Pharmacologic reduction of angiographic vasospasm in experimental subarachnoid hemorrhage: Systematic review and meta-analysis

Document Type

Article

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. © 2012 ISCBFM All rights reserved.

Keywords

animal model, pharmacologic reduction, subarachnoid hemorrhage, translation, vasospasm

Publication Date

9-1-2012

Publication Title

Journal of Cerebral Blood Flow and Metabolism

ISSN

0271678X

E-ISSN

15597016

Volume

32

Issue

9

First Page

1645

Last Page

1658

PubMed ID

22534672

Digital Object Identifier (DOI)

10.1038/jcbfm.2012.57

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