Effect of AMPA on cerebral cortical oxygen balance of ischemic rat brain

We tested the hypothesis that the excitatory neurotransmitter receptor agon ist, alpha amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), would wo rsen cerebral cortical oxygen supply/consumption balance during focal ische mia. In this study, we compared regional cerebral blood flow, arterial and venous O-2 saturation, O-2 extraction and oxygen consumption of ischemic an d AMPA treated ischemic and control regions of rat brain. Ischemia was indu ced by middle cerebral artery (MCA) occlusion in isoflurane (1.4%) anesthet ized Wistar rats. Twenty minutes after MCA occlusion, 10(-5) M AMPA was app lied to the ischemic cortex (IC) for a period of 40 min; the fluid was chan ged every 10 min. After I hr of ischemia, animals were sacrificed and regio nal cerebral blood flow (rCBF) was determined using the C-14-iodoantipyrine autoradiographic technique. Regional arterial and venous oxygen saturation were determined microspectrophotometrically. In control, the cerebral bloo d flow and oxygen consumption of the IC were significantly lower than the c ontralateral cortex (rCBF: 46 +/- 20 vs. 81 +/- 39 ml/min/100g, O-2 consump tion: 2.8 +/- 1.4 vs. 3.6 +/- 1.4 mi O-2/min/100g). 10(-5) M AMPA did not s ignificantly alter regional cerebral blood flow and oxygen consumption of t he IC, but did decrease the average venous O-2 saturation of the IC from 50 .2 +/- 3.9% to 46.7 +/- 1.6%. AMPA also significantly increased the frequen cy of small veins with less than 45% O-2 saturation in the IC (8 out of 56 veins in IC vs. 18 out of 56 veins in AMPA treated IC). Thus, topical appli cation of 10-5 M AMPA to the ischemic area worsens cerebral O-2 balance and suggests that excitatory amino acids contribute to the degree of cerebral ischemia.