Effect of N-Methyl-D-Aspartate Receptor Blockade on the Control of Cerebral O2 Supply/Consumption Balance During Hypoxia in Newborn Pigs |
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Authors: | Williams Jacqueline A. Colon Roberto J. Weiss Harvey R. |
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Affiliation: | (1) Heart and Brain Circulation Laboratory, Departments of Pediatrics and Physiology & Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey, 08854-5635 |
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Abstract: | Using dizocilpine (MK-801), we tested the hypothesis that N-methyl-D-aspartate (NMDA) receptors are important controllers of cerebral O2 supply/consumption balance in newborn piglets both during normoxia and hypoxia. Twenty-five 2 to 7-day-old piglets were anesthetized and divided into four groups: (1) Normoxia (n = 6), (2) Normoxia + MK-801 (n = 6), (3) Hypoxia (n = 6), and (4) Hypoxia + MK-801 (n = 7). Regional cerebral blood flow (rCBF) in ml/min/100 g was measured using 14C-iodoantipyrine, and we determined arterial and venous O2 saturations by microspectrophotometry, calculating cerebral O2 consumption (VO2) in ml O2/min/100 g in the cortex, hypothalamus and pons. MK-801 did not significantly affect regional VO2 or rCBF in normoxic piglets. Hypoxia resulted in an increase in local rCBF compared to controls: from 41 ± 6 to 103 ± 18 in the cortex; 34 ± 7 to 101 ± 20 in the hypothalamus; and 45 ± 10 to 95 ± 11 in the pons. Pretreatment with MK-801 abolished this hypoxic flow effect in the cortex (51 ± 2) and hypothalamus (49 ± 5), but not in the pons (91 ± 17). Similar results were observed for VO2 with control values of 1.9 ± 0.3, 1.6 ± 0.2 and 2.1 ± 0.3 for the cortex, hypothalamus and pons respectively. Hypoxia resulted in an increase in the VO2 to 3.9 ± 0.4 (cortex), 3.8 ± 0.6 (hypothalamus) and 3.9 ± 0.8 (pons). Pretreatment with MK-801 prior to hypoxia abolished these effects in the cortex (2.1 ± 0.2) and hypothalamus (2.1 ± 0.2), but not in the pons (2.9 ± 0.2). These findings suggest that NMDA receptors may play a role in the control of cerebral metabolism during hypoxia in this immature porcine model. |
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Keywords: | Cerebral blood flow newborn pigs glutamate N-methyl-D-aspartate cerebral metabolism hypoxia |
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