Supplementary Material for: High-Dose Cannabidiol-Induced Hypotension after Global Hypoxia-Ischemia in Piglets
Garberg H.T.
Solberg R.
Barlinn J.
Martinez-Orgado J.
Løberg E.-M.
Saugstad O.D.
10.6084/m9.figshare.5057464.v1
https://karger.figshare.com/articles/dataset/Supplementary_Material_for_High-Dose_Cannabidiol-Induced_Hypotension_after_Global_Hypoxia-Ischemia_in_Piglets/5057464
<p><b><i>Background:</i></b> 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. <b><i>Objective:</i></b> To assess the safety and potential neuroprotective effects of high-dose CBD. <b><i>Methods:</i></b> Anesthetized newborn piglets underwent global HI by ventilation with 8% O<sub>2</sub>
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 (<i>n</i> = 9) or CBD (<i>n</i>
= 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. <b><i>Results:</i></b> CBD 50 mg/kg (<i>n</i> =
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 (<i>n</i> = 4) induced significant hypotension in 1 out of 4 piglets, while 10 mg/kg (<i>n</i>
= 5) was well tolerated. A significant negative correlation between the
plasma concentration of CBD and hypotension during drug infusion was
observed (<i>p</i> < 0.005). Neuroprotective effects were evaluated in piglets that did not display significant hypotension (<i>n</i>
= 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. <b><i>Conclusions:</i></b> High-dose CBD can induce severe hypotension and did not offer neuroprotection in the early phase after global HI in piglets.</p>
2017-06-01 09:24:31
Newborn piglet
Cannabidiol
Side effects
Neuroprotection
Neonatal hypoxia-ischemia
Hypoxic-ischemic brain injury
Neonatal hemodynamics
Hypotension