CHRONIC REJECTION CAUSES EARLY DESTRUCTION OF THE INTRINSIC NERVOUS-SYSTEM IN RAT INTESTINAL TRANSPLANTS

Chronic rejection is the major cause of late intestinal allograft dysf unction. We have previously shown that chronic rejection alters the mu scularis externa of the graft. This study determined structural and fu nctional changes to the enteric nerves during chronic rejection. Chron ic rejection was achieved in orthotopic intestinal transplants (ACI to Lewis) by limited immunosuppression. Syngeneic transplants (ACI to AC I) and unoperated ACI rats served as controls. Animals were clinically healthy and showed no significant alterations in the mucosal architec ture on postoperative day 90. Staining for NADPH diaphorase activity ( nitric oxide synthase-containing neurons) and with neurofilament antib ody RT-97 revealed that chronic rejection decreased the number of jeju nal myenteric ganglia by similar to 50%. Inhibitory junction potential s (IJPs) to circular muscle cells were determined by electrical field stimulation (EFS). In controls and syngeneic grafts, EFS caused a stim ulus-dependent increase in IJP amplitude, with a maximal amplitude of 9 +/- 0.4 and 10 +/- 0.8 mV, respectively. Chronic rejection in allogr afts markedly increased the threshold for IJP initiation and decreased the maximal IJP amplitude (5 +/- 0.8 mV). Our data indicate that chro nic rejection severely damages the muscularis and the enteric nervous system before mucosal changes become evident.