Thorac Cardiovasc Surg 2011; 59 - eP170
DOI: 10.1055/s-0030-1269398

AAV2/9-mediated gene transfer of thymosin β4 shows cardioprotective effects in a porcine model of heterotopic heart allotransplantation

J Postrach 1, 2, M Thormann 1, 2, M Schmidt 1, 2, R Hinkel 3, A Bauer 2, 4, L Burdorf 1, E Thein 2, B Reichart 1, C Kupatt 3, M Schmoeckel 5, P Brenner 1
  • 1Herzchirurgische Klinik und Poliklinik der LMU, München, Germany
  • 2Walter-Brendel-Zentrum für Experimentelle Medizin, München, Germany
  • 3Medizinische Klinik I, Klinikum der Universität München, München, Germany
  • 4Klinik für Anästhesiologie der LMU, München, Germany
  • 5Asklepios Klinik St. Georg, Herzchirurgie, Hamburg, Germany

Objectives: We could previously show that the in situ Langendorff reperfusion of a donor heart before transplantation is an efficient technique for AAV2/9 mediated gene transfer into cardiomyocytes. Thymosin β4 is known to be an essential paracrine factor of embryonic endothelial progenitor cell mediated cardiac protection. Therefore we wanted to test, whether pre transplantation gene transfer of thymosin-β4 with this novel technique has a protective effect on cardiac allografts.

Methods: We transplanted hearts from Landrace pigs heterotopically into the abdomen of Munich minipigs. Before explantation donor hearts were isolated and perfused in situ for 45 minutes with autologous blood (+ 100µg VEGF). In the control group 1013 AAV 2/9 with LacZ vector (n=3) and in the thymosin group 1013 AAV 2/9 with thymosin β4 vector were added to the perfusion system (n=3). After 10 days immunosuppression (1mg/kg methylprednisolone, 50–100mg/kg mycophenolate mofetile and 0.3mg/kg tacrolimus) was stopped. Allograft survival, myocardial markers, histopathology and gene expression was assessed.

Results: In the control group allograft survival was 4, 13 (ongoing) and 16 days. Mild to moderate signs of humoral and cellular rejection were found. LacZ expression was detected in all allografts. In the thymosin β4 group survival time was 13 days (pig was sacrificed due to ileus) with excellent allograft function and histologically only mild signs of rejection. The other two experiments are ongoing.

Conclusion: In situ AAV2/9-mediated gene transfer of thymosin β4 into cardiomyocytes demonstrated beneficial effects by attenuation of rejection reaction in this heterotopic heart transplantation model.