Pulmonary lobar transplantation in neonatal swine: a model for treatment of congenital diaphragmatic hernia.
Congenital diaphragmatic hernia (CDH) babies born with severe pulmonary hypoplasia are unsalvageable despite maximal therapy including extracorporeal membrane oxygenation (ECMO). Lung transplantation is a potential treatment for these otherwise doomed infants using ECMO as a bridge to transplantation. Cadaveric, or living related donation of a more mature reduced size lung (pulmonary lobe or segment) may help solve the critical donor shortage problem. We evaluated the physiological response of mature left lower lobe (LLL) transplants in neonatal swine with the hemodynamic conditions of CDH simulated by occlusion of the right pulmonary artery (PA), and also studied the pulmonary function of the mature lobar graft compared with the neonatal lung. LLL transplantation was well tolerated and resulted in minimal alteration in hemodynamic parameters. The response to right PA occlusion was similar pre- and posttransplantation with a fall in cardiac output and a significant rise in pulmonary vascular resistance. Compared with the contralateral native lung, the lobar graft was preferentially ventilated with resultant higher pH (7.65 +/- 0.17 v 7.41 +/- 0.08, P less than .01) and lower pCO2 (17 +/- 6 v 36 +/- 5, P less than .001). The more mature lobar graft was preferentially ventilated due to the increased compliance compared with the neonatal right lung (8.16 +/- 1.28 v 5.48 +/- 0.82 mL/cm, P less than .0001). Reduced size lung transplantation is technically feasible and may help solve the donor problem for severe CDH neonates for whom no effective therapy is currently available.
Crombleholme, TM; Adzick, NS; Hardy, K; Longaker, MT; Bradley, SM; Duncan, BW; Verrier, ED; Harrison, MR
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