Dissociation of vasospasm and secondary effects of experimental subarachnoid hemorrhage by clazosentan.

Abstract:

BACKGROUND AND PURPOSE:Endothelin receptor antagonists such as clazosentan decrease large-artery vasospasm after experimental and clinical subarachnoid hemorrhage. We used clazosentan to gain insight into the pathophysiology of subarachnoid hemorrhage by determining if decreasing vasospasm is associated with alleviation of other secondary complications of subarachnoid hemorrhage such as oxidative stress, endothelial nitric oxide synthase dysfunction, microthromboembolism, and neuronal injury. METHODS:Mice were subjected to subarachnoid hemorrhage by injection of blood into the chiasmatic cistern. They were treated with clazosentan or vehicle by continuous intraperitoneal infusion for 48 hours. Middle cerebral artery vasospasm, superoxide anion radical, peroxynitrite, microthromboemboli, endothelial nitric oxide synthase uncoupling, cerebral blood flow, neuronal injury, and mortality were assessed. RESULTS:Clazosentan preserved cerebral blood flow, alleviated vasospasm, and decreased mortality but did not affect superoxide anion radical, peroxynitrite, or microthromboemboli in the brain. Endothelial nitric oxide synthase uncoupling and neuronal injury also were not reduced by clazosentan. CONCLUSIONS:This study shows large-artery vasospasm is pathophysiologically independent of some other effects of subarachnoid hemorrhage. The findings have implications for development of treatments for this disease.

journal_name

Stroke

journal_title

Stroke

authors

Sabri M,Ai J,Macdonald RL

doi

10.1161/STROKEAHA.110.604728

subject

Has Abstract

pub_date

2011-05-01 00:00:00

pages

1454-60

issue

5

eissn

0039-2499

issn

1524-4628

pii

STROKEAHA.110.604728

journal_volume

42

pub_type

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