Effect of tirilazad mesylate on middle cerebral artery occlusion/reperfusion in nonhuman primates

Etsuro Mori, Julia Ember, Brian R. Copeland, Winston S. Thomas, James A. Koziol, Gregory J. del Zoppo

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Agents with lipid membrane protective properties may theoretically reduci the zone of ischemic damage during cerebral arterial recanalization in the early hours of focal cerebral ischemia. The effect of the putative lipid peroxi dation inhibitor tirilazad mesylate (U74006F) on infarction volume and neurological outcome following 3-hour middle cerebral artery occlusion and sub sequent reperfusion in an awake baboon model was examined in a blinded, randomized placebo-controlled study. Awake subjects (8 each) were assigned randomly to receive either tirilazad mesylate (3 mg/kg) or matched vehicle given 15 min prior to reperfusion, and again at 2,4, 12, and 24 h after reperfusion. Neurological status was serially assessed according to a quantitative scale and infarction volumes were computed on perfusion-fixed specimens at 14 days. A 40% reduction in mean total infarction volume index, normalized foi basal ganglia volume, was seen in the tirilazad group. Persistent and increased improvement in mean neurological score with tirilazad infusion paralleled that of the placebo. Parallel studies on polymorphonuclear leukocyte responses indicated no significant changes in polymorphonuclear leukocyte reactivity. A reduction in infarction volume, predominantly in the cortex/sub- cortical white matter, and an improvement in neurological outcome were observed when tirilazad mesylate was given prior to reperfusion, but after the onset of focal cerebral ischemia.

Original languageEnglish
Pages (from-to)342-349
Number of pages8
JournalCerebrovascular Diseases
Volume5
Issue number5
DOIs
Publication statusPublished - 1995 Jan 1

Keywords

  • 21-Aminosteroid
  • Infarction
  • Middle cerebral artery reperfusion
  • Primate

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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