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Utilization of dielectric properties for assessment of liver ischemia-reperfusion injury in vivo and during machine perfusion.

ABSTRACT: There is a shortage of donor livers and patients consequently die on waiting lists worldwide. Livers are discarded if they are clinically judged to have a high risk of non-function following transplantation. With the aim of extending the pool of available donor livers, we assessed the condition of porcine livers by monitoring the microwave dielectric properties. A total of 21 livers were divided into three groups: control with no injury (CON), biliary injury by hepatic artery occlusion (AHEP), and overall hepatic injury by static cold storage (SCS). All were monitored for four hours in vivo, followed by ex vivo plurithermic machine perfusion (PMP). Permittivity data was modeled with a two-pole Cole-Cole equation, and dielectric properties from one-hour intervals were analyzed during in vivo and normothermic machine perfusion (NMP). A clear increasing trend in the conductivity was observed in vivo in the AHEP livers compared to the control livers. After four hours of NMP, separations in the conductivity were observed between the three groups. Our results indicate that dielectric relaxation spectroscopy (DRS) can be used to detect and differentiate liver injuries, opening for a standardized and reliable point of evaluation for livers prior to transplantation.

SUBMITTER: Hou J

PROVIDER: S-EPMC9249774 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Critical organ shortage results in the utilization of extended donor criteria (EDC) liver grafts. These marginal liver grafts are prone to increased ischemia reperfusion injury (IRI) which may contribute to deteriorated graft function and survival. Experimental data have shown that the calcineurin inhibitor tacrolimus exerts protective effects on hepatic IRI when applied intravenously or directly as a hepatic rinse. Therefore, the aim of the present study is to examine the effects of an ex vivo tacrolimus perfusion on IRI in transplantation of EDC liver grafts. METHODS/DESIGN:The TOP-Study (tacrolimus organ perfusion) is a randomized multicenter trial comparing the ex vivo tacrolimus perfusion of marginal liver grafts with placebo. We hypothesize that a tacrolimus rinse reduces IRI, potentially improving organ survival following transplantation of EDC livers. The study includes livers with two or more EDC, according to Eurotransplant International Foundation's definition of EDC livers. Prior to implantation, livers randomized to the treatment group are rinsed with tacrolimus at a concentration of 20?ng/ml in 1000?ml Custodiol solution and in the placebo group with Custodiol alone. The primary endpoint is the maximum serum alanine transamninase (ALT) level within the first 48?hours after surgery; however, the study design also includes a 1-year observation period following transplantation. The TOP-Study is an investigator-initiated trial sponsored by the University of Munich Hospital. Seven other German transplant centers are participating (Berlin, Frankfurt, Heidelberg, Mainz, Münster, Regensburg, Tübingen) and aim to include a total of 86 patients. DISCUSSION:Tacrolimus organ perfusion represents a promising strategy to reduce hepatic IRI following the transplantation of marginal liver grafts. This treatment may help to improve the function of EDC grafts and therefore safely expand the donor pool in light of critical organ shortage. TRIAL REGISTER:EudraCT number: 2010-021333-31, ClinicalTrials.gov identifier: NCT01564095.

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Utilization of dielectric properties for assessment of liver ischemia-reperfusion injury in vivo and during machine perfusion.

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