Flavio Galvao, Wangles Soler, Daniel Waisberg, Alberto Faria, Eduardo Pompeu, Sergio Ribeiro, Vera Capelozzi, Walcy Teodoro, Ana Velosa, Eleazar Chaib, Luiz D´Aluquerque

Department of Gastroenterology, University of Sao Paulo Medical School, Sao Paulo, Brazil

Introduction: Xenotransplantation and multivisceral transplantation are advanced therapeutic methods that still require a scientific basis. Hyperacute rejection is the mean limitation for these practices.

Objective: To describe the endoscopic and immunopathological features of hyperacute rejection in a model of multivisceral xenotransplantation.

Methods: We recovered from rabbits a graft containing the distal esophagus, stomach, intestine, colon, liver, pancreas and the kidneys, with a common vascular pedicle. Swines (group I, n=13) or rabbits (group II, n=5) were used as recipients. Endoscopy was performed in the stomach, jejunum and ascending colon at four consecutive periods (back table and 10, 90 and 180 minutes after reperfusion). Lesions were graduated in mild, moderate and severe. Biopsies were taken following sacrifice at 180 min after reperfusion.

Results: All the grafts presented normal appearance and urinary debit immediately after graft reperfusion. In group I, the stomach, jejunum, and colon manifested a progression of lesions with predominance of mild lesions after 10 min, mild to moderate lesions after 90 min, and moderate to severe lesions after 180 min. In animals from group II, endoscopy showed normal features at all time points after reperfusion. Histopathological and immunofluorescence analysis confirmed the diagnosis of hyperacute rejection in all organs of the graft in group I, including vessels. In immunofluorescence, large amount of IgM and IgG antibodies could be detected in all organs. Grafts from group II presented normal or mild ischemic/reperfusion injury.

Conclusion: Multivisceral xenotransplantation recipients achieved a rapid progression of endoscopic lesions after transplantation, while animals subjected to allotransplantation showed no immunopathologic and endoscopic alterations. We conclude that multivisceral xenotransplantation is a relevant model for the study of hyperacute rejection and that endoscopy is a useful tool in the assessment of multivisceral xenograft.