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

J Neurosurg Anesthesiol. 2013 Jul;25(3):292-8. doi: 10.1097/ANA.0b013e31827fe3b1.

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.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Blood Pressure / drug effects
  • Body Temperature / physiology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / pathology*
  • CA1 Region, Hippocampal / pathology*
  • Cerebrovascular Circulation / drug effects
  • Dose-Response Relationship, Drug
  • Gerbillinae
  • Heart Rate / drug effects
  • Logistic Models
  • Male
  • Neuroprotective Agents*
  • Paraffin Embedding
  • Propanolamines / pharmacology*
  • Prosencephalon / pathology

Substances

  • Adrenergic beta-Antagonists
  • Neuroprotective Agents
  • Propanolamines
  • esmolol