Dose optimization of early high-dose valproic acid for neuroprotection in a swine cardiac arrest model.

ABSTRACT:

Aim

High-dose valproic acid (VPA) improves the survival and neurologic outcomes after asphyxial cardiac arrest (CA) in rats. We characterized the pharmacokinetics, pharmacodynamics, and safety of high-dose VPA in a swine CA model to advance clinical translation.

Methods

After 8 ​min of untreated ventricular fibrillation CA, 20 male Yorkshire swine were resuscitated until return of spontaneous circulation (ROSC). They were block randomized to receive placebo, 75 ​mg/kg, 150 ​mg/kg, or 300 ​mg/kg VPA as 90-min intravenous infusion (n ​= ​5/group) beginning at ROSC. Animals were monitored for 2 additional hours then euthanized. Experimental operators were blinded to treatments.

Results

The mean(SD) total CA duration was 14.8(1.2) minutes. 300 ​mg/kg VPA animals required

SUBMITTER: Hsu CH 

PROVIDER: S-EPMC8244526 | biostudies-literature | 2020 Mar-Jun

REPOSITORIES: biostudies-literature