Efficacy of adenoviral gene transfer with manganese superoxide dismutase and endothelial nitric oxide synthase in reducing ischemia and reperfusion injury

Objective: Both superoxide dismutase (SOD), a free radical scavenger, and n itric oxide (NO), a vasodilator with anti-inflammatory properties, have bee n shown to protect the myocardium from reperfusion injury. They are known t o interact in vivo, the influence of which on myocardial protection has not been studied. Methods: Four groups of rats (n = 7, per group) were subject ed to experimental infarction following injections into the anterior wall o f the left ventricle with adenoviral vector encoding P-galactosidase (group A), eNOS (group B), Mn-SOD (group C) and both eNOS and MnSOD (group D). He arts were assessed for protein expression and size of infarction. Results: Efficiency of gene up regulation was confirmed by immunostaining for eNOS a nd Mn-SOD, and X-gal staining for P-gal respectively. In B and D, overexpre ssion of eNOS was demonstrated in cardiac myocytes in addition to that in t he endothelium, while in C and D, Mn-SOD was overexpressed in mainly cardio myocytes. Infarct size was 49.7 +/- 4.8% in A, and was significantly reduce d in the other groups (29.8 +/- 2.7%, 21.8 +/- 2.5% and 24.9 +/- 2.4% in B, C and D respectively). Conclusion: Adenoviral gene transfer of Mn-SOD was superior to eNOS in reducing the extent of in vivo ischemia-reperfusion inj ury in the rat heart in our model. The effect of combined application of Mn -SOD and eNOS was not different from their individual effect. (C) 2001 Else vier Science B.V. All rights reserved.