The protection of the acute ischemic myocardium: merits and demerits of the coronary reperfusion.

At first, in order to know the causes of reperfusion injury, we studied myocardial injury by reperfusion in comparison with by Ca overloading, and the salvage of the myocardium from reperfusion and from CA overloading by Ca antagonist, diltiazem (DIL), in 52 anesthetized open-chest dogs. In myocardial mitochondria (Mit), Ca content was increased and Mg content and oxidative phosphorylation (State III) were decreased both by 120 min reperfusion after 60 min occlusion and by Ca overloading. Ca and Mg contents and oxidative phosphorylation of Mit were similarly changed by reperfusion as by Ca overloading. Electron-microscopically, myocardial injury by Ca overloading resembled reperfusion injury. Therefore, Ca inflow to myocardial cells may be one of the determinant factors which induce reperfusion injury. Although myofibrils were disorganized and contraction band necrosis appeared in these two types of myocardial injury, amorphous densities and glanular densities which indicated the irreversible injury of Mit appeared only in reperfusion injury. Then, the myocardial injury be Ca overloading is suspected of being mainly composed of the injury of myofibrils. The myocardial injury be reperfusion and by Ca overloading was prevented by DIL. These facts suggest that DIL may suppress Ca inflow and Mg outflow to myocardial cells. Second, to know the effect of positive isotropic agents on pump failure in acute myocardial infarction, we studied the effect of dobutamine (DOB) on the ischemic myocardium and the salvage of the ischemic myocardium from DOB-induced injury by DIL in 39 anesthetized open-chest dogs. After occlusion, the regional mechanical function of the acute ischemic myocardium was rapidly lost and % systolic shortening was negative level. In this situation, myocardial PCO2 quickly increased and myocardial pH rapidly decreased. These parameters reached peak level after 20 min occlusion. Then, paradoxical improvement phenomenon appeared so that PCO2 decreased and pH increased after that. Myocardial blood flow measured by thermocouples was stable at almost 10% of the preoccluded level for 1 90 min occlusion. These data suggest that anaerobic metabolism and residual aerobic metabolism can not supply the ischemic myocardium with enough energy and that irreversible injury may appear in the ischemic myocardium. As myocardial pH was shown as a mirror-image of PCO2, the mechanism of CO2 and proton production in the ischemic myocardium may be closely related. When DOB was administered after 40 min occlusion, PCO2 increased and pH decreased again. Namely, the metabolic rate of these parameters rose again. But regional mechanical function was not recovered. When DIL was pretreated, PCO2 and pH were not significantly changed by DOB administration from 40 min after occlusion. Therefore, DOB may not always improve the cardiac function of the ischemic myocardium and may cause the ischemic myocardial injury to deteriorate. It is possible that DIL will delay the progression of ischemic myocardial injury due to DOB.