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 by Ca overloading is suspected of being mainly composed of the injury of myofibrils. The myocardial injury by 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 inotropic 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 a 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Miura
M
M
Second Department of Internal Medicine, Akita University School of Medicine, Japan.
Matsu-Oka
H
H
Kanazawa
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002122:Calcium Chloride / Q000009:adverse effects; D002245:Carbon Dioxide / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism / Q000517:prevention & control*; D004110:Diltiazem / Q000494:pharmacology; D004280:Dobutamine / Q000009:adverse effects; D004285:Dogs; D006863:Hydrogen-Ion Concentration; D008274:Magnesium / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D015425:Myocardial Reperfusion / Q000009:adverse effects*; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D010085:Oxidative Phosphorylation / Q000187:drug effects
D002245:Carbon Dioxide; D004280:Dobutamine; D004110:Diltiazem; D008274:Magnesium; D002122:Calcium Chloride; D002118:Calcium