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 nitric oxide (NO), a vasodilator with anti-inflammatory properties, have been shown to protect the myocardium from reperfusion injury. They are known to interact in vivo, the influence of which on myocardial protection has not been studied. Methods: Four groups of rats (n = 7, per group) were subjected to experimental infarction following injections into the anterior wall of 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). Hearts were assessed for protein expression and size of infarction. Results: Efficiency of gene up regulation was confirmed by immunostaining for eNOS and Mn-SOD, and X-gal staining for P-gal respectively. In B and D, overexpression of eNOS was demonstrated in cardiac myocytes in addition to that in the endothelium, while in C and D, Mn-SOD was overexpressed in mainly cardiomyocytes. Infarct size was 49.7 +/- 4.8% in A, and was significantly reduced 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 injury 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 Elsevier Science B.V. All rights reserved.