Recombinant adenovirus-mediated cardiac gene transfer of superoxide dismutase and catalase attenuates postischemic contractile dysfunction

Y. Joseph Woo, Janet C.L. Zhang, C. Vijayasarathy, Ralf M. Zwacka, John F. Englehardt, Timothy J. Gardner, H. Lee Sweeney

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Background - Coronary revascularization entails obligatory myocardial ischemia followed by reperfusion with occasional resultant postischemic contractile dysfunction, a state associated with significant morbidity and mortality. This injury is attributed in part to oxygen free radicals and has been partially ameliorated with exogenous antioxidants, a strategy limited by agent instability, low titer, and inadequate cardiomyocyte uptake. Cardiac gene transfer with antioxidant encoding vectors may significantly enhance intracellular free radical scavenger activity. Methods and Results - C57/BL6 neonatal mice (age, 2 days; n = 131) underwent intrapericardial delivery of recombinant adenoviruses encoding superoxide dismutase (SOD) and catalase (Cat) (n=76) or β-galactosidase (LacZ) as a control (n=55). After 3 days, hearts were explanted, and SOD and Cat transgene expression was detected by Western blot analysis. Spectrophotometric enzyme assays demonstrated enhanced SOD activity 1.6-fold (P<0.0001) and Cat 3.6-fold (P<0.00001) in experimental versus LacZ hearts. Isolated perfused hearts were subjected to 5 minutes of warm ischemia, and at 5, 10, and 15 minutes after initiation of reperfusion, LacZ controls lost 24%, 33%, and 41% of peak systolic apicobasal force, respectively, whereas experimental hearts lost 5%, 12%, and 20% (P<0.001, each time point). In controls, rate of force generation diminished 8%, 17%, and 35%; in experimental hearts, it increased 1% at 5 minutes and decreased 5% and 15% at 10 and 15 minutes (P<0.01, P<0.05, P<0.05). LacZ hearts exhibited dysfunction similar to hearts from uninjected animals (P=NS, each time point). Conclusions - Adenovirus-mediated cardiac gene transfer and expression of SOD and Cat augment antioxidant enzyme activity and minimize contractile dysfunction after ischemic reperfusion in the isolated perfused neonatal mouse heart.

Original languageEnglish
Pages (from-to)II255-II260
Issue number19 SUPPL.
StatePublished - 10 Nov 1998
Externally publishedYes


  • Antioxidants
  • Contractility
  • Ischemia
  • Reperfusion
  • Stunning, myocardial


Dive into the research topics of 'Recombinant adenovirus-mediated cardiac gene transfer of superoxide dismutase and catalase attenuates postischemic contractile dysfunction'. Together they form a unique fingerprint.

Cite this