INCORPORATION OF THE TROPONIN REGULATORY COMPLEX OF POSTISCHEMIC STUNNED PORCINE MYOCARDIUM REDUCES MYOFILAMENT CALCIUM SENSITIVITY IN RABBIT PSOAS SKELETAL-MUSCLE FIBERS

Decreased calcium sensitivity of tension in post-ischemic myocardium i s thought to be a mechanism of depressed function in stunning. The pur pose of this study was to determine if the decrease in calcium sensiti vity of tension results from ischemia and/or reperfusion-induced alter ations in the thin filament regulatory troponin, The experiments utili zed an open-chest porcine model of regional LAD myocardial stunning th at has previously been shown to cause a decrease in calcium sensitivit y of tension in permeabilized myocytes, Stunning was induced by 45 min of low-now ischemia to the left anterior descending (LAD) coronary ar tery perfusion bed, which was followed by 30 min of reperfusion. Regio nal LAD function after reperfusion was 0.5 +/- 2.8%, as assessed by sy stolic wall thickening (v 23.9 +/- 4.1% thickening in control, P < 0.0 01). Core biopsy samples from control circumflex and stunned LAD myoca rdium were acquired from each heart (n = 9) after LAD reperfusion, and were used to obtain purified troponin complexes. Isometric tension-pC a relationships were measured in permeabilized psoas skeletal fibers b efore and after partial exchange of cardiac troponin from either contr ol 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 o f troponin from control circumflex myocardium (pCa(50) = 5.98 +/- 0.02 v 5.96 +/- 0.06), but there was a significant decrease in calcium sen sitivity of tension after exchange of troponin from stunned LAD myocar dium (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 st unned myocardium is, in part, due to ischemia and/or reperfusion-induc ed alterations in the cardiac troponin regulatory complex. (C) 1998 Ac ademic Press Limited.