ALTERED CALCIUM SENSITIVITY OF ISOMETRIC TENSION IN MYOCYTE-SIZED PREPARATIONS OF PORCINE POSTISCHEMIC STUNNED MYOCARDIUM

Postischemic ventricular myocardial dysfunction, termed stunning, is characterized by a persistent but ultimately reversible depression of contractile function. The present study was undertaken to investigate the possibilities that reduced contractile force in stunning is due to a decrease in maximal tension-generating capability or to a decrease in the Ca2+ sensitivity of the myofilaments. The experiments combine an in vivo open-chest porcine heart model of stunning (n=5) with in vitro measures of myocyte myofilament calcium sensitivity from these same hearts. Regional myocardial function in the left anterior descending coronary artery (LAD) perfusion bed of porcine hearts was measured with transmural ultrasonic crystals. The protocol was 45 minutes of low-flow LAD ischemia at 40% of control flow, followed by 30 minutes of postischemic reperfusion at control aerobic flow. Percent systolic wall thickening decreased to 8 +/- 5% of control during ischemia (p<0.05) and returned to 38 +/- 8% of control in the postischemic stunned state (p<0.05). Serial endocardial biopsies were obtained from the preischemic and postischemic myocardium in the LAD perfusion bed and from the aerobically perfused myocardium in the circumflex bed. The biopsies were mechanically disrupted, and myocyte-sized preparations of permeabilized myocardium were attached to a force transducer and a length-changing device to allow for direct measurement of steady-state tension-pCa (i.e., -log[Ca2+]) relations. The pCa for half-maximal activation of tension, i.e., pCa50, in LAD myocardium decreased from 5.88 +/- 0.05 before ischemia to 5.69 +/- 0.03 after ischemia (p<0.05); however, maximal Ca2+-activated tension and the slope of the tension-pCa relation were unaffected by the ischemic episode. We conclude that the Ca2+ sensitivity of isometric tension is reduced and accounts at least in part for the depressed contractile function of stunned myocardium.