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(Circulation. 2002;105:981.)
© 2002 American Heart Association, Inc.

Basic Science Reports

Postischemic Recovery of Contractile Function is Impaired in SOD2^+/- but Not SOD1^+/- Mouse Hearts

Gregory K. Asimakis, PhD; Scott Lick, MD; Cam Patterson, MD

From the Department of Surgery, Division of Cardiothoracic Surgery, the University of Texas Medical Branch (G.K.A., S.L.), Galveston, Tex, and the Carolina Cardiovascular Biology Center and Departments of Medicine, Pharmacology, and Cell and Developmental Biology (C.P.), University of North Carolina, Chapel Hill, NC.

Correspondence to Gregory K. Asimakis, PhD, Surgical Research Building, Rt 0828, The University of Texas Medical Branch, Galveston, TX 77555-0828. E-mail Gasimaki{at}utmb.edu

Background— Reactive oxygen species (ROS) contribute to myocardial stunning. Superoxide dismutase (SOD) is a major defense mechanism against ROS. The purpose of this study was to evaluate the contributions of cytosolic (SOD1) and mitochondrial (SOD2) isoforms to protect against myocardial stunning.

Methods and Results— Isolated hearts from wild-type, heterozygous (+/-) SOD1 and SOD2 knockout mice received 30 minutes of ischemia followed by 60 minutes of reperfusion. After 60 minutes of reperfusion, the heart rate multiplied by the developed pressure (HRxDP) in the wild-type and SOD1^+/- hearts recovered to 92±9 and 85±7 of preischemic baseline values, respectively (P=NS). In contrast, the HRxDP was significantly lower (63±7%) in the SOD2^+/- hearts compared with the wild-type hearts. Western blot analysis and enzymatic activity of tissue lysates confirmed reduction of activities of specific SOD isoforms without compensatory increase in the other isoform in the knockout animals studied.

Conclusions— Postischemic functional recovery is more sensitive to a partial deficiency of SOD2 than a partial deficiency of SOD1. Therefore, modulation of the mitochondrial SOD isoform is a critical determinant in the tolerance of the heart to oxidative stress.

Key Words: free radicals • ischemia • reperfusion • stunning, myocardial

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