NHBD Lung Transplantation

Detta är en avhandling från Per Wierup

Sammanfattning: The waiting list for lung transplantations world-wide is steadily growing. So, the use of lungs from non-heart-beating donors (NHBD) needs to be addressed. Hence, the aim of this thesis was to evaluate, in realistic animal models, the new donor organ concept: NHBD transplantation. Left rat lungs were topically cooled for 2 hours in situ after failed resuscitation, with subsequent transplantation. Five weeks after transplantation, right pneumonectomy was done and blood gases and histology evaluated. Comparison was made with a control transplant group and a group with normal rats after right pneumonectomy. Also, pigs were studied after failed resuscitation with intrapleural topical cooling initiated after 65 minutes. The lungs were cooled for 6 hours in situ after which their function was assessed ex vivo, followed by left lung transplantation and right pneumonectomy, thus making the recipient animals 100% dependent for their survival on the function of the donor lungs assessed ex vivo. Cold flush perfusion was studied in ventilated, isolated rat lungs perfused with either Euro-Collins solution or Perfadex at a pressure of 10, 15, or 20 mmHg. Weight gain was recorded and comparisons were made between values obtained at different perfusion pressures and with the two solutions. All the transplanted rats survived in good condition and at five weeks there were no significant differences in blood gases. The bronchial anastomoses showed normal healing in all cases and the histologic changes in the lung parenchyma were generally mild and focal, interstitial and perivascular mononuclear inflammation. Surprisingly, the transplanted controls demonstrated the most pronounced changes. The gas-exchange function during the ex-vivo evaluation in pigs did not differ from the basal values obtained before CPR. After the subsequent transplantation, all recipient animals survived in good condition at the end of the 24-hour observation period. The blood gas function did not differ significantly from that in the donor animals and the pulmonary vascular resistance was within normal range. In the isolated rat lungs, already at a perfusion pressure of 10 mmHg, there was a macro- and microscopically apparent edema, irrespective of the type of preservation solution. Perfusion pressures of 10 and 20 mmHg gave weight gains of 100% and 350%, respectively, after 3 min of perfusion. There were no statistically significant differences in weight gain or amount of perfused fluid between the different solutions at equal perfusion pressure. The concept of lung transplantation from non-heart-beating donors is feasible, if the lungs are cooled in situ within one hour after failed resuscitation. During cold flush perfusion, the edema formation is related to the perfusion pressure.

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