Antioxidant LY231617 enhances electrophysiologic recovery after global cerebral ischemia in dogs

Thomas J K Toung, Anish Bhardwaj, Mimi Wang, Jeffrey Kirsch, Richard J. Traystman

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objective: The potent antioxidant LY231617 (2,6-bis(1,1- dimethylethyl),4,[[(1-ethyl)amino]methyl]phenol hydrochloride) is cytoprotective in models of focal and global cerebral ischemia. We tested the hypothesis that administration of LY231617, before the insult, would improve recovery of cerebral electrical activity and metabolic function after transient global cerebral ischemia by improving cerebral blood flow (CBF) during the reperfusion period. Design: Randomized, controlled, prospective study. Setting: Research laboratory at a university teaching hospital. Subjects: Twenty-four male beagle dogs. Interventions: All experiments were performed under pento, barbital anesthesia and controlled conditions of normoxia, normocarbia, and normothermia. Twelve control dogs received 20 mL/kg saline (vehicle) bolus into the right atrium and 0.01 mL/kg/min iv, beginning 20 mins before 13 mins of global cerebral ischemia (by aortic occlusion). The dogs in the drug-treated group received LY231617 as a 10- mg/kg bolus 20 mins before ischemia and 5 mg/kg/hr throughout reperfusion (n = 12). CBF was measured using radiolabeled microspheres. Measurements and Main Results: Total CBF, cerebral oxygen consumption, and somatosensory evoked potentials (SEP) were measured during 240 mins of reperfusion. CBF was similar in both vehicle- and LY231617-treated animals at baseline and throughout the experimental period. In all animals, SEP became isoelectric between 60 and 100 secs after cross-clamping of the ascending aorta. SEP amplitude recovery was significantly higher in drug-treated animals compared with controls (73% ± 15% vs. 39% ± 14% [mean ± SEM] from baseline at 126 mins [p <.65] and 86% ± 12% vs. 49% ± 14% from baseline at 240 mins [p <.05]). Conclusions: LY231617 improves recovery of cerebral electrical function after complete transient global ischemia via mechanisms unrelated to cerebral circulatory effects.

Original languageEnglish (US)
Pages (from-to)196-201
Number of pages6
JournalCritical Care Medicine
Volume28
Issue number1
StatePublished - 2000
Externally publishedYes

Fingerprint

LY 231617
Cerebrovascular Circulation
Brain Ischemia
Antioxidants
Dogs
Somatosensory Evoked Potentials
Reperfusion
Ischemia
Barbital
Transient Ischemic Attack
Heart Atria
Microspheres
Constriction
Oxygen Consumption
Teaching Hospitals
Pharmaceutical Preparations
Aorta
Anesthesia
Prospective Studies

Keywords

  • Antioxidant
  • Blood flow
  • Brain
  • Cerebral
  • Global
  • Ischemia
  • Metabolism
  • Peroxidation
  • Radicals
  • Somatosensory evoked potentials

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Toung, T. J. K., Bhardwaj, A., Wang, M., Kirsch, J., & Traystman, R. J. (2000). Antioxidant LY231617 enhances electrophysiologic recovery after global cerebral ischemia in dogs. Critical Care Medicine, 28(1), 196-201.

Antioxidant LY231617 enhances electrophysiologic recovery after global cerebral ischemia in dogs. / Toung, Thomas J K; Bhardwaj, Anish; Wang, Mimi; Kirsch, Jeffrey; Traystman, Richard J.

In: Critical Care Medicine, Vol. 28, No. 1, 2000, p. 196-201.

Research output: Contribution to journalArticle

Toung, TJK, Bhardwaj, A, Wang, M, Kirsch, J & Traystman, RJ 2000, 'Antioxidant LY231617 enhances electrophysiologic recovery after global cerebral ischemia in dogs', Critical Care Medicine, vol. 28, no. 1, pp. 196-201.
Toung, Thomas J K ; Bhardwaj, Anish ; Wang, Mimi ; Kirsch, Jeffrey ; Traystman, Richard J. / Antioxidant LY231617 enhances electrophysiologic recovery after global cerebral ischemia in dogs. In: Critical Care Medicine. 2000 ; Vol. 28, No. 1. pp. 196-201.
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