Neuroprotective effects of dexmedetomidine-hypothermia after asphyxial cardiac arrest in rats

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 15591615
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Akita University
• Principal Investigator: KIMURA Tetsu Akita University, School of Medicine, Research Associate, 医学部, 助手 (00312702)
• Co-Investigator(Kenkyū-buntansha): NISHIKAWA Toshiaki Akita university, School of Medicine, Professor, 医学部, 教授 (50156048) ; GOYAGI Toru Akita university, School of Medicine, Assistant Professor, 医学部, 講師 (30302277) ; TANAKA Makoto Akita university, School of Medicine, Assistant Professor, 医学部, 助教授 (50236634)
• Project Period (FY): 2003 – 2005
• Keywords: cerebral ischemia / alpha2 agonist / hypothermia / dexmedetomidine / glutamate / neuroprotection / cardiac arrest

Research Abstract

Background : We examined whether dexmedetomidine would enhance the neuroprotective effects of hypothermia after asphyxial cardiac arrest in rats. Methods : Male Sprague-Dawley rats, anesthetized with halothane, were assigned to one of four groups (n = 8 for each group) ; control (C, saline 1 ml/kg and temporal muscle temperature 37.5 ℃), dexmedetomidine (D, dexmedetomidine 10 μg/kg and 37.5 ℃), hypothermia (H, saline 1 ml/kg and 35.0 ℃), and dexmedetomidine - hypothermia (DH, dexmedetomidine 10 μg/kg and 35.0 ℃) groups. After obtaining predetermined temporal muscle temperature, either dexmedetomidine or saline was administered intraperitoneally 30 min before insult. Cerebral ischemia was induced with asphyxia of 5 min, resulting in cardiac arrest of about 2 min. Spontaneous circulation was restored by external cardiopulmonary resuscitation and intravenous epinephrine. Neurological examination was assessed at 24, 48, and 72 hours after return of spontaneous circulation, and then the brain was fixed and stained with hematoxylin and eosin. Glutamate concentration in the striatum was measured using microdialysis method. Results Percentages of intact neurons in hippocampal CA1 were smaller in the group C than the other groups (C, D, H, and DH : 26 ± 14, 53 ± 9, 61 ± 5, and 58 ± 21 (mean ± SD), respectively (P < 0.05), whereas percentages of intact neurons in cerebellar Purkinje cells were similar among the groups. Neurological deficit scores were similar among the groups. Glutamate concentrations in the striatum were similar among the four treatment groups. Conclusions : Our results indicate that dexmedetomidine 10 μg/kg and hypothermia have the neuroprotective effects after asphyxial cardiac arrest respectively, whereas the addition of dexmedetomidine to hypothermia does not enhance the effects. Our results also indicate that glutamate concentration changes in the brain are unlikely to contribute to neuroprotective effects of dexmedetomidine and hypothermia.