A comparison of hypothermia and methyl isobutyl amiloride as cerebroprotectants against ischemia

John D. Davis, James J. Vornov, Rafael J Tamargo

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Abstract

Cerebral ischemic reperfusion injury may occur due to rapid realkalinization of neurons. We have previously shown in vitro that blockade of Na+/H+ antiporters by amiloride analogs slows realkalinization and reduces rat hippocampal cell death. We compare here the in vivo efficacy of methyl isobutyl amiloride (MIA), an amiloride analog shown to cross the blood-brain barrier, to that of hypothermia in reducing infarct volume using the rat thread middle cerebral artery (MCA) occlusion model. Thirty-nine male Sprague-Dawley rats were anesthetized with enflurane and equally divided into three groups by treatment: MIA, hypothermia, and control. Ischemia was induced using MCA thread occlusion and maintained for 2 hours. After confirmation of contralateral hemiparesis, the rats were reanesthetized, injected with MIA or carrier, and the suture withdrawn. Standard physiological parameters were monitored in all groups. Animals were killed the following day. Coronally sliced sections were stained in 1% tetrazolium red. Infarct volume was calculated as a percentage of the contralateral hemisphere volume to eliminate the effect of ipsilateral edema. Infarct volume for controls was 44.2 ± 6.4% (mean ± standard error of mean), for MIA group was 53.5 ± 7.5% (Bonferroni-Dunn, p = 0.31), and for hypothermia group was significantly lower at 6.9 ± 4.7% (p = 0.003). Average temperature at onset of ischemia for MIA and control groups was 37.4°C but for hypothermia group it was 31.4°. In addition, the hypothermic group differed physiologically from the other groups by a lower pH secondary to hypoventilation and hypercarbia. We conclude that MIA as administered here is not protective in temporary cerebral ischemia. Hypothermia, however, is confirmed to be an effective protectant in this model.

Original languageEnglish (US)
JournalJournal of Neurosurgery
Volume88
Issue number1
Publication statusPublished - 1998
Externally publishedYes

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ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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