Ex vivo transfection of transforming growth factor-beta(1) gene to pulmonary artery segments in lung grafts

Objective: Proximal pulmonary artery segment transfection may provide benef icial downstream effects on the whole-lung graft. In this study, transformi ng growth factor-beta(1) was transfected to proximal pulmonary artery segme nts, and the efficacy of transforming growth factor-beta(1) transfection wa s examined in ischemia-reperfusion injury and acute rejection models of rat lung transplantation. Methods: In the ischemia-reperfusion injury model, o rthotopic left lung transplantation was performed in F344 rats. In group I, the PPAS was isolated and injected with saline solution. In 2 other groups , lipid67:DOPE:sense (group TI) or antisense transforming growth factor-bet a(1)pDNA construct (group III) was injected instead of saline solution. Aft er cold preservation at 4 degrees C for 18 hours, lung grafts were implante d. Graft function was assessed 24 hours later, In the acute rejection model , donor lung grafts were harvested. Proximal pulmonary artery segments were injected with saline solution (group I) or sense (group II) or antisense l ipid gene construct (group III) and then implanted. Graft function was asse ssed on postoperative day 5, Results: In the ischemia-reperfusion injury st udy, there were no significant differences in oxygenation, wet-to-dry weigh t ratios, graft myeloperoxidase activity, or transforming growth factor-bet a(1) levels in platelet-poor serum or proximal pulmonary artery segment hom ogenates. In the acute rejection study, oxygenation was significantly impro ved in group II receiving transforming growth factor-beta(1) (group TT vs I and III, 136.0 +/- 32.5 vs 54.0 +/- 9.6 mm Hg and 53.8 +/- 14.8 mm Hg; P = .016 and .016). There were no significant pathologic differences. Transfor ming growth factor-p, concentrations from proximal pulmonary artery segment homogenates in group II were significantly higher compared with controls. Conclusions: Ex vivo transfection of transforming growth factor-beta(1) to proximal pulmonary artery segments did not affect reperfusion injury of lun g isografts. In acute rejection, however, es vivo transfection of transform ing growth factor-beta(1) to proximal pulmonary artery segments improved al lograft function. This suggests that transfection to proximal pulmonary art ery segments exerts beneficial downstream effects on the whole-lung allogra ft.