Mitochondrial metabolism and bioenergetic function in an anoxic isolated adult mouse cardiomyocyte model of in vivo cardiac ischemia-reperfusion injury

• DOI: 10.1016/j.redox.2022.102368
• Publication Date: 2022-06-17T08:25:25Z
• Authors: Anja V. Gruszczyk; Alva M. Casey; Andrew M. James; Hiran A. Prag; Nils Burger; Georgina R. Bates; Andrew R. Hall; Fay M. Allen; Thomas Krieg; Kourosh Saeb-Parsy; Michael P. Murphy
• Keywords: Bioenergetics; Hypoxia; Anaerobic glycolysis; Adenine nucleotide

Cell models of cardiac ischemia-reperfusion (IR) injury are essential to facilitate understanding, but current monolayer cell poorly replicate the in vivo IR that occurs within a three-dimensional tissue. Here we show this is for two reasons: residual oxygen present many cellular hypoxia sustains mitochondrial oxidative phosphorylation; and loss lactate from cells into incubation medium during ischemia enables sustain glycolysis. To overcome these limitations, incubated isolated adult mouse cardiomyocytes anoxically while inhibiting efflux. These interventions recapitulated key markers ischemia, notably accumulation succinate adenine nucleotides. Upon reoxygenation after anoxia had accumulated was rapidly oxidized association with extensive superoxide/hydrogen peroxide production injury, mimicking reperfusion injury. This model will enable aspects be assessed vitro.