Incorporation of the troponin regulatory complex of post-ischemic stunned porcine myocardium reduces myofilament calcium sensitivity in rabbit psoas skeletal muscle fibers.

Decreased calcium sensitivity of tension in post-ischemic myocardium is thought to be a mechanism of depressed function in stunning. The purpose of this study was to determine if the decrease in calcium sensitivity of tension results from ischemia and/or reperfusion-induced alterations in the thin filament regulatory troponin. The experiments utilized an open-chest porcine model of regional LAD myocardial stunning that has previously been shown to cause a decrease in calcium sensitivity of tension in permeabilized myocytes. Stunning was induced by 45 min of low-flow ischemia to the left anterior descending (LAD) coronary artery perfusion bed, which was followed by 30 min of reperfusion. Regional LAD function after reperfusion was 0.5+/-2.8%, as assessed by systolic wall thickening (v 23.9+/-4.1% thickening in control, P<0.001). Core biopsy samples from control circumflex and stunned LAD myocardium were acquired from each heart (n=9) after LAD reperfusion, and were used to obtain purified troponin complexes. Isometric tension-pCa relationships were measured in permeabilized psoas skeletal fibers before and after partial exchange of cardiac troponin from either control circumflex (n=6) or stunned LAD (n=8) myocardium for endogenous skeletal troponin. Calcium sensitivity of tension as assessed by pCa50 (i.e. pCa for half-maximal tension) was unchanged after exchange of troponin from control circumflex myocardium (pCa50=5. 98+/-0.02 v 5.96+/-0.06), but there was a significant decrease in calcium sensitivity of tension after exchange of troponin from stunned LAD myocardium (pCa50=5.97+/-0.07 v 5.82+/-0.05, P<0.05). We conclude that the decrease in calcium sensitivity of tension in postischemic stunned myocardium is, in part, due to ischemia and/or reperfusion-induced alterations in the cardiac troponin regulatory complex. Copyright 1998 Academic Press Limited.