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Glyceryl trinitrate for the treatment of ischaemic stroke: Determining efficacy in rodent and ovine species for enhanced clinical translation

Sorby-Adams, Annabel J.; Learoyd, Annastazia E.; Bath, Philip M.; Burrows, Fiona; Farr, Tracy D.; Leonard, Anna V.; Schiessl, Ingo; Allan, Stuart M.; Turner, Renée J.; Trueman, Rebecca C.

Glyceryl trinitrate for the treatment of ischaemic stroke: Determining efficacy in rodent and ovine species for enhanced clinical translation Thumbnail


Authors

Annabel J. Sorby-Adams

Annastazia E. Learoyd

PHILIP BATH philip.bath@nottingham.ac.uk
Stroke Association Professor of Stroke Medicine

Fiona Burrows

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TRACY FARR T.Farr@nottingham.ac.uk
Associate Professor

Anna V. Leonard

Ingo Schiessl

Stuart M. Allan

Renée J. Turner



Abstract

Hypertension is a leading risk factor for death and dependency after ischaemic stroke. However, administering anti-hypertensive medications post-stroke remains contentious with concerns regarding deleterious effects on cerebral blood flow and infarct expansion. This study sought to determine the effect of glyceryl trinitrate (GTN) treatment in both lissencephalic and gyrencephalic pre-clinical stroke models. Merino sheep underwent middle cerebral artery occlusion (MCAO) followed by GTN or control patch administration (0.2 mg/h). Monitoring of numerous physiologically relevant measures over 24 h showed that GTN administration was associated with decreased intracranial pressure, infarct volume, cerebral oedema and midline shift compared to vehicle treatment (p < 0.05). No significant changes in blood pressure or cerebral perfusion pressure were observed. Using optical imaging spectroscopy and laser speckle imaging, the effect of varying doses of GTN (0.69–50 µg/h) on cerebral blood flow and tissue oxygenation was examined in mice. No consistent effect was found. Additional mice undergoing MCAO followed by GTN administration (doses varying from 0–60 µg/h) also showed no improvement in infarct volume or neurological score within 24 h post-stroke. GTN administration significantly improved numerous stroke-related physiological outcomes in sheep but was ineffective in mice. This suggests that, whilst GTN administration could potentially benefit patients, further research into mechanisms of action are required.

Citation

Sorby-Adams, A. J., Learoyd, A. E., Bath, P. M., Burrows, F., Farr, T. D., Leonard, A. V., …Trueman, R. C. (2021). Glyceryl trinitrate for the treatment of ischaemic stroke: Determining efficacy in rodent and ovine species for enhanced clinical translation. Journal of Cerebral Blood Flow and Metabolism, 41(12), 3248-3259. https://doi.org/10.1177/0271678X211018901

Journal Article Type Article
Acceptance Date Apr 19, 2021
Online Publication Date May 26, 2021
Publication Date Dec 1, 2021
Deposit Date May 17, 2021
Publicly Available Date Mar 29, 2024
Journal Journal of Cerebral Blood Flow and Metabolism
Print ISSN 0271-678X
Electronic ISSN 1559-7016
Peer Reviewed Peer Reviewed
Volume 41
Issue 12
Pages 3248-3259
DOI https://doi.org/10.1177/0271678X211018901
Keywords Neurology; Clinical Neurology; Cardiology and Cardiovascular Medicine
Public URL https://nottingham-repository.worktribe.com/output/5556851
Publisher URL https://journals.sagepub.com/doi/10.1177/0271678X211018901