Mechanism of mitochondrial damage after coronary reperfusion.
We investigated the mechanism of the reperfusion-accelerated mitochondrial dysfunction. To clarify this mechanism, we performed the following experiments using 40 mongrel dogs. Experiment I: Prostaglandin (PG) E and F2 alpha levels in the great cardiac vein (GCV) were examined before, during occlusion and after reperfusion of the left anterior descending coronary artery (LAD). Experiment II: Heart mitochondria were prepared from the normal area and the occluded or the reperfused area after 15 min of the LAD occlusion, or after 5 min of reperfusion following the occlusion with or without premedication of indomethacin. The PGE level in the GCV did not change significantly during occlusion, but increased significantly soon after reperfusion. Mitochondrial dysfunction was caused by occlusion and further accelerated by reperfusion. The PG E level in mitochondria isolated from the reperfused area increased significantly. Indomethacin significantly prevented both the increase in PG E and the acceleration of mitochondrial dysfunction by reperfusion. These results suggest that the increase in PG E level is closely related to the reperfusion-accelerated mitochondrial dysfunction, and that premedication with indomethacin significantly prevented the extension of mitochondrial dysfunction induced by coronary reperfusion.
D000818:Animals; D003326:Coronary Circulation; D003327:Coronary Disease / Q000503:physiopathology; D003331:Coronary Vessels; D015237:Dinoprost; D004285:Dogs; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008929:Mitochondria, Heart / Q000502:physiology*; D010477:Perfusion; D011458:Prostaglandins E / Q000097:blood; D011460:Prostaglandins F / Q000097:blood
D011458:Prostaglandins E; D011460:Prostaglandins F; D015237:Dinoprost; D007213:Indomethacin