[New aspects of the pathophysiology of heart failure].
The progression of heart failure is related to activation of neuroendocrine hormone systems. On the level of the myocardium, they contribute to hypertrophy, dilation and remodeling of the ventricles. In addition, vascular alterations with endothelial dysfunction and alterations of skeletal muscle contribute to clinical symptoms of heart failure patients. Changes in ventricular geometry during the progression of cardiac diseases are associated with specific subcellular alterations on the level of the myocytes. Especially, disturbed intracellular Ca2+ handling resulting in altered excitation contraction coupling may lead to impaired systolic and diastolic function. Disturbed Ca2+ homeostasis has been associated with reduced re-uptake capacity of the sarcoplasmic reticulum for Ca2+ and an enhanced activity of the sarcolemmal Na+/Ca2+ exchange. In consequence, alterations in force-frequency behavior were attributed to a decline in intracellular Ca2+ transients at higher stimulation rates. The reduced expression of myocardial beta-adrenoceptors and alterations on the level of the G-proteins result in a reduced activity of adenylate cyclase and reduction in intracellular cAMP content of the myocytes. In consequence, reduced phosphorylation of intracellular functional proteins in the failing human heart contributes to altered Ca2+ handling. The Frank-Starling-mechanism seems to be unaltered in failing isolated human myocardium. Endothelin and angiotensin may contribute to the regulation of myocardial contractility in the human heart, but their functional relevance in the regulation of myocardial contractility under clinical conditions remains to be evaluated.
Pieske
B
B
Abteilung für Kardiologie und Pneumologie, Zentrums Innere Medizin, Georg-August-Universität Göttingen, Deutschand.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006333:Heart Failure / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology; D009490:Neurosecretory Systems / Q000503:physiopathology; D019831:Sodium-Calcium Exchanger / Q000502:physiology
D019831:Sodium-Calcium Exchanger; D002118:Calcium
Neue Aspekte zur Pathophysiologie der Herzinsuffizienz.