Effects of anti-free radical agents on Na+, Ca2+, and function in reperfused rat hearts.
The purpose of the present study was to determine whether the combined administration of superoxide dismutase (SOD) and catalase (CAT) or efforts to maintain the glutathione redox pathways with sulfhydryl agents could improve Na+ imbalance, reduce Ca2+ overload, and enhance recovery of function and metabolites upon reperfusion in isolated ischemic rat hearts, presumably by scavenging oxygen free radicals. After a 30-min exposure to zero-flow ischemia, left ventricular developed pressure (LVDP) and heart rate recovered to 31 and 81% of the preischemic value, respectively, ATP fell by approximately 40%, and 45Ca2+ uptake rose from 0.8 to 10.4 mumol/g dry tissue. A combination of SOD and CAT at low concentrations (5 X 10(4) and 7.5 X 10(4) U/l, respectively) had a beneficial effect on recovery of LVDP (to 59%), reperfusion 45Ca2+ uptake (to 7.9 mumol/g dry tissue), and recovery of Na+ imbalance. When sulfhydryl donors, such as glutathione, cysteine, N-acetyl-L-cysteine, or dithiothreitol, were administered 20 min before induction of ischemia, no significant protective effects were observed. These results indicated that the extracellular free radical scavengers, SOD and CAT, could attenuate partially the ionic imbalance in ischemic-reperfused myocardium and result in improved recovery of contractile function. Attempts to enhance the intrinsic scavenging system were not successful, suggesting that this system may not play an important role in disposing of free radicals.
Tani
M
M
Geisinger Clinic, Weis Center for Research, Danville, Pennsylvania 17822.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002374:Catalase / Q000494:pharmacology*; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology*
D005609:Free Radicals; D012964:Sodium; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D002118:Calcium