Role of mechanical and hormonal factors in cardiac remodeling and the biologic limits of myocardial adaptation.
Patients with chronic congestive heart failure manifest > or = 1 of the following abnormalities: diastolic dysfunction, systolic dysfunction, and arrhythmias. Diastolic dysfunction, one of the first symptoms to occur during hypertensive cardiopathy, depends on both active relaxation of the cardiac muscle and passive ventricular compliance. The ability of the ventricles to relax depends on normal calcium metabolism and adenosine triphosphate concentration. Ability to extrude intracellular calcium is depressed in the hypertrophied, overloaded heart as compared with the normal myocardium. Myocardial fibrosis is the major cause of increased diastolic ventricular stiffness. Left ventricular (LV) hypertrophy and myocardial fibrosis also greatly increase the likelihood of ventricular arrhythmias, in particular by prolonging the QRS interval and facilitating the occurrence of reentry arrhythmias. Findings in animal studies have indicated that such fibrosis, which involves excessive collagen deposition, is independent of LV hypertrophy and that LV hypertrophy does not necessarily result in myocardial fibrosis. Instead, the development of myocardial fibrosis is sensitive to circulating levels of both angiotensin II and aldosterone, and the fibrotic response to each of these substances is independent. The aldosterone antagonist spironolactone prevents myocardial fibrosis in several animal models, thus confirming the importance of aldosterone in the genesis of excessive collagen deposition.
Klug
D
D
Service de Cardiologie A, Hôpital Cardiologique, Lille, France.
Robert
V
V
Swynghedauw
B
B
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology; D006321:Heart / Q000502:physiology / Q000503:physiopathology*; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology*; D006728:Hormones / Q000502:physiology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000503:physiopathology; D016276:Ventricular Function / Q000502:physiology*
D006728:Hormones