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From the Department of Anesthesia and Intensive Care Medicine, Akita University School of Medicine, Akita, Japan.
Address correspondence and reprint requests to Toru Goyagi, MD, Akita University School of Medicine, 1-1-1 Hondo, Akita-city, Akita, 010-8543, Japan. Address e-mail to tgoyagi{at}doc.med.akita-u.ac.jp.
ß-adrenoreceptor antagonists experimentally reduce cardiac and renal injury after ischemia and are also clinically useful for myocardial infarction and severe burns. In addition, ß-adrenoreceptor antagonists provide neuroprotective effects after focal cerebral ischemia in experimental settings. We conducted the present study to compare the neuroprotective effects of several ß-adrenoreceptor antagonists in rat transient focal cerebral ischemia. Halothane-anesthetized normothermic adult male Sprague-Dawley rats were subjected to 2 h of middle cerebral artery occlusion using the intraluminal suture technique confirmed by laser Doppler flowmetry. Rats received an IV infusion of saline 0.5 mL/h, propranolol 100 µg · kg–1 · min–1, carvedilol 4 µg · kg–1 · min–1, esmolol 200 µg · kg–1 · min–1, or landiolol 50 µg · kg–1 · min–1 (n = 6 in each group). Infusion was initiated 30 min before middle cerebral artery occlusion and continued for 24 h. Additional rats received esmolol 50 µg · kg–1 · min–1 or landiolol 10 µg · kg–1 · min–1 intrathecally (IT) via the cisterna magna (n = 5 in each group), according to the same experimental protocol. The neurological deficit score was evaluated at 22 h after reperfusion, and the brains were removed and stained with triphenyltetrazolium chloride for evaluation of infarct volume. Additional rats that received saline, esmolol, and landiolol IV (n = 6 in each group) were allowed to survive for 7 days followed by measurement of infarct size. Neurological deficit scores were smaller in rats treated with propranolol-IV, carvedilol-IV, esmolol-IV, landiolol-IV, esmolol-IT, and landiolol-IT compared with saline-treated rats (P < 0.05). Cortical and striatum infarct volumes were less in the rats receiving ß-adrenoreceptor antagonists via either IV or IT than in saline-treated rats (P < 0.05). We conclude that ß-adrenoreceptor antagonists improve neurological and histological outcomes after transient focal cerebral ischemia in rats independent of administration route.
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