Myocardial Superoxide Dismutase Research Articles

Captopril and ramiprilat protect against free radical injury in isolated working rat hearts

The protection of angiotensin converting enzyme (ACE) inhibitors, captopril and ramiprilat, against free radical-mediated myocardial injury were studied in isolated working rat hearts. Free radicals were generated by electrolysis of Krebs-Henseleit solution with 10 mA direct current for 1 min. Both captopril (360 μmol/l) and ramiprilat (12.5 μmol/l) significantly reduced the decrease of left ventricle dP dt′ max , coronary flow (CF), myocardial superoxide dismutase (SOD) and creatine kinase (CK) activities and the elevation of S-T segment of epicardial ECG as well as the rise of myocardial malondialdehyde (MDA) content caused by electrolysed perfusate. Captopril afforded a dose-dependent protection on cardiac functions with various concentrations of 45, 90, 180 and 360 μmol/l. Iloprost (30 nmol/l), a stable mimetic of prostacyclin, could also alleviate free radical-mediated myocardial injuries. All the beneficial effects of ramiprilat (12.5 μmol/l) were abolished by the administration of indomethacin (5 μmol). In contrast, captopril (90 μmol/l) still exhibited significant protective effects after indomethacin (9 μmol) was administered, though these protective effects were insignificantly weakened. In order to assess the role of sulfhydryl (-SH) group in the effects of captopril, a SH-containing drug S8 and a disulfide DG4, both are deficient in ACE inhibitory properties in vitro, were examined. Data showed that S8 (180 μmol/l) provided a significant protection while DG4 showed no protective effect. It is concluded that ACE inhibitors can protect against free radical-induced myocardial damage. Ramiprilat, a non-SH-containing ACE inhibitor, inhibits free radical-induced damages mainly by stimulation of prostacyclin synthesis and/or release. In addition to this effect, captopril, a SH-containing ACE inhibitor, may exert additional anti-free radical effects by a mechanism which is probably related to the sulfhydryl group.

Effect of oxygen tension on the anti-oxidant enzyme activities of tetralogy of Fallot ventricular myocytes

Since the chronically cyanotic tetralogy of Fallot (TOF) myocardium is more sensitive to reperfusion injury after cardiac surgery than the adult myocardium, we decided to study the regulation of myocardial superoxide dismutase (SOD), catalase and glutathione peroxidase by oxygen tension. TOF myocytes were cultured at a P o 2 of 150 mmHg for 30 days to establish the culture. The cells were then cultured at P o 2 of 150 and 40 mmHg and the myocyte antioxidant enzymes measured at days 3, 7, 14 and 21. On day 21 the myocytes cultured at P o 2 of 40 mmHg were then cultured at 150 mmHg and SOD and catalase activities measured on days 28 and 35. Although there were no differences in the rates of incorporation of 35S-methionine into the myocytes at either P o 2 on these days, the myocytes scavenger enzyme levels were significantly higher by day 14 when cultured at a P o 2 of 150 mmHg than at a P o 2 of 40 mmHg. With the increase in oxygen tension from 40 to 150 mmHg, SOD and catalase activities increased significantly by day 35. The myocytes cultured at P o 2 40 mmHg were more sensitive by day 7 to an hypoxanthine-xanthine oxidase generated free radical injury than the P o 2 150 mmHg cultured cells. The regulation of these enzyme activities by oxygen tension and the increased sensitivity to free radical injury of the myocytes cultured at an oxygen tension of 40 mmHg provide putative evidence that the chronically cyanotic myocardium may be less well protected than the normally perfused myocardium against oxygen-mediated free radical injury and be at higher risk for cardiovascular surgery.