title: Inhibition of neuronal nitric oxide synthase improves microregional O2balance in cerebral ischemia-reperfusion.
abstract: Objectives Return of regional cerebral blood flow (rCBF) in focal cerebral ischaemia may not ensure proper distribution of blood flow to meet metabolic demand. This study was performed to determine how inhibition of neuronal nitric oxide synthase (NOS) during ischaemia-reperfusion would affect microregional O2supply/consumption balances and their variation. Methods Twenty minutes before middle cerebral artery (MCA) occlusion, a NOS inhibitor 7-nitroindazole (7-NI) 50 mg/kg ip (7-NI group) or vehicle (control group) was administered. At 1 hour of ischaemia and 2 hours of reperfusion, rCBF, the size of cortical infarct and arteriolar and venular O2saturations (20-60 μm in diameter) using cryomicrospectrophotometry were determined. Results Ischaemia-reperfusion decreased the average venular O2saturation and the ratio of O2supply/consumption. But, 7-NI treatment improved the average O2supply/consumption ratio and venular O2saturation (57.6 ± 1.3 vs 52.0 ± 3.8%) in ischaemia-reperfusion. The heterogeneity of venular O2saturations reported as coefficient of variation (CV = 100 × SD/mean) was much smaller in the 7-NI than the control group (8.8 vs 15.5). The number of veins with low O2saturation ( < 50%) was also smaller with the 7-NI (4/70) than the control group (18/70). The size of cortical infarct was smaller with 7-NI treatment. Discussion Our data suggest that inhibition of neuronal NOS by 7-NI improved microregional O2balance in the ischaemic-reperfused cortex (IR-C). The improvement in microregional O2balance could be one of the contributing factors to the reduced size of cortical infarct.
authors.forename: Oak Z
authors.initials: OZ
authors.lastname: Chi
authors.forename: Kang H
authors.initials: KH
authors.lastname: Rah
authors.forename: Sylviana
authors.initials: S
authors.lastname: Barsoum
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Harvey R
authors.initials: HR
authors.lastname: Weiss
keywords: Heterogeneity; Ischaemia/reperfusion; Neuronal nitric oxide synthase; Neuroprotection; Regional cerebral blood flow; Venous O2 saturation