title: Pharmacologic reduction of angiographic vasospasm in experimental subarachnoid hemorrhage: systematic review and meta-analysis.
abstract: Animal models have been developed to simulate angiographic vasospasm secondary to subarachnoid hemorrhage (SAH) and to test pharmacologic treatments. Our aim was to evaluate the effect of pharmacologic treatments that have been tested in humans and in preclinical studies to determine if animal models inform results reported in humans. A systematic review and meta-analysis of SAH studies was performed. We investigated predictors of translation from animals to humans with multivariate logistic regression. Pharmacologic reduction of vasospasm was effective in mice, rats, rabbits, dogs, nonhuman primates (standard mean difference of -1.74; 95% confidence interval -2.04 to -1.44) and humans. Animal studies were generally of poor methodologic quality and there was evidence of publication bias. Subgroup analysis by drug and species showed that statins, tissue plasminogen activator, erythropoietin, endothelin receptor antagonists, calcium channel antagonists, fasudil, and tirilazad were effective whereas magnesium was not. Only evaluation of vasospasm >3 days after SAH was independently associated with successful translation. We conclude that reduction of vasospasm is effective in animals and humans and that evaluation of vasospasm >3 days after SAH may be preferable for preclinical models.
authors.affiliation: Division of Neurosurgery, St Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre of the Li Ka Shing Knowledge Institute of St Michael's Hospital, Ontario, Canada.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Zoerle
authors.forename: Don C
authors.initials: DC
authors.lastname: Ilodigwe
authors.forename: Hoyee
authors.initials: H
authors.lastname: Wan
authors.forename: Katarina
authors.initials: K
authors.lastname: Lakovic
authors.forename: Mohammed
authors.initials: M
authors.lastname: Sabri
authors.forename: Jinglu
authors.initials: J
authors.lastname: Ai
authors.forename: R Loch
authors.initials: RL
authors.lastname: Macdonald
mesh_terms: D000818:Animals; D002533:Cerebral Angiography; D003627:Data Interpretation, Statistical; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006801:Humans; D008251:Macaca; D008297:Male; D051379:Mice; D017594:Publication Bias; D011817:Rabbits; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D013045:Species Specificity; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology