Effect of AMPA receptor blockade on the control of cerebral O₂ supply/consumption balance in newborn pigs

Using 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3- benzodiazepine hydrochloride (GYKI 52466), we tested the hypothesis that α- amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are important controllers of cerebral O₂ supply/consumption balance in newborn piglets during both normoxia and hypoxia. Twenty-seven 2- to 7-day-old piglets were anesthetized with α-chloralose and were divided into four groups: 1) normoxia (n = 7), 2) GYKI 52466 (10 mg/kg, n = 7), 3) hypoxia (n = 6), and 4) hypoxia+GYKI 52466 (n = 7). We used [¹⁴C]iodoantipyrine to measure regional cerebral blood flow (rCBF) in mL/min/100 g, and we determined O₂ extraction by microspectrophotometry, calculating cerebral O₂ consumption (VO₂) in mL O₂/min/100 g in the cortex, hypothalamus, and pons. GYKI 52466 had no effect on regional VO₂ or rCBF in normoxic piglets compared with controls. Hypoxia resulted in an increase in local VO₂ and rCBF in the cortex and hypothalamus compared with controls: rCBF from 50 ± 10 to 97 ± 16 and VO₂ from 2.4 ± 0.5 to 3.7 ± 0.4 in the cortex, and rCBF from 41 ± 9 to 99 ± 17 and VO₂ from 2.5 ± 1 to 3.8 ± 0.5 in the hypothalamus. GYKI 52466 abolished this hypoxic flow effect in both the cortex (68 ± 14) and hypothalamus (73 ± 12). GYKI 52466 also blocked the increased VO₂ in the cortex (2.5 ± 0.4) and hypothalamus (3.0 ± 0.5) of the hypoxic group. These findings suggest that the AMPA receptor is an important controller of VO₂ in the cortex and hypothalamus during hypoxia in this immature porcine model.