MK-801 does not prevent impaired cerebrovascular reactivity to CO2 during hypoglycemia in piglets

P. J. St. Jacques, J. R. Kirsch, M. N. Diringer, R. J. Traystman

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

We tested the hypothesis that severe insulin-induced hypoglycemia would depress cerebrovascular reactivity to CO2 via a mechanism that could be prevented by administration of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 in infant piglets. Cerebral blood flow (CBF) was measured (microspheres) in 2- to 3-wk-old pentobarbital-anesthetized piglets during hypocapnia, normocapnia, and hypercapnia. Repeat CBF measurements were made either 1 (n = 5) or 2 h (n = 6) after insulin (200 U/kg iv) to elicit the time course of altered reactivity to CO2. Repeat CBF measurements were made in a third group (n = 5) 2 h after treatment with insulin and MK-801 (1.5 mg/kg iv bolus, 0.15 mg · kg-1 · h-1 iv infusion) to determine whether any alteration in reactivity to CO2 was due to a mechanism involving the NMDA receptor. Cerebrovascular resistance and cerebral O2 consumption (CMR(O2)) were calculated with each measurement of CBF. Cerebrovascular response to CO2 (change in cerebrovascular resistance/change in arterial CO2 tension) was ablated in the group of piglets exposed to 1 or 2 h of hypoglycemia (preinsulin 1-h group, 0.038 ± 0.007; preinsulin 2-h group, 0.023 ± 0.004 mmHg · ml-1 · min · 100 g · mmHg CO2-1). Treatment with MK-801 did not alter normoglycemic CO2 reactivity (preinsulin, 0.032 ± 0.005 mmHg · ml-1 · min · 100 g · mmHg CO2-1) and did not prevent ablation of cerebrovascular CO2 reactivity during hypoglycemia. CMR(O2) was not affected by hypoglycemia in any group. We conclude that severe insulin- induced hypoglycemia causes ablation in cerebrovascular CO2 reactivity via a mechanism that is not related to alteration in global CMR(O2) and that cannot be prevented by pretreatment with the NMDA receptor antagonist MK- 801.

Original languageEnglish (US)
Pages (from-to)H2124-H2130
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume264
Issue number6 33-6
StatePublished - Jan 1 1993

Keywords

  • cerebral blood flow
  • cerebral oxygen metabolism
  • glucose
  • hypercapnia
  • hypocapnia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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