A nonNMDA antagonist, GYKI 52466 improves microscopic O2 balance in the cortex during focal cerebral ischemia.
This study was performed to test whether GYKI 52466, a nonNMDA receptor antagonist, would improve microregional oxygen supply and consumption balance in the focal cerebral ischemic area. Rats were anesthetized with 1.4% isoflurane. For the GYKI Group (n = 8), 10 min before middle cerebral artery (MCA) occlusion, a bolus of 5 mg kg-1 of GYKI 52466 i.v. was administered and was followed by an infusion of 5 mg kg-1 h-1. For the Control Group (n = 8), the same volume of the vehicle was administered. One hour after MCA occlusion, regional cerebral blood flow (rCBF) was measured using the 14C-iodoantipyrine autoradiographic technique. Microscopic arterial and venous oxygen saturations were determined using microspectrophotometry. In the cortex contralateral to MCA occlusion, the average rCBF and the average O2 consumption were lower in the GYKI Group than in the Control Group (rCBF: GYKI 65.5 +/- 24.1 ml 100 g-1 min-1, Control 97.7 +/- 33.4 ml 100 g-1 min-1; O2 consumption: GYKI 3.9 +/- 1.2 ml O2 100 g-1 min-1, Control 6.2 +/- 2.5 ml O2 100 g-1 min-1) without a significant difference in the number of veins with SvO2 < 50%. In the ischemic cortex, the number of veins with SvO2 < 50% was significantly smaller in the GYKI Group (21 veins out of 63) than in the Control Group (45 out of 59) without a significant difference in the average rCBF (GYKI 44.9 +/- 17.7, Control 29.7 +/- 10.4) or regional O2 consumption between these two groups (GYKI 3.3 +/- 1.4, Control 2.7 +/- 1.2). Our data demonstrated that GYKI 52466 was effective in improving microscopic O2 balance in the focal ischemic cortical area of the brain and it decreased O2 consumption in the non-ischemic cortex.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D001794:Blood Pressure; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000098:blood supply / Q000737:chemistry / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006339:Heart Rate; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate