ALTERATIONS IN CALCIUM HANDLING IN CARDIAC-HYPERTROPHY AND HEART-FAILURE

There is conflicting data concerning the effects of cardiac hypertroph y and failure on L-type Ca2+ channel density, the amplitude of the int racellular Ca2+ transients, and the characteristics of Ca2+ sparks. Th ese discrepancies are probably due to multiple factors. First, the eff ects of cardiac hypertrophy on channel expression and cell adaptation are model dependent. Even within the same species, the mechanisms by w hich cardiac hypertrophy and heart failure are generated (genetic alte ration, pressure overload, volume overload, high rate pacing, etc.) in fluence the results obtained. Second, with many animal models and dise ased human hearts, the disease process is not uniformly distributed th roughout the myocardium. Third, the effects on L-type Ca2+ channel beh avior and SR function clearly depend on the extent of disease expressi on. Myocardial contractility increases with cardiac hypertrophy wherea s it decreases with heart failure. Thus, it is difficult to compare re sults from different models of hypertrophy and heart failure at differ ent stages of disease. More consistent data is likely to be obtained f rom longitudinal studies using a single animal model of disease. The c hallenge before us is to develop animal models that mimic human diseas e, which can be studied longitudinally during the progression of the d isease process. This approach coupled with continued improvement in Ca 2+ imaging and a greater understanding of normal E-C coupling, will en able us to identify precisely the abnormalities in E-C coupling that o ccur with the development of cardiac hypertrophy and heart failure and define the appropriate treatment modalities. (C) 1998 Elsevier Scienc e B.V.