RELATIONSHIP BETWEEN ENDOCRINE AND HEMODYNAMIC-ALTERATIONS IN HEART-FAILURE

In contradiction earlier viewpoints, cardiac-failure cannot be defined as a purely hemodynamic problem nor as only a cardiac problem. On the other hand decreased cardiac output (Co), increased filling pressure, increased wallstress and myocardial O2-consumption (MVO2) are the cause of many humoral counterregulations. Therefore, it is not always certain if the observed alterations are the causes or consequences of cardiac failure. The systemic counter-regulations will be modulated by desensitized cardiopulmonary mechanoreceptors, followed by decreased inhibition of central vasomotoric stimuli and endothelial and endocardial function, by altered signal transmission, as well as by altered gene expression within the myocytes. Depending on the degree of insufficiency, it may be attempted, by increase of the preload and of the contractility, to restore the hemodynamic basic situation. Such an attempt is based upon increased activity of the sympathetic nervous system, stimulation of the renin-angiotensin-aldosterone-system (RAAS) or the increased level of ADH. The reduced contractility and response of the myocytes, caused by the downregulation of beta-1-receptors and G(s)-proteins, as well as by the upregulation of G(i)-proteins, and the increased afterload with increased MVO2 and decreased CO all lead to a vicious circle. There are only some mechanisms that are directed against these regulations. The decreased response of the myocardium to endogenous catecholamines, the stimulation of ANP-secretion, as well of the prostaglandin-secretion are among the favorable regulations. They cause increase of natri- and diuresis, improved renal perfusion, vasodilatation, and inhibition of the RAAS and ADH-secretion with reduction of true thirst and craving for salt. As a consequence, preload, afterload, and MVO2 will be decreased, and CO can be slightly increased. Finally, without any therapeutic intervention, the overwhelming unfavorable regulations will lead to the breakdown of the myocardium. Therapeutic interventions in the case of cardiac failure have to target both hemodynamic and humoral regulations, as well as alterations at the cellular and molecular level.