EFFECTS OF THAPSIGARGIN AND KCL ON THE O-2 USE OF THE EXCISED BLOOD-PERFUSED RAT-HEART

We have already reported a curvilinear end-systolic pressure-volume re lation and a linear oxygen consumption per beat (Vo(2))-systolic press ure-volume area (PVA) relation of the left ventricle in the rat blood- perfused whole heart preparation. Recently, we have proposed that a PV A at an appropriate left-ventricular end-diastolic volume (0.15 ml/g), such as PVA(0.15) and the Vo(2) intercept (minimally loaded Vo(2)) of the Vo(2)-PVA relation, can be good indexes for assessing rat left-ve ntricular mechanoenergetics. The minimally-loaded Vo(2) would mainly c onsist of Vo(2) for Ca2+ handling in the excitation-contraction (E-C) coupling and basal metabolism. However, the fraction of the Vo(2) by t he sarcoplasmic reticulum (SR) Ca2+-ATPase in the total Ca2+ handling Vo(2) has not yet been examined. To study this for the first time, we investigated the effects of thapsigargin and KCl on left-ventricular m echanoenergetics. Blockade of the SR Ca2+ pump by thapsigargin (2.5 mu mol/l) decreased PVA(0.15) by 65% and decreased the Vo(2) intercept b y 40% without a change in the slope of the Vo(2)-PVA relation. We meas ured the basal metabolic Vo(2) by intracoronary KCl and found a 75% de crease in the Vo(2) intercept. We conclude that the minimally-loaded V o(2) mainly consists of Vo(2) for Ca2+ handling in the E-C coupling (a t least 40% is consumed by the SR Ca2+ ATPase) and basal metabolism (2 5%). (C) 1998 Academic Press.