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

Abstract

We tested the hypothesis that the excitatory neurotransmitter receptor agonist, alpha amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), would worsen cerebral cortical oxygen supply/consumption balance during focal ischemia. In this study, we compared regional cerebral blood flow, arterial and venous O2 saturation, O2 extraction and oxygen consumption of ischemic and AMPA treated ischemic and control regions of rat brain. Ischemia was induced by middle cerebral artery (MCA) occlusion in isoflurane (1.4%) anesthetized Wistar rats. Twenty minutes after MCA occlusion, 10(-5) M AMPA was applied to the ischemic cortex (IC) for a period of 40 min; the fluid was changed every 10 min. After 1 hr of ischemia, animals were sacrificed and regional cerebral blood flow (rCBF) was determined using the C14-iodoantipyrine autoradiographic technique. Regional arterial and venous oxygen saturation were determined microspectrophotometrically. In control, the cerebral blood flow and oxygen consumption of the IC were significantly lower than the contralateral cortex (rCBF: 46 +/- 20 vs. 81 +/- 39 ml/min/100g, O2 consumption: 2.8 +/- 1.4 vs. 3.6 +/- 1.4 ml O2/min/100g). 10(-5) M AMPA did not significantly alter regional cerebral blood flow and oxygen consumption of the IC, but did decrease the average venous O2 saturation of the IC from 50.2 +/- 3.9% to 46.7 +/- 1.6%. AMPA also significantly increased the frequency of small veins with less than 45% O2 saturation in the IC (8 out of 56 veins in IC vs. 18 out of 56 veins in AMPA treated IC). Thus, topical application of 10(-5) M AMPA to the ischemic area worsens cerebral O2 balance and suggests that excitatory amino acids contribute to the degree of cerebral ischemia.