Int J Med Sci 2019; 16(9):1304-1312. doi:10.7150/ijms.34617

Research Paper

Mild hypothermia during the reperfusion phase protects mitochondrial bioenergetics against ischemia-reperfusion injury in an animal model of ex-vivo liver transplantation—an experimental study

Rui Miguel Martins1,✉, João Soeiro Teodoro2, Emanuel Furtado3, Rui Caetano Oliveira4, José Guilherme Tralhão5, Anabela Pinto Rolo2, Carlos Marques Palmeira2

1. Department of Surgery, Instituto Português de Oncologia de Coimbra, Coimbra, Portugal
2. Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra; and Center of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal
3. Unidade de Transplantação Hepática de Crianças e Adultos, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
4. Department of Pathology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
5. Department of Surgery, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Clínica Universitária de Cirurgia III, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; and Center for Investigation on Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal

Abstract

The organ preservation paradigm has changed following the development of new ways to preserve organs. The use of machine perfusion to preserve organs appears to have several advantages compared with conventional static cold storage. For liver transplants, the temperature control provided by machine perfusion improves organ preservation. In this experimental study, we measured the effects of different temperatures on mitochondrial bioenergetics during the reperfusion phase. An experimental model of ex-vivo liver transplantation was developed in Wistar rats (Rattus norvegicus). After total hepatectomy, cold static preservation occurred at 4ºC and reperfusion was performed at 37ºC and 32ºC using a Langendorff system. We measured parameters associated with mitochondrial bioenergetics in the livers. Compared with the livers that underwent normothermic reperfusion, mild hypothermia during reperfusion caused significant increases in the mitochondrial membrane potential, the adenosine triphosphate content, and mitochondrial respiration, and a significant reduction in the lag phase (all P < 0.001). Mild hypothermia during reperfusion reduced the effect of ischemia-reperfusion injury on mitochondrial activity in liver tissue and promoted an increase in bioenergetic availability compared with normothermic reperfusion.

Keywords: hypothermia, mitochondria, bioenergetics, adenosine triphosphate, liver transplantation

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How to cite this article:
Martins RM, Teodoro JS, Furtado E, Oliveira RC, Tralhão JG, Rolo AP, Palmeira CM. Mild hypothermia during the reperfusion phase protects mitochondrial bioenergetics against ischemia-reperfusion injury in an animal model of ex-vivo liver transplantation—an experimental study. Int J Med Sci 2019; 16(9):1304-1312. doi:10.7150/ijms.34617. Available from http://www.medsci.org/v16p1304.htm