Degradation of the cardiac sarcoplasmic reticulum in acute myocardial ischemia.

The degradation of the sarcoplasmic reticulum (SR) in acute myocardial ischemia was studied with references to the regional irreversibility and to the mechanism of ischemic degradation by the measurements of Ca++-stimulated ATPase activity and composition of the major ATPase protein of the SR and activity of cathepsin B of the SR and lysosome (Ly) fractions. Ca++-stimulated ATPase activity decreased to 66% of that of the nonischemic portion at 20 min after coronary ligation in the subendocardium (Endo) and to 44% at 30 min in the subepicardium (Epi). Composition of the major ATPase protein decreased to 55% and 73% at 30 min in Endo and Epi, respectively. In both SR and Ly fractions cathepsin B exhibited the maximal activity at 6.0-6.5, and pH dependent. And incubation of the SR at pH 6.0 induced the degradation of the ATPase protein quite similarly to that in vivo ischemia. These results suggest that the degradation of the SR membrane of ischemic myocardial cells begins earlier in Endo 20 to 30 min after the cease of the coronary blood flow, and extends to Epi later. Cathepsin B is strongly conceivable to play an initial role of necrotic process of the ischemic myocardial cells by activation inside of the SR in ischemic acidic state.