Protection against postischemic myocardial dysfunction in anesthetized rabbits with scavengers of oxygen-derived free radicals: superoxide dismutase plus catalase, N-2-mercaptopropionyl glycine and captopril.
Postischemic myocardial dysfunction in canine myocardium has been reported to be reduced by scavengers of oxygen-derived free radicals. One potential source of oxygen-derived free radicals in canine myocardium is xanthine oxidase, but human and rabbit myocardium either lack or possess very low levels of this enzyme. Therefore, the effects of scavengers of oxygen-derived free radicals on postischemic myocardial dysfunction produced by 15 min of ischemia and 3 h of reperfusion were evaluated in vivo in the rabbit. Superoxide dismutase (SOD) (45,000 U/kg) and catalase (55,000 U/kg) were given into the left atrium 10 min before ischemia, and followed by an additional 45,000 U/kg of SOD and 55,000 U/kg of catalase given over 85 min. This treatment reduced postischemic myocardial dysfunction, as did sulfhydryl-containing free radical scavengers N-2-mercaptopropionyl glycine (4 mg/kg, i.v.) and captopril (3 mg/kg, i.v.) given 5 min before and 60 min after reperfusion. SOD given alone at the same dose was ineffective, as was enalaprilat (0.3 mg/kg, i.v.), an angiotensin-converting enzyme inhibitor that does not scavenge oxygen-derived free radicals. Thus, postischemic myocardial dysfunction was reduced by scavengers of oxygen-derived free radicals in vivo in a species that is deficient in myocardial xanthine oxidase. This suggests that oxygen-derived free radicals derived from a source other than xanthine oxidase play a role in postischemic myocardial dysfunction.
Koerner
J E
JE
Marion Merrell Dow Research Institute, Cincinnati, Ohio 45215.
Anderson
B A
BA
Dage
R C
RC
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D015773:Enalaprilat / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers; D006339:Heart Rate / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D010100:Oxygen / Q000378:metabolism*; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology; D008625:Tiopronin / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects
D004731:Endotoxins; D016166:Free Radical Scavengers; D002216:Captopril; D008625:Tiopronin; D002374:Catalase; D013482:Superoxide Dismutase; D015773:Enalaprilat; D010100:Oxygen