High-Dose Cannabidiol Induced Hypotension after Global Hypoxia-Ischemia in Piglets.
Neonatology
; 112(2): 143-149, 2017.
Article
em En
| MEDLINE
| ID: mdl-28564654
ABSTRACT
BACKGROUND:
Cannabidiol (CBD) is considered a promising neuroprotectant after perinatal hypoxia-ischemia (HI). We have previously studied the effects of CBD 1 mg/kg in the early phase after global HI in piglets. In contrast to prior studies, we found no evidence of neuroprotection and hypothesized that higher doses might be required to demonstrate efficacy in this animal model.OBJECTIVE:
To assess the safety and potential neuroprotective effects of high-dose CBD.METHODS:
Anesthetized newborn piglets underwent global HI by ventilation with 8% O2 until the point of severe metabolic acidosis (base excess -20 mmol/L) and/or hypotension (mean arterial blood pressure ≤20 mm Hg). Piglets were randomized to intravenous treatment with vehicle (n = 9) or CBD (n = 13). The starting dose, CBD 50 mg/kg, was reduced if adverse effects occurred. The piglets were euthanized 9.5 h after HI and tissue was collected for analysis.RESULTS:
CBD 50 mg/kg (n = 4) induced significant hypotension in 2 out of 4 piglets, and 1 out of 4 piglets suffered a fatal cardiac arrest. CBD 25 mg/kg (n = 4) induced significant hypotension in 1 out of 4 piglets, while 10 mg/kg (n = 5) was well tolerated. A significant negative correlation between the plasma concentration of CBD and hypotension during drug infusion was observed (p < 0.005). Neuroprotective effects were evaluated in piglets that did not display significant hypotension (n = 9) and CBD did not alter the degree of neuronal damage as measured by a neuropathology score, levels of the astrocytic marker S100B in CSF, magnetic resonance spectroscopy markers (Lac/NAA and Glu/NAA ratios), or plasma troponin T.CONCLUSIONS:
High-dose CBD can induce severe hypotension and did not offer neuroprotection in the early phase after global HI in piglets.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Canabidiol
/
Fármacos Neuroprotetores
/
Hipóxia-Isquemia Encefálica
/
Pressão Arterial
/
Hipotensão
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Neonatology
Assunto da revista:
PERINATOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Noruega