Abstract 90: Pyruvate Dehydrogenase is Inhibited in Post Cardiac Arrest Patients

Abstract

Introduction: Pyruvate Dehydrogenase (PDH) activity has been shown to be inhibited in animal models of post-cardiac arrest. This depressed activity has been postulated to be directly related to neurologic injury secondary to aerobic metabolic dysfunction and accumulation of toxic metabolites. The objective of this study was to determine if PDH inhibition occurs after cardiac arrest (CA) in humans. Methods: Patients were enrolled as part of a prospective observational trial of CA at a single urban academic medical center from 1/13 to 4/13. A blood sample was collected as early after ROSC as informed consent could be obtained (<24 hours). Our control group consisted of volunteers with no significant medical history. We used a novel method to measure PDH activity from peripheral blood mononuclear cells isolated from fresh blood. We quantified total PDH in 15mg / ml of isolated protein and determined overall PDH activity (PDH activity / total protein) and specific PDH activity (PDH activity / PDH protein). Wilcoxon rank sum test was used to compare median quantity and activity between the two groups. A p-value < 0.05 was considered statistically significant. All tests of the data were performed in SAS v. 9.3 (SAS Institute Inc., Cary, NC, USA). Results: We enrolled 10 post-arrest patients; average age was 48 and 50% were female. Mortality was 50%. Overall PDH activity was significantly lower in the CA group (2.20 IQR 1.70 - 3.49) compared to controls (8.40 IQR 5.51 - 8.67) (p = .007). PDH quantity was also significantly lower in the CA group (1.26 IQR 0.90 - 2.02) compared to controls (4.88 IQR 3.08 - 6.09) (p = .009). There was no difference in specific PDH activity between the groups (p = 0.84). Conclusions: PDH activity is inhibited in the post-arrest period compared to healthy controls. The main driver of inhibition may be loss of PDH protein as opposed to changes in intrinsic activity. These findings are pertinent as animal models suggest PDH inhibition may drive neurologic injury after CA.