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MK-801 does not prevent impaired cerebrovascular reactivity to CO2 during hypoglycemia in piglets
P J St Jacques1, J R Kirsch, M N Diringer
1Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-4963.
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 (CMRO2) 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. CMRO2 was not affected by hypoglycemia in any group.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Severe hypoglycemia in infant piglets depressed cerebrovascular reactivity to CO2. The N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 did not prevent this effect, indicating the NMDA receptor is not involved.
Area of Science:
- Neuroscience
- Physiology
- Perinatal Medicine
Background:
- Hypoglycemia, particularly in infants, can impact brain function.
- Cerebrovascular reactivity to carbon dioxide (CO2) is crucial for maintaining brain blood flow.
- The role of N-methyl-D-aspartate (NMDA) receptors in regulating cerebrovascular responses during hypoglycemia is not fully understood.
Purpose of the Study:
- To investigate the effect of severe insulin-induced hypoglycemia on cerebrovascular reactivity to CO2 in infant piglets.
- To determine if the NMDA receptor antagonist MK-801 can prevent the depression of cerebrovascular reactivity to CO2 during hypoglycemia.
Main Methods:
- Cerebral blood flow (CBF) was measured in infant piglets using microspheres under varying CO2 levels (hypocapnia, normocapnia, hypercapnia).
- Hypoglycemia was induced using insulin, and cerebrovascular reactivity to CO2 was assessed at 1 and 2 hours post-induction.
- A separate group received both insulin and the NMDA receptor antagonist MK-801 to evaluate its protective effect.
Main Results:
- Severe hypoglycemia significantly ablated cerebrovascular reactivity to CO2 in infant piglets.
- Treatment with MK-801 did not alter normal CO2 reactivity and failed to prevent the loss of reactivity during hypoglycemia.
- Cerebral oxygen consumption (CMRO2) remained unaffected by hypoglycemia in all experimental groups.
Conclusions:
- Severe insulin-induced hypoglycemia depresses cerebrovascular reactivity to CO2 in infant piglets.
- The NMDA receptor system does not appear to mediate this depression of cerebrovascular reactivity to CO2.
- These findings suggest that other mechanisms are responsible for the altered cerebrovascular response to CO2 during hypoglycemia in this model.