Abstract

Introduction: Cytochrome C is an essential component of the electron transport chain loosely bound to the inner mitochondrial membrane. Plasma Cytochrome C levels have shown to be elevated and associated with mortality in an animal model of cardiac arrest. Hypothesis: We hypothesized that cytochrome C levels would be elevated in post-cardiac arrest patients and higher in non-survivors as compared to survivors. Methods: We enrolled adult, out-of-hospital cardiac arrest patients with return of spontaneous circulation as part of the four-center COMICA study. Blood draws were performed after return of spontaneous circulation. We also performed blood draws in controls without acute illness. We measured plasma cytochrome C levels by applying the human cytochrome C Platinum ELISA (eBioceience, CA) kit to a MSD platform (Meso Scale Discovery, MD) to achieve greater dynamic range and sensitivity. We compared groups using the Wilcoxon Rank-Sum test. We used Spearman’s correlation coefficient (rs) to assess the correlation between Cytochrome C levels and initial lactate levels. Results: A total of 103 post-cardiac arrest patients and 40 controls had Cytochrome C levels measured. Cytochrome C levels were higher in post-cardiac arrest patients as compared to control subjects (2.18 nmol/L [quartiles: 0.74, 7.74] vs 0.20 nmol/L [0.03, 1.12], p < 0.001, Figure 1). Fifty-five (53%) patients in the cardiac arrest group died. Patients who died had higher Cytochrome C levels as compared to survivors (3.66 nmol/L [1.40, 14.8] vs. 1.27 nmol/L [0.16, 2.37], p = 0.001, Figure 2). There was also a significant difference in Cytochrome C levels between patients with a good vs. a poor neurological outcome (1.3 nmol/L [0.3, 3.5] vs. 2.8 nmol/L [0.9, 9.9], p = 0.04). Cytochrome C levels were correlated with initial lactate levels (rs = 0.36, p = 0.001). Conclusion: Cytochrome C levels are elevated in post-cardiac arrest patients and non-survivors has higher levels.

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