Mitochondrial dysfunction in adults after out-of-hospital cardiac arrest.

Abstract

While preclinical studies suggest that mitochondria play a pivotal role in ischaemia-reperfusion injury, the knowledge of mitochondrial function in human out-of-hospital cardiac arrest remains scarce. The present study sought to compare oxidative phosphorylation capacity in skeletal muscle biopsies from out-of-hospital cardiac arrest patients to healthy controls. This was a substudy of a randomised trial comparing targeted temperature management at 33°C versus 36°C for out-of-hospital cardiac arrest patients. Skeletal muscle biopsies were obtained from adult resuscitated comatose out-of-hospital cardiac arrest patients 28 hours after initiation of targeted temperature management, i.e. at target temperature prior to rewarming, and from age-matched healthy controls. Mitochondrial function was analysed by high-resolution respirometry. Maximal sustained respiration through complex I, maximal coupled respiration through complex I and complex II and maximal electron transport system capacity was compared. A total of 20 out-of-hospital cardiac arrest patients and 21 controls were included in the analysis. We found no difference in mitochondrial function between temperature allocations. We found no difference in complex I sustained respiration between out-of-hospital cardiac arrest and controls (23 (18-26) vs. 22 (19-26) pmol O2/mg/s, P=0.76), whereas coupled complex I and complex II respiration was significantly lower in out-of-hospital cardiac arrest patients versus controls (53 (42-59) vs. 64 (54-68) pmol O2/mg/s, P=0.01). Furthermore, electron transport system capacity was lower in out-of-hospital cardiac arrest versus controls (63 (51-69) vs. 73 (66-78) pmol O2/mg/s, P=0.005). Mitochondrial oxidative phosphorylation capacity in skeletal muscle biopsies was reduced in out-of-hospital cardiac arrest patients undergoing targeted temperature management compared to age-matched, healthy controls. The role of mitochondria as risk markers and potential targets for post-resuscitation care remains unknown.