Comparison of two gene transfer models for the attenuation of myocardial ischemia-reperfusion injury following preservation for cardiac transplantation

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Abstract

Objective:

Two models of ex vivo gene transfer were compared by examining the protective effect of adenovirus-mediated transfection of a free radical scavenger superoxide dismutase (SOD) during experimental ischemia-reperfusion mimicking preservation for cardiac transplantation.

Methods:

Donor rat hearts (n = 6 per group) were infused (subgroups IA and IB) or continually perfused (subgroups IIA and IIB) with solution containing adenoviral vector carrying β-galactosidase (subgroups IA and IIA) or Mn-SOD (subgroups IB and IIB) over 5 s with 1 h storage and 15 min, at 4 °C, respectively. Hearts were then implanted heterotopically into the abdomen of recipient rats. Four days later, transplanted hearts were collected, connected to Langendorff perfusion apparatus and subjected to 6 h of ischemia followed by 1 h of reperfusion. Cardiac function was evaluated using intraventricular balloon at the beginning of Langendorff perfusion and following ischemia-reperfusion.

Results:

Blue staining from hydrolyses of X-gal by β-galactosidase was confirmed in AdLacZ transduced hearts. Immunoreactivity with anti-human Mn-SOD antibody then staining was positive in AdMnSOD-transduced hearts. Percent recovery of preischemic left ventricular developed pressure (LVDP) increased from 55.9 ± 3.1% to 67.3 ± 6.2% (P = 0.048) and from 58.0 ± 8.0% to 78.9 ± 6.0% (P ≪ 0.001) in subgroups IA, IB, IIA and IIB, respectively. The difference in LVDP recovery between treatment groups of the two transfection methods (IB vs IIB) was significant (P = 0.044).

Conclusion:

Adenoviral Mn-SOD ex vivo delivery using continuous myocardial perfusion is superior to bolus infusion in the attenuation of myocardial ischemia-reperfusion injury.

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