Metabolic adaptations during extreme anoxia in the turtle heart and their implications for ischemia-reperfusion injury.

TitleMetabolic adaptations during extreme anoxia in the turtle heart and their implications for ischemia-reperfusion injury.
Publication TypeJournal Article
Year of Publication2019
AuthorsBundgaard, A, James, AM, Gruszczyk, AV, Martin, J, Murphy, MP, Fago, A
JournalSci Rep
Volume9
Issue1
Pagination2850
Date Published2019 Feb 26
ISSN2045-2322
Abstract

ATP depletion and succinate accumulation during ischemia lead to oxidative damage to mammalian organs upon reperfusion. In contrast, freshwater turtles survive weeks of anoxia at low temperatures without suffering from oxidative damage upon reoxygenation, but the mechanisms are unclear. To determine how turtles survive prolonged anoxia, we measured ~80 metabolites in hearts from cold-acclimated (5 °C) turtles exposed to 9 days anoxia and compared the results with those for normoxic turtles (25 °C) and mouse hearts exposed to 30 min of ischemia. In turtles, ATP and ADP decreased to new steady-state levels during fasting and cold-acclimation and further with anoxia, but disappeared within 30 min of ischemia in mouse hearts. High NADH/NAD ratios were associated with succinate accumulation in both anoxic turtles and ischemic mouse hearts. However, succinate concentrations and succinate/fumarate ratios were lower in turtle than in mouse heart, limiting the driving force for production of reactive oxygen species (ROS) upon reoxygenation in turtles. Furthermore, we show production of ROS from succinate is prevented by re-synthesis of ATP from ADP. Thus, maintenance of an ATP/ADP pool and low succinate accumulation likely protects turtle hearts from anoxia/reoxygenation injury and suggests metabolic interventions as a therapeutic approach to limit ischemia/reperfusion injury in mammals.

DOI10.1038/s41598-019-39836-5
Alternate JournalSci Rep
Citation Key10.1038/s41598-019-39836-5
PubMed ID30808950
PubMed Central IDPMC6391391
Grant ListMC_U105663142 / / RCUK | Medical Research Council (MRC) /
110159/Z/15/Z / / Wellcome Trust (Wellcome) /
4181-00094 / / Natur og Univers, Det Frie Forskningsråd (Natural Sciences, Danish Council for Independent Research) /