Background. Intestinal transplantation (ITx) faces many challenges due to the complexity of surgery and to the multiple immunological reactions that lead to the necessity of rigorous follow-up for early detection of acute cellular rejection (ACR). Our aim was to determine the kinetics of ACR using an experimental ITx model, with emphasis in the characterization of the process using different approaches, including the use of functional assays of absorptive and barrier function. Methods. ITx in rats conducting serial sampling was performed. Clinical monitoring, graft histology, proinflammatory gene expression, and nitrosative stress determination were performed. Also, glucose absorption, barrier function using ovalbumin translocation, and contractile function were analyzed. Results. The model used reproduced the different stages of ACR. Allogeneic ITx recipients showed signs of rejection from postoperative day (POD) 5, with increasing severity until 12 POD. Histological evaluation showed mild rejection in early sampling and severe rejection at late stages, with alterations in all graft layers. IL-6, CXCL 10, IFNg, and nitrite plasmas levels showed behavior coincident with histopathology. Remarkably, allogeneic grafts showed a marked alteration of glucose absorptive capacity from POD 5 that was sustained until endpoint. Coincidently, barrier function alteration was evidenced by luminal ovalbumin translocation to serum. Contractile function was progressively impaired along ACR. Conclusions. Glucose absorption and barrier function are altered at early stages of ACR when histological alterations or gene expression changes were much subtle. This observation may provide simple evaluation tools that could be eventually translated to the clinics to contribute to early ACR diagnosis.
Small Bowel transplantation in rats is a highly complex microsurgical procedure because several technical complications may lead to recipient mortality and transplant failure. Our aim was to report the most common complications associated with orthotopic and heterotopic intestinal transplantation in rats in order to identify the "pitfalls" of the procedure and prevent them. A retrospective multicenter study was performed. All participant centers have established rodent transplant procedures and trained surgeons. Two hundred ninety-three complications from 264 unsuccessful intestinal transplants were reported, representing an overall failure rate of 15% of the procedures performed. Recipient complications were most frequent than donor (257 vs. 36 p<0.0001). Excessive surgical time (11/36); severe hemorrhage (12/36) and inappropriate infusion of the preservation solution in the intestinal graft (11/36) were the most common donor complications. Arterial anastomosis bleeding (50/257), venous anastomosis bleeding (35/257) and portal vein stenosis (26/257) were the most common intraoperative complications in the recipient. To maximize success rate, surgeons should optimize time and avoid bleeding during graft dissection in the donor surgery. After performing a bloodless vascular anastomosis an adequate post-operative management of the animal is mandatory to guarantee survival.
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