EFFECT OF N-METHYL-D-ASPARTATE RECEPTOR BLOCKADE ON THE CONTROL OF CEREBRAL O-2 SUPPLY CONSUMPTION BALANCE DURING HYPOXIA IN NEWBORN PIGS/

Using dizocilpine (MK-801), we tested the hypothesis that N-methyl-D-a spartate (NMDA) receptors are important controllers of cerebral O-2 su pply/consumption balance in newborn piglets both during normoxia and h ypoxia. Twenty-five 2 to 7-day-old piglets were anesthetized and divid ed 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 ce rebral blood flow (rCBF) in ml/min/100 g was measured using C-14-iodoa ntipyrine, and we determined arterial and venous O-2 saturations by mi crospectrophotometry, calculating cerebral O-2 consrtmption (VO2) in m l O-2/min/100 g in the cortex, hypothalamus and pens. MK-801 did not s ignificantly 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 hypotha lamus; and 45 +/- 10 to 95 +/- 11 in the pens. Pretreatment with MK-80 1 abolished this hypoxic flow effect in the cortex (51 +/- 2) and hypo thalamus (49 +/- 5), but not in the pens (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 pens respectively Hyp oxia 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 pens (2.9 +/- 0.2). The se findings suggest that NMDA receptors may play a role in the control of cerebral metabolism during hypoxia in this immature porcine model.