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. © 1994 American Heart Association, Inc. All rights reserved.