title: Quantitative evaluation of the neuroprotective effects of a short-acting β-adrenoceptor antagonist at a clinical dose on forebrain ischemia in gerbils: effects of esmolol on ischemic depolarization and histologic outcome of hippocampal CA1.
abstract: BACKGROUND
  Neuroprotective effects of esmolol in laboratory and clinical settings have been reported. The present study was designed to quantitatively evaluate the neuroprotective effects of esmolol using logistic regression curves and extracellular potentials.
  
  
  METHODS
  In 42 gerbils, bilateral occlusion of common carotid arteries was performed for 3, 5, or 7 minutes (n=7 in each group). In treated animals, esmolol (200 µg/kg/min) was administered for 90 minutes, 30 minutes before the onset of ischemia. Direct current potentials were measured in the bilateral CA1 regions, in which histologic evaluation was performed 5 days later. Relations of neuronal damage with ischemic duration and duration of ischemic depolarization were determined using logistic regression curves.
  
  
  RESULTS
  There was no significant difference in onset time between the 2 groups (the control group vs. the esmolol group: 1.65±0.46 vs. 1.68±0.45 min, P=0.76), and significant differences in durations of ischemic depolarization were not observed with any ischemic duration. However, logistic regression curves indicated that esmolol has a neuroprotective effect from 2.95 to 7.66 minutes of ischemic depolarization (P<0.05), and esmolol prolonged the duration of ischemic depolarization causing 50% neuronal damage from 4.97 to 6.34 minutes (P<0.05). Logistic regression curves also indicated that esmolol has a neuroprotective effect from 3.77 to 7.74 minutes of ischemic duration (P<0.05), and esmolol prolonged the ischemic duration causing 50% neuronal damage from 4.26 to 4.91 minutes (P<0.05).
  
  
  CONCLUSIONS
  Esmolol has neuroprotective effects in the acute phase of ischemia by a mechanism other than shortening the duration of ischemic depolarization.
authors.affiliation: Department of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama City, Okayama, Japan. gmd20012@s.okayama-u.ac.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Danura
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Takeda
authors.forename: Kensuke
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Naito
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Mizoue
authors.forename: Sachiko
authors.initials: S
authors.lastname: Sato
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Morita
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D056547:CA1 Region, Hippocampal / Q000473:pathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005849:Gerbillinae; D006339:Heart Rate / Q000187:drug effects; D016015:Logistic Models; D008297:Male; D018696:Neuroprotective Agents; D016612:Paraffin Embedding; D011412:Propanolamines / Q000494:pharmacology*; D016548:Prosencephalon / Q000473:pathology
chemical_list: D000319:Adrenergic beta-Antagonists; D018696:Neuroprotective Agents; D011412:Propanolamines; C036604:esmolol