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-now 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 pCa(50) (i.e. pCa for half-maximal tension) was unchanged after exchange of troponin from control circumflex myocardium (pCa(50) = 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 (pCa(50) = 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. (C) 1998 Academic Press Limited.