AJP - Gastrointestinal and Liver Physiology, Vol 273, Issue 2 413-G421, Copyright © 1997 by American Physiological Society
Chronic rejection causes early destruction of the intrinsic nervous system in rat intestinal transplants
P. F. Heeckt, W. Halfter, W. H. Schraut and A. J. Bauer
Department of Surgery, University of Pittsburgh, Pennsylvania 15261, USA.
Chronic rejection is the major cause of late intestinal allograft
dysfunction. We have previously shown that chronic rejection alters the
muscularis externa of the graft. This study determined structural and
functional changes to the enteric nerves during chronic rejection. Chronic
rejection was achieved in orthotopic intestinal transplants (ACI to Lewis)
by limited immunosuppression. Syngeneic transplants (ACI to ACI) and
unoperated ACI rats served as controls. Animals were clinically healthy and
showed no significant alterations in the mucosal architecture on
postoperative day 90. Staining for NADPH diaphorase activity (nitric oxide
synthase-containing neurons) and with neurofilament antibody RT-97 revealed
that chronic rejection decreased the number of jejunal myenteric ganglia by
approximately 50%. Inhibitory junction potentials (IJPs) to circular muscle
cells were determined by electrical field stimulation (EFS). In controls
and syngeneic grafts, EFS caused a stimulus-dependent increase in IJP
amplitude, with a maximal amplitude of 9 +/- 0.4 and 10 +/- 0.8 mV,
respectively. Chronic rejection in allografts markedly increased the
threshold for IJP initiation and decreased the maximal IJP amplitude (5 +/-
0.8 mV). Our data indicate that chronic rejection severely damages the
muscularis and the enteric nervous system before mucosal changes become
evident.
