Pathophysiology and therapy of heart failure, new insights and developments. Part II. Cardiac and peripheral alterations during progressive heart failure.
The initial phase of heart failure is characterized by peripheral mechanisms such as sympathetic stimulation and neuroendocrine activation, which attempt to compensate for the decline in cardiac pump function and tissue underperfusion. However, the resulting vasoconstriction and sodium and water retention lead to a vicious circle wherein the subsequent increase in afterload and in circulating volume eventually leads to a further decline in cardiac output, blood pressure and tissue perfusion on the one hand, and to systemic and pulmonary congestion on the other. Intrinsic cardiac alterations during progressive failure preclude efficient cardiac compensation. These alterations include downregulation of the beta-receptor, upregulation of its inhibitor subunit (Gi), changes in adenylate cyclase and phosphodiesterase activity, depletion of catecholamine stores, overexpression of abnormal contractile proteins and inherent changes in ATP-ase activity, a derangement of calcium cycling by the sarcoplasmic reticulum, and abnormalities in myocardial energy production and transfer. These multiple changes underline the importance of the heart per se in heart failure. However, it should be realized that the heart failure syndrome depends to a large extent on various intrinsic alterations in peripheral tissue function. Renal impairment, baroreceptor dysfunction, neuroendocrine activation, abnormalities in skeletal muscle metabolism and in vascular control, and electrolyte disturbances all add to the overall clinical picture. Both cardiac and peripheral alterations in heart failure will markedly affect future diagnostic and therapeutic approaches to this syndrome.
Remme
W J
WJ
Zuiderziekenhuis and STICARES Cardiovascular Research Foundation, Rotterdam, Netherlands.
D000222:Adaptation, Physiological; D000804:Angiotensin II / Q000097:blood / Q000502:physiology; D000242:Cyclic AMP / Q000097:blood / Q000502:physiology; D006333:Heart Failure / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D006439:Hemodynamics; D006706:Homeostasis; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology*; D009638:Norepinephrine / Q000097:blood / Q000502:physiology; D010101:Oxygen Consumption; D010727:Phosphoric Diester Hydrolases / Q000502:physiology; D011311:Pressoreceptors / Q000502:physiology; D012079:Renal Circulation
D000804:Angiotensin II; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D009638:Norepinephrine