Effects of Thapsigargin and KCl on the O2Use 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 (V 2)-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 PVA0.15and the V 2intercept (minimally loaded V 2) of the V 2–PVA relation, can be good indexes for assessing rat left-ventricular mechanoenergetics. The minimally-loaded V 2would mainly consist of V 2for Ca2+handling in the excitation–contraction (E–C) coupling and basal metabolism. However, the fraction of the V 2by the sarcoplasmic reticulum (SR) Ca2+-ATPase in the total Ca2+handling V 2has 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 (2.5μmol/l) decreased PVA0.15by 65% and decreased the V 2intercept by 40% without a change in the slope of the V 2–PVA relation. We measured the basal metabolic V 2by intracoronary KCl and found a 75% decrease in the V 2intercept. We conclude that the minimally-loaded V 2mainly consists of V 2for Ca2+handling in the E–C coupling (at least 40% is consumed by the SR Ca2+ATPase) and basal metabolism (25%).