ALTERED DIASTOLIC [CA2+](I) HANDLING IN HUMAN VENTRICULAR MYOCYTES FROM PATIENTS WITH TERMINAL HEART-FAILURE

To investigate whether the slow diastolic decay of [Ca2+](i) in myocardium of patients with heart failure is a result of alterations of the Ca2+ adenosine triphosphatase of the sarcoplasmic reticulum or the sarcolemma, [Ca2+](i) transients were recorded in voltage-clamped ventricular cells isolated from hearts of patients with terminal heart failure or from undiseased donor hearts. To isolate the [Ca2+](i)-reuptake function of the sarcoplasmic reticulum, myocytes were dialyzed via the patch pipette with Na+-free solution and incubated in Ca2+-free and Na+-free solution to inhibit Na+/Ca2+ exchange. After superfusion with Ca2+-containing, Na+-free medium, the sarcoplasmic reticulum was loaded with Ca2+ through repetitive voltage-clamp pulses to +10 mV. Under these conditions, [Ca2+](i) decay was significantly slower in myocytes from patients with heart failure (538 +/- 66 msec) than in controls (305 +/- 16 msec; p < 0.05). After the addition of 10 mmol/L of caffeine, [Ca2+](i) levels did not show appreciable decay between two voltage-clamp pulses in diseased and undiseased myocytes. We conclude that diastolic decay of [Ca2+](i) in ventricular myocytes from patients with terminal heart failure is partially the result of a decreased rate of Ca2+ reuptake by the sarcoplasmic reticulum. Sarcolemmal Ca2+ adenosine triphosphatase does not contribute significantly to cytoplasmic [Ca2+](i) removal during an individual heartbeat.