Abstract 17637: Combination Therapy With Hypothermic Target Temperature Management and Valproic Acid After Cardiac Arrest

Abstract

Introduction: While hypothermic target temperature management (HTTM) has been regarded as a reliable strategy for post-cardiac arrest treatment, there are no pharmacologic agents proved to be neuroprotective against post-cardiac arrest brain injury. In recent years, many studies have shown that valproic acid (VPA), a well-known antiepileptic drug, is neuroprotective against various brain insults. VPA inhibits histone deacetylase activity and causes hyperacetylation of histones, followed by transcriptional activation of anti-apoptotic genes. In this study we tested the hypothesis that combination therapy of hypothermia and VPA could enhance neuroprotection and improve outcome. Methods: Male Long-Evans rats were instrumented for continuous telemetric EEG recording with video and then subjected to 8-minute asphyxia cardiac arrest. Nine rats that achieved the return of spontaneous circulation (ROSC) were allocated into the following 3 groups. Controlled normothermia (N group, 36.5-37.5 °C, n=3), HTTM (H group, 32-33 °C for 24 hours, n=3) and HTTM with VPA administration (HV group, 32-33 °C for 24 hours, 300 mg/kg, IV, n=3). Three-day survival, best achieved neurologic function score (NFS), the number of seizure event was compared between the 3 groups. Results: The 3-day survival was 33.3% in N group, 33.3 % in H group and 100 % in HV group (p=0.12). The best NFS averaged 263.33 ± 36.67 in N group, 380 ± 64.29 in H group and 468.33 ± 15.90 in HV group (p=0.13). The total number of seizure events in each group averaged 0.33 ± 0.33 in N group, 4.33 ± 2.96 in H group, 0 in HV group (p=0.20). Conclusions: These early results suggest that the combination of HTTM and VPA is a promising strategy that could result in synergistic neuroprotection after cardiac arrest.