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Perfusion of Porcine Kidneys with Macromolecular Heparin Ameliorates Early Ischemia Reperfusion Injury
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
(English)Article in journal (Refereed) Submitted
Abstract [en]

Background: Ischemia-reperfusion injury (IRI) is the most significant antigen-independent nonspecific insult, inevitably linked to organ transplantation. Endothelial glycocalyx is degraded during the earliest events in I/R. Previously we have been able to demonstrate the feasibility of coating the surface of the renal artery and renal tissue during hypothermic machine perfusion preservation (HMP) in a porcine model of brain death with a macromolecular heparin conjugate (CHC; Corline Systems AB, Uppsala, Sweden). The purpose of this study was to assess protective effects of coating the renal vessel walls with a heparin conjugate during hypothermic machine perfusion (HMP) against IRI and early kidney function.

Methods: Brain death was achieved in male landrace pigs (n=6) by raising the intracranial pressure (ICP) through stepwise increasing the volume of an epidurally placed balloon to the point of exceeding the mean arterial pressure (MAP) creating a negative cerebral perfusion pressure (CPP). Both kidneys, (n = 6 in each group) were preserved for 18 h by hypothermic machine perfusion (HMP) in Lifeport® kidney transporters (Organ Recovery Systems, Chicago, IL, USA). In total 50 mg CHC was added to one of the HMP system (experimental group). An ex vivo normothermic perfusion (NP) system was developed with the purpose of evaluating kidneys function. Blood, urine and histological samples were collected during the subsequent 3 hours of NP, with an oxygenated autologous blood using cardiopulmonary bypass machine. The haemostatic dynamics of whole blood clotting and thrombin generation was evaluated by tromboelastography.

Results: Serum creatinine was faster reduced in the experimental group compared to the control group (P=0.023). The total urine volume after 3h of warm perfusion was larger in the experimental group (239±71 mL) compared to the control group (172±42 mL) (Ρ=0.031). Histologically tubular changes were less frequent in the experimental group (P=0.045). No difference was seen between the groups regarding tromboelastography.

Conclusions: Perfusion of porcine kidneys with CHC during HMP ameliorates early IRI and improves organ function close after reperfusion. No increased risk of bleed was seen with this treatment. This is a protective intervention strategy that potentially may improve the outcome of kidney transplantation in a clinical setting.

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URN: urn:nbn:se:uu:diva-222018OAI: oai:DiVA.org:uu-222018DiVA: diva2:710529
Available from: 2014-04-07 Created: 2014-04-07 Last updated: 2014-04-09Bibliographically approved

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Sedigh, Amir
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Transplantation Surgery

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