Neurohormonal Activation (neurohormonal + activation)

Distribution by Scientific Domains

Selected Abstracts

Neurohormonal activation in canine degenerative mitral valve disease: implications on pathophysiology and treatment

M. A. Oyama
Neurohormonal systems play a critical role in canine degenerative mitral valve disease (DMVD). DMVD results in mitral regurgitation, which reduces forward cardiac output and increases intracardiac pressures. These changes trigger neurohormonal responses that ultimately result in maladaptive cardiac remodelling, congestion and heightened morbidity and mortality. Medical therapies such as ACE inhibitors and spironolactone derive their benefit by interrupting or suppressing these neurohormonal responses. Thus, knowledge of neurohormonal mechanisms can lead to a better understanding of how to treat DMVD. [source]

Cardiac hypertrophy and failure: lessons learned from genetically engineered mice

Y. Takeishi
Congestive heart failure is a major and growing public health problem. Because of improved survival of myocardial infarction patients produced by thrombolytic therapy or per-cutaneous revascularization it represents the only form of cardiovascular disease with significantly increased incidence and prevalence. Clinicians view this clinical syndrome as the final common pathway of diverse pathologies such as myocardial infarction and haemodynamic overload. Insights into mechanisms for heart failure historically derived from physiological and biochemical studies which identified compensatory adaptations for the haemodynamic burden associated with the pathological condition including utilization of the Frank Starling mechanism, augmentation of muscle mass, and neurohormonal activation to increase contractility. Therapy has largely been phenomenological and designed to prevent or limit the deleterious effects of these compensatory processes. More recently insights from molecular and cell biology have contributed to a more mechanistic understanding of potential causes of cardiac hypertrophy and failure. Many different analytical approaches have been employed for this purpose. These include the use of conventional animal models which permit serial observation of the onset and progression of heart failure and a sequential analysis of underlying biochemical and molecular events. Neonatal murine cardiomyocytes have been a powerful tool to examine in vitro subcellular mechanisms devoid of the confounding functional effects of multicellular preparations and heterogeneity of cell type. Finally, significant progress has been made by utilizing tissue from human cardiomyopathic hearts explanted at the time of orthotopic transplantation. Each of these methods has significant advantages and disadvantages. Arguably the greatest advance in our understanding of cardiac hypertrophy and failure over the past decade has been the exploitation of genetically engineered mice as biological reagents to study in vivo the effects of alterations in the murine genome. The power of this approach, in principle, derives from the ability to precisely overexpress or ablate a gene of interest and examine the phenotypic consequences in a cardiac specific post-natal manner. In contrast to conventional animal models of human disease which employ some form of environmental stress, genetic engineering involves a signal known molecular perturbation which produces the phenotype. [source]

Glucagon-like Peptide-1 and Myocardial Protection: More than Glycemic Control

Anjali V. Fields MD
Pharmacologic intervention for the failing heart has traditionally targeted neurohormonal activation and ventricular remodeling associated with cardiac dysfunction. Despite the multitude of agents available for the treatment of heart failure, it remains a highly prevalent clinical syndrome with substantial morbidity and mortality, necessitating alternative strategies of targeted management. One such area of interest is the ability to modulate myocardial glucose uptake and its impact on cardioprotection. Glucose-insulin-potassium (GIK) infusions have been studied for decades, with conflicting results regarding benefit in acute myocardial infarction. Based on the same concepts, glucagon-like peptide-1-[7,36] amide (GLP-1) has recently been demonstrated to be a more effective alternative in left ventricular (LV) systolic dysfunction. This paper provides a review on the current evidence supporting the use of GLP-1 in both animal models and humans with ischemic and nonischemic cardiomyopathy. Copyright 2009 Wiley Periodicals, Inc. [source]

Endogenous B-type Natriuretic Peptide: A Limb of the Regulatory Response to Acutely Decompensated Heart Failure

Robert E. Hobbs MD
Abstract Acutely decompensated heart failure (ADHF) represents an episodic failure of cardiorenal homeostasis that may resolve with upregulation of natriuretic peptides, bradykinin, and certain prostacyclins. B-type natriuretic peptide (BNP) has multiple favorable effects, including vasodilation, diuresis, natriuresis, and inhibition of vascular endothelial proliferation and cardiac fibrosis. By antagonizing the effects of activation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system in volume overload, the endogenous BNP response may help rescue patients from episodic ADHF. Although knowledge of BNP physiology is expanding, we still have limited understanding of the heterogeneity of proBNP-derived molecules, including active 32 amino acid BNP and less active junk BNP forms. Emerging evidence suggests that in ADHF, the endogenous BNP response is overwhelmed by neurohormonal activation. This relative BNP deficiency may also be accompanied by physiologic resistance to BNP. Additionally, abnormalities of BNP production may result in a lower proportion of active BNP relative to less active forms that may also be detected by point-of-care tests. Improved detection of the various BNP species may clarify these concepts and facilitate improved clinical management of ADHF. Copyright 2008 Wiley Periodicals, Inc. [source]

Rapid clinical assessment of hemodynamic profiles and targeted treatment of patient with acutely decompensated heart failure

Greegg C. Fonarow M.D.
Abstract Acutely decompensated heart failure (ADHF) is characterized by hemodynamic abnormalities and neurohormonal activation that contribute to heart failure (HF) symptoms, end-organ dysfunction, arrhythmias, and progressive cardiac failure. The management of ADHF in the emergency department (ED) can be simplified and improved by a 2-min bedside assessment that identifies any of four possible hemodynamic profiles on the basis of clinical signs and symptoms. The profiles are based on whether congestion is present or absent (wet or dry) and perfusion is adequate or limited (warm or cold). A wet-warm profile is seen more frequently in the ED than any of the other three profiles (wet-cold, dry-warm, and dry-cold). The four clinically determined profiles have been shown to predict clinical outcomes and may be used to guide initial HF therapy. The goals of treating ADHF are to stabilize the patient, reverse acute hemodynamic abnormalities, rapidly reverse dyspnea and/or hypoxemia caused by pulmonary congestion, and initiate treatments that will decrease disease progression and improve survival. An ideal agent for the wet-warm profile would rapidly reduce pulmonary congestion, produce balanced arterial and venous dilation, promote natriuresis, lack direct positive inotropic effects, and not cause reflex neuroendocrine activation. Intravenous nesiritide in conjunction with loop diuretics has been found safe and effective as initial treatment for patients with the wet-warm profile. For the wet-cold profile, more intensive therapy and invasive hemodynamic monitoring may prove useful. This review will discuss the rapid clinical determination of hemodynamic profiles in patients presenting to the ED with ADHF and the options for their initial medical management. Case studies representing the wet-warm, wet-cold, dry-warm, and dry-cold profiles will be presented and discussed. [source]

The neuro-cardio-endocrine response to acute subarachnoid haemorrhage

Eric A. Espiner
Summary objective Whereas cardiac hormones increase after subarachnoid haemorrhage (SAH), and may contribute to sodium wastage and hyponatraemia, there is controversy concerning the relative roles of atrial natriuretic peptide (ANP) vs. brain natriuretic peptide (BNP) and the factors initiating their secretion. Noting previous work linking stress hormone responses with cardiac injury after SAH, we have studied responses in stress hormones, markers of cardiac injury and the temporal changes in ANP and BNP and related them to changes in sodium status post ictus and during recovery from acute SAH. design, patients, measurements Eighteen patients with verified SAH of variable severity were studied in a single unit for a 14-day period post ictus under controlled conditions of sodium and fluid intake. All received a standardized protocol of daily dexamethasone and nimodipine throughout the study. Severity was graded using criteria of Hess and Hunt at admission. Stress hormones (AVP, catecholamines and admission plasma cortisol), markers of cardiac injury (ECG and daily plasma troponin T) and cardiac hormones (ANP and BNP) were measured daily and related to severity, plasma sodium and renin,aldosterone activity. Hormone levels (ANP, BNP and endothelin) in cerebrospinal fluid (CSF) were also measured in nine patients. results Intense neurohormonal activation (AVP, cortisol and catecholamines) at admission was associated with increased levels of both plasma ANP and BNP whereas levels in CSF were unaffected. In individual patients plasma levels of ANP and BNP were strongly correlated (P < 0001). Cardiac events (abnormal ECG and/or elevated troponin) occurred in six of seven patients graded severe but neither stress hormones nor cardiac peptides differed significantly in patients with mild (n = 11) vs. severe (n = 7) SAH. During the course of a progressive fall in plasma sodium concentration (P = 0001), there was a delayed activation of renin,aldosterone which was inversely correlated with declining levels of plasma ANP/BNP (P < 0002). conclusions Excessive secretion of both ANP and BNP occurs in all patients after acute subarachnoid haemorrhage and is unrelated to severity, stress hormone activation or markers of cardiac injury. Inhibition of renin,aldosterone by cardiac hormones may impair renal sodium conservation and contribute to developing hyponatraemia. In the absence of evidence for activation of natriuretic peptides within the brain, the prompt and consistent increase in both ANP and BNP strongly supports the view that the heart is the source of increased natriuretic peptide secretion after acute subarachnoid haemorrhage. [source]