Sebastian Wiberg1,2, Nis Stride1, John Bro-Jeppesen1, Mathias J Holmberg2,3, Jesper Kjærgaard1, Steen Larsen4,5, Michael W Donnino2,6, Christian Hassager7, Flemming Dela4,8. 1. Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Denmark. 2. Department of Emergency Medicine, Beth Israel Deaconess Medical Center, USA. 3. Research Center for Emergency Medicine, Aarhus University Hospital, Denmark. 4. Center for Healthy Aging, University of Copenhagen, Denmark. 5. Clinical Research Centre, Medical University of Bialystok, Poland. 6. Department of Internal Medicine, Beth Israel Deaconess Medical Center, USA. 7. Department of Cardiology, University of Copenhagen, Denmark. 8. Department of Geriatrics, Bispebjerg Hospital, Denmark.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Authors: Lian Liang; Guozhen Zhang; Hui Li; Cheng Cheng; Tao Jin; Chenglei Su; Yan Xiao; Jennifer Bradley; Mary A Peberdy; Joseph P Ornato; Martin J Mangino; Wanchun Tang Journal: J Am Heart Assoc Date: 2021-04-22 Impact factor: 5.501
Authors: Kei Hayashida; Santiago J Miyara; Koichiro Shinozaki; Ryosuke Takegawa; Tai Yin; Daniel M Rolston; Rishabh C Choudhary; Sara Guevara; Ernesto P Molmenti; Lance B Becker Journal: Front Med (Lausanne) Date: 2021-01-14