Characterization of mitochondrial injury after cardiac arrest (COMICA)

• Published in: Resuscitation 2017-04, Vol.113, p.56-62
• Main Authors: Donnino, Michael W, Liu, Xiaowen, Andersen, Lars W, Rittenberger, Jon C, Abella, Benjamin S, Gaieski, David F, Ornato, Joseph P, Gazmuri, Raúl J, Grossestreur, Anne V, Cocchi, Michaen N, Abbate, Antonio, Uber, Amy, Clore, John, Peberdy, Mary Anne, Callaway, Clifton
• Format: Article
• Language: English
• Subjects: Aged; Cardiac arrest; Cardiopulmonary Resuscitation - methods; Coma - diagnosis; Coma - etiology; Coma - metabolism; Cytochrome c; Cytochromes c - blood; DNA; DNA, Mitochondrial - blood; Emergency; Female; Heart Arrest - complications; Heart Arrest - metabolism; Heart Arrest - therapy; Humans; Male; Middle Aged; Mitochondria; Mitochondria - metabolism; Mortality; Nervous System Diseases - etiology; Nervous System Diseases - metabolism; Post-cardiac arrest; Ribonuclease P - blood; Statistics as Topic; Survival Analysis; Survivors
• ISSN: 0300-9572; 1873-1570
• DOI: 10.1016/j.resuscitation.2016.12.029

Abstract Introduction Mitochondrial injury post-cardiac arrest has been described in pre-clinical settings but the extent to which this injury occurs in humans remains largely unknown. We hypothesized that increased levels of mitochondrial biomarkers would be associated with mortality and neurological morbidity in post-cardiac arrest subjects. Methods We performed a prospective multicenter study of post-cardiac arrest subjects. Inclusion criteria were comatose adults who suffered an out-of-hospital cardiac arrest. Mitochondrial biomarkers were measured at 0, 12, 24, 36 and 48 h after return of spontaneous circulation as well as in healthy controls. Results Out of 111 subjects enrolled, 102 had evaluable samples at 0 h. Cardiac arrest subjects had higher baseline cytochrome c levels compared to controls (2.18 ng/mL [0.74, 7.74] vs. 0.16 ng/mL [0.03, 0.91], p < 0.001), and subjects who died had higher 0 h cytochrome c levels compared to survivors (3.66 ng/mL [1.40, 14.9] vs. 1.27 ng/mL [0.16, 2.37], p < 0.001). There were significantly higher RNAase P (3.3 [1.2, 5.7] vs. 1.2 [0.8, 1.2], p < 0.001) and B2M (12.0 [1.0, 22.9], vs. 0.6 [0.6, 1.3], p < 0.001) levels in cardiac arrest subjects at baseline compared to the control subjects. There were no differences between survivors and non-survivors for mitochondrial DNA, nuclear DNA, or cell free DNA. Conclusions Cytochrome c was increased in post- cardiac arrest subjects compared to controls, and in post-cardiac arrest non-survivors compared to survivors. Nuclear DNA and cell free DNA was increased in plasma of post-cardiac arrest subjects. There were no differences in mitochondrial DNA, nuclear DNA, or cell free DNA between survivors and non-survivors. Mitochondrial injury markers showed mixed results in post-arrest period. Future research needs to investigate these differences.