Comparison of Vasodilators in Dual Vessel Normothermic Ex Vivo Liver Machine Perfusion of Rat Liver Grafts
Department of Surgery, Experimental Surgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Meeting: 2022 American Transplant Congress
Abstract number: 943
Keywords: Hepatic artery, Liver, Machine preservation, Rat
Topic: Basic Science » Basic Science » 15 - Machine Perfusion and Organ Rehabililtation - Basic
Session Information
Session Name: Machine Perfusion and Organ Rehabilitation - Basic
Session Type: Poster Abstract
Date: Sunday, June 5, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: Small animal models of normothermic ex vivo liver machine perfusion (NEVLP) comparable to clinically used protocols are vital to perform translational studies on organ rehabilitation by NEVLP.
*Methods: 12 male Sprague-Dawley rat livers were perfused via the portal vein as well as the hepatic artery using a custom-built small animal perfusion circuit with integrated dialysis circuit for 6 hours. The composition of the erythrocyte-supplemented perfusate and vasodilators were adapted to clinical protocols of NEVLP. Continuous epoprostenol infusion was compared to on demand administration of either verapamil or metamizole with respect to arterial pressure control and perfusion outcome.
*Results: Arterial pressure was maintained best with on demand bolus application with metamizole and Verapamil (Part at 6h: 94.6 vs. 82.9 mmHg, respectively; p=0.58), while epoprostenol led to escalating arterial pressures in 50% of experiments. All experiments showed initial lactate clearance (LactateT0h: 2,98mmol/L ±0,74 SD) with levels slightly increasing after 2h. Epoprostenol resulted in the highest endpoint lactate (2.22 mmol/L ± 1.12 SD). Bile production was greatest with metamizole in total, especially shown within the last hour of perfusion (Bile5h-6h: 1366mg vs. 571mg and 401mg; p<0.001). Repeated administration of metamizole in the second half led to a decrease in bile pH (pHT6: 7.90 ± 0.13). ALT release over the course of the perfusion was lowest with Verapamil compared to metamizole and epoprostenol (86.5 U/L ± 34.2 SD; 137.7 U/L ± 68.0 SD; 153.8 U/L ± 55.9 SD, respectively).
*Conclusions: D. Higher doses of epoprostenol had to be used in our rat NEVLP compared to clinical protocols. It also appears to have a negative effect on lactate clearance by influencing hepatic metabolism. Metamizole shows good results but is not generally approved for clinical use. Verapamil combines high vasodilative efficiency and optimal perfusion outcome in rat liver grafts and thus should be evaluated in transplantation studies after 6 hours of NEVLP.
To cite this abstract in AMA style:
Gassner JM, Strobl F, Michelotto J, Kristina K, Muth V, Zimmer M, Gilles L, Moosburner S, Pratschke J, Sauer I, Raschzok N. Comparison of Vasodilators in Dual Vessel Normothermic Ex Vivo Liver Machine Perfusion of Rat Liver Grafts [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/comparison-of-vasodilators-in-dual-vessel-normothermic-ex-vivo-liver-machine-perfusion-of-rat-liver-grafts/. Accessed May 9, 2025.« Back to 2022 American Transplant Congress