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Intestinal function following allogeneic small intestinal transplantation in the rat
D L Sigalet1, N M Kneteman, R N Fedorak
1Department of Surgery, University of Alberta, Canada.
Transplantation
|February 1, 1992
Summary
Small bowel transplantation (SIT) significantly alters intestinal function, increasing permeability and changing nutrient absorption. These functional changes, potentially due to denervation, minimally impact overall animal well-being after transplantation.
Area of Science:
- Gastroenterology
- Transplantation Immunology
- Surgical Research
Background:
- Small intestinal transplantation (SIT) is a complex procedure with potential functional consequences.
- Understanding the impact of SIT on intestinal function is crucial for improving patient outcomes.
- Investigating both syngeneic and allogeneic models provides insights into immune-mediated and non-immune effects.
Purpose of the Study:
- To investigate the functional alterations in the small intestine following syngeneic and allogeneic transplantation.
- To determine the impact of SIT on nutrient absorption, intestinal permeability, and active transport.
- To explore the potential underlying causes of observed functional changes, such as denervation.
Main Methods:
- Orthotopic total small intestinal transplantation (SIT) performed using a two-stage model in rats.
- Syngeneic (BN----BN, Lew----Lew) and fully allogeneic (BN----Lew) transplantation models were utilized.
- Animals were treated with cyclosporine A, and functional assessments included weight gain, dietary fat absorption, intestinal permeability assays (mannitol, PEG-400, lactulose, 51Cr-EDTA), and glucose transport measurements (short circuit current, uptake rates).
Main Results:
- Syngeneic SIT reduced weight gain in one rat strain, while allogeneic SIT caused initial growth retardation possibly due to graft-versus-host disease, with subsequent normal growth.
- Dietary fat absorption was reduced across all transplanted groups.
- Intestinal permeability increased significantly after both syngeneic and allogeneic SIT, with a more pronounced effect in the allogeneic group.
- Glucose transport showed reduced stimulated current but increased active and passive uptake rates.
- Functional changes were observed without significant alterations in intestinal morphology or signs of rejection.
Conclusions:
- Small bowel transplantation induces significant functional changes in intestinal transport characteristics.
- Increased intestinal permeability and altered nutrient absorption are key findings post-SIT.
- Despite functional alterations, SIT generally has a minimal impact on overall animal well-being, suggesting adaptive mechanisms.
- Denervation of the small intestine following SIT is proposed as the primary cause for the observed functional changes.