RYANODINE RECEPTOR DYSFUNCTION IN PORCINE STUNNED MYOCARDIUM

We investigated the effects of myocardial stunning on the function of the two main Ca2+ transport proteins of the sarcoplasmic reticulum (SR ), the Ca2+-adenosinetriphosphatase and the Ca2+-release channel or ry anodine receptor. Regional myocardial stunning was induced in open-che st pigs (n = 6) by a 10-min occlusion of the left anterior descending coronary artery (LAD) and 2 h reperfusion. SR vesicles isolated from t he LAD-perfused region (stunned) and the normal left circumflex corona ry artery (LC)-perfused region were used to assess the oxalate-support ed Ca-45(2+) uptake, [H-3]ryanodine binding, and single-channel record ings of ryanodine-sensitive Ca2+-release channels in planar lipid bila yers. Myocardial stunning decreased LAD systolic wall thickening to 20 % of preischemic values. The rate of SR Ca-45(2+) uptake in the stunne d LAD bed was reduced by 37% compared with that of the normal LC bed ( P < 0.05). Stunning was also associated with a 38% reduction in the ma ximal density of high-affinity [H-3]ryanodine binding sites (P < 0.05 vs. normal LC) but had no effect on the dissociation constant. The ope n probability of ryanodine-sensitive Ca2+-release channels determined by single channel recordings in planar lipid bilayers was 26 +/- 2% fo r control SR (n = 33 channels from 3 animals) and 14 +/- 2% for stunne d SR (n = 21 channels; P < 0.05). This depressed activity of SR functi on observed in postischemic myocardium could be one of the mechanisms underlying myocardial stunning.