Effects of Thapsigargin and KCl on the O2Use of the Excised Blood-perfused Rat Heart

Abstract We have already reported a curvilinear end-systolic pressure–volume relation and a linear oxygen consumption per beat (V o 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 PVA 0.15 and the V o 2 intercept (minimally loaded V o 2 ) of the V o 2 –PVA relation, can be good indexes for assessing rat left-ventricular mechanoenergetics. The minimally-loaded V o 2 would mainly consist of V o 2 for Ca 2+ handling in the excitation–contraction (E–C) coupling and basal metabolism. However, the fraction of the V o 2 by the sarcoplasmic reticulum (SR) Ca 2+ -ATPase in the total Ca 2+ handling V o 2 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 Ca 2+ pump by thapsigargin (2.5 μ mol/l) decreased PVA 0.15 by 65% and decreased the V o 2 intercept by 40% without a change in the slope of the V o 2 –PVA relation. We measured the basal metabolic V o 2 by intracoronary KCl and found a 75% decrease in the V o 2 intercept. We conclude that the minimally-loaded V o 2 mainly consists of V o 2 for Ca 2+ handling in the E–C coupling (at least 40% is consumed by the SR Ca 2+ ATPase) and basal metabolism (25%).