Extracellular superoxide dismutase transgene overexpression preserves postischemic myocardial function in isolated murine hearts

Edward P. Chen, Hartmuth B. Bittner, R. Duane Davis, Rodney J. Folz, Peter Van Trigt

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Background: Myocardial injury after ischemia and reperfusion may be mediated, at least in part, by oxygen-derived free radicals: this supposition is supported by the observation that significant quantities of these radicals are generated during reperfusion. To directly assess the protective effect of extracellular superoxide dismutase (EC-SOD), this study was diagnosed to investigate the ability of EC-SOD overepression in the hearts of transgenic mice to protect myocardial tissue against ischemia-reperfusion injury by use of an isolated work-performing murine heart preparation and functional analysis. Methods and Results: Ten transgenic mice (EC-SOD, 28 to 31 g) were studied and compared with 10 control mice (Ctl. 28 to 31 g) in terms of preischemic and postischemic myocardial function. All hearts underwent cardiac harvest and arrest, followed by instrumentation and subsequent reperfusion with warm Krebs-Henseleit solution. Preload-dependent functional analysis was then performed to evaluate cardiac output, contractility (dP/dt), heart rate, stroke work, and stroke volume before and after a 7- minute period of warm ischemia. Results are expressed as mean±SEM (ANOVA, paired/unpaired t tests). There was no significant difference in preischemic myocardial performance for Ctl and EC-SOD mice. After warm ischemia, cardiac output in EC-SOD was significantly improved compared with Ctl (EC-SOD, 4.55±0.37 mL/min; Ctl, 2.55±0.28 mL/min; P<.05). Post-ischemic dP/dt, stroke work, and stroke volume were also significantly improved in EC-SOD compared with Ctl mice (EC-SOD, 1808±39 mm Hg/s, 745±67 dyne · cm, and 13.1±1.2 μmL, respectively: Ctl 1497±87 mm Hg/s, 472±83 dyne · cm, and 8.2±1.5 μL: P<.05). Conclusions: EC-SOD overexpressed mice showed significant improvement in postischemic cardiac function compared with Ctl mice. Thus, EC-SOD overexpressed hearts are less susceptible to mild degrees of ischemia-reperfusion injury than normal hearts.

Original languageEnglish (US)
Pages (from-to)II412-II417
JournalCirculation
Volume94
Issue number9 SUPPL.
StatePublished - Nov 1 1996

Keywords

  • antioxidants
  • free radicals
  • ischemia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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