Heterotopic intestinal transplantation aggravates the insult of chronic rejection.
BACKGROUND
Intestinal grafts are placed either heterotopically (out of continuity) or orthotopically (in continuity); the latter is believed to be advantageous, as intraluminal nutrients and intestinal secretions might modulate the intestinal immune status and possibly delay rejection.


METHODS
This study was designed to delineate the effects of heterotopic versus orthotopic allograft position on the morphology and function of intestinal smooth muscle in our rat model of chronic rejection. Syngeneic orthotopic grafts were evaluated to control for changes due to the transplantation process.


RESULTS
Histochemistry of the graft's muscularis externa showed a significant thickening due to hyperplasia and hypertrophy, which was most pronounced in heterotopic grafts (control = 92+/-2.4 microm, syngeneic grafts = 140+/-6.7 microm, orthotopic allografts = 278+/-26.6 microm, heterotopic allografts = 456+/-50 microm). In terms of function, muscle strips from allografts only generated 23% of the total bethanechol-induced contractile force in vitro compared to unoperated controls and syngeneic grafts. The mean resting membrane potential of control and isograft muscle cells was -69 +/- 0.9 mV with a slow-wave amplitude of 20+/-0.5 mV. Chronic rejection hyperpolarized the resting membrane potential of orthotopic allografts (-66 +/- 0.5 mV) and even more so of heterotopic allografts (-58 +/- 3.4 mV). Slow-wave amplitudes were decreased in orthotopic (14+/-0.9 mV) and nearly abolished in heterotopic allografts (2+/-1.2 mV).


CONCLUSIONS
Our data indicate that allografts in heterotopic position are most susceptible to the insult of chronic rejection exemplified by increased proliferative and hypertrophic transformation of intestinal smooth muscle and a marked decrease in mechanical and electrical activity.
Heeckt
P F
PF
Department of Surgery, University of Pittsburgh, Pennsylvania 15261, USA.
Halfter
W M
WM
Schurer
B
B
Schraut
W H
WH
Beger
H G
HG
Bauer
A J
AJ
D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D004594:Electrophysiology / Q000379:methods; D006084:Graft Rejection / Q000473:pathology*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000473:pathology / Q000502:physiology / Q000637:transplantation*; D007421:Intestine, Small / Q000473:pathology / Q000502:physiology / Q000637:transplantation*; D007583:Jejunum / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000473:pathology / Q000502:physiology / Q000637:transplantation*; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D016042:Transplantation, Heterotopic / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D014185:Transplantation, Isogeneic / Q000276:immunology / Q000473:pathology / Q000502:physiology
D018723:Bethanechol