Small bowel transplantation and chronic rejection alter rat intestinal smooth muscle structure and function

P. F. Heeckt, W. M. Halfter, W. H. Schraut, K. K W Lee, A. J. Bauer, A. H. Harken, J. S. Thompson, M. W. Flye, M. G. Sarr, B. D. Schirmer, R. E. Brolin

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Abstract

Background. The purpose of this study was to determine whether morphologic and functional changes in intestinal smooth muscle occur after small bowel transplantation (SBTx) and during chronic rejection. Methods. Orthotopic SBTx was performed in syngeneic (ACI-ACI, n = 6) and allogeneic (ACI-Lewis, n = 6) rat strain combinations. The latter received temporary immunosuppression (cyclosporine 15 mg/kg/body weight on postoperative days 0 to 6 once a day, postoperative days 7 to 28 every other day), which led to clinically quiescent chronic rejection of the graft by 90 days after SBTx. At that time structure and function of the jejunal muscularis externa were evaluated with histochemistry, mechanical organ bath, and intracellular electrical recording techniques. Results. Histochemistry showed a 1.5-fold thickening of the intestinal muscularis externa of syngeneic grafts, although contractile properties and intracellular electrical activity were not significantly different from controls. Allogeneic, chronically rejecting grafts showed a threefold increase in the thickness of the muscularis externa as a result of both smooth muscle hyperplasia and hypertrophy. Muscle strips from chronically rejecting grafts generated only 23% of the maximal contractile force generated by controls (bethanechol 300 μmol/L). Median effective concentration and threshold values were not significantly different. Intracellular electrical activity of circular smooth muscle cells revealed a significantly more depolarized resting membrane potential and a reduction in slow wave amplitude compared with controls. Conclusions. Syngeneic SBTx resulted in a significant thickening of the muscularis externa with an apparent adaptation to control in vitro physiologic function. Allogeneic SBTx subject to chronic rejection leads to profound morphologic changes and functional impairments. Changes in muscle structure and function evolve before the clinical signs of graft rejection.

Original languageEnglish (US)
Pages (from-to)449-457
Number of pages9
JournalSurgery
Volume114
Issue number2
StatePublished - 1993
Externally publishedYes

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Graft Rejection
Smooth Muscle
Transplants
Bethanechol
Muscles
Baths
Membrane Potentials
Immunosuppression
Hypertrophy
Cyclosporine
Smooth Muscle Myocytes
Hyperplasia
Transplantation
Body Weight

ASJC Scopus subject areas

  • Surgery

Cite this

Heeckt, P. F., Halfter, W. M., Schraut, W. H., Lee, K. K. W., Bauer, A. J., Harken, A. H., ... Brolin, R. E. (1993). Small bowel transplantation and chronic rejection alter rat intestinal smooth muscle structure and function. Surgery, 114(2), 449-457.

Small bowel transplantation and chronic rejection alter rat intestinal smooth muscle structure and function. / Heeckt, P. F.; Halfter, W. M.; Schraut, W. H.; Lee, K. K W; Bauer, A. J.; Harken, A. H.; Thompson, J. S.; Flye, M. W.; Sarr, M. G.; Schirmer, B. D.; Brolin, R. E.

In: Surgery, Vol. 114, No. 2, 1993, p. 449-457.

Research output: Contribution to journalArticle

Heeckt, PF, Halfter, WM, Schraut, WH, Lee, KKW, Bauer, AJ, Harken, AH, Thompson, JS, Flye, MW, Sarr, MG, Schirmer, BD & Brolin, RE 1993, 'Small bowel transplantation and chronic rejection alter rat intestinal smooth muscle structure and function', Surgery, vol. 114, no. 2, pp. 449-457.
Heeckt PF, Halfter WM, Schraut WH, Lee KKW, Bauer AJ, Harken AH et al. Small bowel transplantation and chronic rejection alter rat intestinal smooth muscle structure and function. Surgery. 1993;114(2):449-457.
Heeckt, P. F. ; Halfter, W. M. ; Schraut, W. H. ; Lee, K. K W ; Bauer, A. J. ; Harken, A. H. ; Thompson, J. S. ; Flye, M. W. ; Sarr, M. G. ; Schirmer, B. D. ; Brolin, R. E. / Small bowel transplantation and chronic rejection alter rat intestinal smooth muscle structure and function. In: Surgery. 1993 ; Vol. 114, No. 2. pp. 449-457.
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abstract = "Background. The purpose of this study was to determine whether morphologic and functional changes in intestinal smooth muscle occur after small bowel transplantation (SBTx) and during chronic rejection. Methods. Orthotopic SBTx was performed in syngeneic (ACI-ACI, n = 6) and allogeneic (ACI-Lewis, n = 6) rat strain combinations. The latter received temporary immunosuppression (cyclosporine 15 mg/kg/body weight on postoperative days 0 to 6 once a day, postoperative days 7 to 28 every other day), which led to clinically quiescent chronic rejection of the graft by 90 days after SBTx. At that time structure and function of the jejunal muscularis externa were evaluated with histochemistry, mechanical organ bath, and intracellular electrical recording techniques. Results. Histochemistry showed a 1.5-fold thickening of the intestinal muscularis externa of syngeneic grafts, although contractile properties and intracellular electrical activity were not significantly different from controls. Allogeneic, chronically rejecting grafts showed a threefold increase in the thickness of the muscularis externa as a result of both smooth muscle hyperplasia and hypertrophy. Muscle strips from chronically rejecting grafts generated only 23{\%} of the maximal contractile force generated by controls (bethanechol 300 μmol/L). Median effective concentration and threshold values were not significantly different. Intracellular electrical activity of circular smooth muscle cells revealed a significantly more depolarized resting membrane potential and a reduction in slow wave amplitude compared with controls. Conclusions. Syngeneic SBTx resulted in a significant thickening of the muscularis externa with an apparent adaptation to control in vitro physiologic function. Allogeneic SBTx subject to chronic rejection leads to profound morphologic changes and functional impairments. Changes in muscle structure and function evolve before the clinical signs of graft rejection.",
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T1 - Small bowel transplantation and chronic rejection alter rat intestinal smooth muscle structure and function

AU - Heeckt, P. F.

AU - Halfter, W. M.

AU - Schraut, W. H.

AU - Lee, K. K W

AU - Bauer, A. J.

AU - Harken, A. H.

AU - Thompson, J. S.

AU - Flye, M. W.

AU - Sarr, M. G.

AU - Schirmer, B. D.

AU - Brolin, R. E.

PY - 1993

Y1 - 1993

N2 - Background. The purpose of this study was to determine whether morphologic and functional changes in intestinal smooth muscle occur after small bowel transplantation (SBTx) and during chronic rejection. Methods. Orthotopic SBTx was performed in syngeneic (ACI-ACI, n = 6) and allogeneic (ACI-Lewis, n = 6) rat strain combinations. The latter received temporary immunosuppression (cyclosporine 15 mg/kg/body weight on postoperative days 0 to 6 once a day, postoperative days 7 to 28 every other day), which led to clinically quiescent chronic rejection of the graft by 90 days after SBTx. At that time structure and function of the jejunal muscularis externa were evaluated with histochemistry, mechanical organ bath, and intracellular electrical recording techniques. Results. Histochemistry showed a 1.5-fold thickening of the intestinal muscularis externa of syngeneic grafts, although contractile properties and intracellular electrical activity were not significantly different from controls. Allogeneic, chronically rejecting grafts showed a threefold increase in the thickness of the muscularis externa as a result of both smooth muscle hyperplasia and hypertrophy. Muscle strips from chronically rejecting grafts generated only 23% of the maximal contractile force generated by controls (bethanechol 300 μmol/L). Median effective concentration and threshold values were not significantly different. Intracellular electrical activity of circular smooth muscle cells revealed a significantly more depolarized resting membrane potential and a reduction in slow wave amplitude compared with controls. Conclusions. Syngeneic SBTx resulted in a significant thickening of the muscularis externa with an apparent adaptation to control in vitro physiologic function. Allogeneic SBTx subject to chronic rejection leads to profound morphologic changes and functional impairments. Changes in muscle structure and function evolve before the clinical signs of graft rejection.

AB - Background. The purpose of this study was to determine whether morphologic and functional changes in intestinal smooth muscle occur after small bowel transplantation (SBTx) and during chronic rejection. Methods. Orthotopic SBTx was performed in syngeneic (ACI-ACI, n = 6) and allogeneic (ACI-Lewis, n = 6) rat strain combinations. The latter received temporary immunosuppression (cyclosporine 15 mg/kg/body weight on postoperative days 0 to 6 once a day, postoperative days 7 to 28 every other day), which led to clinically quiescent chronic rejection of the graft by 90 days after SBTx. At that time structure and function of the jejunal muscularis externa were evaluated with histochemistry, mechanical organ bath, and intracellular electrical recording techniques. Results. Histochemistry showed a 1.5-fold thickening of the intestinal muscularis externa of syngeneic grafts, although contractile properties and intracellular electrical activity were not significantly different from controls. Allogeneic, chronically rejecting grafts showed a threefold increase in the thickness of the muscularis externa as a result of both smooth muscle hyperplasia and hypertrophy. Muscle strips from chronically rejecting grafts generated only 23% of the maximal contractile force generated by controls (bethanechol 300 μmol/L). Median effective concentration and threshold values were not significantly different. Intracellular electrical activity of circular smooth muscle cells revealed a significantly more depolarized resting membrane potential and a reduction in slow wave amplitude compared with controls. Conclusions. Syngeneic SBTx resulted in a significant thickening of the muscularis externa with an apparent adaptation to control in vitro physiologic function. Allogeneic SBTx subject to chronic rejection leads to profound morphologic changes and functional impairments. Changes in muscle structure and function evolve before the clinical signs of graft rejection.

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