failure are constantly of great interest. In recent years the neurohumoral theory of heart failure has gained attraction. According to this theory, neurohumoral mechanisms play the main role in the pathogenesis of heart failure, especially in its progression. These mechanisms can be divided into 2 categories: vasoconstrictive, mitogenic and antinatriuretic on the one hand and vasodilative, antimitogenic and natriuretic on the other one. The former consists of sympathetic nervous system, renin-angiotensin-aldosterone system, vasopressin, endothelin, cytokines. The latter comprises natriuretic peptides, prostaglandins and nitric oxide. Undoubtedly unfavourable roles of sympathetic system and renin-angiotensin-aldosteron have been shown in the progression of heart failure. Data are being also gathered confirming harmful effects of endothelin and cytokines and possibly of neuropeptide Y and vasopressine. Extensive data exist that demonstrate beneficial influence of natriuretic peptide on heart failure. The roles of nitric oxide as well as recently discovered adrenomedullin and medullipin are far from clear.

Topics: Chronic Disease; Cytokines; Disease Progression; Endothelin-1; Heart Failure; Humans; Natriuretic Agents; Neuropeptide Y; Nitric Oxide; Renin-Angiotensin System; Sympathetic Nervous System; Vasopressins

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Cardiac Output; Clinical Trials as Topic; Female; Heart Failure; Humans; Male; Prognosis; Severity of Illness Index; Vasopressins; Ventricular Function, Left

Topics: Animals; Aquaporin 2; Aquaporin 6; Aquaporins; Edema; Female; Fibrosis; Heart Failure; Humans; Kidney; Models, Biological; Pregnancy; Sodium; Vasodilation; Vasopressins

In congestive heart failure (CHF), low cardiac output decreases the fullness of the arterial circulation. This underfilling of the arterial vascular compartment unloads the baroreceptors, resulting in a sequence of events to maintain arterial circulatory integrity. Among them, the renin-angiotensin-aldosterone axis, the sympathetic nervous system, the non-osmotic release of vasopressin and the endothelins are activated to increase vascular resistance and enhance sodium and water renal retention. Simultaneously, vasodilatory and natriuretic substances such as the natriuretic peptides are activated to counterregulate these vasoconstrictors. In the initial phase of CHF, these events contribute to the cardiorenal adaptation. However, when CHF progresses, they become maladaptive and further depress vantricular performance and increase sodium and water retention. This vicious cycle of CHF provides the rationale for the use of neurohormonal antagonists in CHF. The beneficial effects of angiotensin converting enzyme inhibitors in CHF are well described. Vasopressin V1 receptor antagonists have been associated with peripheral vasodilation and improved cardiac function in some patients with CHF. In CHF animals, the vasopressin V2 receptor antagonist has been demonstrated to reverse the defect in water excretion. Bosentan, an endothelin antagonist, is associated with an increase of cardiac index in patients with CHF. A role for exogenous natriuretic peptides is also under investigation. Modulation of the neurohumoral systems associated with CHF opens a new perspective in the treatment of cardiac edema, principally by improving cardiac performance.

Topics: Animals; Body Water; Endothelin-1; Heart Failure; Homeostasis; Humans; Renin-Angiotensin System; Sodium; Vasopressins

In the early phase of asymptomatic left ventricular dysfunction, neurohumoral systems are activated and are closely associated with the deterioration of left ventricular function and the progression into symptomatic heart failure. Congestive cardiac failure is characterized by an increasing activation of the sympathetic nerve activity, the renin angiotensin aldosterone system, vasopressin and endothelin. Together with a reduced endothelial formation of NO, the activation of neurohumoral systems leads to vaso-construction and retention of sodium and water, and by this, to a deterioration of cardiac function. On the other side, systems are activated like prostaglandins, ANP, BNP, dopamine and bradykinin, which act as vasodilators and increase natriuresis and diuresis. In the early phase of cardiac failure, natriuretic and vasodilator mechanisms are able to counteract vasoconstrictor factors, preventing by this unfavorable effects on left ventricular function.

Topics: Animals; Atrial Natriuretic Factor; Endothelins; Heart Failure; Humans; Neurotransmitter Agents; Nitric Oxide; Renin-Angiotensin System; Sympathetic Nervous System; Vasomotor System; Vasopressins; Ventricular Dysfunction, Left

Heart failure is a pathophysiological state resulting from disturbed cardiac function. It is based on complex molecular processes, many of which are not fully understood. During heart failure adaptive mechanisms, that reinstall altered cardiac function, are activated. The main mechanisms are: a) Alteration of the structure and composition of myocytes by myocardial hypertrophy, reexpression of fetal and neo-natal proteins and the expression of certain proto-oncogenes; b) Activation of the neuroendocrinal system, specifically the sympathetic nervous system, renin-angiotensin-aldosterone system and vasopressin release; c) Activation of autocrine and paracrine systems. However, when these systems are activated beyond a certain limit they contribute to heart failure aggravation. This can also be promoted by alteration of the calcium metabolism inherent in heart failure. The synthesis of the counterregulator atrial natriuretic factor is also increased.

Topics: Atrial Natriuretic Factor; Calcium; Cardiomegaly; Heart Failure; Humans; Neurosecretory Systems; Protein Biosynthesis; Renin-Angiotensin System; Sympathetic Nervous System; Vasopressins

The delicate interplay between vasoconstrictors and vasodilators preserves glomerular filtration in CHF despite marked hypoperfusion. Activation of vasoconstrictive systems seems to depend on the severity and the chronicity of the disease. The importance of renin-angiotensin, sympathetic nerves, vasopressin and counterregulatory ANP, and prostaglandins in CHF has been elucidated. Possible roles of newly identified substances, such as endothelin and EDRF, deserve investigation.

Topics: Animals; Atrial Natriuretic Factor; Dogs; Dopamine; Endothelins; Heart Failure; Kidney; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Nitric Oxide; Prostaglandins; Rats; Renin-Angiotensin System; Sympathetic Nervous System; Vasopressins; Water-Electrolyte Imbalance

Topics: Animals; Atrial Natriuretic Factor; Heart Failure; Humans; Kidney Tubules; Neurotransmitter Agents; Prostaglandins; Renin-Angiotensin System; Signal Transduction; Vasopressins; Water-Electrolyte Imbalance

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Heart Failure; Humans; Kidney; Renin-Angiotensin System; Sodium; Vasopressins

Heart failure is a syndrome characterized by the activation of neurohumoral mechanisms (sympathoadrenergic, renin-angiotensin, vasopressin) which cause peripheral vasoconstriction, sodium retention and myocardial hypertrophy. In acute myocardial disfunction these systems can play a critical role in patient survival, however, they can directly worsen myocardial function and patient prognosis on a long-term basis. Other neurohumoral systems activated in heart failure (atrial natriuretic factor, prostaglandins, dopamine) tend to counterbalance the vasoconstrictive, sodium retentive mechanisms. Though their secretion is increased in heart failure, it is however not sufficient, and peripheral vasoconstriction and sodium retention prevail. Moreover the role of local factors, such as tissue renin-angiotensin system, EDRF and endothelin secretion has been recently pointed out. Neurohumoral activation is directly related to the severity of the clinical and hemodynamic impairment and prognosis of the patient with heart failure. A thorough evaluation of the neurohumoral mechanisms is therefore of paramount importance for the assessment of patients with heart failure. Neurohumoral activation can be roughly assessed using some simple laboratory measurements: plasma sodium concentration, for example, is inversely related to the degree of activation of many neurohormones such as norepinephrine, angiotensin II, vasopressin and atrial natriuretic factor. The method most commonly used to assess neurohumoral activity relies on the direct measurement of the plasma concentrations. It must be noted, however, that plasma levels are critically dependent on many factors besides hormone secretion and metabolism. For example, 3-4 days on a low sodium diet or standing for at least 2 hours can increase plasma renin activity in a normal subject from 1.5 to 5-10 pg/ml/hr. Plasma concentrations of neurohormones are related to the factors controlling their secretion: for example, "normal" values of plasma renin activity in presence of fluid retention and edema are to be judged as excessively elevated. Autonomic nervous system activity can also be assessed studying reflexes in which this system is involved (orthostasis, cold pressor test, phenylephrine test...). Another method consists in the study of the spontaneous variability of some parameters controlled by this system, such as heart rate and blood pressure. The most reliable method is based on the power spectral analysis of heart rat

Topics: Adrenal Glands; Atrial Natriuretic Factor; Heart Failure; Humans; Hyponatremia; Neurotransmitter Agents; Renin-Angiotensin System; Sympathetic Nervous System; Vasopressins

Ventricular failure is accompanied by a series of neurohormonal responses that result in vasoconstriction. Vasoconstriction develops and is mediated by norepinephrine, angiotensin II, and vasopressin. Vasoconstriction maintains blood pressure but contributes to deterioration in ventricular function. Baroreceptor dysfunction contributes to the syndrome by failing to ameliorate the sympathetic overstimulation. Drug therapy has historically included positive inotropes until recent data suggested that these drugs contributed to worsened survival. The role of digitalis glycosides in patients with ventricular failure who are in normal sinus rhythm remains a subject of scrutiny. Thus far, no long-term oral positive inotrope has replaced digoxin. Vasodilator therapy and interference with the neurohormonal response have become the major approaches to pharmacologic management of ventricular failure. Angiotensin-converting enzyme inhibitors have shown convincingly that they improve survival, slow the course of disease progression, and block the neurohormonal response to ventricular failure. New treatments for ventricular failure must be directed at long-term gain rather than short-term hemodynamic results.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Constriction, Pathologic; Digoxin; Heart Failure; Heart Ventricles; Hemodynamics; Humans; Norepinephrine; Survival Rate; Vasodilator Agents; Vasopressins

The pressor action of vasopressin (AVP) in humans was investigated with the specific anti-vasopressor V1 antagonist d(CH2)5-O(Me)-Tyr-AVP. A single 0.5-mg intravenous bolus of this agent inhibited the pressor effect of AVP by about 80%. Normally hydrated humans had no blood pressure response to this dose, but this agent did prevent the blood pressure rise in response to exogenous AVP given in doses up to 200 milli-units/kg. Patients with severe hypertension, especially that associated with end-stage renal disease, tended to respond with moderate increases in blood pressure and plasma AVP after sodium overload and had a modest blood pressure fall (10-20 mmHg) in response to a single intravenous bolus of the AVP antagonist. Patients with an impaired sympathetic nervous system had increased sensitivity to the pressor action of AVP, in keeping with knowledge derived from experimental studies. These data suggest an interaction between AVP and alpha-adrenergic function, whereby the latter tends to attenuate the pressor action of AVP although it facilitates the release of AVP in response to various stimuli. In patients with congestive heart failure, the direct pressor action of AVP appears to contribute to increased systemic vascular resistance in about 30% of cases, i.e., those with plasma AVP concentrations well above the normal range. In these subjects, circulating AVP concentrations correlated with a decrease in vascular resistance in response to the V1 antagonist.

Topics: Animals; Arginine Vasopressin; Clinical Trials as Topic; Heart Failure; Humans; Hypertension; Sympathetic Nervous System; Vasopressins

Several changes in neuroendocrine activity follow failure of cardiac function to satisfy peripheral requirements and contribute to the clinical syndromes of heart failure. Afferent pathways are poorly understood and triggers are both central and peripheral, involving attenuation of atrial and arterial baroreceptor activity. Efferent sympathetic activity is generally increased with resulting vasoconstriction, but responses are organ-specific and differ among heart, kidney, lung and skeletal muscle. Changes in cardiac sympathetic activity are inadequately understood. Enhanced cardiac norepinephrine spillover contrasts with reduced tissue concentration and impaired activity of synthetic enzymes and neuronal catecholamine uptake. Beta-receptor down-regulation further complicates overall adrenergic responsiveness and the balance between enhancement of contractile function and reduction in arrhythmia threshold. Activation of the renin-angiotensin system is potentiated by the sympathetic nervous system and may contribute to vasoconstrictor hyporesponsiveness. Angiotensin II may in turn facilitate the central and peripheral effects of sympathetic activation and the release of vasopressin from the pituitary. Our understanding of the role of vasodilator peptides in heart failure remains rudimentary. It is likely that vasoconstrictor neuroendocrine response adversely influences optimal cardiac function in heart failure and may promote arrhythmogenesis. The neuroendocrine response in individual organs, however, requires intensive study.

Topics: Animals; Coronary Circulation; Heart; Heart Failure; Humans; Norepinephrine; Pressoreceptors; Renin-Angiotensin System; Sympathetic Nervous System; Vasopressins

This article reviews the evidence that congestive heart failure is accompanied by an increased plasma norepinephrine concentration and that this is due not only to a reduced tissue clearance of the substance but also to a marked increase in sympathetic nerve activity. It also reports data that indicate that the sympathetic activation is associated with an activation of the renin-angiotensin system and an increased plasma level of vasopressin. At which degree of congestive heart failure these phenomena become manifest is not clear, but some studies suggest that the sympathetic and renin-angiotensin systems may be normal in asymptomatic congestive heart failure but already somewhat activated when this condition reaches New York Heart Association class II. There is also evidence that this activation, though initially compensatory, is eventually responsible for a number of adverse cardiovascular effects that account for the negative relationship between this event and survival. Finally, the article discusses the inability of the increased plasma level of atrial natriuretic peptide that characterizes congestive heart failure to offset the adverse effects of the neurohumoral activation and the variable influence of drug treatment on this phenomenon. This is not impossible to achieve, however, because heart transplantation appears to rapidly normalize a major factor in the increased sympathetic activity observed before surgical intervention, that is, impairment of the arterial baroreflex.

Topics: Animals; Atrial Natriuretic Factor; Dogs; Heart Failure; Humans; Neurotransmitter Agents; Renin-Angiotensin System; Sympathetic Nervous System; Vasopressins

In heart failure, neurohumoral factors are activated, influencing ventricular performance by modulation of pre- and afterload. There is evidence from experimental models of congestive heart failure that in the early phase of the disease the sympathetic nervous system and atrial natriuretic peptide secretion are activated. Despite a reduction in cardiac output, decreased blood pressure and stimulated sympathetic nerve activity, atrial natriuretic peptide seems to be able to significantly suppress the renin-angiotensin-aldosterone system. In later phases of the disease, when more profound circulatory impairment develops, the renin system is activated and peripheral vascular resistance increases and renal blood flow decreases. In very severe heart failure, when dilutional hyponatraemia develops, plasma levels of vasopressin are inappropriately increased by nonosmolar stimuli. At the time the renin system is activated, there is an imbalance between vasodilator and vasoconstrictor mechanisms, favouring vasoconstriction which, completing the vicious circle, leads to deterioration of cardiac function.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Dogs; Heart Failure; Humans; Renal Circulation; Renin; Renin-Angiotensin System; Vasopressins

Topics: Blood Volume; Combined Modality Therapy; Heart Failure; Humans; Hyponatremia; Inappropriate ADH Syndrome; Liver Cirrhosis; Nephrotic Syndrome; Vasopressins

Despite the interest in neurotransmitter and hormonal influences in heart failure in the last decade, the issues surrounding their contribution to the pathophysiology of congestive heart failure have become more complex. This must be considered in view of the pathway of hormonal stimulation and inhibition (Fig. 3) and the multiple steps where abnormal responses can interrupt these pathways. It is reasonable to state that the extent of neurotransmitter and hormonal activity in stage IV heart patients, treated with digoxin and diuretics, has been characterized. However, these observations cannot be extended to other stages of CHF, and assumptions cannot be made regarding either the untreated patient, or the nature of disease progression. Furthermore, there is insufficient information regarding the direct effect of these hormonal systems, with the exception of norepinephrine, on the myocardium. These issues must be the focus of future studies.

Topics: Atrial Natriuretic Factor; Heart Failure; Humans; Kidney; Neurotransmitter Agents; Sodium; Vasopressins

Topics: Catecholamines; Chronic Disease; Heart Failure; Hemodynamics; Humans; Myocardial Contraction; Renin-Angiotensin System; Vasopressins

Topics: Animals; Blood Pressure; Heart Failure; Hemodynamics; Humans; Hypertension; Receptors, Cell Surface; Vasopressins

Congestive heart failure (CHF) is not only reflected by such mechanical problems as forward- and backward failure, but it is also associated with a complex pattern of compensatory neuro-endocrine mechanisms, e.g., enhanced activity of both the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS); enhanced release of vasopressin from the pituitary gland; enhanced release of the atrial natriuretic factor (ANF) from the cardiac atria. These neuro-endocrine mechanisms not only operate as such but also display a complex pattern of mutual interactions. These mechanisms, though potentially beneficial short-term, may also be harmful when persisting during progression of the disease. For this reason they offer potential targets in the treatment of CHF besides the classical measures aimed directly at improving cardiac contractility. The following groups of drugs are discussed as therapeutic measures that suppress the aforementioned detrimental compensatory mechanisms: various types of vasodilator drugs; diuretics; beta 1-adrenoceptor blocking agents in low dosage; saralasin; ACE-inhibitors. So far, the enhanced release of vasopressin and ANF have not offered realistic new therapeutic targets in CHF, although their pathophysiologic issue is highly relevant.

Topics: Atrial Natriuretic Factor; Cardiotonic Agents; Heart Failure; Humans; Renin-Angiotensin System; Sympathetic Nervous System; Vasopressins

Topics: Atrial Natriuretic Factor; Catecholamines; Heart Failure; Humans; Pituitary Hormones; Renin-Angiotensin System; Vasopressins

Topics: Adaptation, Physiological; Animals; Catecholamines; Heart Failure; Humans; Myocardium; Neurosecretion; Pressoreceptors; Renin-Angiotensin System; Sympathetic Nervous System; Vasopressins

Congestive cardiac failure causes activation of various neurohumoral responses that increase total peripheral resistance and promote salt and water retention. These effects increase blood pressure and organ perfusion in the short term, but ultimately cause further cardiac decompensation by increasing ventricular afterload and cardiac work. The role of the renin-angiotensin-aldosterone system and the catecholamines is partially understood, and blockade of these systems as a treatment of heart failure is now established. The role of vasopressin in heart failure is more controversial, but there is now compelling evidence that vasopressin may have important vasoconstrictor actions in addition to its fluid retaining properties. Atrial natriuretic factor is a newly described cardiac hormone released from the atrium. Atrial natriuretic factor causes natriuresis, diuresis, vasodilatation, suppression of thirst, and suppression of both renin and aldosterone. These actions largely counteract the effects of the renin-angiotensin system and vasopressin. Plasma atrial natriuretic factor has been reported to be markedly elevated in human and experimental heart failure, and may act to limit the neurohumoral response to reduced cardiac output. This review summarizes our understanding of the vasoactive hormones and reports experimental evidence supporting a pathophysiological role for vasopressin and atrial natriuretic factor in congestive cardiac failure.

Topics: Animals; Atrial Natriuretic Factor; Heart Failure; Humans; Renin-Angiotensin System; Sympathetic Nervous System; Vasopressins

Congestive heart failure (CHF) represents a pathophysiologic state in which cardiac output is inadequate to meet the metabolic needs of multiple organ systems. The primary pathologic event in CHF is a marked, sustained reduction in the intrinsic contractility of the heart. A review of the current knowledge regarding the etiology and progression of CHF reveals that it is associated with profound biochemical, peripheral hemodynamic (increased peripheral vascular resistance), and electrolyte disturbances. In addition to sodium and water retention, CHF is often associated with hypokalemia and hypomagnesemia as well as tissue deficits in K and Mg. Cardiac glycosides and diuretics (loop and distal types) often exacerbate, or result in, hypokalemia and hypomagnesemia, which may lead to cardiac arrhythmias and sudden cardiac death. Deficits in extracellular and vascular tissue Mg lead to peripheral vasoconstriction; this together with K deficits and the release of neurohumoral substances may be responsible in large measure for the increase in peripheral vascular resistance commonly noted in CHF. More attention must be paid to the careful monitoring of electrolyte levels (Na, K, Mg) in tissues (possibly lymphocytes) and plasma of CHF patients. Deficits in either K or Mg must be corrected in CHF. The nonspecific vasodilator properties of Mg2+ together with its ability to unload the heart should be considered as an important adjunct tool in the management of CHF.

Topics: Adenosine Triphosphate; Calcium; Coronary Disease; Digitalis; Heart Failure; Humans; Magnesium; Magnesium Deficiency; Myocardial Contraction; Myocardium; Oxygen Consumption; Plants, Medicinal; Plants, Toxic; Potassium; Sodium; Vasopressins

For 2 decades evidence accumulated that supported the Gauer-Henry hypothesis tying blood volume changes to the control of vasopressin (VP). By the mid 1970's this left atrial hypothesis was generally accepted even though there was a significant body of conflicting data and several definitive questions that had not been answered. In the last decade numerous investigations have addressed these questions and although there are better answers for some, others remain elusive. Pertinent work during the past 10 years is reviewed in the framework of some of these questions. The emphasis is placed on the location of the primary volume receptors, determination of the threshold for effects on VP, the degree of volume-pressure receptor and volume-osmotic receptor interactions, and species differences.

Topics: Animals; Aorta; Blood Volume; Chronic Disease; Dogs; Haplorhini; Heart Atria; Heart Failure; Humans; Osmotic Pressure; Pressoreceptors; Rats; Receptors, Angiotensin; Receptors, Cell Surface; Receptors, Vasopressin; Vasopressins

Topics: Blood Volume; Coronary Vasospasm; Heart Failure; Humans; Osmolar Concentration; Pressoreceptors; Prostaglandins E; Renin; Vascular Resistance; Vasopressins; Water-Electrolyte Balance

Topics: Adrenergic alpha-Antagonists; Animals; Calcium Channel Blockers; Heart Failure; Humans; Norepinephrine; Renin-Angiotensin System; Sympathetic Nervous System; Vasodilator Agents; Vasopressins

These essays have traced the evolution of three great convective systems of the body: ventilation, circulation and excretion. We have seen how the ventilatory system evolved with an inherent susceptibility to flooding, how the kidney came to need an enormous blood flow and how a high blood pressure grew out of the explosive demands of muscular activity. Success and survival in the animal kingdom have overwhelmingly depended on physical mobility and strength. To ensure this the body makes use of the neuro-endocrine defence reaction which is also life-saving in injury. The reaction favours the retention of water and salt by directing blood away from the kidney and by endocrine activity. When the output of the diseased heart decreases, the body reacts in the way for which nature has programmed it. It cannot distinguish. But now the neuro-endocrine response persists. But now the neuro-endocrine response persists. Over weeks or months or years the retention of saline threatens the cardiac patient with drowning in his own juice. And every hour of the day and night be is running for his life.

Topics: Adrenal Cortex Hormones; Animals; Biological Evolution; Heart Failure; Hormones; Humans; Renin-Angiotensin System; Sympathetic Nervous System; Vasopressins; Water-Electrolyte Balance

Edema is a collection of fluid within the body's interstitial space which occurs when there is an alteration of the Starling forces which control transfer of fluid from the vascular compartment to surrounding tissue spaces. Generalized edema results when altered Starling forces affect all capillary beds, such as occurs in cardiac failure, cirrhosis, and nephrotic syndrome. Common to these conditions is the development of increased total body sodium and water content. The kidneys play an essential role in the retention of this sodium and water. In this article we shall discuss the signals the kidneys receive for sodium and water retention in these edematous disorders (afferent mechanisms). We shall also examine the means by which the kidney responds to these signals and retains sodium and water (efferent mechanisms). As shall become apparent these edematous states may share many of the same afferent and efferent mechanisms for sodium and water retention.

Topics: Blood Volume; Body Water; Cardiac Output; Edema; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Liver Cirrhosis; Nephrotic Syndrome; Renal Circulation; Renin-Angiotensin System; Sodium; Vasopressins

Neurohumoral vasoconstrictor systems may play an important role in the hemodynamic derangement and natural history of congestive heart failure (CHF) by raising impedance to left ventricular ejection and shifting blood centrally to augment cardiac filling. Activation of the sympathetic nervous system, and renin-angiotensin system, and the antidiuretic hormone-vasopressin system can be demonstrated in clinical CHF by increased plasma levels of norepinephrine, renin activity, and arginine vasopressin. Because the magnitude of increase in each of these hormones varies widely from patient to patient, profiling of the neurohumoral response might provide new insight into the mechanisms of regulation of the circulation in CHF and into specific management with drugs to inhibit or reverse the vasoconstrictor process. Preliminary encouraging experience with converting-enzyme inhibitors to block formation of angiotensin II and alpha-receptor blockers to inhibit norepinephrine-induced vasoconstriction raise the possibility that selective therapy may eventually have a place in long-term management of CHF. Controlled trials in a larger patient population are now required.

Topics: Angiotensin II; Animals; Heart Failure; Hemodynamics; Humans; Neurotransmitter Agents; Renin; Sympathetic Nervous System; Vasoconstriction; Vasodilator Agents; Vasopressins

Topics: Animals; Blood Volume; Coronary Circulation; Diuresis; Dogs; Heart Failure; Heart Rate; Humans; Reflex; Vagus Nerve; Vasopressins

Topics: Acetylcholine; Acute Kidney Injury; Angiotensin II; Animals; Bradykinin; Diuretics; Dogs; Dopamine; Electric Stimulation; Epinephrine; Heart Failure; Hemorrhage; Humans; Hypotension; Isoproterenol; Kidney Cortex; Kidney Transplantation; Liver Cirrhosis; Norepinephrine; Oxytocin; Prostaglandins; Regional Blood Flow; Transplantation, Homologous; Ureter; Vasomotor System; Vasopressins; Vena Cava, Inferior; Water-Electrolyte Balance

Topics: Acetazolamide; Aldosterone; Angiotensin II; Benzothiadiazines; Catecholamines; Diuretics; Ethacrynic Acid; Furosemide; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Organomercury Compounds; Renin; Sodium Chloride Symporter Inhibitors; Vasopressins; Water-Electrolyte Balance

Topics: Addison Disease; Ascites; Edema; Extracellular Space; Heart Failure; Humans; Hyponatremia; Intestinal Secretions; Kidney Failure, Chronic; Liver Cirrhosis; Potassium; Sodium; Vasopressins; Water-Electrolyte Balance

Topics: Animals; Body Fluids; Cell Membrane Permeability; Chlorides; Dogs; Extracellular Space; Heart Failure; Humans; Hyponatremia; Infant Nutrition Disorders; Kidney; Liver Cirrhosis; Neoplasms; Osmolar Concentration; Potassium; Respiratory Insufficiency; Sodium; Vasopressins; Water; Whipple Disease

Topics: Acute Kidney Injury; Animals; Blood; Cardiac Glycosides; Dehydration; Diuretics; Glomerular Filtration Rate; Heart Failure; Hyponatremia; Kidney Failure, Chronic; Liver Cirrhosis; Mineralocorticoid Receptor Antagonists; Nephrotic Syndrome; Sodium; Syndrome; Vasopressins; Water

Topics: Aldosterone; Heart Failure; Hemodynamics; Humans; Kidney; Regional Blood Flow; Sodium; Sympathetic Nervous System; Vasopressins; Venous Pressure; Water

Topics: Aldosterone; Angiotensin II; Animals; Arteriovenous Anastomosis; Cardiac Volume; Catecholamines; Diuretics; Heart Failure; Hemodynamics; Hypertension; Kidney; Kidney Tubules; Oxygen; Sodium; Vascular Resistance; Vasomotor System; Vasopressins; Veins; Water-Electrolyte Balance

Topics: Aged; Aldosterone; Angiotensin II; Animals; Blood Pressure; Body Weight; Diet, Sodium-Restricted; Dogs; Endocrine Glands; Heart Atria; Heart Failure; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Renal Veins; Renin; Sodium; Vasopressins; Water-Electrolyte Balance

Topics: Adrenal Insufficiency; Animals; Congenital Hypothyroidism; Diabetes Insipidus; Heart Failure; Humans; Liver Cirrhosis; Osmolar Concentration; Pituitary Diseases; Vasopressins

Topics: Bloodletting; Carbonic Anhydrase Inhibitors; Chlorides; Diet, Sodium-Restricted; Digitalis Glycosides; Diuresis; Diuretics; Ethacrynic Acid; Furosemide; Heart Failure; Humans; Hyperkalemia; Hypokalemia; Hyponatremia; Kidney Glomerulus; Kidney Tubules; Mineralocorticoid Receptor Antagonists; Organomercury Compounds; Spironolactone; Steroids; Thiazines; Triamterene; Uracil; Vasopressins; Water-Electrolyte Balance; Xanthenes

Topics: Adrenal Glands; Adrenal Medulla; Edema; Endocrine Glands; Heart; Heart Failure; Humans; Hyperaldosteronism; Shock; Thyroxine; Vasopressins

Topics: Aldosterone; Digitalis; Digitalis Glycosides; Diuretics; Edema; Electrolytes; Heart Failure; Hypokalemia; Physiology; Potassium; Sodium; Toxicology; Vasopressins

Depressed hemodynamics stimulates arginine vasopressin (AVP) release, but the relationship between plasma AVP levels (P-AVP) and cardiac parameters, especially in patients with stage D heart failure (HF) receiving guideline-directed medical therapy, has not examined. METHODS AND RESULTS: Data including P-AVP were obtained from 162 in-hospital patients with stage D HF and from 80 patients receiving ventricular assist device (VAD, n=46) or heart transplantation (HTx, n=34) at 3 months after surgery. In the HF group, considerably high P-AVP (5.9±6.1 pg/ml) negatively correlated with serum sodium concentration (S-Na, 135.3±5.8 mEq/L, r=-0.548 [P<0.01]) and cardiac index (CI, 2.2±0.5 L·min(-1)·m(-2), r=-0.458 [P<0.01]). After VAD/HTx treatment, improvement in the CI (2.7±0.5 L·min(-1)·m(-2)[P<0.01] vs. HF) was accompanied by normalization of serum sodium concentration (S-Na; 138.2±2.0 mEq/L [P<0.01] vs. HF) and suppressed release of AVP (1.7±3.4 pg/ml [P<0.01] vs. HF). P-AVP positively correlated with only S-Na (r=0.454 [P<0.01]), whereas no correlation was observed with CI after VAD/HTx treatment. P-AVP ≥5.3 pg/ml well predicted poor 2-year survival in HF group (60% [P<0.01] vs. 90%).. Low cardiac output stimulates AVP release via a non-osmotic process that results in hyponatremia and poor prognosis in patients with stage D HF. After sufficient recovery of cardiac output by cardiac replacement therapy, AVP release is suppressed and is mainly regulated by serum osmolality.

Topics: Adult; Aged; Cardiac Output, Low; Heart Failure; Humans; Hyponatremia; Middle Aged; Vasopressins; Water-Electrolyte Balance

The study investigated whether the number of participants enrolled per site in an acute heart failure trial is associated with participant characteristics and outcomes.. Whether and how site enrollment volume affects clinical trials is not known.. A total of 4,133 participants enrolled among 359 sites were grouped on the basis of total enrollment into 1 to 10, 11 to 30, and >30 participants per site and were compared for outcomes (cardiovascular mortality or heart failure hospitalization).. Per-site enrollment ranged from 0 to 75 (median 6; 77 sites had no enrollment). Regional differences in enrollment were noted between North and South America, and Western and Eastern Europe (p < 0.001). Participants from sites with fewer enrollments were more likely to be older and male, have lower ejection fraction and blood pressure as well as worse comorbidity and laboratory profile, and were less likely to be on angiotensin-converting enzyme inhibitors or aldosterone antagonists. During a median follow-up of 9.9 months, 1,700 (41%) participants had an outcome event. Compared to event rate at sites with >30 participants (32%), those with 1 to 10 (51%, hazard ratio [HR]: 1.77, 95% confidence interval [CI]: 1.56 to 2.02) and 11 to 30 (42%, HR: 1.44, 95% CI: 1.28 to 1.62) participants per site groups had worse outcomes. This relationship was comparable across regions (p = 0.43). After adjustment for risk factors, participants enrolled at sites with fewer enrollees were at higher risk for adverse outcomes (HR: 1.26, 95% CI: 1.08 to 1.46 for 1 to 10; HR: 1.22, 95% CI: 1.07 to 1.38 for 11 to 30 vs. >30 participant sites). Higher proportion of participants from site with >30 participants completed the protocol (45.5% for <10, 61.7% for 11 to 30, and 68.4% for sites enrolling >30 participants; p < 0.001).. Baseline characteristics, protocol completion, and outcomes differed significantly among higher versus lower enrolling sites. These data imply that the number of participant enrolled per site may influence trials beyond logistics.

Topics: Aged; Aged, 80 and over; Benzazepines; Clinical Protocols; Double-Blind Method; Europe; Europe, Eastern; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Internationality; Male; Middle Aged; North America; Patient Selection; Prospective Studies; South America; Survival Rate; Tolvaptan; Treatment Outcome; Vasopressins

Low lymphocyte count has been shown to be an independent prognostic marker in heart failure (HF) in the outpatient setting. Limited data exist regarding whether relative lymphocyte count correlates with postdischarge outcomes in patients hospitalized for HF.. We performed a post hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial, which randomized 4133 patients hospitalized for worsening HF with an ejection fraction ≤40% within 48 hours of admission to tolvaptan or placebo for a median follow-up of 9.9 months. The primary end points of all-cause mortality and cardiovascular mortality or HF hospitalization were analyzed in patients with available baseline complete blood counts (n=3717). Lymphocyte percentage was analyzed as a continuous variable. Times to events were compared using log-rank tests and multivariable Cox regression models. Patients with low lymphocyte percentage tended to be older and had higher rates of comorbid disease (diabetes mellitus, atrial fibrillation, and renal insufficiency). Low lymphocyte counts were associated with wide QRS duration, high natriuretic peptides, and low ejection fraction, blood pressure, and serum sodium. These patients were less likely to receive evidence-based HF medications. After adjusting for 22 known clinical risk factors, a 10% decrease in lymphocytes was associated with an increased hazard of all-cause mortality (adjusted hazard ratio 1.31 [95% CI: 1.14-1.150], P<0.001) and cardiovascular mortality or HF hospitalization (adjusted hazard ratio 1.14 [95% CI: 1.04-1.25], P=0.007) in the first 100 days postdischarge. Lymphopenia during hospitalization normalizes in majority of patients in the early postdischarge period.. Low relative lymphocyte count during hospitalization for HF is an independent predictor of poor outcomes in the early postdischarge period, beyond traditional prognostic indicators.

Topics: Aged; Benzazepines; Female; Follow-Up Studies; Heart Failure; Humans; Inpatients; Kaplan-Meier Estimate; Lymphocyte Count; Male; Middle Aged; Predictive Value of Tests; Prognosis; Regression Analysis; Stroke Volume; Tolvaptan; Vasopressins

Arginine vasopressin (AVP) V(2) receptor antagonism is a new approach to the management of hyponatraemia in congestive heart failure (CHF). The aim of this study was to investigate the efficacy and safety of satavaptan, an oral AVP V(2)-receptor antagonist, in patients with dilutional hyponatraemia.. A total of 118 patients (90 with CHF) with dilutional hyponatraemia (serum sodium 115-132 mmol/L) were randomized to double-blind treatment with placebo or to 25 or 50 mg/day of satavaptan for 4 days, followed by non-comparative open-label satavaptan therapy for up to 343 days. The response rate (sodium ≥ 135 mmol/L and/or an increase in ≥ 5 mmol/L above baseline) was significantly higher with satavaptan 50 mg than with placebo (61.0 vs. 26.8%; P= 0.0035), with a trend towards significance with satavaptan 25 mg (48.6%, P= 0.0599). Median times to response were 3.30 and 2.79 days with satavaptan 25 and 50 mg/day, respectively, both shorter than placebo (>4 days; P= 0.0278 and P= 0.0004, respectively). Satavaptan therapy was effective in CHF patients, with response rates higher with both satavaptan 25 mg/day (53.6%) and 50 mg/day (57.1%) than with placebo (23.5%; P= 0.019 and P= 0.009, respectively). Sodium responses were maintained during open-label therapy after a temporary study drug discontinuation period. Higher rates of adverse events occurred with the 50 mg/day dose, including rapid correction of hyponatraemia.. In patients with dilutional hyponatraemia, V(2) receptor antagonism with satavaptan was effective in increasing serum sodium concentrations. The long-term open-label treatment results demonstrate sustained efficacy of satavaptan in maintaining normal sodium levels. Trial Registration clinicaltrials.gov Identifier: NCT00274326.

Topics: Adult; Aged; Antidiuretic Hormone Receptor Antagonists; Body Weight; Double-Blind Method; Female; Heart Failure; Humans; Hyponatremia; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Sodium; Spiro Compounds; Treatment Outcome; Vasopressins; Young Adult

Hospitalization for acute decompensated heart failure (ADHF) involves substantial morbidity and mortality. Current management strategies have major limitations, and there has been little progress in the development of newer therapies. Arginine vasopressin-receptor antagonists may have promise in the treatment of ADHF in view of their ability to facilitate diuresis. This pilot study was designed to evaluate the efficacy and safety of intravenous conivaptan, a dual arginine vasopressin V(1A)/V(2)-receptor antagonist, in treating ADHF.. In a double-blind, multicenter trial, 170 patients hospitalized for worsening heart failure and given standard therapy were randomly assigned to treatment with conivaptan (20-mg loading dose followed by 2 successive 24-hour continuous infusions of 40, 80, or 120 mg/d) or placebo. The conivaptan and placebo groups did not differ significantly in patient or clinician assessments of global and respiratory status at 48 hours. There was no evidence of worsening heart failure in any group. Conivaptan at each dosage increased urine output significantly more than placebo at 24 hours (P

Topics: Acute Disease; Aged; Antidiuretic Hormone Receptor Antagonists; Area Under Curve; Benzazepines; Disease Progression; Diuresis; Double-Blind Method; Female; Heart Failure; Humans; Male; Middle Aged; Pain Measurement; Pilot Projects; Receptors, Vasopressin; Vasopressins

Our aim was to examine continental and regional differences in baseline characteristics and post-discharge clinical outcomes in the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan) trial.. Continental and regional differences in clinical trials of acute heart failure syndromes (AHFS) have not been well studied.. We analyzed data from the EVEREST trial, which randomized 4,133 patients hospitalized for worsening (HF) and left ventricular ejection fraction < or =40% to oral tolvaptan, a vasopressin antagonist, or placebo and followed for a median of 9.9 months. Baseline characteristics, mortality, and outcomes were analyzed across North America (n = 1,251), South America (n = 688), Western Europe (564 patients), and Eastern Europe (n = 1,619).. There were major differences between the 4 groups in the severity, etiology, and management of HF. Unadjusted 1-year mortality and cardiovascular mortality/HF hospitalization were 30.4% and 52.5% in North America, 27.2% and 41.6% in South America, 27.1% and 47.3% in Western Europe, and 20.5% and 35.3% in Eastern Europe. After adjustment, South American patients had the highest overall mortality (hazard ratio: 1.42, 95% confidence interval: 1.15 to 1.76), while Eastern European patients had the lowest cardiovascular death and HF hospitalization rate (hazard ratio: 0.84, 95% confidence interval: 0.73 to 0.97), compared with patients in North America.. Major continental and regional differences in HF severity, etiology, and management exist among AHFS patients, resulting in varied post-discharge outcomes, despite pre-defined selection criteria. These differences should be taken into account when planning global trials in AHFS. (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan [EVEREST]; NCT00071331).

Topics: Aged; Aged, 80 and over; Benzazepines; Double-Blind Method; Female; Heart Failure; Hospitalization; Humans; Internationality; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Revascularization; Pacemaker, Artificial; Prospective Studies; Tolvaptan; Vasopressins

The role of the vasopressin system after acute myocardial infarction is unclear. Copeptin, the C-terminal part of the vasopressin prohormone, is secreted stoichiometrically with vasopressin. We compared the prognostic value of copeptin and an established marker, N-terminal pro-B-type natriuretic peptide (NTproBNP), after acute myocardial infarction.. In this prospective single-hospital study, we recruited 980 consecutive post-acute myocardial infarction patients (718 men, median [range] age 66 [24 to 95] years), with follow-up over 342 (range 0 to 764) days. Plasma copeptin was highest on admission (n=132, P<0.001, day 1 versus days 2 to 5) and reached a plateau at days 3 to 5. In the 980 patients, copeptin (measured at days 3 to 5) was elevated in patients who died (n=101) or were readmitted with heart failure (n=49) compared with survivors (median [range] 18.5 [0.6 to 441.0] versus 6.5 [0.3 to 267.0] pmol/L, P<0.0005). With logistic regression analysis, copeptin (odds ratio, 4.14, P<0.0005) and NTproBNP (odds ratio, 2.26, P<0.003) were significant independent predictors of death or heart failure at 60 days. The area under the receiver operating characteristic curves for copeptin (0.75) and NTproBNP (0.76) were similar. The logistic model with both markers yielded a larger area under the curve (0.84) than for NTproBNP (P<0.013) or copeptin (P<0.003) alone, respectively. Cox modeling predicted death or heart failure with both biomarkers (log copeptin [hazard ratio, 2.33], log NTproBNP [hazard ratio, 2.70]). In patients stratified by NTproBNP (above the median of approximately 900 pmol/L), copeptin above the median (approximately 7 pmol/L) was associated with poorer outcome (P<0.0005). Findings were similar for death and heart failure as individual end points.. The vasopressin system is activated after acute myocardial infarction. Copeptin may predict adverse outcome, especially in those with an elevated NTproBNP (more than approximately 900 pmol/L).

Topics: Adult; Aged; Aged, 80 and over; Area Under Curve; Biomarkers; England; Female; Follow-Up Studies; Glycopeptides; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors; ROC Curve; Survival Analysis; Treatment Outcome; Ultrasonography; Vasopressins

Diuretics are frequently required to treat fluid retention in patients with congestive heart failure (CHF). Unfortunately, they can lead to a decline in renal function, electrolyte depletion, and neurohumoral activation. Arginine vasopressin (AVP) promotes renal water reabsorption via the V2 receptor, and its levels are increased in CHF. This study was designed to assess the effects of a single oral dose of tolvaptan, a selective V2-receptor blocker, in the absence of other medications, on renal function in human CHF and to compare this to the effects of a single oral dose of furosemide. We hypothesized that V2-receptor antagonism would yield a diuresis comparable to furosemide but would not adversely affect renal hemodynamics, plasma electrolyte concentration, or neurohumoral activation in stable human CHF. Renal and neurohumoral effects of tolvaptan and furosemide were assessed in an open-label, randomized, placebo-controlled crossover study in 14 patients with NYHA II-III CHF. Patients received placebo or 30 mg of tolvaptan on day 1 and were crossed over to the other medication on day 3. On day 5, all subjects received 80 mg of furosemide. Tolvaptan and furosemide induced similar diuretic responses. Unlike tolvaptan, furosemide increased urinary sodium and potassium excretion and decreased renal blood flow. Tolvaptan, furosemide, and placebo did not differ with respect to mean arterial pressure, glomerular filtration rate, or serum sodium and potassium. We conclude that tolvaptan is an effective aquaretic with no adverse effects on renal hemodynamics or serum electrolytes in patients with mild to moderate heart failure.

Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Cross-Over Studies; Diuretics; Female; Furosemide; Heart Failure; Hemodynamics; Humans; Kidney; Male; Middle Aged; Placebos; Potassium; Sodium; Tolvaptan; Urination; Vasopressins; Water; Water-Electrolyte Balance

The purpose of this study was to confirm earlier reports that low-dose vasopressin (LDVP) analogues promote urine output in patients with hepatorenal syndrome (HRS) and to check whether this mode of therapy could also be effective in renal shutdown due to nonhepatic conditions.. A prospective, open, interventional study.. An intermediate-level (step-down) medical intensive care unit within a general medical ward of a large university-affiliated hospital.. Eighteen successive hospitalized patients with HRS (mean age 65 +/- 13 years) and 11 patients with end-stage congestive heart failure (CHF) (mean age 81 +/- 5 years) who failed to restore urine output with conventional treatment (fluids, dopamine, and diuretics) given for at least 24 h.. The patients received LDVP (1 IU h-1) continuously in addition to the conventional treatment.. Urine output and creatinine clearance every 24 h.. In the HRS group, before treatment the urine output was 155 +/- 9 mL 24 -1h (mean +/- SD). After treatment with LDVP for 24, 48, and 72 h, urine output improved to 1067 +/- 87, 1020 +/- 501, and 1311 +/- 988 mL 24 -1h, respectively (P < 0.0001 for all measures; two-tailed paired t-test). In the CHF group, before treatment the urine output was 99 +/- 99 mL 24 -1h. After treatment with LDVP for 24, 48, and 72 h, this improved to 1125 +/- 994 mL 24 -1h (P = 0.0028), 1821 +/- 1300 mL 24 -1h (P = 0.004), and 2920 +/- 2423 mL 24 -1h (P = 0.0012), respectively. The improvement in urine output was not accompanied by a parallel improvement in creatinine clearance. The overall outcome did not change, and all patients except two in each group succumbed to their end-stage disease, due to nonrenal causes.. LDVP is effective in restoring urine output both in HRS and in CHF. This suggests that LDVP affects mechanisms not specifically related to liver disease. LDVP may be useful in critical patients with renal shutdown whilst awaiting liver or heart transplantation.

Topics: Aged; Aged, 80 and over; Anuria; Creatinine; Diuresis; Drug Administration Schedule; Female; Heart Failure; Hepatorenal Syndrome; Humans; Male; Middle Aged; Prospective Studies; Renal Agents; Treatment Outcome; Vasopressins

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

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

Previous studies have demonstrated that continuous infusion of furosemide results in increased diuresis and natriuresis compared with bolus administration of the drug in patients with severe heart failure. We reasoned that continuous infusion of furosemide caused less activation of neurohumoral mechanisms, since other studies have shown that bolus administration of furosemide may activate this system. We therefore tested the hypothesis that continuous administration of furosemide would increase water and sodium excretion due to less activation of neurohormones. Eight patients with severe heart failure were studied during continuous infusion over 24 h and bolus injections of furosemide twice daily in a randomized cross-over study. Bolus administration of furosemide increased diuresis and natriuresis significantly in the first 4 h after administration compared with continuous administration, but this was later reversed, resulting in similar 24 h total output. The neurohormones measured at baseline were all markedly elevated. Neither regimens of furosemide caused any further significant changes in neurohumoral response except that pro-ANF decreased more during the first 8 h after bolus administration compared to continuous infusion. This study has demonstrated that bolus administration of furosemide in conventional doses is equally effective as continuous intravenous infusion in patients with severe heart failure. This may be due to maximal neurohormonal activation in severe heart failure (NYHA III-IV) which could not be further activated by bolus administration.

Topics: Atrial Natriuretic Factor; Blood Pressure; Brain; Catecholamines; Cross-Over Studies; Diuresis; Diuretics; Endothelin-1; Endothelins; Female; Furosemide; Heart Failure; Heart Rate; Hormones; Humans; Infusions, Intravenous; Injections, Intravenous; Male; Middle Aged; Natriuresis; Neuropeptide Y; Protein Precursors; Vasopressins

The HeartMate left ventricular assist device has been successfully used as a bridge to cardiac transplantation. Because many patients exhibit marked clinical improvement in their heart failure after HeartMate implantation, we studied the physiological effect of this device on the neurohormonal axis.. In 13 patients awaiting transplant (mean cardiac index, 1.7 +/- 0.3 L.min-1.m-2) who underwent HeartMate implantation, venous atrial natriuretic peptide, epinephrine, norepinephrine, plasma renin activity, angiotensin, and arginine vasopressin were measured immediately before insertion and at explant/transplantation. Mean time to explant was 86 +/- 40 days. All patients were taken off inotropic medications within 1 month. Mean cardiac index on support before explant was 3.1 +/- 0.9 L.min-1.m-2. Plasma renin activity decreased from 57 +/- 56 ng.mL-1.h-1 at baseline (before insertion) to 3 +/- 3 ng.mL-1.h-1 at explant (mean percent change, 92%; P < .001). Angiotensin II level decreased from 237 +/- 398 U/L at baseline to 14 +/- 14 U/L at explant (mean percent change, 73%; P < .001). Plasma epinephrine level fell from 6800 +/- 1323 pg/mL at baseline to 46 +/- 46 pg/mL at explant (mean percent change, 86%; P < .001). Norepinephrine level decreased from 2953 +/- 1457 pg/mL at baseline to 518 +/- 290 pg/mL at explant (mean percent change, 79%; P < .001). Atrial natriuretic peptide fell from baseline values of 227 +/- 196 to 168 +/- 40 pg/mL at explant (mean percent change, -49%; P = 519); and arginine vasopressin level decreased from 6 +/- 6 pg/mL at baseline to 0.8 +/- 0.5 pg/mL (mean percent change, 69%; P = .002).. We provide data supporting that the neurohormonal axis markedly improves after HeartMate implantation, providing biochemical confirmation of the improvement in hemodynamic status.

Topics: Adult; Angiotensin II; Atrial Natriuretic Factor; Catecholamines; Female; Heart Failure; Heart-Assist Devices; Hemodynamics; Humans; Male; Middle Aged; Neurosecretory Systems; Prostheses and Implants; Renin; Vasopressins; Ventricular Function, Left

Neurohormonal activation with increased plasma renin activity and norepinephrine and vasopressin levels is characteristic of congestive heart failure and contributes to further decompensation and poor prognosis. We treated 20 such patients with the centrally acting sympathoinhibitory drug clonidine 0.15 mg BID and obtained hemodynamic measurements by cardiac catheterization and plasma neurohormone levels before and 2 to 3 hours after the first dose; in 7 patients, these measurements were taken again after 1 week of therapy. The initial dose produced significant decreases of 8% in mean arterial pressure, 23% in right atrial pressure, 21% in pulmonary capillary wedge pressure, 19% in mean pulmonary artery pressure, and 12% in heart rate, a 17% increase in stroke volume; and no significant changes in cardiac output and systemic vascular resistance. All changes remained virtually constant after 1 week. Plasma norepinephrine decreased by 28% after the initial dose and 62% after 1 week (P < 0.1), whereas plasma renin activity remained essentially unchanged. Plasma vasopressin tended to increase, its levels being inversely correlated with those of posttreatment norepinephrine (r = -.48 P < .03). Patients with baseline norepinephrine levels > 0.400 ng/mL has significantly poorer baseline hemodynamic parameters and tended to show more improvement with clonidine, although their data remained significantly worse than patients whose baseline norepinephrine was within the normal range. Sympathetic suppression with clonidine in congestive heart failure reduces preload, heart rate, and arterial pressure, all indexes of myocardial energy demand; the lack of significant reduction in systemic vascular resistance and increase in cardiac output might be attributable in part to enhanced release of vasopressin.2+ f2p4

Topics: Administration, Oral; Adult; Aged; Clonidine; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Pilot Projects; Renin; Sympathetic Nervous System; Sympatholytics; Vasopressins

Despite almost three centuries of use, the appropriate dosage of digitalis in patients with chronic heart failure and normal sinus rhythm has not been well studied.. We studied 22 patients with heart failure who were receiving constant daily doses of digoxin, diuretics, and angiotensin-converting enzyme (ACE) inhibitors. In 18 patients, the oral daily dose of digoxin was increased from a mean of 0.20 +/- 0.07 to 0.39 +/- 0.11 mg/day corresponding to an increase in the serum digoxin concentration from 0.67 +/- 0.22 to 1.22 +/- 0.35 ng/mL. Radionuclide and echocardiographic left ventricular ejection fraction; maximal treadmill time; heart failure score; serum concentrations of norepinephrine, aldosterone, atrial natriuretic factor, and antidiuretic hormone; and plasma renin activity were obtained before and after the increase in digoxin dose. Subsequently, 9 patients were randomized to receive digoxin and 9 to receive placebo and radionuclide ejection fraction measured after 12 weeks. With the higher dose of digoxin compared with the lower dose, there was a significant increase in radionuclide ejection fraction from 23.7 +/- 9.6% to 27.1 +/- 11.8% (P = .007). No significant changes were noted in heart failure score; exercise tolerance; serum concentrations of norepinephrine, atrial natriuretic factor, and antidiuretic hormone; and plasma renin activity. There was, however, an increase in serum aldosterone concentration. Twelve weeks after the patients were randomized to receive digoxin or placebo, there was a significant decrease in ejection fraction (from 29.4 +/- 10.4% to 23.7 +/- 8.9%) in the placebo group but not in patients who continued to receive digoxin (P = .002).. The increase in maintenance digoxin dose, while maintaining serum concentrations within therapeutic range, resulted in a significant increase in left ventricular ejection fraction that was not associated with significant changes in heart failure score, exercise tolerance, and neurohumoral profile.

Topics: Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Cardiotonic Agents; Digoxin; Diuretics; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heart Failure; Humans; Male; Middle Aged; Norepinephrine; Renin; Single-Blind Method; Stroke Volume; Vasopressins; Ventricular Function, Left

An enzyme-linked immunosorbent assay is described for the measurement of ouabain in human plasma. This assay is specific for ouabain, strophanthidin, and ouabagenin, with other steroids, including digoxin and vasopressor hormones, exhibiting negligible cross-reactivity. Assay sensitivity was 0.06 nmol/L if 1 mL plasma was extracted and less than 0.005 nmol/L when 20 mL plasma was analyzed. Extracted plasma samples showed ouabainlike immunoreactivity that diluted in parallel with the ouabain standard curve. Repeated extraction and assay of single plasma samples, however, did not produce consistent results in the assay. Increased specificity was obtained by high-performance liquid chromatography of sample extracts before assay. When high-performance liquid chromatographic profiles of plasma spiked with ouabain standard or following bolus intravenous injections of ouabain into normal human volunteers were compared with profiles of unspiked plasma, there was no support for the immunoreactive material in the latter samples being ouabain. We propose that if ouabain is present in the human circulation, its concentration is less than 0.005 nmol/L.

Topics: Animals; Antibodies; Antibody Specificity; Chromatography, High Pressure Liquid; Cross Reactions; Digoxin; Enzyme-Linked Immunosorbent Assay; Female; Fetal Blood; Heart Failure; Humans; Kidney Failure, Chronic; Ouabain; Pre-Eclampsia; Pregnancy; Rabbits; Sensitivity and Specificity; Steroids; Strophanthidin; Vasopressins

In an open trial 5 mg ramipril daily for 2 weeks was administered to 11 patients with congestive heart failure. 24-hour plasma profiles of atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), angiotensin II (Ang II) and aldosterone (Aldo) were determined before and on days 1 and 15 of ramipril treatment, respectively. Urinary sodium excretion was also measured at the same time points. There were no relevant differences in the 24-hour profiles of ANP and ADH. Ang II values dropped as expected on the first day of ramipril treatment from 11.2 pg/ml to 2.9 pg/ml at 3 h post administration and from 6.7 pg/ml (predose) to 1.8 pg/ml at 2 h post administration on day 15. Plasma aldosterone values increased slightly from day 1 to day 15, sodium excretion increased from 125.9 mmol to 166.5 mmol/24 h; however, both changes in the 24-hour profiles were nonsignificant. A clinically relevant improvement in the severity of CHF was observed. From a total of 121 reported symptoms according to McKee et al., 35 showed an improvement; 81 remained unchanged, in only 5 symptoms a deterioration was observed. According to the NYHA-classification 5 patients improved from grade III to II, 6 remained unchanged.. ACE inhibition does not induce changes in ANP or ADH levels in the resting state while Ang II decreases. A slight increase in aldosterone levels may be due to increased sodium excretion.

Topics: Aged; Aged, 80 and over; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Female; Heart Failure; Humans; Male; Middle Aged; Radioimmunoassay; Ramipril; Sodium; Vasopressins

Fifteen patients with congestive heart failure (New York Heart Association III) were randomly assigned to treatment with either captopril or ramipril, a newly developed angiotensin converting enzyme inhibitor. Both groups were similar with respect to baseline hemodynamic measurements and plasma levels of norepinephrine, renin and vasopressin. The group receiving ramipril showed hemodynamic changes comparable to the group receiving captopril on the seventh day of treatment. The stroke volume index increased by 20% versus 21%, respectively, and the total peripheral resistance decreased by 13% versus 20%, respectively. The decrease in blood pressure and the tendency to decrease heart rate were similar in both groups. All patients had reactive hyperreninemia during therapy with the converting enzyme inhibitor. The resting elevated plasma norepinephrine decreased in both groups significantly, whereas vasopressin did not change. The hemodynamic improvement was more pronounced and comparable in both groups during exercise. Thus, ramipril is equally effective compared with captopril in the treatment of patients with severe congestive heart failure.

Topics: Adult; Aged; Bridged Bicyclo Compounds; Bridged-Ring Compounds; Captopril; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Ramipril; Random Allocation; Renin; Vasoconstriction; Vasopressins

Fifty patients with congestive heart failure received, by infusion, 15 ml/kg body weight water load, and systemic hemodynamic, renal function, and neurohumoral parameters values were measured before, 2 days, and 1 month after randomly allocating patients to prazosin or captopril therapy. Both prazosin and captopril caused similar and persistent hemodynamic changes, but important differences existed between their renal and neurohumoral effects. After 1 month of continuous therapy, captopril increased creatinine clearance from 71 to 84 ml/min/1.73(2) (p less than .05), increased the water load excreted in 5 hr from 50% to 71% (p less than .005), and increased 5 hr sodium excreted from 6.8 to 14.7 meq (p less than .005), Captopril also caused a decrease in plasma norepinephrine from 568 to 448 pg/ml (p less than .005), in plasma epinephrine from 94 to 73 pg/ml (p less than .05), and in plasma aldosterone from 57 to 28 ng/dl (p less than .005), without changing plasma vasopressin. These beneficial effects were greater after 1 month of therapy than after 2 days. The only beneficial effect of prazosin was to increase water excretion from 49% to 59% (p less than .05). The long-term response to captopril was similar in patients with higher (greater than 2.5 ng/ml/hr) and lower renin levels. However, in patients with lower renin levels, prazosin decreased pulmonary capillary wedge pressure (24.8 to 21.8 mm Hg, p less than .05), decreased plasma arginine vasopressin (1.16 to 0.75 pg/ml, p less than .05), increased water excretion (62% to 85%, p less than .005), and decreased plasma epinephrine (81 to 46 pg/ml, p less than .05), while in patients with higher renin levels none of these beneficial effects were noted. We conclude that captopril produces long-term beneficial renal and neurohumoral effects that prazosin does not despite similar hemodynamic changes with the two drugs, that these effects are at least partially dependent on the initial neurohumoral and hemodynamic status of the patient, and that through hemodynamic improvement vasodilators may chronically interrupt vasopressin overstimulation.

Topics: Captopril; Heart Failure; Hemodynamics; Humans; Prazosin; Renin; Time Factors; Vasopressins; Water-Electrolyte Balance

A double blind cross over study was performed to compare the long term hormonal, haemodynamic, and clinical responses to specific inhibition of the renin-angiotensin-aldosterone system (captopril) and of the alpha 1 adrenoceptors of the sympathetic system (prazosin) both at rest and during upright exercise in patients with chronic heart failure. Sixteen patients completed one month's treatment with each drug. During conventional diuretic treatment (control) plasma renin activity, aldosterone, and noradrenaline were increased at rest and on exercise. Control left ventricular filling pressures were raised, and correlated significantly with plasma renin activity both at rest and on exercise. Systemic vascular resistance was increased at rest, and its reduction during exercise correlated inversely with the increase in plasma renin activity and plasma noradrenaline. After one month's treatment with captopril there were reductions in plasma aldosterone, weight, left ventricular filling pressure, and systemic vascular resistance at rest and on exercise. Dyspnoea was relieved and exercise capacity increased. The greater fall in systemic vascular resistance on exercise no longer correlated with the increase in plasma renin activity. During treatment with prazosin there were increases in plasma noradrenaline and, transiently, in plasma aldosterone. Fluid retention occurred, and left ventricular filling pressure was unchanged. Compared with control values systemic vascular resistance was reduced at rest but not on exercise. Dyspnoea and exercise capacity did not improve. In chronic heart failure, vasodilatation by inhibition of the alpha adrenergic system with prazosin causes compensatory stimulation of the renin-angiotensin-aldosterone system and does not result in clinical benefit. Inhibition of the renin-angiotensin-aldosterone system with captopril causes secondary vasodilatation at rest and on exercise and results in improvement in symptoms and exercise capacity.

Topics: Aged; Captopril; Clinical Trials as Topic; Double-Blind Method; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Prazosin; Renin-Angiotensin System; Rest; Vasodilation; Vasopressins

The effects of human alpha atrial natriuretic factor following bolus injection of increasing doses and during a continuous 30 minute infusion were investigated in 7 patients with severe congestive cardiac failure (NYHA III-IV). The natriuretic factor was measured in plasma before and after the bolus application or infusion. The plasma levels were raised in 6 patients. A significant inverse correlation was observed between the basal levels of the atrial factor and cardiac output. In addition, there was a dose-dependent fall in preload and afterload as well as in the peripheral vascular resistance and there was an improvement in cardiac performance. The alpha atrial natriuretic factor inhibited aldosterone and cortisol secretion and promoted diuresis and the urinary excretion of sodium and potassium. The plasma concentrations of renin, noradrenaline, vasopressin, 6-keto-prostaglandin F1 alpha, the stable metabolite of prostacyclin, and prostaglandin E2 remained unchanged.

Topics: Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Central Venous Pressure; Clinical Trials as Topic; Diuresis; Dose-Response Relationship, Drug; Heart Failure; Hemodynamics; Humans; Hydrocortisone; Natriuresis; Prostaglandins E; Prostaglandins F; Renin; Vasopressins

Acute heart failure (AHF) due to acute myocardial infarction (AMI) is likely to involve cardiogenic shock (CS), with neuro-hormonal activation. A relationship between AHF, CS and vasopressin response is suspected. This study aimed to investigate the implication of vasopressin on hemodynamic parameters and tissue perfusion at the early phase of CS complicating AMI. Experiments were performed on male Wistar rats submitted or not to left coronary artery ligation (AMI and Sham). Six groups were studied Sham and AMI treated or not with either a vasopressin antagonist SR-49059 (Sham-SR, AMI-SR) or agonist terlipressin (Sham-TLP, AMI-TLP). Animals were sacrificed one day after surgery (D

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Heart Failure; Male; Myocardial Infarction; Rats; Rats, Wistar; Shock, Cardiogenic; Stroke Volume; Vasopressins; Ventricular Function, Left

Preserved urinary excretion of aquaporin 2, an index for the function of vasopressin V2 receptor (V2-R), has been reported to predict a favorable response of heart failure patients to treatment with tolvaptan. In this study, we investigated the long-term effects of tolvaptan treatment on clinical outcomes and V2-R function in patients with acute decompensated heart failure (ADHF). We enrolled 90 consecutive patients who were hospitalized in Sapporo Medical University Hospital for ADHF and treated with tolvaptan in the BOREAS-ADHF registry and analyzed patients who continued taking tolvaptan after discharge. The effect of tolvaptan treatment on rehospitalization for HF or death was investigated according to whether the V2-R function was preserved (first morning urine osmolarity ≥ 352 mOsm/L, High-Uosm) or impaired (Uosm < 352 mOsm/L, Low-Uosm). During a median follow-up period of 443 days, significantly fewer patients in the High-Uosm group experienced adverse events than did patients in the Low-Uosm group (P < 0.001). Among the patients with High-Uosm, early commencement of tolvaptan administration (on or before day 7 of hospitalization, Early/High-Uosm) significantly reduced adverse events compared to late administration (after day 7 of hospitalization, Late/High-Uosm). Uosm measured during the long-term follow-up period after discharge was significantly reduced compared to that before commencement of tolvaptan administration in the Late/High-Uosm group (from 468 ± 88 to 395 ± 108 mOsm, -18.3 ± 19.6%, P < 0.05) but not in the Early/High-Uosm group (from 478 ± 115 to 455 ± 133 mOsm, -0.50 ± 35.3%, P = 0.66). These findings indicate that early commencement and long-term continuation of tolvaptan treatment attenuate functional impairment of V2-R and improve clinical outcomes in ADHF patients with preserved V2-R function.

Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Heart Failure; Humans; Receptors, Vasopressin; Tolvaptan; Vasopressins

Given the various effects of sacubitril/valsartan in heart failure, a deeper understanding of atrial natriuretic peptide (ANP) actions is warranted. Natriuresis is a fundamental action of ANP in acute heart failure (AHF), whereas the diuretic effect of ANP is different in each patient according to the diversity of renal response to ANP, which is affected by baseline plasma ANP status and deficiency of circulating ANP. Meanwhile, associations between other neuroendocrine hormones and the diuretic response to ANP are unclear. This study investigated the impact of pivotal neuroendocrine hormones on the diuretic effects of exogenous ANP, carperitide.. Plasma ANP, renin, aldosterone, and vasopressin levels and the diuretic effect of 0.0125 μg/kg/min of carperitide alone for the first 6 h were prospectively evaluated in 75 patients with AHF. Lower ANP levels were significantly associated with a greater diuretic response to exogenous ANP (r = -0.35, P = 0.002). Additionally, higher vasopressin levels were significantly related to the poor diuretic effects of exogenous ANP (r = -0.54, P < 0.001). Plasma ANP and vasopressin concentrations were not significantly correlated (r = 0.19, P = 0.10). Baseline systolic blood pressure, renal function, and prior use of loop diuretics did not predict the diuretic response to exogenous ANP, whereas vasopressin levels independently predicted a diuretic response to exogenous ANP (P < 0.001), as well as lower plasma ANP levels (P = 0.027).. Vasopressin status was significantly associated with the diuretic response to exogenous ANP in AHF, independent of plasma ANP status. The results may provide a better understanding of the actions of sacubitril/valsartan.

Topics: Atrial Natriuretic Factor; Diuretics; Heart Failure; Humans; Neurosecretory Systems; Valsartan; Vasopressins

Tolvaptan, a vasopressin type-2 receptor antagonist, is utilized to ameliorate fluid retention following cardiac surgery. However, the optimal timing of tolvaptan administration considering novel biomarkers remains unknown. We prospectively included patients who underwent cardiac surgery between 2016 and 2020. We measured perioperative trends of free water reabsorption mediators including plasma arginine vasopressin and urine aquaporin-2. A total of 20 patients (68 [60, 75] years old, 18 men) were included. Urine volume decreased gradually after the initial 3 hours following cardiac surgery. The plasma arginine vasopressin level increased significantly with a peak at postoperative 6 hours, whereas the urine aquaporin-2 level increased later with a delayed peak at postoperative 12 hours. As a result, urine aquaporin-2 relative to the plasma arginine vasopressin level, which represents the activity of the collecting ducts and indicates predicted responses to tolvaptan, was a minimum at postoperative 6 hours. Tolvaptan administration immediately after cardiac surgery might not be recommended given the transient refractoriness to tolvaptan probably due to the stunning of kidney collecting ducts.

Topics: Aged; Antidiuretic Hormone Receptor Antagonists; Aquaporin 2; Arginine Vasopressin; Biomarkers; Body Fluids; Cardiac Surgical Procedures; Female; Heart Failure; Hemodynamics; Humans; Kidney; Male; Middle Aged; Postoperative Care; Prospective Studies; Tolvaptan; Vasopressins

BACKGROUND The aim of this study was to assess the impact of norepinephrine (NE), norepinephrine plus vasopressin (NE+VAS) and dopamine in patients with sepsis and heart failure. MATERIAL AND METHODS Data were extracted from the Medical Information Mart for Intensive Care III database, v1.4. Adults aged >18 years in an Intensive Care Unit (ICU) who had heart failure and took vasopressors were included. The patients were divided into 3 groups: NE, NE+VAS, and dopamine. Differences in survival, treatment time, and organ function among the 3 groups were compared. Propensity score matching (PSM) was used to screen for possible prognostic differences, and regression analysis was used to further analyze and predict prognoses. RESULTS A total of 1864 patients were included. There were significant differences among the 3 groups in 7-, 28-, and 90-day mortality after PSM. The 5-year survival rates among the 3 groups also were significantly different (P<0.001). After Cox regression analysis, NE+VAS was an independent risk factor affecting 5-year survival (P<0.001). After multiple linear regression, dopamine was the factor related to ICU and hospital lengths of stay. CONCLUSIONS Compared with NE or dopamine alone, NE+VAS can reduce survival in patients with sepsis and heart failure who need vasopressors. Compared with the other 2 treatment options, dopamine can shorten ICU and hospital stays for these patients.

Topics: Acute Disease; Aged; Cardiotonic Agents; Cohort Studies; Critical Illness; Dopamine; Female; Heart Failure; Humans; Length of Stay; Male; Norepinephrine; Retrospective Studies; Sepsis; Survival Rate; Vasoconstrictor Agents; Vasopressins

Phosphodiesterase-9 (PDE9) reduces natriuretic peptide (NP) signaling and may be involved in the pathophysiology of heart failure (HF).. This study investigated for the first time the integrated hemodynamic, endocrine, and renal effects of phosphodiesterase-9 inhibition (PDE9-I).. A total of 8 normal sheep and 8 sheep with pacing-induced HF received incremental intravenous boluses of PDE9-I (30, 100, and 300 mg PF-04749982 at 1-h intervals).. PDE9-I dose-dependently increased plasma cyclic guanosine monophosphate (cGMP) in normal sheep (p < 0.05) while concurrently reducing circulating atrial natriuretic peptide levels (p < 0.01). Similar trends were evident in HF, resulting in significant elevations in the cGMP/NP ratio in both states (p < 0.001 and p < 0.05, respectively). PDE9-I also produced progressive falls in arterial pressure (HF: p < 0.001), atrial pressure (Normal: p < 0.001; HF: p < 0.001), and peripheral resistance (HF: p < 0.001), and transiently increased cardiac output at the top dose (Normal: p < 0.05; HF: p < 0.001). Inhibition of PDE9 had a negligible effect on circulating hormones at the lower doses, but post-high dose, acutely increased renin activity (Normal: p < 0.001; HF: p < 0.05), vasopressin (Normal: p < 0.001; HF: p < 0.01), and cyclic adenosine monophosphate (HF: p < 0.001). Plasma aldosterone increased briefly after high-dose PDE9-I in normal sheep, and fell following the top dose in HF. PDE9-I dose-dependently increased urinary cGMP in both states (both p < 0.001). In HF, this was associated with increases in urine volume (p < 0.01), sodium excretion (p < 0.01), and creatinine clearance (p < 0.001).. PDE9-I improves NP efficacy in conjunction with beneficial hemodynamic and renal effects in experimental HF. These results support a role for PDE9 in HF pathophysiology and suggest its inhibition may constitute a novel therapeutic approach to this disease.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Adenosine Monophosphate; Aldosterone; Animals; Atrial Natriuretic Factor; Atrial Pressure; Blood Pressure; Cardiac Output; Creatinine; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Guanosine Monophosphate; Heart Failure; Phosphodiesterase Inhibitors; Renin; Sheep; Sodium; Urine; Vascular Resistance; Vasopressins

Topics: Acute Kidney Injury; Animals; Diuretics; Heart Failure; Humans; Rats, Wistar; Tolvaptan; Vasopressins

Heart failure (HF) remains the most common reason for hospital admission in patients aged >65 years. Despite modern drug therapy, mortality and readmission rates for patients hospitalized with HF remain high. This necessitates further research to identify early patients at risk for readmission to limit hospitalization by timely adjustment of medical therapy. Implantable devices can monitor left ventricular (LV) hemodynamics and remotely and continuously detect the early signs of decompensation to trigger interventions and reduce the risk of hospitalization for HF. Here, we report the first preclinical study validating a new batteryless and easy to implant LV-microelectromechanical system to assess LV performance.. A miniaturized implantable wireless pressure sensor was adapted for implantation in the LV apex. The LV-microelectromechanical system sensor was tested in a canine model of HF. The wireless pressure sensor measurements were compared with invasive left heart catheter-derived measurements at several time points. During different pharmacological challenge studies with dobutamine or vasopressin, the device was equally sensitive compared with invasive standard procedures. No adverse events or any observable reaction related to the implantation and application of the device for a period of 35 days was observed.. Our miniaturized wireless pressure sensor placed in the LV (LV-microelectromechanical system) has the potential to become a new telemetric tool to earlier identify patients at risk for HF decompensation and to guide the treatment of patients with HF.

Topics: Animals; Cardiac Catheterization; Cardiac Pacing, Artificial; Disease Models, Animal; Dobutamine; Dogs; Echocardiography; Equipment Design; Heart Failure; Hemodynamics; Male; Miniaturization; Predictive Value of Tests; Remote Sensing Technology; Reproducibility of Results; Time Factors; Transducers, Pressure; Vasopressins; Ventricular Function, Left

Arginine vasopressin is a potent vasoconstrictory hormone and arginine vasopressin release is upregulated in heart failure (HF). The aim of this study was to evaluate if copeptin (the C-terminal part of provasopressin) is related to invasive hemodynamics in HF.. Right heart catheterization was performed in patients with advanced HF referred for evaluation for heart transplantation. Sixty-five patients (mean age 54 ± 12 years, left ventricular ejection fraction 19 ± 8% and median copeptin levels of 16.7 pmol/l (interquartile range: 11-30 pmol/l) were included. In multivariate analysis, increased levels of log (copeptin) were associated with a reduced CI (r = 0.65 and p = 0.04).. Increased copeptin levels in plasma are associated with hemodynamic parameters obtained at right heart catheterization in patients with HF, in particular-reduced cardiac index. Copeptin could be a useful biomarker for abnormal resting hemodynamics in HF.

Topics: Adult; Aged; Biomarkers; Female; Glycopeptides; Heart Failure; Heart Transplantation; Hemodynamics; Humans; Male; Middle Aged; Neurophysins; Protein Precursors; Vasopressins

We conducted this study to assess the clinical application of obestatin and arginine vasopressin (AVP) levels in cases of acute renal failure (ARF) and acute heart failure (AHF).. 30 cases of ARF, 30 cases of AHF, 30 cases of ARF complicated with AHF, and 30 cases of healthy subjects (control group) were successively selected. An ELISA test was conducted to detect levels of obestatin and AVP. Routine biochemistry testing was applied to detect the levels of serum creatinine and calculate the glomerular filtration rate (GFR). Electrochemiluminescence double antibody sandwich fluorescence immune testing was applied to detect NT-proBNP and color Doppler ultrasound diagnostic apparatus was applied to detect renal arterial resistive index (RI) and left ventricular ejection fraction (LVEF). The 30-day mortality was documented.. Compared to other groups, the group of patients suffering from ARF complicated with AHF had significantly higher levels of obestatin and AVP, and significantly higher levels of serum creatinine, NT-proBNP and RI; however, their GFR and LVEF levels were the lowest. Differences were statistically significant (p < 0.05). Levels of obestatin and AVP are positively correlated with serum creatinine, NT-proBNP and RI levels, but negatively correlated with GFR and LVEF levels. The mortality rate of the group suffering from ARF complicated with AHF was markedly increased (p = 0.035). The obestatin and AVP levels of the death group were significantly higher than that of the survival group. However, the comparison among levels of serum creatinine, GFR, NT-proBNP, RI and LVEF revealed no statistical significance (p > 0.05).. Obestatin and AVP levels were closely related to the severity of ARF and AHF and survival prognosis, which could be a sensitive indicator for diagnoses and prognoses.

Topics: Acute Disease; Acute Kidney Injury; Adult; Aged; Female; Ghrelin; Glomerular Filtration Rate; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neurophysins; Peptide Fragments; Protein Precursors; Vasopressins; Ventricular Function, Left

Despite the pathophysiological importance of neurohumoral activation in patients with heart failure (HF), the precise underlying mechanisms contributing to elevated vasopressin (VP) activation in HF remains unknown. Carbon monoxide (CO) is a gaseous neurotransmitter in the central nervous system that stimulates VP neuronal firing activity. Recently, we showed that the excitatory effect of CO on VP neurons in the hypothalamic paraventricular nucleus (PVN) was mediated by inhibition of nitric oxide (NO). Given that previous studies showed that VP neuronal activity is enhanced, whereas NO inhibitory signaling is blunted in HF rats, we tested whether an enhanced endogenous CO availability within the PVN contributes to elevated VP neuronal activity and blunted NO signaling in HF rats. We found that both haeme-oxygenase 1 (the CO-synthesizing enzyme) protein and mRNA expression levels were enhanced in the PVN of HF compared with sham rats (∼18% and ∼38%, respectively). We report that in sham rats, bath application of a CO donor (tricarbonyldichlororuthenium dimer) increased the firing activity of identified PVN VP neurons (P < .05), whereas inhibition of endogenous CO production (Tin-protoporphyrin IX [SnPP]) failed to affect neuronal activity. In HF rats, however, SnPP decreased VP activity (P < .05), an effect that was occluded by previous NO synathase blockade NG-nitro-larginine methyl ester. Finally, we found that SnPP increased the mean frequency of γ-aminobutyric acid inhibitory postsynaptic currents in VP neurons in HF (P < .05) but not sham rats. Our results support an enhanced endogenous CO excitatory signaling in VP neurons, which likely contributes to blunted NO and γ-aminobutyric acid inhibitory function in HF rats.

Topics: Animals; Carbon Monoxide; Disease Models, Animal; Heart Failure; Heme Oxygenase-1; Inhibitory Postsynaptic Potentials; Male; Metalloporphyrins; Neurons; Nitric Oxide; Organometallic Compounds; Paraventricular Hypothalamic Nucleus; Protoporphyrins; Rats; Rats, Wistar; Vasopressins

Topics: Aldosterone; Antidiuretic Hormone Receptor Antagonists; Arginine; Benzazepines; Biomarkers; Diuresis; Dose-Response Relationship, Drug; Evidence-Based Medicine; Heart Failure; Humans; Predictive Value of Tests; Prognosis; Renin-Angiotensin System; Sensitivity and Specificity; Severity of Illness Index; Tolvaptan; Treatment Outcome; Vasopressins

During the past 50 years the molecular mechanisms of renal reabsorption of sodium and water have been described and molecules specifically interfering with these mechanisms have been developed (diuretics, vasopressin receptor antagonists). Chronic hyponatremia is caused by relative excess of free water, it occurs within a broad spectrum of diseases associated with hypervolemia (heart failure, liver cirrhosis), normovolemia and hypovolemia and it is a negative prognostic factor for patients with chronic heart failure and cirrhotic ascites. Vaptans (vasopressin antagonists, vasopressin V2-receptor inhibitors) reduce reabsorption of water in the distal nephron, they increase free water excretion and normalize serum concentrations of sodium in normovolemic and hypervolemic conditions associated with hyponatremia. Hyponatremia can be corrected (depending on cause, severity and speed of development) through the reduction of fluid intake, administration of a hypertonic solution NaCl, diuretics, oral administration of urea and by vaptans. The role of vaptans in the treatment of hyponatremia should be defined even better, in Europe vaptans can be used to treat the syndrome of inadequate antidiuretic hormone secretion (SIADH).Key words: hyponatremia - liver cirrhosis - heart failure - syndrome of inadequate secretion ADH - tolvaptan - vasopressin.

Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Europe; Heart Failure; Humans; Hyponatremia; Inappropriate ADH Syndrome; Liver Cirrhosis; Receptors, Vasopressin; Sodium; Tolvaptan; Vasopressins

Thiazolidinediones are highly beneficial in the treatment of type II diabetes. However, they are also associated with edema and increased risk of congestive heart failure. Several studies demonstrated that rosiglitazone (RGZ) increases the abundance of aquaporin-2 (AQP2) at the plasma membrane of renal cells. The aim of this study was to investigate whether RGZ might activate a transduction pathway facilitating AQP2 membrane accumulation in renal cells.. We analyzed the effect of RGZ on renal AQP2 intracellular trafficking in MCD4 renal cells by confocal microscopy and apical surface biotinylation. Cytosolic Ca(2+) dynamics were measured by a video-imaging approach in single cell. Transient Receptor Potential (TRP) channels expression was determined by RT-PCR.. We showed that in MCD4 cells, short-term exposure to RGZ dramatically increases the amount of apically expressed AQP2 independently on cAMP production, PKA activation and AQP2 phosphorylation. RGZ elicited a cytosolic Ca(2+) transient due to Ca(2+) influx prevented by ruthenium red, suggesting the involvement of TRP plasma membrane channels. We identified TRPV6 as the possible candidate mediating this effect.. Taken together these results provide a possible molecular mechanism explaining the increased AQP2 membrane expression under RGZ treatment: in renal cells RGZ elicits Ca(2+) transients facilitating AQP2 exposure at the apical plasma membrane, thus increasing collecting duct water permeability. Importantly, this effect suggests an unexplored application of RGZ in the treatment of pathological states characterized by impaired AQP2 trafficking at the plasma membrane.

Topics: Aquaporin 2; Calcium Channels; Calcium Signaling; Cell Line; Cell Membrane; Cyclic AMP; Edema; Endocytosis; Epithelial Cells; Gene Expression; Heart Failure; Humans; Kidney; Rosiglitazone; Signal Transduction; Thiazolidinediones; TRPV Cation Channels; Vasopressins

Topics: Cardiac Output, Low; Heart Failure; Humans; Hyponatremia; Vasopressins; Water-Electrolyte Balance

Apelin and vasopressin levels are regulated in opposite directions to maintain body fluid homeostasis.. We thus assessed plasma apelin to copeptin ratios, with plasma copeptin concentrations as a reliable index of vasopressin secretion, in pathological states combining high levels of vasopressin secretion with hyponatremia.. We carried out a cross-sectional study including 113 healthy subjects, 21 hyponatremic patients with the syndrome of inappropriate antidiuretic hormone (SIADH), and 16 normonatremic and 16 hyponatremic patients with chronic heart failure (CHF) in an academic hospital.. Individual apelin to copeptin ratios were plotted against natremia and compared with those of 10 healthy subjects of a previous study acutely challenged by water loading or hypertonic saline infusion. We calculated the percentage of SIADH/CHF patients whose apelin to copeptin ratio for a given natremia lies outside the 95% prediction limits of the physiological relationship.. In healthy subjects, median (interquartile range) plasma apelin and copeptin concentrations were 254 fmol/mL (225-311) and 4.0 fmol/mL (2.6-6.9), respectively. Sex- and age-adjusted plasma apelin concentrations were 26% higher in SIADH and normonatremic and hyponatremic CHF patients than in healthy subjects. Sex- and age-adjusted plasma copeptin concentration was 75%, 187%, and 207% higher in SIADH and normonatremic and hyponatremic CHF patients, respectively, than in healthy subjects. During an acute osmotic challenge, the plasma apelin to copeptin ratio decreased exponentially with natremia. Apelin to copeptin ratios as a function of natremia were outside the 95% predicted physiological limits for 86% of SIADH patients and 81% of hyponatremic CHF patients.. Inappropriate apelin concentrations and apelin to copeptin ratios as a function of natremia in SIADH and CHF patients suggest that the increase in plasma apelin secretion cannot compensate for the higher levels of vasopressin release and may contribute to the corresponding water metabolism defect.

Topics: Adolescent; Adult; Aged; Apelin; Biomarkers; Cross-Sectional Studies; Female; Glycopeptides; Heart Failure; Humans; Hyponatremia; Inappropriate ADH Syndrome; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Models, Biological; Neurophysins; Pituitary Gland, Posterior; Protein Precursors; Saline Solution, Hypertonic; Up-Regulation; Vasopressins; Young Adult

Topics: Arginine Vasopressin; Heart Failure; Humans; Receptors, Vasopressin; Severity of Illness Index; Vasopressins

Pediatric heart failure (HF) is an important cause of morbidity and mortality in childhood. This article presents guidelines for the recognition, diagnosis, and early medical management of HF in infancy, childhood, and adolescence. The guidelines are intended to assist practitioners in office-based or emergency room practice, who encounter children with undiagnosed heart disease and symptoms of possible HF, rather than those who have already received surgical palliation. The guidelines have been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and are accompanied by practical Recommendations for their application in the clinical setting, supplemented by online material. This work does not include Recommendations for advanced management involving ventricular assist devices, or other device therapies.

Topics: Adolescent; Algorithms; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Arrhythmogenic Right Ventricular Dysplasia; Biomarkers; Canada; Cardiomyopathies; Cardiotonic Agents; Catecholamines; Child; Child, Preschool; Combined Modality Therapy; Death, Sudden, Cardiac; Diagnosis, Differential; Diuretics; Echocardiography; Electrocardiography, Ambulatory; Evidence-Based Medicine; Heart Defects, Congenital; Heart Failure; Humans; Infant; Magnetic Resonance Imaging; Myocarditis; Myocardium; Prognosis; Risk Factors; Societies, Medical; Vasodilator Agents; Vasopressins

Topics: Benzazepines; Female; Heart Failure; Humans; Male; Patient Selection; Tolvaptan; Vasopressins

Conivaptan is a nonspecific arginine vasopressin receptor antagonist that has been used as therapy in adults who have hypervolemic hyponatremia due to congestive heart failure. Its use in children with congestive heart failure has not been reported. We describe the use of conivaptan in a 4-month-old infant girl with severe hypervolemic hyponatremia and heart failure. A therapeutic weight-based dose was extrapolated from the adult dose. Conivaptan therapy was administered for 48 hours, after which the patient recovered from her hyponatremia without untoward effects. Arginine vasopressin receptor antagonists such as conivaptan may be useful as therapy for hyponatremia associated with heart failure. Further studies are required before conivaptan can be recommended for routine use in children.

Topics: Benzazepines; Female; Heart Failure; Hormone Antagonists; Humans; Hyponatremia; Infant; Neurophysins; Protein Precursors; Severity of Illness Index; Treatment Outcome; Vasopressins

Topics: Antidiuretic Hormone Receptor Antagonists; Heart Failure; Humans; Hyponatremia; Morpholines; Sodium; Spiro Compounds; Vasopressins

To evaluate the relationship between leg edema, nocturnal urine volume (NUV), and the secretion of antidiuretic hormone (ADH) during the night, and to investigate the principal factors affecting nocturnal polyuria in older men.. A total of 74 male inpatients more than 50 years of age were enrolled in this study. Blood count, standard chemistry panel, brain natriuretic peptide (BNP), urinary ADH (u-ADH), urinary creatinine (u-Cre), and urinary osmolarity were measured at 6:00 am. Keeping a frequency volume chart, bioelectric impedance analysis was performed at 5 pm. Leg edema was measured as an edema ratio, using the following formula: extracellular water [L)/(extracellular water [L) + intracellular water [L)) in legs.. A total of 66 patients were evaluated. NUV had a significant positive correlation with leg edema (r = 0.32, P = .008), negative correlation with u-ADH/u-Cre (r = -0.37, P = .003) but not BNP. Leg edema had a significant positive correlation with the level of BNP (r = 0.33, P = .012) and negative correlation with u-ADH/u-Cre (r = -0.4, P = .001). However a partial correlation showed that there was no significant correlation between NUV and leg edema. A multivariate logistic model showed that only u-ADH/u-Cre was an independent predictive variable of nocturnal polyuria.. This study suggested that leg edema influenced nocturnal urine volume with an associated decrease in ADH secretion but not directly. ADH secretion during the night was the principal factor affecting NP in older men.

Topics: Aged; Blood Pressure; Edema; Heart Failure; Humans; Leg; Male; Middle Aged; Natriuretic Peptide, Brain; Nocturia; Osmolar Concentration; Polyuria; Vasopressins

Although acute administration of urocortin 2 has beneficial actions in heart failure, the integrated hemodynamic, hormonal, and renal effects of sustained urocortin 2 treatment in this disease have not been investigated. In the current study, we administered a 4-day infusion of a vehicle control (0.9% saline; n=6) or urocortin 2 (0.75 μg/kg per hour; n=6) to sheep with pacing-induced heart failure. Compared with time-matched controls, infusion of urocortin 2 produced rapid (30-minute) and persistent (4-day) improvements in cardiac contractility (day 4: control 905±73 versus urocortin 2 1424±158 mm Hg/s; P<0.001) and output (2.6±0.1 versus 3.8±0.3 L/min; P<0.001), together with reductions in left atrial pressure (28±1 versus 12±1 mm Hg; P<0.001) and peripheral resistance (30±2 versus 20±2 mm Hg/L per min; P<0.001). In contrast, urocortin 2-induced falls in mean arterial pressure were not established until the second day (day 4: 74±2 versus 72±2 mm Hg; P<0.05). Prolonged urocortin 2 administration was associated with sustained (days 0 to 4) declines in plasma renin activity (day 4: 1.33±0.27 versus 0.73±0.20 nmol/L per hour; P<0.001), aldosterone (970±383 versus 396±96 pmol/L; P<0.05), vasopressin (2.4±0.8 versus 1.3±0.1 pmol/L; P<0.05), endothelin 1 (7.2±0.7 versus 4.5±0.4 pmol/L; P<0.01), and atrial (269±27 versus 150±19 pmol/L; P<0.001) and B-type (65±9 versus 29±6 pmol/L; P<0.001) natriuretic peptides, as well as an acute transient rise in plasma cortisol (day 1: P<0.001). Chronic urocortin 2 also persistently augmented urinary sodium (day 4: 4-fold increase; P<0.001) and creatinine (1.4-fold; P<0.001) excretion and creatinine clearance (1.5-fold; P<0.01) compared with control. Food consumption was temporarily suppressed (P<0.05). In conclusion, 4-day urocortin 2 administration induces sustained improvements in hemodynamics and renal function, in association with inhibition of multiple vasoconstrictor/volume-retaining systems. These findings support the therapeutic potential for urocortin 2 in heart failure.

Topics: Aldosterone; Animals; Blood Pressure; Cardiac Output; Creatinine; Endocrine System; Endothelin-1; Female; Heart; Heart Failure; Hemodynamics; Infusions, Intravenous; Kidney; Mice; Oligopeptides; Renin; Sheep; Sodium; Time Factors; Urocortins; Vascular Resistance; Vasopressins

Measurement of plasma concentrations of the biomarker copeptin may help identify patients with heart failure at high and low risk of mortality, although the value of copeptin measurement in elderly patients is not fully known.. To evaluate the association between plasma concentrations of copeptin, a surrogate marker of vasopressin, combined with concentrations of the N-terminal fragment of the precursor to B-type natriuretic peptide (NT-proBNP), and mortality in a cohort of elderly patients with symptoms of heart failure.. Primary health care population in Sweden enrolling 470 elderly patients with heart failure symptoms between January and December 1996. Clinical examination, echocardiography, and measurement of peptide concentrations were performed, with follow-up through December 2009.. All-cause mortality and cardiovascular mortality.. After a median follow-up of 13 years, there were 226 deaths from all causes, including 146 deaths from cardiovascular causes. Increased concentration of copeptin was associated with increased risk of all-cause mortality (fourth quartile vs first quartile: 69.5% vs 38.5%, respectively; hazard ratio [HR], 2.04 [95% confidence interval {CI}, 1.38-3.02]) and cardiovascular mortality (fourth quartile vs first quartile: 46.6% vs 26.5%; HR, 1.94 [95% CI, 1.20-3.13]). The combination of elevated NT-proBNP concentrations and elevated copeptin concentrations also was associated with increased risk of all-cause mortality (copeptin fourth quartile: HR, 1.63 [95% CI, 1.08-2.47]; P = .01; NT-proBNP fourth quartile: HR, 3.17 [95% CI, 2.02-4.98]; P < .001). Using the 2 biomarkers simultaneously in the evaluation of cardiovascular mortality, there was a significant association for copeptin in the presence of NT-proBNP (log likelihood trend test, P = .048) and a significant association for NT-proBNP (fourth quartile: HR, 4.68 [95% CI 2.63-8.34]; P < .001).. Among elderly patients with symptoms of heart failure, elevated concentrations of copeptin and the combination of elevated concentrations of copeptin and NT-proBNP were associated with increased risk of all-cause mortality.

Topics: Aged; Aged, 80 and over; Biomarkers; Cause of Death; Cohort Studies; Female; Glycopeptides; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pituitary Gland; Predictive Value of Tests; Prognosis; Risk; Sweden; Vasopressins

The hypothalamic nonapeptide vasopressin is a known player in the pathogenesis of chronic heart failure. According to the large body of clinical evidence, vasopressin has an impact on salt and water imbalance, hyponatremia, and subsequent renal insufficiency - the most common and destructive co-morbidity of patients afflicted with chronic heart failure. Despite the well-documented elevated levels of vasopressin in the blood of such patients, its expression in the magnocellular hypothalamic nuclei and transport to the posterior pituitary has not yet been investigated. In addition, the literature almost lacks the information on the contribution of another member of nonapeptide family, oxytocin, in the pathogenesis of this disease. Here we present a postmortem analysis of vasopressin and oxytocin-immunoreactive neurons and their terminals in the posterior pituitary of 8 male patients (53.8+/-9.3 years) who had died from CHF and 9 male controls (54.6+/-11.8 years). In line with previous clinical reports, our study on hypothalami of chronic heart failure patients revealed a significant increase in the relative profile density (+29%) of vasopressin-positive neurons in the hypothalamic supraoptic nucleus. Consistently we found a significant increase in the relative optic density of vasopressin-immunoreactivity in the posterior pituitary (+33%) of these patients. In contrast, the similar analysis applied for oxytocin neurons revealed no statistically significant differences to controls. In conclusion, our study provides the morphological evidence for activation of vasopressin (but not oxytocin) expression and vasopressin transport to the posterior pituitary in patients with chronic heart failure.

Topics: Cadaver; Chronic Disease; Gene Expression; Heart Failure; Humans; Hypothalamo-Hypophyseal System; Male; Middle Aged; Oxytocin; Vasopressins

Heart failure constitutes a significant source of morbidity and mortality in the United States, and its incidence and prevalence continue to grow, increasing its burden on the healthcare system. Renal dysfunction in patients with heart failure is common and has been associated with adverse clinical outcomes. This interaction, termed the cardiorenal syndrome, is a complex phenomenon characterized by a pathophysiologic disequilibrium between the heart and the kidney, in which malfunction of 1 organ consequently promotes the impairment of the other. Multiple neurohumoral mechanisms are involved in this cardiorenal interaction, including the deficiency of and/or resistance to compensatory natriuretic peptides, leading to sodium retention, volume overload and organ remodeling. Management of patients with the cardiorenal syndrome can be challenging and should be individualized. Emerging therapies must address the function of both organs to secure better clinical outcomes. To this end, a multidisciplinary approach is recommended to achieve optimal results.

Topics: Adenosine; Heart Failure; Humans; Kidney Diseases; Natriuretic Agents; Ultrafiltration; Vasopressins

We assessed the hemodynamic effects of guideline therapy in experimental cardiogenic shock and compared this treatment with a combination containing an alternative vasopressor (arginine vasopressin, AVP). Our hypothesis was that combined dobutamine-norepinephrine still is the superior inopressor therapy assessed by ventriculoarterial matching in both systole and diastole. Cardiogenic shock (CS) was induced by coronary microembolization in 16 pigs. Dobutamine (Dobu, 2ug/kg/min) alone and combined with either norepinephrine (NE, 100 ng/kg/min) or the pure vasopressor AVP (0.001 u/kg/min) were infused. In CS, Dobu increased cardiac output (CO) and central venous oxygen saturation (SVO₂) from 74 ± 3 mL/kg and 37 ± 2% to 103 ± 8 mL/kg and 49 ± 3%. Adding NE resulted in a further improvement of CO (125 ± 9 mL/kg) and SVO₂ (59 ± 4%) because of an increased heart rate and contractility with minimal change in systemic vascular resistance. Also, energy transfer from the ventricle to the arterial system was restored partly by Dobu and was normalized by supplementing NE. In contrast, supplemental AVP further worsened the shock state by decreasing CO (70 ± 6 mL/kg) and SVO₂ (45 ± 5%) compared with Dobu alone. Combined Dobu-NE has an efficient hemodynamic profile in CS. A pure afterload increasing substance used in acute ischemic CS aggravates the shock state by causing a ventriculoarterial mismatch despite its use in combination with an inotropic compound.

Topics: Animals; Cardiotonic Agents; Disease Models, Animal; Dobutamine; Drug Therapy, Combination; Heart Failure; Hemodynamics; Male; Norepinephrine; Orchiectomy; Shock, Cardiogenic; Swine; Vasodilator Agents; Vasopressins; Ventricular Function, Left

Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Chronic Disease; Heart Failure; Humans; Hyponatremia; Sodium; Tolvaptan; Vasopressins

Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Heart Failure; Humans; Hyponatremia; Tolvaptan; Treatment Outcome; Vasopressins

Hospitalizations for acute heart failure syndromes (AHFS) are associated with high post-discharge morbidity and mortality. The potential role of vasopressin antagonists (VA) in AHFS was presented at the 2008 European Society of Cardiology Working Group on Acute Cardiac Care Meeting held in Versailles, France from 25-28 October 2008. This report represents a summary of the presentation at this meeting.

Topics: Acute Disease; Congresses as Topic; France; Heart Failure; Hormone Antagonists; Humans; Treatment Outcome; Vasopressins; Ventricular Remodeling

Neuroendocrine factors play an important role in the pathogenesis of chronic heart failure. Despite numerous clinical and experimental studies, the role of the hypothalamic-pituitary-adrenal axis and glucocorticoid hormones is not fully characterised. Here we present a study of plasma cortisol concentration in 74 chronic heart failure patients, divided into four groups based on NYHA functional classes I-IV, and in 17 control subjects. In parallel, we performed morphological analysis of the hypothalamic-pituitary-adrenal axis components from 8 male patients who had died from chronic heart failure, and 9 male controls. In our study we applied immunohistochemical method and quantitative analysis to investigate an expression of hypothalamic neurohormones (corticotropin-releasing hormone, vasopressin) and adrenocorticotropin hormone in the pituitary, as well as performed general histological examination of the adrenal cortex. Measurement of morning cortisol concentration in plasma of chronic heart failure patients revealed neither difference compared to controls nor with the severity of the disease. Despite this, a two-fold increase in the density of corticotropin-releasing hormone-immunoreactive neurons as well as a two-fold increase in the number of corticotropin-releasing hormone neurons co-expressing vasopressin in the hypothalamic paraventricular nucleus were found. In the anterior pituitary the density of adrenocorticotropin hormone-immunoreactive cells was significantly increased. General histological analysis of the adrenal cortex revealed a drastic thinning of the zona fasciculata and dystrophic changes in corticocytes. Structural changes, observed in the adrenal cortex, suggest a relative glucocorticoid deficiency, which may contribute to corticotropin-releasing hormone and adrenocorticotropin hormone upregulation in hypothalamus and pituitary of chronic heart failure patients.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Aged, 80 and over; Corticotropin-Releasing Hormone; Female; Heart Failure; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Immunohistochemistry; Male; Middle Aged; Pituitary-Adrenal System; Vasopressins

We report the quantification of a hemodynamic profile sufficient to support consciousness during cardiopulmonary resuscitation. A 62-yr-old man experienced cardiac arrest while being evaluated for heart failure after heart transplantation. During the emergency, hemodynamic data were obtained from bedside monitors and reviewed at regular intervals. His mean arterial blood pressure and heart rate were correlated with consciousness during cardiopulmonary resuscitation. A mean arterial blood pressure of 50 mm Hg with a heart rate of 100 bpm supported consciousness during cardiac arrest. This case helps to validate the recent emphasis on hard, fast, basic life support.

Topics: Blood Pressure; Cardiomyopathy, Dilated; Cardiopulmonary Resuscitation; Consciousness; Epinephrine; Fatal Outcome; Heart Arrest; Heart Failure; Heart Rate; Heart Transplantation; Humans; Male; Middle Aged; Monitoring, Physiologic; Time Factors; Vasoconstrictor Agents; Vasopressins; Withholding Treatment

Urocortin 2 (Ucn2), a novel peptide with therapeutic potential in heart failure, and diuretics have opposing effects on renal function and the renin-angiotensin-aldosterone system. Because any prospective new treatment is likely to be used in conjunction with standard diuretic therapy, it is necessary to investigate the combined effects of these agents.. Ucn2 and furosemide were administered for 3 hours, both singly and combined, in 7 sheep with pacing-induced heart failure. Compared with time-matched controls, separate Ucn2 and furosemide administration significantly increased urine output (furosemide>Ucn2), urine sodium (furosemide>Ucn2), potassium (furosemide>Ucn2), and creatinine excretion (Ucn2>furosemide) and creatinine clearance (Ucn2>furosemide). Compared with furosemide treatment alone, Ucn2+furosemide produced a further diuresis (P<0.05), natriuresis (P<0.05), and a sustained increase in creatinine excretion (P<0.05) and clearance (P<0.05), without additional potassium elimination. All active treatments reduced mean arterial pressure (Ucn2+furosemide=furosemide>Ucn2), left atrial pressure (Ucn2+furosemide>Ucn2>furosemide), and peripheral resistance (Ucn2+furosemide=Ucn2>furosemide), whereas only Ucn2, singly and in combination with furosemide, increased cardiac output and dP/dt(max). In contrast to the increase in plasma renin activity elicited by furosemide alone, Ucn2 and Ucn2+furosemide markedly reduced plasma renin activity. All active treatments decreased plasma aldosterone (Ucn2+furosemide=Ucn2>furosemide), whereas only Ucn2 and Ucn2+furosemide reduced vasopressin and natriuretic peptide concentrations.. Ucn2 cotreatment with furosemide enhanced hemodynamic and renal function and diuretic responsiveness (without additional potassium depletion) in experimental heart failure. Furthermore, Ucn2 reversed furosemide-induced increases in plasma renin activity and induced greater decreases in plasma aldosterone and vasopressin. These data indicate that adjunct Ucn2 therapy with diuretics in heart failure is beneficial.

Topics: Aldosterone; Animals; Biomarkers; Cardiac Pacing, Artificial; Cardiovascular Agents; Corticotropin-Releasing Hormone; Creatinine; Disease Models, Animal; Diuretics; Drug Administration Schedule; Drug Therapy, Combination; Female; Furosemide; Heart Failure; Hemodynamics; Infusions, Intra-Arterial; Kidney; Mice; Natriuresis; Potassium; Renin; Renin-Angiotensin System; Sheep; Time Factors; Urination; Urocortins; Vasopressins

This study sought to develop a model that estimates the post-operative risk of right ventricular (RV) failure in left ventricular assist device (LVAD) candidates.. Right ventricular failure after LVAD surgery is associated with increased morbidity and mortality, but identifying LVAD candidates at risk for RV failure remains difficult.. A prospectively collected LVAD database was evaluated for pre-operative clinical, laboratory, echocardiographic, and hemodynamic predictors of RV failure. Right ventricular failure was defined as the need for post-operative intravenous inotrope support for >14 days, inhaled nitric oxide for > or =48 h, right-sided circulatory support, or hospital discharge on an inotrope. An RV failure risk score (RVFRS) was created from multivariable logistic regression model coefficients, and a receiver-operating characteristic curve of the score was generated.. Of 197 LVADs implanted, 68 (35%) were complicated by post-operative RV failure. A vasopressor requirement (4 points), aspartate aminotransferase > or =80 IU/l (2 points), bilirubin > or =2.0 mg/dl (2.5 points), and creatinine > or =2.3 mg/dl (3 points) were independent predictors of RV failure. The odds ratio for RV failure for patients with an RVFRS < or =3.0, 4.0 to 5.0, and > or =5.5 were 0.49 (95% confidence interval [CI] 0.37 to 0.64), 2.8 (95% CI 1.4 to 5.9), and 7.6 (95% CI 3.4 to 17.1), respectively, and 180-day survivals were 90 +/- 3%, 80 +/- 8%, and 66 +/- 9%, respectively (log rank for linear trend p = 0.0045). The area under the receiver-operating characteristic curve for the RVFRS (0.73 +/- 0.04) was superior to that of other commonly used predictors of RV failure (all p < 0.05).. The RVFRS, composed of routinely collected, noninvasive pre-operative clinical data, effectively stratifies the risk of RV failure and death after LVAD implantation.

Topics: Databases as Topic; Female; Health Status Indicators; Heart Failure; Heart Ventricles; Heart-Assist Devices; Hemodynamics; Humans; Male; Middle Aged; Odds Ratio; Phenylephrine; Preoperative Care; Prospective Studies; Risk Assessment; Risk Factors; ROC Curve; Vasopressins

This study sought to evaluate the predictive value of copeptin over the entire spectrum of heart failure (HF) and compare it to the current benchmark markers, B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP).. Vasopressin has been shown to increase with the severity of chronic HF. Copeptin is a fragment of pre-pro-vasopressin that is synthesized and secreted in equimolar amounts to vasopressin. Both hormones have a short lifetime in vivo, similar to BNPs, but in contrast to vasopressin, copeptin is very stable in vitro. The predictive value of copeptin has been shown in advanced HF, where it was superior to BNP for predicting 24-month mortality.. This was a long-term observational study in 786 HF patients from the whole spectrum of heart failure (New York Heart Association [NYHA] functional class I to IV, BNP 688 +/- 948 pg/ml [range 3 to 8,536 pg/ml], left ventricular ejection fraction 25 +/- 10% [range 5% to 65%]).. The NYHA functional class was the most potent single predictor of 24-month outcome in a stepwise Cox regression model. The BNP, copeptin, and glomerular filtration rate were related to NYHA functional class (p < 0.0001 for trend). Copeptin was the most potent single predictor of mortality in patients with NYHA functional class II (p < 0.0001) and class III (p < 0.0001). In NYHA functional class IV, the outcome of patients was best predicted by serum sodium, but again, copeptin added additional independent information.. Increased levels of copeptin are linked to excess mortality, and this link is maintained irrespective of the clinical signs of severity of the disease. Copeptin was superior to BNP or NT-proBNP in this study, but the markers seem to be closely related.

Topics: Austria; Biomarkers; Disease Progression; Female; Glomerular Filtration Rate; Glycopeptides; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; ROC Curve; Severity of Illness Index; Stroke Volume; Time Factors; Vasopressins

Impaired urinary dilution leading to water retention and hyponatremia may occur in patients with cardiac failure, cirrhosis, pregnancy, hypothyroidism, glucocorticoid and mineralocorticoid deficiency. The mechanisms for these defects predominantly involve the non-osmotic stimulation of arginine vasopressin release with upregulation of aquaporin 2 water channel expression and trafficking to the apical membrane of the principal cells of the collecting duct. These perturbations are reversed by V2 vasopressin receptor antagonists. In contrast, urinary concentration defects leading to polyuria are vasopressin-resistant. They may involve several factors, such as impaired counter-current concentration secondary to downregulation of Na-K-2Cl co-transporter. Vasopressin-resistant downregulation of aquaporin 2 expression has also been described as a factor in impaired urinary concentration.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Aquaporin 2; Arginine Vasopressin; Blood Volume; Female; Heart Failure; Homeostasis; Humans; Hyponatremia; Liver Cirrhosis; Models, Biological; Polyuria; Pregnancy; Pregnancy Complications; Pressoreceptors; Sodium-Potassium-Chloride Symporters; Urine; Vasopressins; Water-Electrolyte Balance

Topics: Acute Disease; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Diuresis; Heart Failure; Humans; Receptors, Vasopressin; Vasopressins

Acute myocardial infarction (AMI) is associated with left ventricular (LV) dysfunction and clinical heart failure. Arginine vasopressin is elevated in heart failure and the C-terminal of provasopressin (Copeptin) is associated with adverse outcome post-AMI. The aim of this study was to describe the association between Copeptin with LV dysfunction, volumes, and remodeling and clinical heart failure post-AMI.. We studied 274 subjects with AMI. Copeptin was measured from plasma at discharge and subjects underwent echocardiography at discharge and follow-up (median 155 days). Subjects were followed for clinical heart failure for a median of 381 days. Remodeling was assessed as the change (Delta) in LV volumes between echo examinations. Copeptin correlated directly with wall motion index score (WMIS) and inversely with LV ejection fraction (LVEF) at discharge (WMIS, r=0.276, P < .001; LVEF, r=-0.188, P=.03) and follow-up (WMIS, r=0.244, P < .001; LVEF, r=-0.270, P < .001) and with ventricular volumes at follow-up (LVEDV, r=0.215, P=.002; LVESV, r=0.299, P < .001). Copeptin was associated with ventricular remodeling; DeltaEDV; r=0.171, P=0.015, DeltaESV; r=0.186, P=.008. Subjects with increasing LVESV had higher levels of Copeptin (median 6.30 vs. 5.75 pmol/L, P=.012). Subjects with clinical heart failure (n=30) during follow-up had higher Copeptin before discharge (median 13.55 vs. 5.80, P < .001). In a Cox proportional hazards model, Copeptin retained association with clinical heart failure. Kaplan-Meier assessment revealed increased risk in subjects with Copeptin >6.31 pmol/L.. Copeptin is associated with LV dysfunction, volumes, and remodeling and clinical heart failure post-AMI. Measurement of Copeptin may provide prognostic information and the AVP system may be a therapeutic target in post-MI LV dysfunction.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Follow-Up Studies; Glycopeptides; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Survival Rate; Vasopressins; Ventricular Dysfunction, Left; Ventricular Remodeling

Topics: Adaptation, Psychological; Attitude to Health; Cell Transplantation; Coronary Artery Bypass; Forecasting; Genetic Therapy; Heart Failure; Heart-Assist Devices; Hematopoietic Stem Cells; Humans; Morale; Myoblasts, Cardiac; Natriuretic Peptides; Purinergic P1 Receptor Antagonists; Survival Rate; Ultrafiltration; Vasopressins

Vasopressin (AVP) stimulates sodium reabsorption and Na,K,2Cl-cotransporter (NKCC2) protein level in the thick ascending limb (TAL) of Henle's loop in rats. Rats with congestive heart failure (CHF) have increased protein level of NKCC2, which can be normalized by angiotensin II receptor type-1 (AT(1)) blockade with losartan.. In this study, we investigated whether CHF rats displayed changes in AVP stimulated cAMP formation in the TAL and examined the role of AT(1) receptor blockade on this system.. CHF was induced by ligation of the left anterior descending coronary artery (LAD). SHAM-operated rats were used as controls. Half of the rats were treated with losartan (10 mg kg day(-1) i.p.).. CHF rats were characterized by increased left ventricular end diastolic pressure. Measurement of cAMP in isolated outer medullary TAL showed that both basal and AVP (10(-6) m) stimulated cAMP levels were significantly increased in CHF rats (25.52 +/- 4.49 pmol cAMP microg(-1) protein, P < 0.05) compared to Sham rats (8.13 +/- 1.14 pmol cAMP microg(-1) protein), P < 0.05). Losartan significantly reduced the basal level of cAMP in CHF rats (CHF: 12.56 +/- 1.93 fmol microg(-1) protein vs. Los-CHF: 7.49 +/- 1.08, P < 0.05), but not in Sham rats (SHAM: 4.66 +/- 0.59 vs. Los-SHAM: 4.75 +/- 0.71). AVP-mediated cAMP accumulation was absent in both groups treated with losartan (Los-SHAM: 4.75 +/- 0.71 and Los-CHF: 7.49 +/- 1.08).. The results indicate that the increased NKCC2 protein level in the mTAL from CHF rats is associated with increased cAMP accumulation in this segment. Furthermore, the finding that AT(1) receptor blockade prevents AVP-mediated cAMP accumulation in both SHAM and CHF rats suggests an interaction between angiotensin II and AVP in regulation of mTAL Na reabsorption.

Topics: 1-Methyl-3-isobutylxanthine; Adenylyl Cyclases; Angiotensin II Type 1 Receptor Blockers; Animals; Cyclic AMP; Disease Models, Animal; Dose-Response Relationship, Drug; Heart Failure; Kidney Cortex; Kidney Medulla; Loop of Henle; Losartan; Male; Phosphodiesterase Inhibitors; Rats; Rats, Wistar; Sodium-Potassium-Chloride Symporters; Sodium-Potassium-Exchanging ATPase; Solute Carrier Family 12, Member 1; Vasopressins

Topics: Body Fluids; Body Water; Fluid Therapy; Heart Failure; Humans; Purinergic P1 Receptor Antagonists; Ultrafiltration; Vasodilator Agents; Vasopressins

In the treatment of heart failure, the effects of therapeutic agents on life prognosis remains unclear. We investigated the effects of long-term oral administration of a nonpeptide, selective, vasopressin V2 receptor antagonist, OPC-31260, on Sprague-Dawley rats that were treated with adriamycin to induce progressive water retention.. Intraperitoneal saline was administered to 14 rats as a control (Group 1). A total cumulative dose of 15 mg/kg of adriamycin was administered intraperitoneally in six equal doses over a period of 2 weeks to another 52 rats. Adriamycin-treated rats were further divided into Group 2, which received saline (p.o.), and Group 3, which received 50 mg/kg (p.o.) of V2 antagonist. Oral administration continued every day for 6 weeks. Group 1 rats also received saline (p.o.) for 6 weeks.. The V2 antagonist decreased urine osmolality and increased diuresis of rats in Group 3. Urinary excretion of electrolytes was not increased by the V2 antagonist in Group 3. Serum osmolality was likewise unchanged by the V2 antagonist in Group 3. Plasma concentrations of vasopressin were significantly higher in Group 3 than in the other groups (Group 1, 4.0+/-1.1 pg/ml; Group 2, 4.2+/-1.5 pg/ml; Group 3, 8.5+/-1.0 pg/ml; p<0.05). During the experimental period, survival rate was higher in Group 3 than in Group 2 (Group 1, 100%; Group 2, 59%; Group 3, 83%).. Our data show that administration of orally active V2 antagonist did not reduce the survival of adriamycin-treated rats through continuous aquaretic action, despite elevated plasma levels of vasopressin.

Topics: Administration, Oral; Animals; Antibiotics, Antineoplastic; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Doxorubicin; Heart Failure; Male; Osmolar Concentration; Rats; Rats, Sprague-Dawley; Survival Analysis; Urine; Vasopressins

Topics: Emergency Medical Services; Heart Failure; Humans; Meta-Analysis as Topic; Treatment Outcome; United States; Vasoconstrictor Agents; Vasopressins

To observe the changes of plasma renin activity, antidiuretic hormone and brain natriuretic peptide in chronic heart failure (CHF) and their correlation with hyponatremia.. Plasma levels of PRA, ADH, and BNP were measured by radioimmunology in 76 CHF patients. Forty-one out of 76 CHF patients with hyponatremia and 35 CHF patients without hyponatremia were identified by serum sodium. The rates of rehospitalization within 3 months were compared in two groups.. Levels of plasma renin activity, ALD, and BNP in CHF patients with hyponatremia were notably higher than those in patients without hyponatremia classified by New York Heart Association (NYHA) grade II - IV: PRA [(2.7 +/- 1.0) ng.ml(-1).h(-1) vs. (1.8 +/- 0.7) ng.ml(-1).h(-1), (4.3 +/- 1.2) ng.ml(-1).h(-1) vs. (3.0 +/- 0.9) ng.ml(-1).h(-1), (5.6 +/- 1.3) ng.ml(-1).h(-1) vs. (3.5 +/- 1.1) ng.ml(-1).h(-1), respectively, P < 0.05], ADH [(59.7 +/- 17.4) ng/L vs. (48.6 +/- 15.3) ng/L, (68.4 +/- 17.6) ng/L vs. (56.3 +/- 19.2) ng/L, (75.3 +/- 20.0) ng/L vs. (51.4 +/- 16.2) ng/L, respectively, P < 0.05] and BNP [(276.4 +/- 75.2) ng/L vs. (185.3 +/- 55.3) ng/L, (380.1 +/- 113.6) ng/L vs. (258.5 +/- 62.1) ng/L, (564.0 +/- 125.2) ng/L vs. (405.3 +/- 102.9) ng/L, respectively, P < 0.05]. In the simple regression analyses, hyponatremia was negative correlated with PRA, ADH and BNP (r = -0.31, P < 0.05; r = -0.28, P < 0.05, r = -0.80, P < 0.01). The rate of rehospitalization within 3 months in hyponatremia group was higher than that in control group.. There is relation of hyponatremia to the changes of plasma renin activity, antidiuretic hormone and brain natriuretic peptide in chronic heart failure. Hyponatremia may accelerate the excretion of plasma PRA, ADH and BNP in chronic heart failure. Neuroendocrine activation in patients of congestive heart failure with hyponatremia is higher than that of normal natremia group.

Topics: Aged; Aged, 80 and over; Female; Heart Failure; Humans; Hyponatremia; Male; Middle Aged; Natriuretic Peptide, Brain; Renin; Sodium; Vasopressins

Yamanouchi is developing conivaptan, a diuretic and active vasopressin V1a and V2 antagonist, which has an aquaretic effect, for the potential treatment of hyponatremia and heart failure. In January 2004, Yamanouchi submitted an NDA in the US for injectable conivaptan for the treatment of hyponatremia and, in December 2004, the FDA issued approval, although additional safety data were requested.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Clinical Trials as Topic; Clinical Trials, Phase III as Topic; Diuretics; Edema; Heart Failure; Humans; Hyponatremia; Molecular Structure; Structure-Activity Relationship; Vasopressins

Nociceptin, the endogenous ligand of the inhibitory G protein-coupled opioid receptor-like 1 receptor, produces aquaresis (i.e., increases the excretion of solute-free urine) in rats. However, the mechanism underlying this effect has not yet been explained. Using immunohistochemistry, we found the opioid receptor-like 1 receptor in the rat kidney colocalized with the vasopressin-regulated water channel aquaporin-2 in inner medullary collecting ducts. We investigated the aquaretic effect of opioid receptor-like 1 receptor stimulation by infusing the selective nociceptin analog ZP120C; volume depletion was prevented by computer-driven, servo-controlled intravenous volume replacement with 50 mM glucose. ZP120C induced a marked and sustained aquaresis in normal and congestive heart failure rats in the absence of changes in vasopressin plasma concentrations. The ZP120C-induced aquaresis was associated with downregulation of the aquaporin-2 protein level in both rat groups, suggesting that opioid receptor-like 1 receptor stimulation produces aquaresis by inhibiting the vasopressin type-2 receptor-mediated stimulation on collecting duct water reabsorption. However, substantial amounts of PKA-mediated serine 256 phosphorylated aquaporin-2 were still present after 4 h of ZP120C treatment. Furthermore, neither preincubation with nociceptin nor ZP120C inhibited vasopressin-mediated cAMP accumulation in isolated collecting ducts. We conclude that renal opioid receptor-like 1 receptor stimulation in normal and congestive heart failure rats produces aquaresis by a direct renal effect, via aquaporin-2 downregulation, through a mechanism not involving inhibition of vasopressin type-2 receptor-mediated cAMP production.

Topics: Animals; Aquaporin 2; Aquaporins; Down-Regulation; Heart Failure; Immunohistochemistry; Infusions, Intravenous; Kidney Tubules, Collecting; Male; Nociceptin; Nociceptin Receptor; Opioid Peptides; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Urine; Vasodilator Agents; Vasopressins

The standard treatment for right heart failure includes aggressive fluid resuscitation, inotropic agents, and avoiding drugs, such as diuretics or nitrates, or maneuvers that decrease pre-load. Even an increase in vagal tone caused by the insertion of a bladder catheter can acutely decrease preload and lead to cardiogenic shock. Other modalities include early reperfusion therapy and pacemaker implantation for complete heart block or loss of atrioventricular synchrony. Acute right heart failure carries a very high mortality because of the limited options available for its management. Among newer treatments, inhaled nitric oxide and intravenous vasopressin have shown promise for acute right ventricular failure.

Topics: Administration, Inhalation; Female; Free Radical Scavengers; Heart Failure; Humans; Middle Aged; Nitric Oxide; Recurrence; Vasoconstrictor Agents; Vasopressins; Ventricular Dysfunction, Right

To investigate the changes of plasma urotensinII (UII) levels in patients with congestive heart failure (CHF) of different severities and their clinical implications.. Plasma UII was determined by radioimmunoassay in 45 patients with CHF and 20 healthies control subjects. In all the subjects, the left ventricular fraction (LVEF) and the ratio of E/A were measured by echocardiography.. The plasma UII level was significantly lowered in CHF patients in comparison with that in control subjects (1.41+/-1.09 pg/ml vs 4.35+/-1.22 pg/ml, P=0.000). A significant correlation of plasma UII level with LVEF (r=0.540, P=0.000) and the E/A ratio was observed (r=0.539, P=0.000), and the severity of CHF was shown to be inversely correlated with plasma UII levels in the patients (r=-0.656, P=0.000), which was elevated after treatment.. UII might play a role in the pathophysiological process of CHF, and its plasma level may serve as an indicator of the severity of CHF.

Topics: Adult; Aged; Aged, 80 and over; Female; Heart Failure; Humans; Male; Middle Aged; Urotensins; Vasopressins

Abnormal gastric tonometric variables, a surrogate for splanchnic ischemia, occur in approximately 50% of patients at the end of routine cardiac operations and are associated with postoperative morbidity. We sought to determine whether gastric tonometric variables deteriorate after left ventricular assist device insertion and to explore the association between abnormal gastric tonometric variables and vasoconstrictor use.. Nineteen patients who had insertion of a left ventricular assist device were enrolled in a prospective, observational study. Automated air tonometry was used to determine the difference between gastric and arterial partial pressure of carbon dioxide (CO2 gap) at five time points perioperatively.. Compared with baseline, systemic blood flow was significantly increased at the end of operation (1.9 +/- 0.6 versus 2.9 +/- 0.7 L x min(-1) x m(-2), p < 0.0001). Tonometric variables, which were normal at baseline, became abnormal in 90% of patients (baseline CO2 gap 4 +/- 2 mm Hg versus end of operation CO2 gap 24 +/- 15 mm Hg, p < 0.0001). Elevated CO2 gaps correlated with larger doses of norepinephrine (r = 0.69, p = 0.001) and vasopressin (r = 0.88, p < 0.0001). Abnormal gastric tonometric variables at the end of operation correlated with postoperative intensive care unit length of stay (r = 0.70, p = 0.0009) and multiple organ dysfunction score (r = 0.64, p = 0.0033).. Despite a significant increase in systemic blood flow after left ventricular assist device implantation, abnormal gastric tonometric variables developed and were associated with larger vasoconstrictor dose. These data provide evidence that gastric ischemia can develop independently of changes in systemic blood flow and support the potential role of vasoconstrictors as a cause of splanchnic ischemia.

Topics: Acid-Base Equilibrium; Adult; Aged; Carbon Dioxide; Catheters, Indwelling; Critical Care; Dose-Response Relationship, Drug; Female; Gastric Mucosa; Heart Failure; Heart-Assist Devices; Humans; Ischemia; Male; Manometry; Middle Aged; Monitoring, Physiologic; Norepinephrine; Postoperative Complications; Prospective Studies; Splanchnic Circulation; Vasoconstrictor Agents; Vasopressins

Impaired regulation of salt and water balance in left ventricular dysfunction and heart failure can lead to pulmonary and peripheral edema and hyponatremia. Previous studies of disordered water regulation in heart failure have used models of low cardiac output with normal cardiac function (e.g., inferior vena cava ligation). We investigated thirst and vasopressin (AVP) secretion in a rat myocardial infarction model of chronic left ventricular dysfunction/heart failure in response to a 24-h water deprivation period. Thirst (implied from water drunk), hematocrit, plasma renin activity, and plasma AVP concentrations increased with water deprivation vs. ad libitum water access. Thirst and plasma AVP concentrations were significantly positively correlated with infarct size after 24-h water deprivation but not under ad libitum water access conditions. The mechanism by which this occurs is unclear but could involve increased osmoreceptor sensitivity, altered stimulation of baroreceptors, the renin-angiotensin system, or altered central neural control.

Topics: Animals; Body Weight; Disease Models, Animal; Heart Failure; Myocardial Infarction; Organ Size; Rats; Rats, Sprague-Dawley; Thirst; Vasopressins; Ventricular Dysfunction, Left; Water Deprivation; Water-Electrolyte Balance

Myocardial infarction often induces congestive heart failure accompanied by a significant increase in plasma vasopressin concentration. To delineate the role of vasopressin in the pathogenesis of congestive heart failure, the acute hemodynamic and aquaretic effects of conivaptan (YM087, 4'-(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzoazepine-6-carbonyl)-2-phenylbenzanilide monohydrochloride), a combined vasopressin V(1A) and V(2) receptor antagonist, were assessed in rats with heart failure induced by myocardial infarction. Left coronary artery ligation resulted in decreased left ventricular systolic pressure and first derivatives of left ventricular developed pressure, as well as increased left ventricular end-diastolic pressure, lung and right ventricular weight. Single oral administration of conivaptan (0.3 to 3.0 mg/kg) dose-dependently increased urine volume and decreased urine osmolality in heart failure rats. Furthermore, conivaptan (3.0 mg/kg) attenuated the changes in left ventricular end-diastolic pressure, lung and right ventricular weight induced by heart failure while reducing blood pressure. These results show that vasopressin plays a significant role in elevating vascular tone through vasopressin V(1A) receptors and plays a major role in retaining free water through vasopressin V(2) receptors in this model of congestive heart failure. Additionally, conivaptan, with its dual vasopressin V(1A) and V(2) receptor-inhibiting properties, could exert a beneficial effect on cardiac function in the congestive heart failure rat model.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Dose-Response Relationship, Drug; Heart Failure; Hemodynamics; Male; Myocardial Infarction; Rats; Rats, Wistar; Vasopressins

To describe neuroendocrine responses that develop in dogs subjected to prolonged periods of ventricular pacing.. 14 adult male hound-type dogs.. Samples were obtained and neuroendocrine responses measured before (baseline) and after 3 periods of ventricular pacing. A pacemaker was used to induce heart rates of 180, 200, and 220 beats/min (BPM). Each heart rate was maintained for 3 weeks before increasing to the next rate. Atrial natriuretic peptide, antidiuretic hormone, aldosterone, norepinephrine, epinephrine, and dopamine concentrations and plasma renin activity were measured. Severity of left ventricular compromise was estimated.. Shortening fraction decreased significantly with increasing heart rates (mean +/- SE, 35.5 +/- 1.4, 25.0 +/- 1.4, 19.5 +/- 1.9, and 12.2 +/- 2.3 for baseline, 180 BPM, 200 BPM, and 220 BPM, respectively). Atrial natriuretic peptide concentrations increased significantly at 180 BPM (44.1 +/- 3.0 pg/mL) and 200 BPM (54.8 +/- 5.5 pg/mL), compared with baseline concentration (36.8 +/- 2.6 pg/mL). Dopamine concentration increased significantly at 200 BPM (70.4 +/- 10.4 pg/mL), compared with baseline concentration (44.2 73 pg/mL). Norepinephrine concentrations increased significantly from baseline concentration (451 +/- 46.2 pg/mL) to 678 +/- 69.8, 856 +/- 99.6, and 1,003 +/- 2676 pg/mL at 180, 200, and 220 BPM, respectively.. Dogs subjected to ventricular pacing for 9 weeks developed neuroendocrine responses similar to those that develop in humans with more chronic heart failure and, except for epinephrine concentrations, similar to those for dogs subjected to ventricular pacing for < 6 weeks.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Catecholamines; Dogs; Dopamine; Echocardiography; Epinephrine; Heart Failure; Heart Rate; Male; Norepinephrine; Vasopressins

This study was designed to examine the effect of losartan treatment on renal tubular function in rats with mild congestive heart failure (CHF) induced by ligation of the left anterior descending artery. In rats with CHF, there was a significant decrease in daily sodium excretion, which caused sodium retention relative to control rats. Renal function studies revealed that glomerular filtration rate and proximal tubular sodium handling were normal. However, expression of the Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) in the thick ascending limb of Henle's loop was increased. Moreover, vasopressin-mediated renal water reabsorption, as evaluated by the aquaretic response to selective V(2)-receptor blockade, was significantly increased. Losartan treatment normalized expression of NKCC2 and decreased expression of the vasopressin-regulated water channel aquaporin-2. This was associated with normalization of daily sodium excretion and normalization of the aquaretic response to V(2)-receptor blockade. Together, these results indicate that, in rats with CHF, losartan treatment inhibits increased sodium reabsorption through NKCC2 in the thick ascending limb of Henle's loop and water reabsorption through aquaporin-2 in the collecting ducts, which may be involved in improving renal function in losartan-treated CHF rats.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Antihypertensive Agents; Aquaporin 2; Aquaporin 6; Aquaporins; Benzazepines; Female; Glomerular Filtration Rate; Heart Failure; Kidney Tubules, Collecting; Loop of Henle; Losartan; Rats; Rats, Wistar; Receptors, Vasopressin; Renal Circulation; Sodium; Sodium-Potassium-Chloride Symporters; Solute Carrier Family 12, Member 1; Vasopressins; Water; Water-Electrolyte Balance

Heart failure (HF) is characterized by activation of both neurohumoral and sympathetic nervous systems. Specifically, HF is associated with increases in vasopressin (VP) and endothelin (ET) and in arterial baroreflex dysfunction. Hypothesis was that central ET-1 potentiates VP secretion in HF due to impaired pressor response and diminished arterial baroreflex inhibition. Male Sprague-Dawley rats were studied 42 to 54 days after sham or coronary ligation (HF) and 7 days after sinoaortic denervation (SAD). Conscious rats received intracerebroventricular artificial cerebrospinal fluid (CSF), 10 pmol of ET-1, 40 nmol BQ123, or both. Basal mean arterial pressure (MAP) did not differ, but heart rate and left ventricular end-diastolic pressure were significantly higher in HF and HF/SAD. Baseline VP was higher in both HF and HF/SAD: 5.9 +/- 0.4 pg/ml and 5.6 +/- 0.7 pg/ml versus sham 2.8 +/- 0.2 and sham-SAD 1.6 +/- 0.2 (p < 0.001). ET-1 increased MAP in sham rats by 16.0 +/- 1.4 mm Hg, but only by 7.4 +/- 2.2 mm Hg in HF (p < 0.05 versus sham) and 5.8 +/- 2.4 mm Hg in HF/SAD (p < 0.01 versus sham SAD). Tachycardic response was attenuated in HF/SAD compared with HF alone. After ET-1, VP increased by 3.3 +/- 2.7 pg/ml in sham and 13.3 +/- 2.6 pg/ml in HF (p < 0.05), but only by 2.3 +/- 0.7 pg/ml in HF/SAD (p < 0.01 versus HF). BQ123 blocked all responses to exogenous ET-1 but had no effect on baseline values. Thus, ET-evoked a lower pressor response in HF due to an impaired ability to increase heart rate and cardiac output. ET-1-induced VP release in HF was higher than in controls as a result of lower pressor response or impaired arterial baroreflex. In contrast to rats with normal left ventricular function, sinoaortic denervation in HF failed to potentiate either pressor response or VP secretion. These findings suggest that acute, though modest, increases in afterload may increase left atrial pressure more in HF/SAD such that cardiopulmonary reflexes may be activated or natriuretic peptides may be released that further restrain both pressor and VP responses.

Topics: Animals; Endothelin-1; Heart Failure; Male; Pressoreceptors; Rats; Rats, Sprague-Dawley; Vasopressins

Heart failure is a leading cause of morbidity and mortality. In the United States, there are more than 5 million patients with heart failure and over 500,000 newly diagnosed cases each year. Numerous advances have been made in our understanding of the pathophysiologic mechanisms contributing to sodium and water retention in this condition. Important alterations in the sympathetic nervous system and the renin-angiotensin-aldosterone system have been described in heart failure, allowing the use of mechanism-specific treatments such as beta-adrenergic receptor antagonism and angiotensin-converting enzyme inhibition. As our understanding of the roles of the natriuretic peptides and the arginine vasopressin-aquaporin-2 system in the pathophysiology of heart failure evolves, treatments directed toward the alterations in these systems in heart failure can be further developed.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Body Fluids; Heart Failure; Humans; Natriuretic Peptide, Brain; Neurosecretory Systems; Renin-Angiotensin System; Sodium; Sympathetic Nervous System; Vasopressins; Water Intoxication; Water-Electrolyte Imbalance

The use of phosphodiesterase inhibitors such as milrinone in the treatment of severe heart failure is frequently restricted because they cause vasodilation and hypotension. In patients with decompensated heart failure with hypotension after treatment with milrinone, low doses of vasopressin restored blood pressure without inhibiting the inotropic effect of milrinone.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Blood Pressure; Cyclic Nucleotide Phosphodiesterases, Type 3; Heart Failure; Humans; Hypotension; Injections, Intravenous; Milrinone; Myocardial Contraction; Phosphodiesterase Inhibitors; Pulmonary Wedge Pressure; Retrospective Studies; Treatment Outcome; Vascular Resistance; Vasoconstrictor Agents; Vasopressins

With developing congestive heart failure (CHF), activation of the vasopressin V(1a) and angiotensin II type 1 (AT(1)) receptors can occur. In the present study, we examined the direct effects of V(1a) receptor blockade (V(1a) block), selective AT(1) receptor blockade (AT(1) block), and dual V(1a)/AT(1) receptor blockade (dual block) with respect to left ventricular (LV) function and contractility during the progression of CHF. LV and myocyte functions were examined in pigs with pacing CHF (rapid pacing, 240 beats/min, 3 weeks, n = 10), pacing CHF with concomitant V(1a) block (SR49059, 60 mg/kg, n = 8), pacing CHF with concomitant AT(1) block (irbesartan, 30 mg/kg, n = 7), or pacing CHF with dual block (n = 7). LV end-diastolic dimension and peak wall stress were reduced in all receptor blockade groups compared with CHF values. However, LV fractional shortening was increased only in the dual block group compared with CHF values (29 +/- 3 versus 21 +/- 2, P <.05). Basal LV myocyte percent shortening increased in the dual block group compared with CHF values (3.44 +/- 0.23 versus 2.88 +/- 0.11, P <. 05). Although V(1a) or AT(1) block reduced LV loading conditions, only dual block resulted in improved LV and myocyte shortening.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Antidiuretic Hormone Receptor Antagonists; Atrial Natriuretic Factor; Blood Pressure; Heart Failure; Hemodynamics; Male; Myocardial Contraction; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Sodium; Swine; Vasopressins; Ventricular Function, Left

Treatment of maladaptive neurohormonal activation in congestive heart failure (CHF) has been successful because basic cardiovascular science findings have been confirmed or dismissed through the use of well-controlled, large-scale clinical trials. It should be no surprise that this exciting approach is evolving toward novel agents and devices directed toward other pathways involved in CHF neurohormonal/cytokine activation. Several of these are in advanced clinical development and are likely to play prominent roles in CHF therapy in the near future.

Topics: Angiotensin Receptor Antagonists; Cardiac Pacing, Artificial; Heart Failure; Humans; Immunotherapy; Renin-Angiotensin System; Tumor Necrosis Factor-alpha; Vasopressins

Pharmacology of conivaptan hydrochloride (YM087) was investigated in in vitro and in vivo studies. In radioligand binding study, YM087 showed high affinity for both V1A and V2 receptors in animal and human species. Affinity of YM087 for V1A and V2 receptors was comparable to that of vasopressin (AVP). In functional antagonistic activity study, YM087 concentration-dependently inhibited AVP-induced intracellular Ca2+ elevation via human V1A receptors and AVP-stimulated cAMP accumulation via human V2 receptors. Intravenous administration of YM087 dose-dependently inhibited AVP-induced pressor responses and produced a dose-dependent aquaresis in rats and dogs. Oral administration of YM087 showed a potent and long-lasting antagonistic activity on V1A and V2 receptors. YM087 was effective in dogs with heart failure and in heart failure rats with hyponatremia and edema. These results reveal that YM087 is the first orally active V1A/V2 receptor antagonist and suggest that YM087 may be useful in the treatment of congestive heart failure and hyponatremia.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Calcium; Cyclic AMP; Dogs; Female; Heart Failure; Humans; Hyponatremia; In Vitro Techniques; Male; Radioligand Assay; Rats; Vasopressins

Topics: Aged; Aged, 80 and over; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiopulmonary Bypass; Drug Therapy, Combination; Follow-Up Studies; Heart Failure; Heart Transplantation; Humans; Hypotension; Male; Middle Aged; Vasodilation; Vasodilator Agents; Vasopressins

Plasma vasopressin (AVP) levels are often elevated in congestive heart failure (CHF). To determine the significance of AVP in CHF, we performed clearance studies on the UM-X7.1 strain of cardiomyopathic (CM) hamsters with moderate heart failure and age-matched healthy controls. Exogenous AVP or a selective V2 agonist (0.3 ng.kg-1. min-1) reduced the fractional excretion of sodium (FENa) and water (FEH2O) by 40-46% in the control group. Although the CM hamsters exhibited a blunted physiological response to the V2 agonist, their urinary cAMP levels were fivefold that of normal and reflect an altered regulation of V2 receptor signalling during CHF. Additional studies also showed that infusion of a V2 antagonist (0.3 ng.kg-1. min-1) produced natriuresis and diuresis in CM hamsters (FENa: 7.9 +/- 1.1 vs. 4.8 +/- 0.6%, p < 0.05; FEH2O: 2.2 +/- 3 vs. 1.5 +/- 0. 2%, p < 0.05) but did not decrease fluid reabsorption in the normal hamsters. In conclusion, the attenuated renal response to exogenous AVP in CM hamsters may be attributed to an enhanced endogenous AVP response during CHF.

Topics: Animals; Body Water; Cricetinae; Cyclic AMP; Diuresis; Glomerular Filtration Rate; Heart Failure; Kidney; Male; Mesocricetus; Natriuresis; Sodium; Vasopressins

Previous short-term studies demonstrated that treatment with clonidine produced significant hemodynamic improvement in patients with congestive heart failure (CHF). In this study we followed 12 CHF patients (10 M, 2 F age 63+/-11, 10 with ischemic cardiomyopathy and 2 with dilated cardiomyopathy) treated with 0.15 or 0.075 mg oral clonidine twice daily for 13+/-5 months (range 6-23). with functional evaluation at baseline, 6 weeks and 6 months. There was suppression of circulating catecholamines, associated with significant ameliorations in NYHA class, in duration of exercise tolerance (from 246+/-68 sec to 362+/-30 and 459+/-70 sec, respectively p < 0.02), in ejection fraction (from 32+/-7% to 35+/-5 and 39+/-7% p < 0.04) and in left ventricular enlargement as assessed echocardiographically. There were also improvements in a number of electrophysiologic parameters calculated by computerized analysis of ambulatory ECG tapes, such as heart rate variability, indicating diminished propensity to malignant arrhythmias, as confirmed by decreases in the numbers of isolated premature ventricular contractions, couplets and episodes of non-sustained ventricular tachycardia. The data suggest that chronic central sympathetic suppression with clonidine in CHF results in significant functional amelioration and improved electrophysiologic stability.

Topics: Administration, Oral; Catecholamines; Chronic Disease; Clonidine; Echocardiography; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Neural Inhibition; Prospective Studies; Renin; Sympathetic Nervous System; Sympatholytics; Vasopressins

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

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

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

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

In conclusion, plasma levels of the endothelial-derived vasoconstrictor endothelin-1 (but not those of other neurohormonal vasoconstrictor factors), measured during exercise correlated closely with objective variables of exercise capacity in patients with heart failure. These findings suggest that endothelin-1 may contribute to exercise intolerance in patients with heart failure, perhaps by limiting the ability of the peripheral vasculature to dilate during exercise.

Topics: Adult; Aged; Endothelins; Exercise Tolerance; Heart Failure; Humans; Male; Middle Aged; Norepinephrine; Oxygen Consumption; Pulmonary Gas Exchange; Vasopressins

Topics: Diabetes Insipidus; Heart Failure; Humans; Hyponatremia; Kidney; Kidney Concentrating Ability; Male; Middle Aged; Vasopressins; Water-Electrolyte Balance

Plasma atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), plasma renin activity (PRA), and circulatory haemodynamics were studied in five patients with chronic congestive heart failure undergoing ultrafiltration on two consecutive days. The patients were in the New York Heart Association class IV, and were considered candidates for heart transplantation. A mean of 3.3 +/- 0.5 litres of fluid was removed during each ultrafiltration. Plasma ANP concentration remained unchanged during ultrafiltration: 369 +/- 151 pg/ml at start and 316 +/- 116 pg/ml at the end, while plasma ADH concentration and PRA increased from 5.1 +/- 2.1 to 7.5 +/- 3.4 pg/ml (P less than 0.02), and 5.9 +/- 3.0 to 7.7 +/- 3.2 ng/ml (P less than 0.03) respectively (n = 10). After treatment, plasma ADH and PRA declined to baseline values within 1 h. Pulmonary artery, pulmonary capillary wedge, and right atrial pressures decreased significantly, while blood pressure and heart rate remained constant during ultrafiltration. A volume of 3.3 +/- 0.5 litres of fluid was removed, and caused an increase in colloid osmotic pressure from 22.0 +/- 3.0 to 33.7 +/- 3.9 mmHg (P less than 0.02). It was unexpected that plasma ANP concentration did not decline. Due to long-standing severe heart failure the atrial wall may have lost some of its elastic properties, resulting in less ability to adapt to reduced filling pressures. Accordingly, atrial wall stretch remained unchanged, explaining the constant ANP levels. Ultrafiltration treatment caused an increased responsiveness to diuretic therapy, and four patients survived long enough to receive heart transplants.

Topics: Adult; Atrial Natriuretic Factor; Heart Failure; Hemodynamics; Hemofiltration; Hormones; Humans; Male; Middle Aged; Renin; Vasopressins

Overall 210 patients aged 60-74 years suffering from coronary heart disease associated with chronic circulatory failure, stages I, IIA and IIB, 53 patients aged 45-59 years and 20 healthy persons aged 45-74 years were examined for the renin-angiotensin-aldosterone system and antidiuretic hormone. Renin activity, the concentration of aldosterone and vasopressin in blood plasma were investigated by radioimmunoassay. In the initial stage of heart failure, the elderly persons showed up more marked renin activation in blood plasma, followed by its lowering as decompensation progressed as well as an increase in the concentration of aldosterone and vasopressin, which resulted in the progress of circulatory failure.

Topics: Aged; Aldosterone; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Renin; Renin-Angiotensin System; Sex Characteristics; Vasopressins

In patients with congestive heart failure (CHF), overactivity of the sympathetic nervous system may be accompanied by an impairment of the baroreflex control mechanism. To evaluate the reflex responses of the sympathetic nervous system, the renin-angiotensin system and vasopressin release to baroreceptor unloading, 38 patients with left ventricular dysfunction were studied. Hemodynamic data, and plasma norepinephrine, renin activity and vasopressin concentrations were measured before and 60 minutes after administration of high-dose hydralazine (0.4 mg/kg intravenously). On the basis of blood pressure response to vasodilator administration, patients were divided arbitrarily into those with a decrease in mean arterial blood pressure greater than or equal to 15 mm Hg (group A; n = 12) and those with a decrease less than 15 mm Hg (group B; n = 26) compared with control values. In response to hydralazine, heart rate decreased in group A from 100 to 92 beats/min (p less than 0.001) and increased in group B from 90 to 96 beats/min (p less than 0.05). In group A, hemodynamic changes induced by hydralazine were accompanied by a decrease in plasma norepinephrine from 822 to 518 pg/ml (p less than 0.01) and an increase in plasma vasopressin from 8.4 to 45.2 pg/ml (p less than 0.001). In group B, plasma norepinephrine and vasopressin did not change significantly (407 vs 447, and 8.4 vs 8.3 pg/ml, respectively). Plasma renin activity remained unchanged in group A and increased in group B (p less than 0.001). The data show that baroreceptor-mediated release of vasopressin is not impaired in patients with CHF and a defective sympathetic reflex control mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Cardiac Catheterization; Chronic Disease; Female; Heart Failure; Hemodynamics; Humans; Hydralazine; Male; Middle Aged; Norepinephrine; Pressoreceptors; Renin; Sympathetic Nervous System; Vasopressins

The effects of angiotensin-converting-enzyme (ACE) inhibitors on circulatory regulating mechanisms in congestive heart failure (CHF) were studied by comparison of plasma levels of catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), substance P (SP-LI), calcitonin gene-related peptide (CGRP-LI), vasopressin (ADH-LI), atrial natriuretic peptide (ANP-LI) and renin activity (PRA) in patients with severe CHF (NYHA III-IV) with (n = 15) or without (n = 17) ACE inhibitors in addition to digoxin and diuretic therapy. Data were also compared with those for healthy subjects (n = 31) and patients with moderate CHF (NYHA I-II). Catecholamines and NPY-LI were increased to the same extent in both groups with severe CHF. CGRP-LI showed no changes relative to controls in any of the patient groups, and was not affected by ACE inhibitors. The SP-LI level was significantly increased in all patient groups. Patients with severe CHF on ACE inhibition had a SP-LI level of 4.05 +/- 0.79 pmol l-1, compared to a concentration of 2.28 +/- 0.30 pmol l-1 (P less than 0.05) in the patient group with a comparable degree of CHF but without ACE inhibition. In the latter group, an inverse relationship appeared between the SP-LI and the serum sodium levels (r = -0.68, P less than 0.05). The patients with severe CHF who received ACE inhibitors had significantly lower ADH-LI levels than the patients with a comparable degree of CHF who were not treated with ACE inhibitors, while the ANP-LI levels was increased to a similar extent in both groups.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Calcitonin Gene-Related Peptide; Catecholamines; Digoxin; Diuretics; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Middle Aged; Renin; Substance P; Vasopressins

Previous studies from our department revealed that congestive heart failure (CHF) is paralleled by a decrease in number of sarcolemmal beta-receptors due to excessive levels of circulating endogenous catecholamines. In contrast, the myocardial H2-receptor system proved to be not affected (Am. Heart J. 101; 569, 1981). The first clinically tested specific H2-receptor agonist impromidine (IMP) turned out to be a potent stimulator in patients with CHF which were insensitive to catecholamine stimulation (Pharmacol. Ther. 24; 165, 1984). Though the overall results of such an H2-receptor stimulation were salutary with favourable hemodynamic effects, the narrow therapeutic range, high costs of synthesis and the arrhythmogenic potential of IMP limited its broad clinical application in large scale trials. - Recently developed phenylpyridylalkylguanidines (J. Med. Chem. 32, 1963, 1989) were investigated under in vitro and in vivo conditions in the guinea-pig under physiologic and pathophysiologic conditions using IMP as reference. - Compounds tested were arpromidine (INN) (BU-E-50) and the difluorinated analogues BU-E-75 and BU-E-76, all guanidine-type H2-agonists with additional H1-antagonistic properties due to a pheniramine like moiety. In the isolated perfused heart all three new compounds were more potent in increasing cardiac contractile force and coronary flow but less effective on heart rate and less arrhythmogenic. The same could be established under in vivo conditions where BU-E-76 was more potent than BU-E-75, arpromidine and IMP, respectively, in augmenting LVdp/dt, LVP, cardiac output and systemic blood pressure, but all compounds revealed to have less chronotropic and arrhythmogenic potentials. In the vasopressin-induced acute heart failure model BU-E-76 and BU-E-75 normalized all contractile parameters in contrast to arpromidine and IMP. Within minutes it is concluded that the new H2-receptor agonists may represent a promising therapeutic improvement for treatment of CHF patients with a cardiovascular profile superior to IMP and conventional catecholamines.

Topics: Animals; Cardiac Output; Cardiotonic Agents; Guanidines; Guinea Pigs; Heart Failure; Heart Rate; Hemodynamics; Imidazoles; Impromidine; Receptors, Histamine H2; Stroke Volume; Vasopressins

The purpose of the present study was to measure plasma levels of atrial natriuretic peptide (ANP) in patients with acute myocardial infarction without heart failure, and also to assess the temporal sequence of changes of plasma ANP during the first hours of recovery from myocardial infarction. The study was performed in 22 patients who were admitted to the Intensive Care Unit with the diagnosis of acute myocardial ischaemia that had an evolution of less than 6 h. Blood samples were drawn on admission and at 1, 8, and 24 h, and plasma concentrations of ANP, renin, aldosterone, epinephrine, norepinephrine and vasopressin were measured. Compared with control subjects, on admission patients showed increased plasma levels of ANP, as well as increased plasma renin activity (PRA), aldosterone, norepinephrine, epinephrine, dopamine, and antidiuretic hormone (ADH). ANP, but not renin or aldosterone plasma values, decreased with time, and there was a significant correlation between ANP and time after onset of pain. No increase in plasma creatinine was observed during the hospital stay, and the patients showed a negative fluid balance. No relationship was found between the location or extension of the infarction, or morphine treatment and ANP plasma levels. The high levels of ANP seem to counteract the haemodynamic and fluid-retention effects of the vasoconstrictive factors released after myocardial infarction.

Topics: Aldosterone; Analysis of Variance; Atrial Natriuretic Factor; Catecholamines; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Regression Analysis; Renin; Time Factors; Vasopressins

We evaluated the effects of dopamine (DA) infusion (1.5 micrograms.kg-1.min-1 for 60 min) on secretion of atrial natriuretic factor (ANF) in 10 healthy subjects and 10 patients with congestive heart failure (CHF) (NYHA Classes III and IV). During DA infusion plasma levels of ANF were significantly raised in healthy subjects while the high basal values of ANF in CHF patients were significantly reduced; this trend was also evident for plasma noradrenaline (NA) levels in both groups. Diuresis, natriuresis and glomerular filtration rate were significantly increased while blood pressure, heart rate and central venous pressure remained unchanged in both groups. These findings indicate that DA infusion may affect the release of ANF. Changes in plasma NA concentration suggest that the sympathetic nervous system may be involved in this phenomenon.

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Diuresis; Dopamine; Female; Glomerular Filtration Rate; Heart Failure; Heart Rate; Humans; Infusions, Parenteral; Male; Middle Aged; Norepinephrine; Renin; Vasopressins

In chronic heart failure, neurohumoral mechanisms play an important role in the regulation of cardiac performance directly, by influencing systolic and diastolic function of the myocardium, and indirectly, by modulating pre- and afterload. The important vasoconstrictor, fluid and sodium retaining factors are the renin-angiotensin-aldosterone system, sympathetic nerve activity and vasopressin; the vasodilator, volume and sodium eliminating factors are atrial natriuretic peptide, vasodilator prostaglandins, such as prostacyclin and prostaglandin E2, dopamine, bradykinin and, possibly, endothelium-derived relaxing factor and vasoactive intestinal peptide. There is evidence from experimental and clinical studies that sympathetic nerve activity is stimulated in the early phase of the disease, as is the secretion of atrial natriuretic peptide, which increases in proportion to an increased preload. In early or mild heart failure, atrial natriuretic peptide suppresses the activity of the renin-angiotensin-aldosterone system, may prevent an increase in peripheral vascular resistance and preserves renal blood flow. In more severe heart failure, the renin-angiotensin-aldosterone system is activated, leading to an increase of peripheral and renal vascular resistance and fluid and sodium retention. This is associated with an increased production of vasodilator prostaglandins. In severe heart failure, mostly in connection with hyponatraemia, a non-osmolar inappropriately high secretion of vasopressin can be demonstrated. These findings suggest that early therapeutic intervention to suppress unfavourable neurohumoral mechanisms or to support protective factors, such as atrial natriuretic peptide, may be of particular importance in the treatment of congestive heart failure, delaying progression of the disease, which would improve survival.

Topics: Animals; Atrial Natriuretic Factor; Dogs; Heart Failure; Prostaglandins; Renal Circulation; Renin-Angiotensin System; Sympathetic Nervous System; Vasopressins

Vasopressin, like angiotensin, has both vasoconstrictor and fluid retaining properties and therefore may make an important contribution to the pathogenesis of low output congestive heart failure. The study aimed to examine the relative importance of the renin-angiotensin system and vasopressin in an animal model of heart failure.. The acute haemodynamic effects of vasopressin receptor blockade with a selective antagonist, d(CH2)5DAVP (AVPA) (30 micrograms.kg-1) and angiotensin converting enzyme inhibition with captopril (1 mg.kg-1) were compared. The effect of combined blockade (ie, vasopressin receptor antagonist + angiotensin converting enzyme inhibitor) was also examined.. Rabbits, 2.5-3.5 kg, with doxorubicin induced cardiomyopathy and heart failure (n = 20) were used. There were 15 controls.. Both AVPA and captopril produced significant increases in cardiac output (11% and 13% respectively) and falls in peripheral vascular resistance (21% and 17% respectively). Inhibition of the two vasoconstrictor systems was additive and resulted in a fall in peripheral vascular resistance to levels found in normal animals.. Vasopressin and angiotensin II make equal contributions to the raised peripheral vascular resistance observed in this model of heart failure. Vasopressin inhibition may be useful in the treatment of heart failure either alone or as an adjunct to angiotensin converting inhibition.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Blood Pressure; Captopril; Cardiac Output; Disease Models, Animal; Female; Heart Failure; Male; Rabbits; Vascular Resistance; Vasopressins

Plasma atrial natriuretic factor, aldosterone, renin activity, and antidiuretic hormone were studied in low output heart failure syndromes: cardiogenic shock in ten patients with acute myocardial infarction of the anterior wall (first group), hypovolemic shock after melena from peptic ulcer in ten subjects (second group), and hypotension with bradycardia syndrome in ten patients with acute myocardial infarction of the inferior wall (third group). Circulating atrial natriuretic factor in patients with cardiogenic shock (102.4 +/- 7.4 pg/ml) was significantly higher than in healthy volunteers matched for sex and age (8.4 +/- 0.3 pg/ml). In these patients there was a positive correlation between atrial natriuretic factor and central venous pressure values. Atrial natriuretic factor and central venous pressure values in the second and third groups were within normal range. Plasma aldosterone was high in all groups, plasma renin activity was elevated in the first and third groups, and high antidiuretic hormone was observed in the first and second groups. These findings indicate that in low output heart failure syndromes only hemodynamic changes affecting the atria stimulate atrial natriuretic factor release. No correlations were found between plasma atrial natriuretic factor and other hormones. In particular, high atrial natriuretic factor levels in the patients with cardiogenic shock did not inhibit release of aldosterone, renin, or antidiuretic hormone. It may be surmised that in these patients the hemodynamic effects override the inhibitory effects of atrial natriuretic factor.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Blood Volume; Bradycardia; Cardiac Output, Low; Female; Heart Failure; Humans; Male; Melena; Middle Aged; Myocardial Contraction; Myocardial Infarction; Peptic Ulcer Hemorrhage; Renin; Shock, Cardiogenic; Vascular Resistance; Vasopressins; Venous Pressure

The status of the renin-angiotensin-aldosterone system and the time course of vasopressin levels were studied in patients with an implanted cardiostimulator. Activation of plasma renin due to renal hypoperfusion in an inadequate stimulation was demonstrated to be followed by a rise in aldosterone and vasopressin concentrations and by an increase in blood volumes. Activation of angiotensin II and vasopressin resulted in higher peripheral resistance. Altered humoral regulation of the circulation retained 6-12 months after cardiostimulator implantation, by maintaining myocardial overload with volume and resistance.

Topics: Aldosterone; Angiotensin II; Blood Volume; Heart Failure; Hemodynamics; Humans; Pacemaker, Artificial; Renin-Angiotensin System; Sick Sinus Syndrome; Time Factors; Vascular Resistance; Vasopressins

The dynamics of the content of blood aldosterone and vasopressin after hemosorption studied in 17 patients with decompensated chronic cor pulmonale revealed a significant reduction of their concentration. Reduction of the content of hormones in the blood occurred due to the effect of the sorbent and is not related to the influence of heparine.

Topics: Adult; Aldosterone; Chronic Disease; Drug Interactions; Female; Heart Failure; Hemoperfusion; Heparin; Humans; Male; Middle Aged; Pulmonary Heart Disease; Vasopressins

These experiments assessed the hemodynamic and aquaretic effects of an arginine vasopressin (AVP) antagonist with dual V1V2-receptor inhibiting properties in rats with congestive heart failure resulting from ischemic cardiomyopathy. The compound d(CH2)5-D-Tyr(Et)VAVP was used in these studies. Rats with limited or extensive myocardial infarcts (i.e., with less than 50% or greater than 66% necrosis of the left ventricular wall, respectively, induced by left coronary ligation) and sham-operated controls received the AVP antagonist (100 micrograms/kg i.v.) 4 weeks later. This agent produced an 18% increase in cardiac output (p less than 0.05) and 13% decrease in systemic vascular resistance in the severely damaged rats, both changes being significantly different from those seen in the normal controls or the rats with limited infarcts. All animals exhibited increases in urinary output of 4-10-fold over baseline. We conclude that the hemodynamic and renal effects of this agent are beneficial in animals with left ventricular dysfunction.

Topics: Animals; Antihypertensive Agents; Arginine Vasopressin; Diuresis; Heart Failure; Male; Rats; Rats, Inbred Strains; Ultrasonography; Vascular Resistance; Vasopressins

Patients with chronic heart failure (CHF) have increased plasma levels of the antidiuretic hormone arginine vasopressin (AVP). The stimulus for increased AVP secretion is unknown, but appears to involve a nonosmotic drive which alters normal osmoregulatory mechanisms. Centrally acting alpha 2-adrenergic agonists suppress AVP secretion in experimental animals. To examine the hypothesis that such effects might be apparent on the chronically elevated AVP levels in patients with CHF, we measured AVP, heart rate (HR), mean arterial pressure (MAP), and plasma norepinephrine (NE) after 4 mg oral guanabenz in nine patients with this disease. Plasma NE decreased from 513 +/- 131 to a minimum of 371 +/- 117 pg/ml (p less than 0.02) 5 h postdrug. HR decreased from 80 +/- 9.3 to 74 +/- 10 beats/min (p less than 0.05) and MAP decreased from 88 +/- 8.5 to 83 +/- 10 mm Hg (p less than 0.05). Plasma AVP, however, did not change from baseline levels of 5.6 +/- 1.6 pg/ml. Serum osmolality was also constant. These data do not support a possible role for acute increases of alpha 2-adrenergic activity in suppressing the increased plasma AVP levels of CHF, at least under basal conditions at constant osmolality.

Topics: Adrenergic alpha-Agonists; Adult; Blood Pressure; Female; Guanabenz; Heart Failure; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged; Norepinephrine; Time Factors; Vasopressins

Isolated ultrafiltration was performed in 107 patients with refractory heart failure (HF) which developed in the presence of different cardiovascular diseases. The beneficial action of isolated ultrafiltration in 71 patients (68%) with refractory HF was determined by complex interaction of the effects provoked by ultrafiltrate removal. Among those effects of paramount importance was correction of secondary hyperaldosteronism and reduction of the concentration of antidiuretic hormone accompanied by the improvement of liver and heart functions.

Topics: Acute Disease; Adult; Aged; Diuresis; Heart Failure; Hemofiltration; Humans; Middle Aged; Renin-Angiotensin System; Vasopressins

The positive action exerted by isolated ultrafiltration on 69 patients with refractory heart failure was shown to be due to the complex interaction of effects produced by ultrafiltrate removal. Among the effects, a leading role is played by therapy for hyperaldosteronism and reduction of antidiuretic hormone levels along with improvement of the functional status of the liver and heart.

Topics: Adult; Aged; Aldosterone; Drug Resistance; Female; Heart Failure; Hemofiltration; Humans; Hyperaldosteronism; Male; Middle Aged; Renin; Vasopressins

The biochemical abnormalities associated with heart failure include dysfunction of contractile proteins, functional impairment of energy-linked enzymes and disruption of cell membrane structure. The haemodynamic impairment resulting from cardiac dysfunction activates several neurohormonal systems, notably the renin-angiotensin-aldosterone system, sympatho-adrenal system and vasopressin release, whilst clinically important factors include an enlarged heart, increased systolic wall stress and an increased myocardial oxygen demand. An inverse relationship exists between systolic wall stress (afterload) and contractile function in heart failure. Moreover the increased systolic wall stress that occurs as a result of reduced cardiac output raises myocardial oxygen consumption, causing cardiac function to deteriorate still further. Diastolic abnormalities play an important role in hypertrophic disorders, in ventricular dilatation and in cases of myocardial ischaemia. The therapeutic objectives are therefore to decrease heart size, to reduce wall stress and oxygen demand, and to enhance diastolic distensibility.

Topics: Catecholamines; Heart; Heart Failure; Hemodynamics; Humans; Myocardial Contraction; Myocardium; Renin-Angiotensin System; Vasopressins

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; Heart Failure; Humans; Hypertension; Receptors, Angiotensin; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface; Receptors, Vasopressin; Vasopressins

The degree of activation of neurohormonal mechanisms appears to depend on the severity and acuteness of cardiac impairment as well as the status of the extracellular fluid volume. Vasoconstrictive antinatriuretic mechanisms are markedly activated in severe decompensated cardiac failure. These are accompanied by parallel increases in endogenous vasodilatory natriuretic activities that modulate the powerful vasoconstrictive mechanisms. During chronic compensation, many of these neuroendocrine mechanisms returned to the baseline normal level. In addition to endocrine and neurogenic mechanisms, local autocrine-paracrine systems in the blood vessel wall may also contribute to the regulation of vascular tone. The role of these systems in congestive heart failure has not been systematically studied. It is possible that they may contribute to the long-term regulation of vascular tone and therefore may play an increasing role in the pathogenesis of ventricular remodeling, dilatation and progressive congestive heart failure.

Topics: Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Dopamine; Heart Failure; Humans; Natriuresis; Neurotransmitter Agents; Norepinephrine; Prognosis; Prostaglandins; Renin-Angiotensin System; Sympathetic Nervous System; Thromboxanes; Vasoconstriction; Vasodilation; Vasopressins

In patients with congestive heart failure, atrial natriuretic factor may serve as a counter-regulatory hormone, offsetting the vasoconstrictive and volume-retentive effects of the sympathetic nervous system, the renin-angiotensin-aldosterone system and vasopressin. Indeed, the plasma levels of atrial natriuretic factor and the vasoconstrictor hormones are often simultaneously elevated in these patients. It is not known, however, whether atrial natriuretic factor remains responsive to sudden reductions in atrial pressure in patients with chronic heart failure, or is unresponsive like the vasoconstrictor systems. To examine this issue, the plasma concentrations of atrial natriuretic factor and the vasoconstrictor hormones were measured in 20 normal subjects and 12 patients with chronic congestive heart failure during incremental lower body negative pressure, an intervention that lowers atrial pressure. In the normal subjects, incremental lower body negative pressure at -10, -20 and -40 mm Hg decreased central venous pressure and pulse pressure. At maximal lower body negative pressure, plasma atrial natriuretic factor levels decreased from 51 +/- 5 to 27 +/- 3 pg/ml (p less than 0.01), whereas increases occurred in plasma levels of norepinephrine (194 +/- 11 to 385 +/- 70 pg/ml, p less than 0.01), renin activity (1.4 +/- 0.2 to 3.9 +/- 0.1 ng/ml per h, p less than 0.01) and vasopressin (1.3 +/- 0.1 to 6.4 +/- 2.4 pg/ml, p less than 0.05). In the patients with congestive heart failure, lower body negative pressure also reduced central venous pressure. Baseline plasma atrial natriuretic factor levels were markedly elevated, averaging 438 +/- 138 pg/ml, and decreased to 317 +/- 87 pg/ml at maximal lower body negative pressure (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Atria; Heart Failure; Humans; Hypotension; Male; Middle Aged; Norepinephrine; Renin; Vasopressins

Cardiac transplantation in 10 patients with congestive heart failure resulted in reduction of high plasma concentrations of atrial natriuretic peptide (ANP), preoperatively five-fold above normal, to a level two-fold above normal, which was maintained throughout a 12-week follow-up period. Cardiac function was normalized in all patients. Transient increases in plasma ANP, in four cardiac recipients 3-10-fold their basal levels, could neither be related to rejection episodes nor to cardiac dysfunction, but rather to signs of fluid and sodium retention. High plasma ANP levels in cardiac transplant recipients suggest that the capacity to secrete ANP is preserved in the transplanted heart.

Topics: Adolescent; Adult; Aldosterone; Atrial Natriuretic Factor; Female; Follow-Up Studies; Heart Failure; Heart Transplantation; Hemodynamics; Humans; Male; Middle Aged; Myocardium; Prospective Studies; Renin; Vasopressins

The objective of this study was to assess the hemodynamic and neurohumoral (plasma renin activity, aldosterone, epinephrine, norepinephrine, vasopressin, and atrial natriuretic peptide) determinants of systemic vascular resistance in 35 patients with stable congestive heart failure. In the supine position, although activation of the various neurohumoral systems tended to occur in the same patients, there was little correlation between activation of any of the neurohumoral systems, as reflected by circulating levels, and systemic vascular resistance. There was also little correlation between changes in circulating neurohormones and changes in either mean arterial pressure or systemic vascular resistance in the standing position. Acutely reducing the activity of the renin-angiotensin system with the use of captopril did not improve the correlation between other neurohumoral and hemodynamic variables. In fact there was no correlation between the effects of acute captopril therapy and baseline renin values. These results support the concept that activation of one or another vasoconstrictor neurohumoral system varies from patient to patient and that the effects of their activation are tempered by activation of parallel vasodilator systems and by attenuation of neurohormone release and effector organ response.

Topics: Adaptation, Physiological; Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Captopril; Epinephrine; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Posture; Renin; Renin-Angiotensin System; Vascular Resistance; Vasopressins

We studied the effects of alpha-human atrial natriuretic factor (alpha-h-ANF) on diuresis, glomerular filtration rate (GFR), natriuresis, atrial blood pressure (BP), heart rate (HR) and plasmatic levels of aldosterone, renin activity (PRA), antidiuretic hormone (ADH) in 21 patients with congestive heart failure (CHF), (NYHA, class IV) and 15 healthy volunteers. Three different doses (25, 50 and 100 micrograms) of alpha-h-ANF were administered; each subject received only one dose. Protocol was as follows: 2 periods of 30 minutes each before alpha-h-ANF administration; 2 periods of 15 minutes and 3 of 30 minutes each after it. Aldosterone, PRA, ADH and plasmatic level of ANF were measured by radioimmunoassay. In patients with CHF 25 and 50 micrograms of alpha-h-ANF produced a significant increase in diuresis, GFR, and natriuresis but no modification of BP. On the contrary BP decreased significantly after 100 micrograms of alpha-h-ANF, without changes in renal function. In healthy volunteers the effects of alpha-h-ANF appeared simultaneously and to same degree after each dose. Both in patients and healthy subjects alpha-h-ANF administration had little effect on aldosterone, renin and ADH secretion. The effects of alpha-h-ANF in patients with CHF may be caused by a lowered receptor sensitivity due to a high level of ANF and to their different haemodynamic status.

Topics: Aged; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Diuresis; Female; Glomerular Filtration Rate; Heart Failure; Heart Rate; Hemodynamics; Humans; Kidney; Male; Middle Aged; Natriuresis; Renin; Vasopressins

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Glomerular Filtration Rate; Heart Failure; Humans; Hyponatremia; Hypotension; Renin-Angiotensin System; Risk Factors; Vasopressins

The pathogenesis of hyponatremia remains debated; therefore, we determined the roles of plasma vasopressin, fluid intake and renal free water excretion in hyponatremic medical patients. We evaluated 100 consecutive hypo-osmolar hyponatremic patients (PNa = 127 +/- 0.7 mM l-1) in a prospective manner. We observed: hyponatremia was often found in association with advanced congestive cardiac failure (twenty-five of 100 patients), liver cirrhosis (16%) and primary volume contraction (29%). There was a 17% in-hospital mortality of hyponatremic patients. This was primarily related to the severity of underlying illnesses rather than to hyponatremia per se. The most consistently observed laboratory finding of hyponatremia was non-osmotic vasopressin stimulation; mean observed PADH was 4.7 +/- 0.7 pg ml-1 and vasopressin was detectable by radioimmunoassay (RIA) in 91% of all patients. In addition to vasopressin stimulation we also found evidence of advanced 'circulatory underfilling' in most hyponatremic patients. Mean urinary osmolality was hypertonic to plasma (441 +/- 17.4 m0sm kg H2O-1). This applied to patients with hyponatremic cardiac failure, liver cirrhosis and volume contraction. Almost all of these patients received high ceiling diuretics. (v) Spontaneous mean daily fluid intake was 2.4 +/- 0.2 l. In summary, our findings suggest that disturbances of vasopressin, fluid intake and renal free water excretion co-operate in the pathogenesis of hyponatremia. In clinical states of advanced circulatory underfilling the occurrence of hyponatremia indicates a poor prognosis of the patient.

Topics: Aged; Drinking; Female; Heart Failure; Humans; Hyponatremia; Kidney Diseases; Liver Cirrhosis; Male; Middle Aged; Vasopressins

Topics: Adult; Aged; Chronic Disease; Epinephrine; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Physical Exertion; Renin; Vasopressins

The mechanisms involved in the abnormal water excretion in patients with congestive heart failure (CHF) are poorly understood. Intrarenal mechanisms (decreased glomerular filtration rate, increased proximal tubular reabsorption) and extrarenal mechanisms (nonosmotic stimulation of arginine vasopressin (AVP)) have been suggested, but their relative importance is unknown. Also, the relationships with altered intracardiac hemodynamics have not been previously assessed. Based on plasma and "platelet" AVP determinations, intracardiac measurements, and other hormonal determinations performed in a series of patients with severe CHF, we conclude that plasma AVP and platelet AVP are the major determinants of the abnormal water excretion in patients with severe CHF. In these patients, enhanced AVP release may be the result of baroreceptor stimulation from a decreased effective arterial blood volume, possibly sensed at specific intraventricular cardiac sites.

Topics: Arginine Vasopressin; Blood Platelets; Blood Volume; Heart Failure; Humans; Renin; Vasopressins

The effect of circulating arginine vasopressin (AVP) on blood pressure, heart rate, and skin blood flow was assessed in normotensive subjects, mild hypertensive patients, and patients with congestive heart failure, utilizing the specific antagonist of AVP at the vascular receptor level, d(CH2)5Tyr(Me)AVP (5 micrograms/kg i.v.). The renin system of the normal volunteers treated with the AVP antagonist was either intact or acutely blocked with the angiotensin converting-enzyme inhibitor captopril (25 mg p.o.). In some volunteers, the cardiovascular effect of AVP released by Finnish sauna or cigarette smoking was studied. In patients with congestive heart failure, hemodynamic measurements (pressures and cardiac output) were obtained invasively. Acute blockade of AVP vascular receptors produced no cardiovascular effect unless plasma AVP levels were markedly elevated. In our experience, abnormally high circulating AVP appears to be responsible for the decrease in skin blood flow induced by cigarette smoking and to some extent for the maintenance of vascular tone in the rare patients with particularly severe congestive heart failure.

Topics: Angiotensin II; Arginine Vasopressin; Heart Failure; Hemodynamics; Humans; Hypertension; Smoking; Steam Bath; Vasopressins

The hemodynamic and hormonal changes produced by adriamycin-induced cardiomyopathic congestive heart failure in rabbits were studied. Adriamycin cardiomyopathy in rabbits led to ventricular dilatation, pleural and pericardial effusions, hepatic congestion, and ascites. These pathological changes were associated with the maintenance of a normal blood pressure but a lowered cardiac output and increased total peripheral resistance. Plasma renin activity and plasma norepinephrine were increased twofold in rabbits with congestive cardiac failure. However, plasma vasopressin and osmolality were normal, whereas an increased vascular sensitivity to the infusion of exogenous vasopressin was demonstrated. Despite the normal levels of plasma vasopressin, administration of a specific vascular vasopressin antagonist led to a fall in blood pressure, a significant increase in cardiac output, and a decrease in total peripheral resistance. No such hemodynamic changes occurred on infusing normal rabbits with the vascular vasopressin antagonist, nor did any significant hemodynamic changes occur on injecting vehicle in rabbits with heart failure. These results suggest that in adriamycin-induced cardiomyopathic heart failure in rabbits, there is activation of the renin-angiotensin system and the sympathetic nervous system together with an increased sensitivity to vasopressin. These three hormonal systems help to maintain blood pressure by increasing total peripheral resistance in this experimental model of heart failure.

Topics: Animals; Doxorubicin; Female; Heart Failure; Hormones; Infusions, Intravenous; Male; Rabbits; Vascular Resistance; Vasopressins

Alterations in the peripheral circulation by influencing aortic impedance and venous capacitance have a remarkable effect on cardiac performance in patients with left ventricular dysfunction. Systemic vasoconstriction in heart failure is influenced by activation of the sympathetic nervous system (increased plasma norepinephrine), the renin-angiotensin system (increased PRA) and the antidiuretic hormone system (increased arginine vasopressin). The level of plasma norepinephrine is related weakly to the severity of resting left ventricular dysfunction and strongly to the subsequent risk of mortality. Attenuation of reflex responsiveness to low pressure mechanoreceptors (orthostatic tilt) and to carotid and aortic baroreceptors (nitroprusside infusion) occurs in heart failure and the degree of abnormality also may be related to mortality. Vasodilation with consequent improvement in left ventricular function may be accomplished by non-specific dilators (nitroprusside, nitrates, hydralazine, nitrendipine) or by specific interference with neurohumoral mechanisms (sympathetic blockade, converting enzyme blockade, AVP blockade). Plasma norepinephrine may be reduced by central or presynaptic mechanisms (guanabenz, bromocriptine, captopril). The hemodynamic effect of this anti-sympathetic effect appears to be related to the relative influence on cardiac vs. peripheral sympathetic tone and/or concomitant effects of the drugs. Long-term trials are needed to determine whether chronic inhibition of the sympathetic nervous system will have a salutary effect on the hemodynamics, symptomatology and prognosis of cardiac failure.

Topics: Catecholamines; Heart Failure; Humans; Neurotransmitter Agents; Norepinephrine; Renin; Renin-Angiotensin System; Sympathetic Nervous System; Vascular Resistance; Vasoconstriction; Vasopressins

Plasma concentrations of antidiuretic hormone (ADH) were measured in 8 patients with congestive heart failure (CHF) of NYHA functional class III-IV, before and during treatment with captopril, 6.25-25.0 mg t.i.d., added to their drug regimen. Before captopril treatment, plasma ADH was high, 2.5 times the upper limit of normal reference values. During treatment with captopril, plasma ADH levels were normalized, and remained so throughout the study, for at least 6 months. Plasma levels of angiotensin II were also reduced to a normal level. Reduction of plasma ADH during captopril treatment in CHF may partly depend on reduced angiotensin II formation, and may be beneficial by improving water balance. Atrial natriuretic peptide (ANP), was measured by radioimmunoassay in 17 patients with CHF. The highest levels were measured in the most severe CHF cases, and intermediate high values on NYHA functional class I-II patients. Plasma ANP concentrations in control patients (n = 18) without cardiac diseases ranged between 0 and 30 pg/ml. In two patients with paroxysmal supraventricular tachycardia, associated with transient polyuria, high plasma ANP concentrations were noticed during tachycardic episodes. Thus, ANP appears to be a circulating hormone in humans, and is released into the blood in clinical conditions associated with raised preload and atrial wall stretch.

Topics: Aged; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Captopril; Female; Heart Failure; Humans; Male; Middle Aged; Renin; Tachycardia, Paroxysmal; Vasopressins

Ten patients with advanced congestive heart failure were treated with an arginine vasopressin V1 antagonist during hemodynamic monitoring to determine the contribution of vasopressin to vasoconstriction in this disorder. The vasopressin antagonist caused a decrease in systemic vascular resistance in the three patients whose plasma vasopressin was greater than 4.0 pg/ml (average for the group was 2.4 +/- 0.6). Plasma vasopressin concentration correlated with the percent decrease of systemic vascular resistance (r = 0.70, p less than 0.025), serum sodium (r = 0.72, p less than 0.02) and serum creatinine (r = 0.85, p less than 0.005). To compare the relative roles of vasopressin, the renin-angiotensin system and the sympathetic nervous system, these patients also received captopril and phentolamine. Captopril decreased systemic vascular resistance by 20% (p less than 0.05), mostly in patients with high plasma renin activity. Levels of plasma renin activity ranged between 1 and 46 ng/ml per h (average 14.7 +/- 5.7) and correlated with serum sodium (r = 0.77, p less than 0.025), serum creatinine (r = 0.73, p less than 0.025) and right atrial pressure (r = 0.67, p less than 0.05). Phentolamine decreased systemic vascular resistance in all patients (average 34%, p less than 0.01), but the decrease did not correlate with the pretreatment norepinephrine concentration. Norepinephrine levels were elevated in all patients (694 +/- 110 pg/ml) and correlated with baseline stroke volume index (r = 0.75, p less than 0.025) and plasma renin activity (r = 0.67, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Arginine Vasopressin; Captopril; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Phentolamine; Renin; Renin-Angiotensin System; Sympathetic Nervous System; Vascular Resistance; Vasoconstriction; Vasopressins

Vasopressin's role as a vasoconstrictor in chronic heart failure, was examined in rabbits with adriamycin cardiomyopathic congestive heart failure. Chronic adriamycin treatment resulted in a decrease in cardiac output (829 +/- 38-610 +/- 36 ml/min, P less than 0.005) and blood pressure (83 +/- 2-76 +/- 3 mmHg, P less than 0.01), and an increase in peripheral resistance (8,377 +/- 381-10,170 +/- 657 dyn-s-cm-5, P less than 0.05). Plasma renin activity (4.7 +/- 0.6-10.9 +/- 2.8 ng angiotensin I/ml X h) and norepinephrine (0.7 +/- 0.1-1.3 +/- 0.2 pmol/ml, P less than 0.05) increased while plasma vasopressin levels did not change. Vasopressin infusion, however, produced significantly greater increases in peripheral resistance in animals with heart failure than in controls. Moreover, a specific vasopressin vascular antagonist reduced blood pressure (7 +/- 3%) and peripheral resistance (14 +/- 4%) and increased cardiac output (10 +/- 3%) in animals with heart failure but had no cardiovascular effects in normal rabbits. These results suggest that vascular sensitivity to vasopressin is increased in heart failure, and that it contributes significantly to the increased afterload in heart failure despite normal plasma levels. In this model of severe, chronic heart failure the sympathetic, renin-angiotensin, and vasopressin systems all appear to be activated.

Topics: Animals; Blood Pressure; Cardiac Output; Doxorubicin; Female; Heart Failure; Heart Rate; Male; Norepinephrine; Rabbits; Renin; Vascular Resistance; Vasoconstriction; Vasopressins

Neurohumoral factors were assessed in 14 subjects with chronic, stable New York Heart Association functional class II or III congestive heart failure and nine comparably aged normal subjects at rest and during moderate (50 W) and strenuous (100 W) upright exercise. Heart failure was associated with elevated plasma renin activity and plasma antidiuretic hormone (ADH) concentrations at rest. However, plasma renin activity almost doubled (from 4.7 +/- 0.6 to 8.4 +/- 1.1 ng/ml per hour) during strenuous exercise in subjects with heart failure, and changed only minimally in normal control subjects. Plasma ADH concentration did not change during exercise in the presence of heart failure, but rose in normal subjects during strenuous exercise to levels comparable to those of subjects with heart failure. Similar plasma osmolality values were present in both groups. Circulating norepinephrine concentrations were insignificantly elevated by heart failure both at rest and during exercise, and plasma epinephrine concentrations were similar. These findings suggest independent neurohumoral activation during exercise in the presence of congestive heart failure, with predominant activation of the renin-angiotensin-aldosterone axis.

Topics: Adult; Aged; Epinephrine; Female; Heart Failure; Humans; Male; Middle Aged; Norepinephrine; Osmolar Concentration; Physical Exertion; Renin; Rest; Vasopressins

Topics: Heart Failure; Humans; Kidney; Renin-Angiotensin System; Sodium; Vasopressins; Water-Electrolyte Imbalance

Topics: Heart Failure; Hemodynamics; Humans; Vasoconstriction; Vasopressins

Topics: Atrial Natriuretic Factor; Heart; Heart Failure; Hemodynamics; Humans; Physical Exertion; Vasopressins

To assess the role of vasopressin (AVP) in congestive heart failure (CHF), we investigated 10 patients with CHF refractory to conventional treatment, before and 60 minutes after intravenous administration of 5 micrograms/kg of d(CH2)5Tyr(Me)AVP, a specific antagonist of AVP at the vascular receptor level. Heart rate, systemic arterial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac index by thermodilution, and cutaneous blood flow by laser-Doppler technique were measured. In 9 patients there was no significant hemodynamic and cutaneous blood flow response to the AVP antagonist. Plasma AVP was 2.3 +/- 0.8 pg/ml and plasma osmolality 284 +/- 14 mosm/kg H2O. The tenth patient had the most severe CHF. His plasma AVP was 55 pg/ml and plasma osmolality 290 mosm/kg. He responded to the AVP antagonist with a marked decrease in systemic arterial pressure from 115/61 to 79/41 mm Hg, in pulmonary arterial pressure from 58/31 to 33/13 mm Hg and in pulmonary capillary wedge pressure from 28 to 15 mm Hg. Simultaneously cardiac index increased from 1.1 to 2.21 X min-1 X m-2 and cutaneous blood flow rose 5-fold. Thus, most patients with CHF have only moderately elevated plasma AVP and its role in determining peripheral vascular resistance appears to be limited. AVP may become important in rare patients presenting with marked hemodynamic instability and very high plasma AVP.

Topics: Adult; Arginine Vasopressin; Female; Heart Failure; Hemodynamics; Humans; Male; Osmolar Concentration; Vasopressins

To elucidate the effect of bed rest used as an adjunct to increased diuretic treatment, twelve patients with chronic congestive heart failure (CHF) had a 50% increase in loop diuretic dosage and were allocated to either continuous bed rest or bed rest during nights only. The 24-hour bed rest group reduced their weight significantly (mean +/- SEM: 2.00 +/- 0.79 kg, P less than 0.001), whereas the night bed rest group had no significant weight reduction (1.10 +/- 0.37 kg, 0.1 less than P less than 0.2) during three days of observation. Furthermore, the 24-hour bed rest group had a significantly increased diuresis (P less than 0.05) during the first day of the study and a tendency towards increased natriuresis. The cumulated diuresis for the two groups (24-hour bed rest versus night bed rest) during the three days of study were 7773 +/- 700 ml and 5861 +/- 909 ml (0.05 less than P less than 0.1), respectively. Plasma concentrations of adrenaline, noradrenaline, renin and aldosterone were increased, as measured in the supine position. No significant differences were found between the two groups. Plasma concentrations of antidiuretic hormone were within normal limits. In conclusion, continuous bed rest is a reasonable adjunct to diuretic treatment in patients with CHF.

Topics: Adult; Aged; Aldosterone; Bed Rest; Body Weight; Chronic Disease; Combined Modality Therapy; Diuretics; Epinephrine; Female; Heart Failure; Humans; Male; Middle Aged; Natriuresis; Norepinephrine; Posture; Prospective Studies; Renin; Vasopressins

We examined renal function and Na+ balance in a patient with congestive heart failure who was treated with demeclocycline (DMC) on three separate occasions under strict metabolic balance conditions. Natriuresis and reversible renal insufficiency, which could not be explained solely on the basis of negative Na+ balance, developed on each occasion. In contrast to reports of an association between elevated serum DMC levels and renal insufficiency in patients with cirrhotic edema, the renal insufficiency in this patient with cardiac edema occurred in the absence of high DMC levels. Consequently, markedly elevated serum DMC levels do not appear to be a prerequisite for the development of natriuresis or renal insufficiency in edematous patients receiving this drug. In an attempt to clarify the mechanism of the natriuresis, we also examined the effects of DMC on Na+ transport in an in-vitro model system, the toad urinary bladder. DMC inhibited aldosterone-stimulated Na+ transport, but had no effect on Na+ transport when the latter was jointly stimulated by ADH and theophylline. Despite this selective inhibition of the natriferic effect of aldosterone in vitro, it is unlikely that such a mechanism completely accounts for the natriuresis observed in-vivo since the natriuresis is generally of large magnitude and is usually accompanied by some degree of kaliuresis, and DMC had no consistent effect on urinary aldosterone excretion. Consequently, other mechanisms must be sought to explain the natriuretic effect of DMC in edematous patients. Likewise, mechanisms other than negative Na+ balance (perhaps primary alterations in renal hemodynamics) must underly the development of renal insufficiency in such individuals.

Topics: Administration, Oral; Aldosterone; Animals; Anura; Biological Transport; Blood Urea Nitrogen; Body Weight; Demeclocycline; Glomerular Filtration Rate; Heart Failure; Humans; In Vitro Techniques; Kidney Failure, Chronic; Male; Middle Aged; Natriuresis; Nephrons; Potassium; Sodium; Theophylline; Vasopressins

Hamsters of the BIO 14.6 strain characteristically develop cardiomyopathy as they age, and hamsters of this strain have overt signs of heart failure by 11 months of age. Plasma levels of the posterior pituitary hormone arginine-vasopressin (AVP) were found to be elevated (approximately 2-fold) in 11 month old BIO 14.6 hamsters, compared to age-matched hamsters of a control strain. AVP appeared inappropriately elevated in these animals, since they were neither hyperosmotic nor markedly hypotensive. The elevated levels of AVP observed in these animals appears to contribute to vasomotor tone, since intravenous administration of a specific antagonist of the vasoconstrictor action of AVP [d(CH2)5Ome(TYR)AVP] elicited a fall in arterial pressure (9 +/- 2 mm Hg, n = 6, p less than 0.05). The AVP antagonist had no effect on arterial pressure in hamsters of a control strain, and vehicle administration had no effect on arterial pressure in either strain. These data indicate that inappropriately elevated levels of AVP contribute to the cardiovascular state of myopathic hamsters. Since elevated plasma AVP has been noted in human congestive heart failure, these results suggest that AVP may contribute to the cardiovascular status during congestive heart failure.

Topics: Age Factors; Animals; Cardiomyopathies; Cricetinae; Disease Models, Animal; Heart Failure; Mesocricetus; Rodent Diseases; Vasoconstriction; Vasopressins

Plasma antidiuretic hormone (ADH), PRA, plasma osmolality, and the parameters of renal water excretion were measured after overnight dehydration and for 5 h after an oral load in 14 patients with congestive heart failure (CHF) treated with diuretics (group 1), 8 hypertensive patients without CHF also treated with diuretics (group 2), and 11 patients with coronary artery disease but without CHF who were not treated with diuretics (group 3). Under basal conditions, mean plasma osmolality was lower in group 1 than in group 3, but was not different in groups 1 and 2. Mean plasma ADH was higher in group 1 than in group 2 or 3. In response to the water load, plasma osmolality and plasma ADH levels decreased in the 3 groups. ADH levels remained significantly greater in group 1 than in groups 2 and 3 from 2-4 h after the water load despite more marked hypoosmolality in group 1 compared with that in either of the 2 control groups. Plasma ADH was significantly correlated with plasma osmolality only in the 2 control groups. Mean PRA was greater in patients with CHF and patients without CHF treated with diuretics than in untreated patients. Cumulative water excretion was lower in patients with CHF than in patients in the 2 control groups from 2-5 h after the water load. At 5 h, the mean percentage excretion of the ingested loads was 56.8%, 90.7%, and 91.2% in the patients of groups 1, 2, and 3 respectively. Free water clearance was lower and minimal urinary osmolality was greater in the patients with CHF than in those in the 2 control groups. Two patients with CHF, who excreted more than 75% of the water load, also had low plasma basal ADH levels. These data show that patients with CHF have an inappropriate response of plasma ADH to a marked fall in plasma osmolality. This disorder is not due to the diuretic therapy, since hypertensive patients treated with diuretics behaved similarly to untreated patients without CHF. The reasons for this inappropriate response of plasma ADH during a water load in patients with CHF are probably multifactorial.

Topics: Adult; Body Water; Diuretics; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Osmolar Concentration; Renin; Vasopressins

Topics: Captopril; Diuretics; Heart Failure; Humans; Hyponatremia; Osmolar Concentration; Plasma; Renin-Angiotensin System; Thirst; Vasopressins

An increased activity of vasoconstrictor mechanisms may play an important role in circulatory adjustments to heart failure. Thus, hemodynamic data and the plasma hormones epinephrine (E), norepinephrine (NE) and arginin vasopressin (AVP) as well as the plasma renin activity (PRA) were assessed in 50 patients undergoing coronary angiography and right heart catheterization. Patients were classified into three groups according to severity of left ventricular (LV) dysfunction as assessed by ejection fraction (LVEF): those with normal left ventricular function (group 1 (n = 12): LVEF greater than or equal to 55%, mean 70 +/- 3%) and those with moderate (group 2 (n = 16): LVEF 54-35%, mean 43 +/- 2%) or severe LV dysfunction (group 3 (n = 22): LVEF less than 35%, mean 22 +/- 1%). At rest plasma NE concentrations in patients with heart failure (group 2: 187 +/- 17 pg/ml; group 3: 299 +/- 27 pg/ml) did not differ significantly from control values (199 +/- 26 pg/ml). During exercise, NE concentrations increased in all patients (p less than 0.001). This increase in plasma NE was more pronounced in group 3 (753 +/- 71 pg/ml) than in group 1 (262 +/- 37) and group 2 (388 +/- 64). A significant inverse correlation was found between plasma NE and stroke index at rest (r = -0.592, p less than 0.001) as well as during exercise (r = -0.659, p less than 0.001). PRA was elevated at rest and during exercise in patients of group 3 but not of group 2 as compared with control patients (p less than 0.05). Plasma E and AVP were similar in all groups. Patients of group 3 were subdivided according to exercise capacity into patients who tolerated a maximum work load of 50 watts or more (group 3A) and those who did not tolerate a work load exceeding 25 watts (group 3B). At rest and during exercise, patients of group 3A had a higher stroke index than patients of group 3B. In contrast, there was no significant difference in LVEF between group 3A and 3B (22 +/- 2 vs 20 +/- 1%). During exercise patients with low exercise capacity (group 3B) had higher NE levels than patients with less impaired exercise capacity (group 3A) (948 +/- 86 vs 590 +/- 65 pg/ml, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Chronic Disease; Coronary Vessels; Epinephrine; Female; Heart Failure; Heart Ventricles; Hemodynamics; Humans; Male; Norepinephrine; Renin; Sodium; Vasoconstriction; Vasoconstrictor Agents; Vasopressins

Topics: Adult; Aged; Angiotensin II; Angiotensinogen; Angiotensins; Blood Pressure; Captopril; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Proline; Renin; Time Factors; Vasopressins

In advanced heart failure, severe edema develops associated with hyponatremia. In 20 patients with severe congestive heart failure, we studied plasma antidiuretic hormone (ADH) concentrations related to hemodynamics and plasma osmolality. Prazosin was used to test the acute response to changes in atrial receptors and hemofiltration to test the response to changes in volume receptors. One group of the patients had inappropriately high ADH values (14.5 +/- 8.8 pg/ml) in relation to their plasma osmolality, which was well below normal values (276 +/- 23 mosmol/kg water) with no apparent osmoregulatory control. The other group showed a normal relationship of ADH and plasma osmolality (3.9 +/- 1.0 pg/ml; 289 +/- 8 mosmol/kg water), Only in the normal regulating group did lowering of left atrium pressure by prazosin result in a rise in ADH related to the decrease in pressure. Inappropriately high ADH secretion could be reversed by hemofiltration. This suggests that the syndrome of "dilutional hypo-osmolality" in severe congestive heart failure may be caused by an inappropriately high ADH secretion in which the osmoreceptor system is dominated by nonosmolar stimuli; however, it cannot be ruled out that associated hemodynamic effects in the kidney or other intrarenal or hormonal factors contribute to this mechanism.

Topics: Adult; Edema; Heart Failure; Hemodynamics; Humans; Hyponatremia; Middle Aged; Osmolar Concentration; Prazosin; Vasopressins

1. Congestive heart failure was induced in dogs by rapid pacemaker stimulation of the heart (240-280/min) for 14 days. This represents a model of low output heart failure which permits the study of the development and reversal of congestive heart failure in an anatomically intact circulation in the unanaesthetized animal. 2. Cardiac output was reduced by 54%. Pulmonary artery pressure gradually increased by a factor of 2.4 and pulmonary capillary pressure rose to 4.6 times basal values. The animals retained a mean of 1.1 litres of fluid. 3. At the same time there was a gradual increase of plasma levels of renin, angiotension II, aldosterone, noradrenaline and adrenaline. After the pacemaker stimulation was discontinued all hormone levels returned to normal, the retained fluid was excreted, and intracardiac pressures and cardiac output returned to baseline values. 4. When heart failure was established at the end of the pacemaker stimulation period an inappropriately high secretion of antidiuretic hormone in relation to plasma osmolality was observed in five of six dogs. 5. It is concluded that beside the well-known non-hormonal renal factors, these hormone systems may be involved in the formation of oedema in congestive heart failure. The inappropriately high levels of antidiuretic hormone may cause hyponatraemia by water retention, representing a state of 'dilutional hypo-osmolality'.

Topics: Animals; Cardiac Output; Cardiac Pacing, Artificial; Disease Models, Animal; Dogs; Heart Failure; Renin-Angiotensin System; Sympathetic Nervous System; Time Factors; Vasopressins

Topics: Arginine Vasopressin; Heart Failure; Humans; Hyponatremia; Radioimmunoassay; Vasopressins

The renal response to left atrial balloon inflation in normal dogs was compared with that in dogs with chronic congestive heart failure (CHF). CHF was induced by the production of an aortocaval fistula below the level of the renal arteries. CHF dogs showed elevated left ventricular end-diastolic pressure, enlarged hearts, a depression of myocardial contractility, pulmonary edema, ascites, and peripheral edema. They also showed significant decreases in urine flow, creatinine clearance, para-aminohippurate clearance, sodium and potassium excretion, fractional sodium excretion, osmolar clearance, arterial blood pressure, and heart rate. Balloon distension of the left atrium evoked a significant increase in urine flow and free-water clearance in the normal group. The reflex nature of this response was indicated by its blockade after bilateral cervical vagotomy. In contrast, the CHF group did not exhibit significant changes in urine flow or free-water clearance during balloon inflation. Plasma antidiuretic hormone (ADH) was significantly elevated in the CHF group; however, balloon distension reduced plasma ADH in both groups of dogs. Plasma renin activity was significantly elevated in the CHF dogs and was not changed by balloon distension in either group of dogs. It is concluded that animals with high-output CHF do not exhibit the atrial-diuretic reflex in spite of their ability to reduce ADH levels by atrial distension.

Topics: Animals; Blood Pressure; Dogs; Edema; Female; Heart Failure; Heart Rate; Kidney; Male; Sodium; Vasopressins; Water

Topics: Blood Volume; Diuretics; Heart Failure; Hospitalization; Humans; Hyperglycemia; Hyponatremia; Kidney Failure, Chronic; Liver Cirrhosis; Stress, Physiological; Surgical Procedures, Operative; Vasopressins

The hypothalamohypophyseal neurosecretory system (HHNS) was examined in the deceased from myocardial infarctions and chronic cardiac insufficiency. All 80 cases of infarctions showed in increased functional activity of the HHNS, irrespective of the time from the beginning of the disease. If the infarction was complicated by decompensation, the HHNS was characterized by hypervasopressure accompanied by occurrence of small vacuolized cells in the supraoptical nuclei with a low secretion content and high activity of biosynthetical enzymes, and a drop of secretion in the neurohypophysis. In chronic cardiac insufficiency (50 cases) there were 2 variants of changes in the HHNS, which correlated with the level of sympathetic nervous system activity (which was vitally determined from the diurnal catecholamine excretion). With high sympathetic activity, the changes in the HHNS were identical to those in myocardial infarctions, complicated by decompensation. The low activity was associated with HHNS depletion, which correlated with patients' nonsusceptibility to pathogenetic therapy.

Topics: Acute Disease; Chronic Disease; Glutamate Dehydrogenase; Heart Failure; Humans; Hypothalamo-Hypophyseal System; Myocardial Infarction; NADPH Dehydrogenase; Potassium; Sodium; Sympathetic Nervous System; Vasopressins

The hypothesis that receptors in the heart or pulmonary vasculature initiate a reflex that influences urine flow was derived from experiments designed to evaluate the effect of mechanical ventilation on renal function. These experiments indicated that urine flow usually decreases during positive-pressure breathing and usually increases during negative-pressure breathing. It was surmised that impulses from certain cardiopulmonary receptors affect the secretion of ADH, which in turn influences urine flow. A subsequent investigation appeared to localize the pertinent receptors to the left atrium, but the results of this particular investigation were influenced by several complication factors that have not been widely appreciated. The apparent localization of volume-regulating recpetors to the left atrium and the accumulating evidence that atrial receptors do respond to changes in atrial pressure or atrial volume triggered a myriad of further studies on the function of left receptors. Nearly all these studies employed indirect techniques that produced changes in systemic and pulmonary hemodynamics in addition to changes in left atrial pressure. Nevertheless, it often was assumed that if changes in left pressure were produced, any concomitant changes in circulating ADH or in urine flow were attributable to a reflex elicited from atrial receptors. Mush of the data obtained were interpreted as being compatible with the elft atrial volume-receptor hypothesis, but very liggle of the data pertained to left atrial receptors specifically.

Topics: Animals; Atrial Function; Biological Assay; Blood Pressure; Blood Volume; Cardiac Surgical Procedures; Cardiac Tamponade; Denervation; Diuresis; Dogs; Extracellular Space; Heart Failure; Hemorrhage; Hypothalamus; Immersion; Kidney; Mechanoreceptors; Natriuresis; Nerve Fibers, Myelinated; Positive-Pressure Respiration; Posture; Radioimmunoassay; Regional Blood Flow; Sensory Receptor Cells; Tachycardia; Vagotomy; Vagus Nerve; Vasopressins; Veratridine

The antidiuretic hormone (ADH) content in the blood plasma in comparison with its osmosis, the mass of circulating blood and the Na/K ratio in the urine was studied in 59 patients with rheumatic heart disease, atherosclerotic cardiosclerosis and chronic nonspecific affections of the lungs with and without circulatory insufficiency. The blood plasma ADH level is shown to increase significantly only with circulatory insufficiency of the IIB-III stage, whereas the plasma osmosis first has a tendency to rise and then gradually declines. This may suggest a deranged regulation of the ADH secretion with a higher osmosis of the plasma. No clear-cut parallelism between changes in the ADH level, the mass of circulating blood and plasma, the Na/K ratio in the urine and diurnal urinary output could be noted.

Topics: Animals; Blood Circulation; Diuresis; Heart Failure; Humans; Kidney; Osmolar Concentration; Pulmonary Heart Disease; Rats; Rheumatic Heart Disease; Vasopressins

Topics: Aldosterone; Angiotensin II; Heart Failure; Hematuria; Humans; Kidney; Kidney Failure, Chronic; Natriuresis; Renin; Vasopressins

Topics: Adult; Animals; Diuresis; Female; Heart Failure; Humans; Hypertension; Liver Cirrhosis; Male; Rats; Vasopressins; Water-Electrolyte Balance

Topics: Aged; Creatinine; Desoxycorticosterone; Diuresis; Edema; Heart Failure; Humans; Hypertension; Infusions, Parenteral; Male; Middle Aged; Osmolar Concentration; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatitis; Sodium; Time Factors; Urea; Urinary Catheterization; Urination Disorders; Vasopressins; Water-Electrolyte Balance

Topics: Aldosterone; Catecholamines; Heart Failure; Hemodynamics; Humans; Hyperaldosteronism; Hypokalemia; Hyponatremia; Kidney; Potassium; Renin; Sodium; Vasopressins; Water; Water-Electrolyte Balance

Topics: Heart Failure; Humans; Hyponatremia; Liver Cirrhosis; Myxedema; Pituitary Diseases; Radioimmunoassay; Vasopressins

Topics: Aged; Heart Failure; Humans; Kidney; Male; Natriuresis; Osmolar Concentration; Sodium; Vasopressins; Water-Electrolyte Balance

Topics: Aerospace Medicine; Blood Pressure; Cardiac Output; Cardiac Volume; Electrocardiography; Extracellular Space; Heart; Heart Failure; Humans; Osmolar Concentration; Space Flight; Vasopressins; Weightlessness

Topics: Animals; Dogs; Heart Failure; Humans; Vasopressins

Topics: Adult; Aldosterone; Catecholamines; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Renin; Vasopressins; Water-Electrolyte Balance

Topics: Adrenal Insufficiency; Animals; Ascites; Diuresis; Edema; Heart Failure; Humans; Male; Methods; Rats; Vasopressins

Topics: Acid-Base Equilibrium; Blood Cell Count; Cortisone; Depression; Diabetes Insipidus; Diuresis; Electrocardiography; Heart Failure; Hemorrhage; Humans; Hypophysectomy; Kidney Diseases; Methods; Pituitary Diseases; Pituitary Neoplasms; Postoperative Care; Postoperative Complications; Posture; Preoperative Care; Sodium; Time Factors; Vasopressins

1. Study of the delayed responses to lethal doses of endotoxin in cats is complicated by acute pulmonary vasoconstriction which results in hypotension, cardiac failure and pulmonary oedema. This acute response is abolished if the animal is pretreated with aspirin (10-100 mg/kg). In these cats, pretreated with aspirin, arterial pressure and right atrial pressure remain unchanged in the first 2 h after administration of endotoxin. Later, arterial pressure falls and the animals die but no haemorrhagic lung lesions are visible.2. These results confirm our previous conclusion that the delayed lethal response to endotoxin is an independent action and not a secondary consequence of the acute response. The mechanism of the action of aspirin is discussed and it is suggested that it prevents the release by endotoxin of vasoactive substances, possibly from platelets.3. In cats pretreated with aspirin, administration of endotoxin results in a marked mesenteric vasoconstriction. Although arterial pressure does not decrease significantly, superior mesenteric arterial flow decreases to 20% of control in the first hour after endotoxin and remains at this low level until the animal dies. Mesenteric ischaemia may contribute to the cat's death.4. The mesenteric vasoconstriction is not reduced by prior administration of phenoxybenzamine and is only slightly reduced after phenoxybenzamine, hypophysectomy and nephrectomy. It is concluded that catecholamines, vasopressin and angiotensin play at most a minor role in the mechanism of this vasoconstriction and that other unknown factors are predominant.

Topics: Angiotensin II; Animals; Aspirin; Blood Platelets; Blood Pressure; Cats; Endotoxins; Heart Failure; Hypophysectomy; Hypotension; Ischemia; Mesenteric Arteries; Nephrectomy; Phenoxybenzamine; Pulmonary Edema; Time Factors; Vasoconstrictor Agents; Vasopressins

Topics: Aldosterone; Animals; Cats; Dogs; Edema; Heart Atria; Heart Failure; Humans; Kidney; Mechanoreceptors; Pulmonary Artery; Renin; Vasopressins

Topics: Aldosterone; Aminohippuric Acids; Animals; Aorta; Ascites; Blood Pressure; Dogs; Edema; Female; Glomerular Filtration Rate; Heart Failure; Norepinephrine; Renin; Sodium; Tricuspid Valve; Vasopressins; Water-Electrolyte Balance

Topics: Diuresis; Ethanol; Heart Failure; Humans; Natriuresis; Pituitary Function Tests; Pituitary Gland; Vasopressins; Water-Electrolyte Balance

Topics: Heart Failure; Humans; Liver Cirrhosis; Lung Diseases; Neoplasms; Nephrosis; Vasopressins; Water-Electrolyte Balance

Topics: Adolescent; Adult; Aged; Aldosterone; Coronary Disease; Female; Heart Failure; Humans; Male; Middle Aged; Pulmonary Heart Disease; Rheumatic Heart Disease; Vasopressins; Water-Electrolyte Balance

Topics: Adolescent; Adult; Aged; Body Weight; Child; Diuretics; Edema; Female; Heart Failure; Hematocrit; Humans; Lung; Lung Compliance; Male; Middle Aged; Oxygen; Positive-Pressure Respiration; Pulmonary Edema; Radiography; Respiration, Artificial; Respiratory Function Tests; Respiratory Insufficiency; Sodium; Vasopressins; Water-Electrolyte Balance

Topics: Heart Failure; Humans; Hyponatremia; Vasopressins; Water Intoxication

Topics: Animals; Biological Assay; Eclampsia; Edema; Female; Heart Failure; Humans; Male; Methods; Nephrotic Syndrome; Pregnancy; Rats; Vasopressins

Topics: Adult; Aged; Aldosterone; Arteriosclerosis; Blood Pressure; Blood Volume; Cardiac Output; Chronic Disease; Digitalis Glycosides; Diuretics; Electrocardiography; Female; Heart Diseases; Heart Failure; Humans; Hypertension; Kidney; Male; Middle Aged; Mitral Valve Insufficiency; Mitral Valve Stenosis; Regional Blood Flow; Serum Albumin, Radio-Iodinated; Vasopressins

Topics: Adult; Aged; Blood Pressure; Blood Volume; Chronic Disease; Female; Furosemide; Heart Failure; Humans; Kidney Function Tests; Lanatosides; Male; Middle Aged; Osmosis; Potassium; Renal Artery; Sodium; Urine; Vasopressins

Topics: Aged; Heart Failure; Humans; Hyponatremia; Hypopituitarism; Male; Myxedema; Propylthiouracil; Triiodothyronine; Vasopressins

Topics: Ammonium Chloride; Animals; Bicarbonates; Blood Flow Velocity; Blood Gas Analysis; Carbon Dioxide; Cyanides; Dogs; Glucagon; Heart Arrest; Heart Failure; Humans; Hydrogen-Ion Concentration; Liver Diseases; Lymph; Oxygen; Oxygen Consumption; Shock, Hemorrhagic; Thoracic Duct; Vasopressins

Topics: Adolescent; Adult; Aged; Edema; Female; Heart Failure; Humans; Male; Middle Aged; Nephrotic Syndrome; Pregnancy; Vasopressins

Topics: Aldosterone; Angiotensin II; Estrogens; Glucocorticoids; Heart Failure; Humans; Kidney; Progesterone; Vasopressins; Water-Electrolyte Balance

Topics: Adolescent; Adult; Animals; Aortic Diseases; Ascites; Biological Assay; Blood; Dogs; Edema; Female; Heart Failure; Hematocrit; Humans; Male; Mitral Valve Insufficiency; Potassium; Secretory Rate; Sodium; Urine; Vasopressins; Venae Cavae

Topics: Adult; Animals; Diabetes Insipidus; Diuresis; Dogs; Female; Heart Failure; Humans; Kidney; Liver; Male; Middle Aged; Sodium Chloride; Vasopressins; Water

Topics: Adult; Chlorides; Creatinine; Diuresis; Heart Failure; Humans; Mannitol; Middle Aged; Potassium; Sodium; Vasopressins

Topics: Angiotensins; Blood Pressure Determination; Central Nervous System Stimulants; Heart Arrest; Heart Failure; Humans; Hypotension; Pharmacology; Postoperative Care; Postoperative Complications; Shock; Sympathomimetics; Toxicology; Vascular Diseases; Vasopressins; Water-Electrolyte Balance

Topics: Aldosterone; Blood Circulation; Blood Volume; Cardiovascular Diseases; Heart Failure; Humans; Kidney; Physiology; Sodium; Vasopressins; Water

Topics: Arteriosclerosis; Diabetes Insipidus; Diuresis; Glucose; Heart Failure; Humans; Hypernatremia; Hyponatremia; Injections, Intravenous; Isotonic Solutions; Mannitol; Myocarditis; Osmosis; Potassium; Urine; Vasopressins; Water-Electrolyte Balance

Topics: Diuretics; Edema; Heart Failure; Kidney Diseases; Liver Diseases; Organomercury Compounds; Physiology; Vasopressins

Topics: Acute Kidney Injury; Atropine; Biomedical Research; Blood Volume; Convalescence; Dehydration; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Edema; Epinephrine; Female; Heart Failure; Hemorrhage; Humans; Hypertonic Solutions; Menstruation; Pharmacology; Placebos; Pregnancy; Renal Insufficiency; Salivation; Sweating; Uremia; Vasopressins; Water-Electrolyte Balance

Topics: Arginine Vasopressin; Blood Chemical Analysis; Edema; Heart Failure; Humans; Obesity; Vasopressins

Topics: Arginine Vasopressin; Electrophoresis, Paper; Heart Failure; Humans; Vasopressins

Topics: Heart Failure; Humans; Patient Discharge; Schizophrenia; Vasopressins; Water; Water Intoxication

Topics: Aldosterone; Heart Failure; Humans; Natriuresis; Vasopressins; Water; Water-Electrolyte Balance

Topics: Aldosterone; Angiotensin Amide; Angiotensin II; Heart Defects, Congenital; Heart Failure; Humans; Hypertension; Kidney; Vasopressins

Topics: Arginine Vasopressin; Edema; Heart Failure; Humans; Liver Cirrhosis; Vasopressins

Topics: Heart Failure; Humans; Liver Cirrhosis; Vasopressins; Water; Water-Electrolyte Balance

Topics: Animals; Chlorothiazide; Desoxycorticosterone; Desoxycorticosterone Acetate; Heart Failure; Rats; Vasopressins; Water-Electrolyte Balance

Topics: Aldosterone; Arginine Vasopressin; Heart Failure; Humans; Vasopressins

Topics: Cortisone; Electrolytes; Heart Failure; Humans; Vasopressins

Topics: Arginine Vasopressin; Choline; Heart Failure; Theophylline; Vasopressins

Topics: Edema; Heart Failure; Hormones; Liver Cirrhosis; Pituitary Gland; Pituitary Gland, Posterior; Vasopressins; Water