Lung growth after reduced size transplantation in a sheep model

Back ground The growth of mature allografts is a critical issue in pediatri c lung transplantation. This study explores the architectural changes of ma ture sheep lung when submitted to two different compensatory growth forces: either transplantation into a neonatal host or expansion in an otherwise e mpty adult hemithorax. Methods. Right upper lobes (RUL) (mean+/-SEM, 66.7+/-1.9 kg) from 4- to 5-y ear old (adult sheep) were transplanted into newborn (n=6) lambs (5.4+/-0.3 kg, 5+/-2 days old) that were then allowed to survive for 45 days. Changes in pulmonary volume and architecture were measured before and after transp lantation. Allografts were compared with both normal adult RUL (n=10) and a dult (65.8+/-2.2 kg and 4 to 5 year old) RUL that remained in situ for 45 d ays after resection of the corresponding middle and lower lobes (n=6). Stat istical differences were analyzed using two-sample and paired t tests. Results. In adult animals, RUL remaining in the otherwise empty hemithorax compensated by an 85% increase in volume (251.5+/-18.7 ml vs. 466+/-32.8 ml ) (P<0.0001). Concomitant increases in total internal alveolar surface area (48%) and alveolar size were prominent. The number of alveoli per volume d ecreased proportionately to the increases in volume (P<0.0001). There was n o significant change in the calculated number of alveoli (345.6+/-40.5 x 10 (6)) compared with the normal adult RUL (402.4+/-40.7x10(6)) (P=0.37). Tran splant recipients received a reduced-size normal adult RUL (49%) in volume (125.3+/-21.5 ml). Allografts 45 days after transplantation showed a 73% in crease in volume (216.4+/-21.3 ml) (P<0.0001) with a parallel (83%) increas e in total internal alveolar surface area (P=0.008). The number of alveoli per volume remained constant (P=0.21) despite the increase in volume. There was therefore a significant increase in the calculated number of alveoli f rom before transplantation (172.5+/-35.9x10(6)) compared with that observed 45 days after transplantation (389.7+/-77.7x10(6)) (P=0.012). Conclusions. We conclude that mature sheep RUL parenchyma compensates with dilation of the respiratory structures in the adult animal, whereas there i s alveolar multiplication when transplanted into newborn recipients.