Biochemical and morphological changes in myocardium during coronary occlusion and reperfusion in canine hearts: effects of propranolol on myocardial damage.
To clarify the mechanism of irreversible myocardial damage, we studied the relationship between ischaemic mitochondrial dysfunction and leakage of lysosomal enzymes, and the effects of propranolol on myocardial damage. Open chest anaesthetised dogs were divided into six groups: 30 min occlusion of the left anterior coronary artery (LAD); 2 h LAD occlusion; 2 h LAD occlusion after premedication with 0.3 mg.kg-1 propranolol; 30 min LAD occlusion/l h reperfusion; 2 h LAD occlusion/l h reperfusion; and 2 h LAD occlusion/l h reperfusion after propranolol premedication. After occlusion or reperfusion, heart mitochondria were prepared from normal and occluded or reperfused areas, and mitochondrial function (rate of oxygen consumption in State III, and respiratory control index) was measured polarographically. Myocardial tissue was fractionated and activities of lysosomal enzymes (N-acetyl-beta-glucosaminidase and beta-glucuronidase) were measured. Electron microscopic studies were performed. Thirty min occlusion induced mitochondrial dysfunction without leakage of lysosomal enzymes. Reperfusion for 1 h reversed these changes. However occlusion for 2 h induced mitochondrial dysfunction associated with the leakage of lysosomal enzymes, and mitochondrial dysfunction was not reversed by 1 h reperfusion. Propranolol reduced mitochondrial dysfunction after 2 h occlusion and prevented leakage of lysosomal enzymes. Mitochondrial function was fairly well maintained after 1 h reperfusion in dogs premedicated with propranolol. Structural changes in mitochondria were observed in the 2 h occlusion/l h reperfusion group, and were reduced by premedication with propranolol. These results suggest that irreversible injury of ischaemic mitochondria is closely linked with instability of lysosomal membranes, and that propranolol prevented irreversible myocardial mitochondrial dysfunction.
Ogawa
T
T
Department of Internal Medicine, Faculty of Medicine, University of Nagoya, Japan.
Sugiyama
S
S
Hieda
N
N
Ito
T
T
Satake
T
T
Ozawa
T
T
D000818:Animals; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D007425:Intracellular Membranes / Q000187:drug effects / Q000648:ultrastructure; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D011433:Propranolol / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
D011433:Propranolol