Sarcoplasmic Reticulum Calcium Uptake

To investigate the mechanism underlying postischemic cardiac dysfunction (myocardial stunning), contractility and adenine nucleotide metabolism were studied in three groups of isolated perfused rabbit hearts (control, ischemic, and reperfused), whereas Ca2` uptake by the sarcoplasmic reticulum (SR) was measured in homogenates obtained from them. The hearts were Langendorff-perfused under constant pressure with Krebs-Henseleit solution at 37°C. Global normothermic ischemia was produced by closing the perfusion line. In the reperfused group, after 15 minutes of ischemia, Krebs-Henseleit solution was perfused for 10 minutes. Developed left ventricular pressure (control, 104±6.3 mm Hg) and left ventricular dP/dt (2,063±256.6 mm Hg sec-') were significantly decreased in reperfused hearts (left ventricular pressure, 78+5.9 mm Hg; left ventricular dP/dt, 1,339±216.3 mm Hg * sec-'). Myocardial ATP content (control, 13.6+0.98 ,umol/g dry wt) decreased during ischemia (4.5±+1.23 ,umol/g) but was restored to control level on reperfusion (11.8±0.68 ,umol/g). Maximum velocity of Ca2` uptake by the SR (V..) (control, 49.3±2.54 nmol min-1. mg'1) was significantly depressed by ischemia (36.3±+1.94 nmol* min'1 * mg'1) but was restored to the control value after a 10-minute reperfusion (45.3+0.79 nmol * min-1 * mg-'). Apparent dissociation constant Kca and the Hill coefficient for Ca2` uptake were not different between control, ischemia, and reperfusion. To test for the possible role of the SR Ca2+-release channel in the effect of ischemia and reperfusion, we measured Ca2` uptake after incubation of homogenates with 610 ,M ryanodine. The changes in Vm,. caused by ischemia and reperfusion were qualitatively similar to those observed in experiments without ryanodine (76.3+±5.08, 54.0±5.08, and 69.7+2.82 nmol * min` * mg-1 for control, ischemia, and reperfusion, respectively). These results suggest an effect of ischemia on the SR Ca2` pumping without an effect on the Ca2+-release process. The recovery of Ca2` uptake during reperfusion indicates that neither an altered uptake of Ca2` by the SR nor an abnormal function of the release channels is the major cause of myocardial stunning. (Circulation Research 1992;71:1123-1130)