| Autor: |
Hefler J; Department of Surgery, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada., Hatami S; Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.; Canadian Donation & Transplantation Research Program, Edmonton, Alberta, Canada., Thiesen A; Department of Laboratory Medicine & Pathology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada., Wagner MJ; Department of Surgery, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada., Mainardi G; Department of Surgery, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada., Himmat S; Department of Surgery, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada., Karvellas CJ; Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada., Bigam DL; Department of Surgery, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada., Freed DH; Department of Surgery, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.; Canadian Donation & Transplantation Research Program, Edmonton, Alberta, Canada., Shapiro AMJ; Department of Surgery, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.; Canadian Donation & Transplantation Research Program, Edmonton, Alberta, Canada.; Clinical Islet Transplant Program, University of Alberta, Edmonton, Alberta, Canada. |
| Abstrakt: |
BACKGROUND Ischemia/reperfusion injury (IRI) is an inherent problem in organ transplantation, owing to the obligate period of ischemia that organs must endure. Cyclosporine A (CsA), though better know as an immunosuppressant, has been shown to mitigate warm IRI in a variety of organ types, including the liver. However, there is little evidence for CsA in preventing hepatic IRI in the transplant setting. MATERIAL AND METHODS In the present study, we tested the effect of CsA on hepatic IRI in a large-animal ex vivo model of donation after circulatory death (DCD). Porcine donors were pre-treated with either normal saline control or 20 mg/kg of CsA. Animals were subject to either 45 or 60 minutes of warm ischemia before hepatectomy, followed by 2 or 4 hours of cold storage prior to reperfusion on an ex vivo circuit. Over the course of a 12-hour perfusion, perfusion parameters were recorded and perfusate samples and biopsies were taken at regular intervals. RESULTS Peak perfusate lactate dehydrogenase was significantly decreased in the lower-ischemia group treated with CsA compared to the untreated group (4220 U/L [3515-5815] vs 11 305 [10 100-11 674]; P=0.023). However, no difference was seen between controls and CsA-treated groups on other parameters in perfusate alanine or asparagine aminotransferase (P=0.912, 0.455, respectively). Correspondingly, we found no difference on midpoint histological injury score (P=0.271). CONCLUSIONS We found minimal evidence that CsA is protective against hepatic IRI in our DCD model. |
