Faculty Collaboration Database

Reversal of delayed vasospasm by an inhibitor of the synthesis of 20-HETE. Am J Physiol Heart Circ Physiol 2005 Nov;289(5):H2203-11

Date

06/21/2005

Pubmed ID

15964920

DOI

10.1152/ajpheart.00556.2005

Scopus ID

2-s2.0-27144490317 (requires institutional sign-in at Scopus site)   38 Citations

Abstract

This study characterized the time course of changes in cerebral blood flow (CBF) and vascular diameter in a dual-hemorrhage model of subarachnoid hemorrhage (SAH) in rats and examined whether acute blockade of the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) with N-(3-chloro-4-morpholin-4-yl)phenyl-N'-hydroxyimido formamide (TS-011) can reverse delayed vasospasm in this model. Rats received an intracisternal injection of blood (0.4 ml) on day 0 and a second injection 2 days later. CBF was sequentially measured using laser-Doppler flowmetry, and the diameters of the cerebral arteries were determined after filling the cerebral vasculature with a casting compound. CBF fell to 67% of control after the first intracisternal injection of blood but returned to a value near control 24 h later. CBF again fell to 63% of control after a second intracisternal injection of blood and remained 30% below control for 5 days. The fall in CBF after the second intracisternal injection of blood was associated with a sustained 30% reduction in the diameters of the middle cerebral, posterior communicating, and basilar arteries. Acute blockade of the synthesis of 20-HETE with TS-011 (0.1 mg/kg i.v.), 5 days after the second SAH, increased the diameters of the cerebral arteries, and CBF returned to control. These results indicate that the rats develop delayed vasospasm after induction of the dual-hemorrhage model of SAH and that blockade of the synthesis of 20-HETE fully reverses cerebral vasospasm in this model. They also implicate 20-HETE in the development and maintenance of delayed cerebral vasospasm.

Author List

Takeuchi K, Renic M, Bohman QC, Harder DR, Miyata N, Roman RJ

MESH terms used to index this publication - Major topics in bold

Animals
Anterior Cerebral Artery
Arachidonic Acid
Basilar Artery
Cerebrovascular Circulation
Cisterna Magna
Formamides
Hydroxyeicosatetraenoic Acids
Injections
Laser-Doppler Flowmetry
Male
Middle Cerebral Artery
Morpholines
Rats
Rats, Sprague-Dawley
Subarachnoid Hemorrhage
Vasospasm, Intracranial