Abstract Body (Do not enter title and authors here): Introduction: Out-of-hospital cardiac arrest (OHCA) is associated with severe metabolic and acid-base disturbances, driven in part by mitochondrial dysfunction. Impaired mitochondrial function leads to lactic acidosis and impaired oxygen extraction. Ubiquinol and alpha-lipoic acid are important components of mitochondrial aerobic respiration. ALA functions as an important cofactor for multiple enzyme complexes in the Krebs cycle, while Coenzyme Q10 is a key electron carrier in the mitochondrial electron transport chain. In this study, we measured the cellular oxygen consumption rates (OCR) and the effects of in vitro Coenzyme Q10 and alpha-lipoic acid administration on mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) from OHCA patients.
Hypothesis: Administration of Coenzyme Q10 and ALA improves cellular oxygen consumption parameters in patients post-OHCA.
Methods: Blood samples were collected from a cohort of patients post-OHCA and healthy controls. Cellular OCR parameters were measured in PBMCs pre- and post treatment with Coenzyme Q10 or ALA. The mitochondrial respiration was measured using an XFe96 Extracellular Flux Analyzer and XF Cell Mito Stress Test Kit (Seahorse Bioscience). A linear mixed-effects model was used to compare the OCR parameters between controls and post-OHCA patients and to estimate the treatment effect of Coenzyme Q10 and ALA, including a group-by-treatment interaction term.
Results: A total of 53 patients with OHCA and 53 controls were included. Basal (4.88 [IQR:3.24, 7.76] vs. 6.97 [IQR:4.40, 9.86] pmol/min/µg protein, p=0.039) and maximal OCR (12.32 [IQR:7.06, 31.08] vs 29.2 [IQR:19.4, 40.42], p=<0.0001) were significantly lower in the OHCA patients compared to the healthy controls. Basal (33%, p<0.001) and maximal (47%, p=0.03) OCR increased after Coenzyme Q10 treatment in OHCA patients but not in healthy controls (Table 1). Basal (135%,p<0.001) and maximal (89%, p=0.03) OCR also increased after ALA treatment in OHCA patients but not in healthy controls (Table 2).
Conclusion: Mitochondrial metabolic profiles of OHCA patients demonstrated lower baseline cellular oxygen consumption when compared to healthy controls.Mitochondrial respiration increased significantly in PBMCs from cardiac arrest patients when treated with Coenzyme Q10 and ALA. These results suggest that Coenzyme Q10 and ALA could potentially have therapeutic benefits in cardiac arrest via metabolic effects on mitochondrial cellular respiration.