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J Thorac Cardiovasc Surg 1998;115:450-454
© 1998 Mosby, Inc.

CARDIOPULMONARY SUPPORT AND PHYSIOLOGY

Physiologic Effects Of Extracellular Superoxide Dismutase Transgene Overexpression On Myocardial Function After Ischemia And Reperfusion Injury

From the Division of Cardiovascular and Thoracic Surgery and the Division of Pulmonary and Critical Care Medicine (R.J.F.), Duke University Medical Center, Durham, N.C.

Read at the Seventy-seventh Annual Meeting of The American Association for Thoracic Surgery, Washington, D.C., May 4-7, 1997.

Received for publication May 6, 1997; revisions requested May 30, 1997; revisions received Oct. 28, 1997; accepted for publication Oct. 29, 1997. Address for reprints: Edward P. Chen, MD, University of California, San Francisco, S-343, Box 0470, San Francisco, CA 94143.

Abstract

Objective: Myocardial injury after ischemia and reperfusion may be mediated, in part, by oxygen-derived free radicals. In this study the protective effects of extracellular superoxide dismutase overexpression were directly assessed in the hearts of transgenic mice, after ischemia and reperfusion injury, using an isolated work-performing murine heart preparation and computerized analysis of functional data.

Methods: A blinded study was performed to compare cardiac function in the hearts of both transgenic mice with a 3.5-fold overexpression of myocardial extracellular superoxide dismutase (n = 6, 22 to 26 gm) and littermate controls (n = 8, 22 to 26 gm). Preload-dependent cardiac output, contractility, heart rate, stroke work, and stroke volume were evaluated in the two groups before and after a 6-minute period of normothermic ischemia.

Results: No differences were found between extracellular superoxide dismutase hearts and control hearts in any parameter of myocardial function before ischemia. After ischemia, decreases in cardiac output occurred in both groups; however, this decrease was larger in control mice compared with extracellular superoxide dismutase mice. A higher percentage of recovery was also observed in the contractility, heart rate, stroke work, and stroke volume of extracellular superoxide dismutase hearts compared with control hearts.

Conclusion: After global normothermic ischemia and subsequent reperfusion, decreases in cardiac function occurred in both extracellular superoxide dismutase and control mice; however, a higher percentage of recovery was observed in the extracellular superoxide dismutase overexpressed hearts. These data suggest that extracellular superoxide dismutase transgene overexpression significantly improves preservation of myocardial function after ischemia and reperfusion injury.

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