Induction of Cerebral Thrombosis With Phenytoin in Rats

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Background and PurposeThis study was conducted to explore whether intra-arterial infusion of phenytoin causes cerebral ischemia and to examine the mechanism of cerebral ischemia induced by phenytoin.MethodsTen rats were infused with phenytoin (150 mu L, 3.75 mg) retrogradely from the left external carotid artery, followed by perfusion of carbon black transcardially. The removed brain was photographed from above, and the nonperfused area was compared with control rats (n equals 10) with the use of an image analyzer. Eight animals with or without phenytoin treatment were perfusion-fixed for transmission electron microscopic analyses of cerebral vasculature. To determine the effect of tissue plasminogen activator (TPA) on phenytoininfused rat cerebrum, 20 rats were treated with or without TPA (120 000 IU) 5 minutes after the phenytoin infusion (n equals 10 each).ResultsAll rats suffered from respiratory distress 25 to 40 minutes after the injection and received carbon black transcardially. The nonperfused area was seen in the territory of the left internal carotid artery. Thrombi were observed from arterioles to capillaries. Under electron microscopy, endothelial cells were partially exfoliated, and the vascular lumen was obstructed by thrombi predominantly consisting of platelets. Eight rats with TPA survived more than 60 minutes, whereas only 2 rats survived without the treatment (P less than .005). Nonperfused areas were 7 plus minus 5% and 50 plus minus 11% of cerebral surface area in rats with and without TPA treatment, respectively (P less than .001).ConclusionsIntra-arterial infusion of phenytoin results in a nonperfused area in rat cerebrum primarily due to thrombosis of arterioles and capillaries.(Stroke. 1996;26:2081-2086.)

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