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Eur J Cardiothorac Surg 2006;29:772-778
© 2006 Elsevier Science NL

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

Heart Science Centre, Imperial College at Harefield Hospital, Harefield, Middlesex UB9 6JH, UK

Received 12 September 2005; received in revised form 11 December 2005; accepted 13 December 2005.

^_* Corresponding author. Address: 67 Glenfrith Close, Leicester LE3 9QQ, UK. Tel.: +44 1162877711. (Email: haitham7{at}hotmail.com).

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 ß-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 ß-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.

Key Words: Adenoviral gene transfer • Transplantation • Ischemia–reperfusion • Superoxide dismutase

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