Tirilazad treatment does not decrease early brain injury after transient focal ischemia in cats

Reiko Takeshima, Jeffrey Kirsch, Raymond C. Koehler, Richard J. Traystman

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background and Purpose We tested the hypothesis that administration of the antioxidant tirilazad mesylate improves electrophysiological recovery and decreases infarct volume after transient focal cerebral ischemia in cats. Methods Halothane-anesthetized cats underwent 90 minutes of left middle cerebral artery and bilateral common carotid artery occlusion followed by 180 minutes of reperfusion. Cats were assigned to receive tirilazad (1.5 mg/kg plus 0.2 mg/kg per hour IV infusion) either at the beginning (n=9) or conclusion (n=9) of ischemia. Control cats received an equal volume of diluent (citrate buffer, pH 3.0; n=7) at the beginning and conclusion of ischemia in a blinded fashion. Infarct volume was measured by 2, 3, 5-triphenyltetrazolium chloride staining. Results Blood flow to the left temporoparietal cortex decreased to less than 10 mL/min per 100 g with ischemia but was minimally affected on the right side. Blood flow distribution during ischemia or reperfusion was not different in the tirilazad-treated groups. No group demonstrated postischemic hyperemia or delayed hypoperfusion. Somatosensory evoked potential recorded over the left cortex was ablated during ischemia and recovered to less than 15% of baseline amplitude at 180 minutes of reperfusion in all groups. There were no differences among groups in infarct volume of left hemisphere (pretreatment, 25±6% [mean±SE]; posttreatment, 33±5%; control, 28±8% of hemisphere) or caudate nucleus (pretreatment, 46±7%; posttreatment, 41±10%; control, 55±13% of hemisphere). Conclusions In an experimental model of focal ischemia involving severe reductions of blood flow followed by reperfusion in cats, administration of tirilazad at the onset of either ischemia or reperfusion does not ameliorate infarct volume assessed during early reperfusion. Our study does not address potential efficacy of tirilazad in the setting of a different dosing strategy or duration of reperfusion.

Original languageEnglish (US)
Pages (from-to)670-676
Number of pages7
JournalStroke
Volume25
Issue number3
StatePublished - 1994
Externally publishedYes

Fingerprint

Brain Injuries
Reperfusion
Cats
Ischemia
Somatosensory Evoked Potentials
Caudate Nucleus
Common Carotid Artery
Transient Ischemic Attack
Hyperemia
Middle Cerebral Artery
Halothane
tirilazad
Citric Acid
Buffers
Theoretical Models
Antioxidants
Staining and Labeling

Keywords

  • 2
  • 3
  • 5-triphenyltetrazolium chloride
  • Lipid peroxidation
  • Middle cerebral artery occlusion
  • Oxygen radical
  • Somatosensory evoked potentials
  • Stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing
  • Neuroscience(all)

Cite this

Takeshima, R., Kirsch, J., Koehler, R. C., & Traystman, R. J. (1994). Tirilazad treatment does not decrease early brain injury after transient focal ischemia in cats. Stroke, 25(3), 670-676.

Tirilazad treatment does not decrease early brain injury after transient focal ischemia in cats. / Takeshima, Reiko; Kirsch, Jeffrey; Koehler, Raymond C.; Traystman, Richard J.

In: Stroke, Vol. 25, No. 3, 1994, p. 670-676.

Research output: Contribution to journalArticle

Takeshima, R, Kirsch, J, Koehler, RC & Traystman, RJ 1994, 'Tirilazad treatment does not decrease early brain injury after transient focal ischemia in cats', Stroke, vol. 25, no. 3, pp. 670-676.
Takeshima, Reiko ; Kirsch, Jeffrey ; Koehler, Raymond C. ; Traystman, Richard J. / Tirilazad treatment does not decrease early brain injury after transient focal ischemia in cats. In: Stroke. 1994 ; Vol. 25, No. 3. pp. 670-676.
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title = "Tirilazad treatment does not decrease early brain injury after transient focal ischemia in cats",
abstract = "Background and Purpose We tested the hypothesis that administration of the antioxidant tirilazad mesylate improves electrophysiological recovery and decreases infarct volume after transient focal cerebral ischemia in cats. Methods Halothane-anesthetized cats underwent 90 minutes of left middle cerebral artery and bilateral common carotid artery occlusion followed by 180 minutes of reperfusion. Cats were assigned to receive tirilazad (1.5 mg/kg plus 0.2 mg/kg per hour IV infusion) either at the beginning (n=9) or conclusion (n=9) of ischemia. Control cats received an equal volume of diluent (citrate buffer, pH 3.0; n=7) at the beginning and conclusion of ischemia in a blinded fashion. Infarct volume was measured by 2, 3, 5-triphenyltetrazolium chloride staining. Results Blood flow to the left temporoparietal cortex decreased to less than 10 mL/min per 100 g with ischemia but was minimally affected on the right side. Blood flow distribution during ischemia or reperfusion was not different in the tirilazad-treated groups. No group demonstrated postischemic hyperemia or delayed hypoperfusion. Somatosensory evoked potential recorded over the left cortex was ablated during ischemia and recovered to less than 15{\%} of baseline amplitude at 180 minutes of reperfusion in all groups. There were no differences among groups in infarct volume of left hemisphere (pretreatment, 25±6{\%} [mean±SE]; posttreatment, 33±5{\%}; control, 28±8{\%} of hemisphere) or caudate nucleus (pretreatment, 46±7{\%}; posttreatment, 41±10{\%}; control, 55±13{\%} of hemisphere). Conclusions In an experimental model of focal ischemia involving severe reductions of blood flow followed by reperfusion in cats, administration of tirilazad at the onset of either ischemia or reperfusion does not ameliorate infarct volume assessed during early reperfusion. Our study does not address potential efficacy of tirilazad in the setting of a different dosing strategy or duration of reperfusion.",
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N2 - Background and Purpose We tested the hypothesis that administration of the antioxidant tirilazad mesylate improves electrophysiological recovery and decreases infarct volume after transient focal cerebral ischemia in cats. Methods Halothane-anesthetized cats underwent 90 minutes of left middle cerebral artery and bilateral common carotid artery occlusion followed by 180 minutes of reperfusion. Cats were assigned to receive tirilazad (1.5 mg/kg plus 0.2 mg/kg per hour IV infusion) either at the beginning (n=9) or conclusion (n=9) of ischemia. Control cats received an equal volume of diluent (citrate buffer, pH 3.0; n=7) at the beginning and conclusion of ischemia in a blinded fashion. Infarct volume was measured by 2, 3, 5-triphenyltetrazolium chloride staining. Results Blood flow to the left temporoparietal cortex decreased to less than 10 mL/min per 100 g with ischemia but was minimally affected on the right side. Blood flow distribution during ischemia or reperfusion was not different in the tirilazad-treated groups. No group demonstrated postischemic hyperemia or delayed hypoperfusion. Somatosensory evoked potential recorded over the left cortex was ablated during ischemia and recovered to less than 15% of baseline amplitude at 180 minutes of reperfusion in all groups. There were no differences among groups in infarct volume of left hemisphere (pretreatment, 25±6% [mean±SE]; posttreatment, 33±5%; control, 28±8% of hemisphere) or caudate nucleus (pretreatment, 46±7%; posttreatment, 41±10%; control, 55±13% of hemisphere). Conclusions In an experimental model of focal ischemia involving severe reductions of blood flow followed by reperfusion in cats, administration of tirilazad at the onset of either ischemia or reperfusion does not ameliorate infarct volume assessed during early reperfusion. Our study does not address potential efficacy of tirilazad in the setting of a different dosing strategy or duration of reperfusion.

AB - Background and Purpose We tested the hypothesis that administration of the antioxidant tirilazad mesylate improves electrophysiological recovery and decreases infarct volume after transient focal cerebral ischemia in cats. Methods Halothane-anesthetized cats underwent 90 minutes of left middle cerebral artery and bilateral common carotid artery occlusion followed by 180 minutes of reperfusion. Cats were assigned to receive tirilazad (1.5 mg/kg plus 0.2 mg/kg per hour IV infusion) either at the beginning (n=9) or conclusion (n=9) of ischemia. Control cats received an equal volume of diluent (citrate buffer, pH 3.0; n=7) at the beginning and conclusion of ischemia in a blinded fashion. Infarct volume was measured by 2, 3, 5-triphenyltetrazolium chloride staining. Results Blood flow to the left temporoparietal cortex decreased to less than 10 mL/min per 100 g with ischemia but was minimally affected on the right side. Blood flow distribution during ischemia or reperfusion was not different in the tirilazad-treated groups. No group demonstrated postischemic hyperemia or delayed hypoperfusion. Somatosensory evoked potential recorded over the left cortex was ablated during ischemia and recovered to less than 15% of baseline amplitude at 180 minutes of reperfusion in all groups. There were no differences among groups in infarct volume of left hemisphere (pretreatment, 25±6% [mean±SE]; posttreatment, 33±5%; control, 28±8% of hemisphere) or caudate nucleus (pretreatment, 46±7%; posttreatment, 41±10%; control, 55±13% of hemisphere). Conclusions In an experimental model of focal ischemia involving severe reductions of blood flow followed by reperfusion in cats, administration of tirilazad at the onset of either ischemia or reperfusion does not ameliorate infarct volume assessed during early reperfusion. Our study does not address potential efficacy of tirilazad in the setting of a different dosing strategy or duration of reperfusion.

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