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Dose optimization of early high-dose valproic acid for neuroprotection in a swine cardiac arrest model
- Source :
- Resuscitation Plus, Vol 1, Iss, Pp 100007-(2020), Resuscitation Plus
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
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 more adrenaline to maintain mean arterial pressure ≥80 mmHg and had worse lactic acidosis. There was a strong linear correlation between plasma free VPA Cmax and brain total VPA (r2 = 0.9494; p
- Subjects :
- Valproic Acid
Mean arterial pressure
lcsh:Specialties of internal medicine
business.industry
Cmax
Pharmacokinetic
Pharmacology
Return of spontaneous circulation
Swine model
medicine.disease
Placebo
Cardiac arrest
Pharmacodynamics biomarker
Pharmacokinetics
Histone acetylation
lcsh:RC581-951
Pharmacodynamics
Ventricular fibrillation
medicine
Valproic acid
lipids (amino acids, peptides, and proteins)
business
Earth-Surface Processes
medicine.drug
Experimental Paper
Subjects
Details
- Language :
- English
- ISSN :
- 26665204
- Volume :
- 1
- Database :
- OpenAIRE
- Journal :
- Resuscitation Plus
- Accession number :
- edsair.doi.dedup.....c2b6e5b20d4e971388b2b435f52b09f6