Mechanisms Underlying Myocardial Stunning

A bstract The effect of myocardial stunning on mitochondrial function was examined in rabbit hearts. After global normothermic ischemia followed by reperfusion, we previously found that mitochondrial high energy phosphate content was not significantly diminished. To determine whether myocardial stunning results from altered excitation‐contraction coupling, we examined function and calcium uptake by sarcoplasmic reticulum (SR). Hearts were subjected to global ischemia under normothermic conditions. Ischemic hearts had significantly lower velocity of Ca 2 + uptake by the SR (V max 36.3 ± 1.94 nmol/min per mg vs 49.3 ± 2.54 nmol/min per mg control) but velocity was restored by reperfusion. Similarly, myocardial ATP content was decreased during ischemia (4.5 ± 1.23 μmol/g dry weight vs 13.6 ± 0.98 μmol/g control) but returned to normal during reperfusion. Incubation of homogenates with 610 μM ryanodine did not alter the difference in V max between control, ischemic, or reperfused hearts, suggesting that ischemia affects SR Ca 2 + pumping without affecting Ca 2 + release. Recovery of calcium uptake during reperfusion also indicates that SR Ca 2 + ATPase function is not the major cause of myocardial stunning. Potentiated contractions were studied in a Langendorff heart model, revealing that postrest potentiation (PRP) and peak paired‐pulse potentiation (PPP) increase as a result of ischemia. On reperfusion, PPP also increased, but there was a decrease in PRP of left ventricular pressure (LVP) and LV dP/dt (PRP LV dP/dt = 127% preischemia vs 112% at 2 min postischemia), indicating than an impairment of an SR function other than Ca 2 + ATPase occurs during myocardial stunning.