EFFECTS OF ACUTE REJECTION AND ANTIREJECTION THERAPY ON ARTERIES AND VEINS FROM CANINE SINGLE-LUNG ALLOGRAFTS

Experiments were designed to compare the function of the endothelium a nd smooth muscle in intralobar pulmonary arteries acid veins of transp lanted lungs during acute rejection and after treatment of rejection. Single lung allografts were performed in dogs. Dogs were monitored for 5 days to allow good recovery from the operation and resolution of ea rly chest radiographic changes. In group I, immunosuppression (cyclosp orine A, azathioprine, and methylprednisone) was withdrawn to allow re jection, which typically occurred after 3 days. In group II, immunosup pression was reinstituted at this time during acute rejection until th e chest roentgenograms again cleared (approximately after 6 days). The blood vessels were studied at this time. Rings were cut from intralob ar pulmonary arteries and veins of the allotransplanted lungs and susp ended for the measurement of isometric force in organ chambers. Contra ctions of arteries and veins to phenylephrine but not endothelin-1 wer e significantly reduced during acute rejection. In arteries and veins, endothelium-dependent relaxations to bradykinin but not the calcium i onophore A23187 were reduced with rejection. Relaxations of the smooth muscle to histamine increased with rejection in both blood vessels. R elaxations to nitric oxide were reduced with rejection in veins but no t arteries. Treatment of rejection reversed all responses toward those observed in arteries and veins in lungs from dogs not undergoing tran splantation. These results suggest that responses of the endothelium a nd smooth muscle of pulmonary arteries and veins of transplanted lungs are altered similarly during rejection. Further, treatment of rejecti on restores function of the pulmonary blood vessels of lung allografts toward that observed in unoperated lungs.