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 isola ted ventricular myocytes from patients with terminal heart failure. Th e aim of this study was to evaluate if alterations of intracellular [C a2+](i) handling and triggering Ca2+ currents in cardiomyopathic hamst ers (strain BIO 14.6) with congestive heart failure might be similar t o changes found in myocytes of patients with terminal heart failure an d, therefore, if the hamster might serve as a model for heart failure in man. Cells were isolated from hearts of hamsters developing heredit ary cardiomyopathy (CMP) (strain BIO 14.6) at 12-14 months of age with overt signs of congestive heart failure. Results were compared with a ge-matched, undiseased control animals (CTRL). [Ca2+](i) transients an d Ca2+ currents were recorded simultaneously from isolated cells under voltaqe clamp perfused internally with the Ca2+ indicator, Fura-2. Ca2 + current densities in myocytes from CMP hamsters were -6.6 +/- 0.6 ve rsus -8.3 +/- 0.5 mu A/cm(2) (P < 0.05) in CTRL. Resting [Ca2+](i) lev els were not significantly different. Peak [Ca2+](i) transients were s ignificantly decreased in CMP cells (450 +/- 52 nM versus 1031 +/- 98 nM in CTRL, P < 0.05). The rate of diastolic [Ca2+](i) decay was slowe r 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 th at changes of intracellular [Ca2+](i) handling may play an important r ole in altered contractility of the myocardium of hamsters with heredi tary cardiomyopathy in the late stage of congestive heart failure. The cardiomyopathic hamster (strain BIO 14.6) has a limited value as a mo del for alterations of intracellular [Ca2+](i) handling in patients wi th terminal heart failure.