Neurohormonal Hypothesis in Heart Failure

A ccording to the neurohormonal model, heart failure is a syndrome that develops because an initial heart injury activates endogenous neurohormonal systems that exert a deleterious effect to the myocardium and on the circulation. This new model regards heart failure primarily as a neurohormonal disorder with main pathophysiologic abnormality the activation of various neurohormonal systems. Arterial underfilling wether from high or low output heart failure is the predominant determinant of the neurohormonal hypothesis since it leads to activation of various compensatory competitive mechanisms in order to restore intrarterial volume and thus preserve blood flow to organs like brain and kidneys. In detail this arterial underfilling is sensed by certain mechanoreceptors on the highpressure side of the circulation like the left ventricle, the carotid sinus, the aortic arch and the renal afferent arterioles. Arterial underfilling stimulates these mechanoreceptors and afferent and efferent signals leads to activation of several compensatory – competitive mechanisms which restore arterial circulatory integrity (Figure 1). These compensatory competitive mechanisms are: 1. Activation of the sympathetic adrenergic system. 2. Activation of the renin – angiotensin – aldosterone system (RAAS). 3. Non-osmotic vasopressin release. 4. Stimulation of thirst. 5. Release of biologically active molecules like natriuretic peptides, prostaglandins, endothelins, nitric oxide and cytokines. The use of two contradictory terms to describe the above mechanisms, ie compensatory – competitive is due to that, these mechanisms when activated for a short term are truly compensatory since they appear able to sustain and modulate LV function in a setting of arterial underfilling, whereas if activated for long term like in chronic heart failure, are competitive since they adversely affect the hemodynamic condition and exert deleterious effect on the heart and on the circulation (Figure 2). Two are the main key points of the neurohormonal hypothesis: a. These mechanisms exert their deleterious effects on the heart and the circulation independently of the hemodynamic status of the patient. b. The long-term activation of these mechanisms leads to overexpression of biologically active molecules which in turn produce direct end-organ damage in the heart (LV remodeling) and the circulation (endothelium, kidneys) leading to progression of heart failure. In other words, the activation of these compensatory – competitive mechanisms accordingly to neurohormonal hypothesis is not simply the result of cardiac dysfunction but can also contribute to the development of cardiac dysfunction. In terms of the neurohormonal hypothesis, the means by which the above compensatory – competitive mechanisms accomplish their short-term beneficial effects as well as their long-term adverse effects is the overexpression of portfolios Neurohormonal Hypothesis in Heart Failure