INTRACELLULAR CALCIUM HANDLING IN ISOLATED VENTRICULAR MYOCYTES FROM CARDIOMYOPATHIC HAMSTERS (STRAIN BIO-14.6) WITH CONGESTIVE-HEART-FAILURE

Intracellular [Ca2+](i) handling has been shown to be altered in isolated ventricular myocytes from patients with terminal heart failure. The aim of this study was to evaluate if alterations of intracellular [Ca2+](i) handling and triggering Ca2+ currents in cardiomyopathic hamsters (strain BIO 14.6) with congestive heart failure might be similar to changes found in myocytes of patients with terminal heart failure and, therefore, if the hamster might serve as a model for heart failure in man. Cells were isolated from hearts of hamsters developing hereditary cardiomyopathy (CMP) (strain BIO 14.6) at 12-14 months of age with overt signs of congestive heart failure. Results were compared with age-matched, undiseased control animals (CTRL). [Ca2+](i) transients and Ca2+ currents were recorded simultaneously from isolated cells undervoltaqe clamp perfused internally with the Ca2+ indicator, Fura-2. Ca2+ current densities in myocytes from CMP hamsters were -6.6 +/- 0.6 versus -8.3 +/- 0.5 mu A/cm(2) (P < 0.05) in CTRL. Resting [Ca2+](i) levels were not significantly different. Peak [Ca2+](i) transients were significantly decreased in CMP cells (450 +/- 52 nM versus 1031 +/- 98 nM in CTRL, P < 0.05). The rate of diastolic [Ca2+](i) decay was slower in cells from CMP animals (t1/2: 167 +/- 19 versus 109 +/- 16 ms P < 0.05). A moderate negative correlation was found between cell surface area and [Ca2+](i) transients (r= -0.42; P< 0.05). It is concluded that changes of intracellular [Ca2+](i) handling may play an important role in altered contractility of the myocardium of hamsters with hereditary cardiomyopathy in the late stage of congestive heart failure. The cardiomyopathic hamster (strain BIO 14.6) has a limited value as a model for alterations of intracellular [Ca2+](i) handling in patients with terminal heart failure.