Ex vivo transfection of transforming growth factor-beta1 gene to pulmonary artery segments in lung grafts.
OBJECTIVE
Proximal pulmonary artery segment transfection may provide beneficial downstream effects on the whole-lung graft. In this study, transforming growth factor-beta1 was transfected to proximal pulmonary artery segments, and the efficacy of transforming growth factor-beta1 transfection was examined in ischemia-reperfusion injury and acute rejection models of rat lung transplantation.


METHODS
In the ischemia-reperfusion injury model, orthotopic 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 II) or antisense transforming growth factor-beta1pDNA construct (group III) was injected instead of saline solution. After cold preservation at 4 degrees C for 18 hours, lung grafts were implanted. 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 lipid gene construct (group III) and then implanted. Graft function was assessed on postoperative day 5.


RESULTS
In the ischemia-reperfusion injury study, there were no significant differences in oxygenation, wet-to-dry weight ratios, graft myeloperoxidase activity, or transforming growth factor-beta1 levels in platelet-poor serum or proximal pulmonary artery segment homogenates. In the acute rejection study, oxygenation was significantly improved in group II receiving transforming growth factor-beta1 (group II 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. Transforming growth factor-beta1 concentrations from proximal pulmonary artery segment homogenates in group II were significantly higher compared with controls.


CONCLUSIONS
Ex vivo transfection of transforming growth factor-beta1 to proximal pulmonary artery segments did not affect reperfusion injury of lung isografts. In acute rejection, however, ex vivo transfection of transforming growth factor-beta 1 to proximal pulmonary artery segments improved allograft function. This suggests that transfection to proximal pulmonary artery segments exerts beneficial downstream effects on the whole-lung allograft.
Yano
M
M
Division of Cardiothoracic Surgery and the Departmentof Surgery, Department of Pathology, Washington University Schoolof Medicine, St Louis, MO, USA.
Mora
B N
BN
Ritter
J M
JM
Scheule
R K
RK
Yew
N S
NS
Mohanakumar
T
T
Patterson
G A
GA
D000208:Acute Disease; D000818:Animals; D006084:Graft Rejection / Q000517:prevention & control*; D016040:Lung Transplantation; D008297:Male; D009926:Organ Preservation; D011651:Pulmonary Artery; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000517:prevention & control*; D014162:Transfection / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000235:genetics*
D016212:Transforming Growth Factor beta