Effects of thapsigargin and KCl on the O2 use of the excised blood-perfused rat heart.

We have already reported a curvilinear end-systolic pressure-volume relation and a linear oxygen consumption per beat (Vo2)-systolic pressure-volume area (PVA) relation of the left ventricle in the rat blood-perfused whole heart preparation. Recently, we have proposed that a PVA at an appropriate left-ventricular end-diastolic volume (0.15 ml/g), such as PVA0.15 and the Vo2 intercept (minimally loaded Vo2) of the Vo2-PVA relation, can be good indexes for assessing rat left-ventricular mechanoenergetics. The minimally-loaded Vo2 would mainly consist of Vo2 for Ca 2+ handling in the excitation-contraction (E-C) coupling and basal metabolism. However, the fraction of the Vo2 by the sarcoplasmic reticulum (SR) Ca2+-ATPase in the total Ca2+ handling Vo2 has not yet been examined. To study this for the first time, we investigated the effects of thapsigargin and KCl on left-ventricular mechanoenergetics. Blockade of the SR Ca2+ pump by thapsigargin (2.5 micromol/l) decreased PVA 0. 15 by 65% and decreased the Vo2 intercept by 40% without a change in the slope of the Vo2-PVA relation. We measured the basal metabolic Vo2 by intracoronary KCl and found a 75% decrease in the Vo2 intercept. We conclude that the minimally-loaded Vo2 mainly consists of Vo2 for Ca2+ handling in the E-C coupling (at least 40% is consumed by the SR Ca2+ ATPase) and basal metabolism (25%).