Beta-adrenoreceptor antagonists attenuate brain injury after transient focal ischemia in rats.
Beta-adrenoreceptor antagonists experimentally reduce cardiac and renal injury after ischemia and are also clinically useful for myocardial infarction and severe burns. In addition, beta-adrenoreceptor antagonists provide neuroprotective effects after focal cerebral ischemia in experimental settings. We conducted the present study to compare the neuroprotective effects of several beta-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 microg x kg(-1) x min(-1), carvedilol 4 microg x kg(-1) x min(-1), esmolol 200 microg x kg(-1) x min(-1), or landiolol 50 microg x kg(-1) x 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 microg x kg(-1) x min(-1) or landiolol 10 microg x kg(-1) x 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 beta-adrenoreceptor antagonists via either IV or IT than in saline-treated rats (P < 0.05). We conclude that beta-adrenoreceptor antagonists improve neurological and histological outcomes after transient focal cerebral ischemia in rats independent of administration route.
Goyagi
Toru
T
Department of Anesthesia and Intensive Care Medicine, Akita University School of Medicine, Akita, Japan. tgoyagi@doc.med.akita-u.ac.jp
Kimura
Tetsu
T
Nishikawa
Toshiaki
T
Tobe
Yoshitsugu
Y
Masaki
Yoko
Y
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology; D000077261:Carvedilol; D006221:Halothane / Q000494:pharmacology; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009203:Myocardial Infarction / Q000188:drug therapy; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D018685:Anesthetics, Inhalation; D002227:Carbazoles; D009025:Morpholines; D011412:Propanolamines; D013778:Tetrazolium Salts; D000077261:Carvedilol; C077049:landiolol; C009591:triphenyltetrazolium; D014508:Urea; D011433:Propranolol; C036604:esmolol; D006221:Halothane