Superoxide dismutase plus catalase improves post-ischaemic recovery in the diabetic heart.
Streptozotocin induced diabetic rat hearts were perfused under constant flow conditions with or without 1 x 10(5) U.litre-1 each of superoxide dismutase and catalase (SOD + CAT). Total global ischaemia was produced for 20 min followed by 30 min of reperfusion at pre-ischaemic flow rates. After 5 min of reperfusion, isovolumic LV developed pressure was reduced in diabetic hearts, at 22 (SEM 11)% of baseline v 67(12)% in controls, with increased frequency of ventricular fibrillation (VF) (3/10 v 10/11 hearts). SOD + CAT improved isovolumic LV developed pressure to 67(8)% of baseline during early reperfusion of diabetic hearts but did not affect non-diabetic hearts. SOD + CAT also increased the adenylate energy charge potential in post-ischaemic diabetic hearts to 0.826(0.011) v 0.781(0.012) in diabetic controls, and reduced the incidence and duration of reperfusion induced VF in diabetic hearts. SOD + CAT augmented the production of prostacyclin in coronary effluents during early reperfusion of diabetic hearts, from (baseline) 11.5(1.7) to 18.1(3.0) ng.min-1.g-1 at 2 min, compared with 11.1(1.6) to 12.5(1.9) ng.min-1.g-1 at same interval in diabetic controls. Indomethacin prevented the protective effect of the free radical scavengers on function and VF. In contrast, perfusion with the prostacyclin analogue, iloprost (3 x 10(-8) M), alone completely prevented early post-ischaemic dysfunction and reduced VF from 559(172) to 16(8) s. Oxygen derived free radicals may mediate reperfusion induced contractile dysfunction and VF in acutely diabetic hearts following brief episodes of myocardial ischaemia. The beneficial effects of SOD + CAT appear to be mediated mainly by an increase in prostacyclin production during early reperfusion.
Pieper
G M
GM
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
D000818:Animals; D002374:Catalase / Q000627:therapeutic use*; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005609:Free Radicals; D066298:In Vitro Techniques; D015425:Myocardial Reperfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000627:therapeutic use*
D005609:Free Radicals; D002374:Catalase; D013482:Superoxide Dismutase