Free radical scavengers in myocardial ischemia.
Reperfusion of ischemic myocardium is recognized as potentially beneficial because mortality is directly related to infarct size, and the latter is related to the severity and duration of ischemia. However, reperfusion is associated with extension of the injury that is additive to that produced by ischemia alone. The phenomenon of reperfusion injury is caused in large part by oxygen-derived free radicals from both extracellular and intracellular sources. The loci of oxygen-free radical formation include: myocardial sources (mitochondria), vascular endothelial sources (xanthine oxidase and other oxidases), or the inflammatory cellular infiltrate (neutrophils). Experimental studies have shown that free radical scavengers and agents that prevent free radical production can reduce myocardial infarct size in dogs subjected to temporary regional ischemia followed by reperfusion. Superoxide dismutase and catalase, which catalyze the breakdown of superoxide anion and hydrogen peroxide, respectively, limit experimental myocardial infarct size. The free radical scavenging agent N-(2-mercaptopropionyl)glycine (MPG) is reported to be effective in limiting infarct size. The ischemic-reperfused myocardium derives significant protection when experimental animals are pretreated with the xanthine oxidase inhibitor allopurinol. Neutrophils also serve as a significant source of oxygen-derived free radicals at the site of tissue injury. A number of agents have been shown to directly inhibit neutrophil-derived oxygen free radical formation and neutrophil accumulation within the reperfused myocardium. These agents include ibuprofen, nafazatrom, BW755C, prostacyclin, and iloprost. Thus, free radical scavengers and agents that prevent free radical formation can provide significant protection to the ischemic-reperfused myocardium.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000493:Allopurinol / Q000494:pharmacology; D009202:Cardiomyopathies / Q000503:physiopathology*; D002374:Catalase / Q000494:pharmacology; D003326:Coronary Circulation; D011464:Epoprostenol / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism*; D007052:Ibuprofen / Q000494:pharmacology; D016285:Iloprost; D009504:Neutrophils / Q000473:pathology; D010100:Oxygen / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D047069:Pyrazolones; D013482:Superoxide Dismutase / Q000494:pharmacology; D008625:Tiopronin / Q000494:pharmacology
D005609:Free Radicals; D011720:Pyrazoles; D047069:Pyrazolones; D000493:Allopurinol; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D008625:Tiopronin; D011464:Epoprostenol; D002374:Catalase; D013482:Superoxide Dismutase; D016285:Iloprost; C018845:nafazatrom; D010100:Oxygen; D007052:Ibuprofen