BACKGROUND: Superoxide dismutase (SOD) is a potent candidate for myocardial protection against ischemia-reperfusion injury; however, its clinical significance by means of exogenous administration remains controversial. METHODS: To determine a role of endogenously overexpressed manganese SOD (Mn-SOD) in myocardial tolerance, rat hearts were transfected with Mn-SOD gene (group M) or no gene (group C) through intracoronary infusion of hemagglutinating virus of Japan (HVJ) liposome. Each group was divided into two subgroups to be subjected to ischemia-reperfusion using Langendorff apparatus with (subgroups M+ and C+) or without (M- and C-) administration of recombinant SOD. RESULTS: Mn-SOD overexpression was confirmed in M with ELISA, activity measurement, and immunohistochemistry. The highest recoveries of maximum and minimum dp/dt and the least creatine phosphokinase (CPK) leakage were observed in M+. These recoveries were higher in M- than in C- and C+. CONCLUSIONS: Thus, endogenous overexpression of Mn-SOD improved myocardial tolerance and its protective effect was enhanced by exogenous administration of SOD. These results suggest a possible strategy for myocardial protection with SOD: a combination of endogenous introduction through gene transfer with exogenous administration.
BACKGROUND: Superoxide dismutase (SOD) is a potent candidate for myocardial protection against ischemia-reperfusion injury; however, its clinical significance by means of exogenous administration remains controversial. METHODS: To determine a role of endogenously overexpressed manganese SOD (Mn-SOD) in myocardial tolerance, rat hearts were transfected with Mn-SOD gene (group M) or no gene (group C) through intracoronary infusion of hemagglutinating virus of Japan (HVJ) liposome. Each group was divided into two subgroups to be subjected to ischemia-reperfusion using Langendorff apparatus with (subgroups M+ and C+) or without (M- and C-) administration of recombinant SOD. RESULTS:Mn-SOD overexpression was confirmed in M with ELISA, activity measurement, and immunohistochemistry. The highest recoveries of maximum and minimum dp/dt and the least creatine phosphokinase (CPK) leakage were observed in M+. These recoveries were higher in M- than in C- and C+. CONCLUSIONS: Thus, endogenous overexpression of Mn-SOD improved myocardial tolerance and its protective effect was enhanced by exogenous administration of SOD. These results suggest a possible strategy for myocardial protection with SOD: a combination of endogenous introduction through gene transfer with exogenous administration.
Authors: Y Kobayashi; N Fukushima; Y Sawa; S Ohtake; G Matsumiya; K Horiguchi; N Kawaguchi; N Matsuura; Y Kaneda; H Matsuda Journal: Jpn J Thorac Cardiovasc Surg Date: 2001-09