Improved ultrastructural lung preservation with prostaglandin E1 as donor pretreatment in a primate model of heart-lung transplantation.
Donor pretreatment with prostaglandin E1 as a pulmonary vasodilator has developed as a simple, effective means to provide excellent preservation in heart-lung transplantation. This study was undertaken to investigate the degree of ultrastructural preservation of the lung with prostaglandin E1 and other pulmonary vasodilators in a primate heart-lung transplantation model. Heart-lung transplantation was performed in 14 African green monkeys. Donor cardiac preservation was achieved with cold crystalloid cardioplegic solution (10 ml/kg). Lung preservation was achieved with cold, modified Euro-Collins solution delivered into the main pulmonary artery (60 ml/kg total). Vasodilator agents were administered intravenously 15 minutes before aortic crossclamping. The heart-lung grafts were stored at 4 degrees C for 6 hours. Three groups of animals were studied: five donors with prostaglandin E1 (0.1 to 4.0 micrograms/kg per minute), five donors with prostacyclin (0.1 to 0.35 micrograms/kg per minute), and four donors with nitroprusside (0.8 to 5.0 micrograms/kg per minute). After transplantation, arterial blood gas measurements and lung biopsies were performed at 1- and 3-hour intervals. Five formalin blocks per specimen were sectioned for hematoxylin and eosin staining. Cellular preservation and endothelial cell swelling were evaluated with electron microscopy. The specimens were graded for alveolar hemorrhage, endothelial cell swelling, and cellular preservation (grade 0, minimal, to grade 3, severe) and a mean score was obtained for each preservative agent. Prostaglandin E1-treated specimens demonstrated the least amount of endothelial swelling (mean score of 1.0) compared with prostacyclin- and nitroprusside-treated specimens (mean scores of 1.4 and 2.7, respectively). All nitroprusside-treated specimens demonstrated moderate to severe endothelial cell swelling. Interstitial and alveolar hemorrhage was noted in poorly preserved specimens, but there were no significant differences between groups. We conclude that prostaglandin E1 provides improved cellular preservation by decreasing the extent of endothelial cell swelling as observed on electron microscopy.
Department of Surgery, Yale University School of Medicine, New Haven, CT 06510.
R S
RS
Higgins
G V
GV
Letsou
J A
JA
Sanchez
R N
RN
Eisen
G J
GJ
Smith
K L
KL
Franco
G L
GL
Hammond
J C
JC
Baldwin
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D002522:Chlorocebus aethiops; D004727:Endothelium / Q000648:ultrastructure; D011464:Epoprostenol / Q000494:pharmacology; D016041:Heart-Lung Transplantation; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure*; D008854:Microscopy, Electron; D009599:Nitroprusside / Q000494:pharmacology; D009926:Organ Preservation / Q000379:methods*; D011292:Premedication
D009599:Nitroprusside; D011464:Epoprostenol; D000527:Alprostadil