Effect of N-methyl-D-aspartate receptor blockade on the control of cerebral O2 supply/consumption balance during hypoxia in newborn pigs.
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.
Department of Pediatrics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08854-5635, USA.
J A
JA
Williams
R J
RJ
Colon
H R
HR
Weiss
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure; D001921:Brain / Q000098:blood supply*; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D010313:Partial Pressure; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013552:Swine
D016194:Receptors, N-Methyl-D-Aspartate; D002245:Carbon Dioxide; D016291:Dizocilpine Maleate; D010100:Oxygen