Incorporation of the Troponin Regulatory Complex of Post-ischemic Stunned Porcine Myocardium Reduces Myofilament Calcium Sensitivity in Rabbit Psoas Skeletal Muscle Fibers

Abstract

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 (v23.9±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±0.02v5.96±0.06), but there was a significant decrease in calcium sensitivity of tension after exchange of troponin from stunned LAD myocardium (pCa50=5.97±0.07v5.82±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.