Dose optimization of early high-dose valproic acid for neuroprotection in a swine cardiac arrest model
| العنوان: | Dose optimization of early high-dose valproic acid for neuroprotection in a swine cardiac arrest model |
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| المؤلفون: | Sarita Raghunayakula, Cindy H. Hsu, Jinhui Liao, Danielle C. Leander, Mohamad H. Tiba, Robert W. Neumar, Zachary Pickell, Kevin R. Ward, Brandon C. Cummings, Thomas H. Sanderson, Hasan B. Alam, Brendan M. McCracken, Manjunath P. Pai, Tulasi Jinka, Carmen I. Colmenero, Anne M. Weitzel |
| المصدر: | Resuscitation Plus, Vol 1, Iss, Pp 100007-(2020) Resuscitation Plus |
| بيانات النشر: | Elsevier, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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 |
| اللغة: | English |
| تدمد: | 2666-5204 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c2b6e5b20d4e971388b2b435f52b09f6 http://www.sciencedirect.com/science/article/pii/S2666520420300072 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c2b6e5b20d4e971388b2b435f52b09f6 |
| قاعدة البيانات: | OpenAIRE |
Full Text via ClinicalKey | تدمد: | 26665204 |
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