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

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.