Onset of reduced Ca2+ sensitivity of tension during stunning in porcine myocardium

Recent data suggest that reduced Ca2+ sensitivity of tension is a mechanism of the post-is,hemic myocardial dysfunction, termed stunning, The purpose of the present study was to determine whether the decrease in myofilament Ca2+ sensitivity occurs during ischemia or during the subsequent period of reperfusion. Serial biopsies from an in vivo open-chest porcine model of regional LAD myocardial stunning (n = 6) were used to obtain in vitro measurements of Ca2+ sensitivity of tension in myocardium from the LAD bed. Regional ventricular myocardial function was assessed from percentage systolic myocardial wall thickening (%Th) and the load-independent end-systolic pressure wall thickness relation (ESPTR). Stunning was induced by 45 min of low now LAD ischemia (43 +/- 4 ml/min/100 gm) followed by 30 min of reperfusion with control aerobic now (117 +/- 7 ml/min/100 g). Endocardial biopsies were obtained from the LAD bed during pre-ischemia, ischemia (immediately prior to reperfusion), and post-ischemia (after 30 min of reperfusion), Biopsies were mechanically disrupted and single cell-sized preparations of permeabilized myocardium were attached to a force transducer to measure directly steady-state tension-pCa relationships. The %Th decreased to 7 +/- 11% of control during ischemia (P < 0.001) and returned to 30 +/- 11% of control in the post-ischemic stunned state (P < 0.001). Stunning resulted in a significant leftward shift of the ESPTR as compared to control, indicating depressed regional myocardial function. The pCa (-log[Ca2+]) for half maximal activation of tension, i.e. pCa(50), was 5.96 +/- 0.04 in control myocardium and was unchanged during ischemia (5.95 +/- 0.03), but significantly decreased to 5.82 +/- 0.04 upon reperfusion (P < 0.05). These data show that the decrease in Ca2+ sensitivity of tension associated with stunning occurs during reperfusion, and supports the idea that reperfusion injury is a mechanism of myocardial stunning. (C) 1996 Academic Press Limited