Impact of Focal Ischemia/Reperfusion on the Microcirculation in Cerebral Cortex in Rats

The aim of this study was to evaluate the impact of focal ischemia/reperfusion (I/R) on the basal vasodilator tone produced in the cerebral microcirculation by nitric oxide and prostacyclin and to determine if superoxide dismutase has a protective effect. The experiments were performed on 83 anesthetized and mechanically ventilated adult male Wistar rats. Cerebrocortical microflow (LDF) was continuously monitored using a laser Doppler probe. Focal cerebral ischemia (decrease of LDF to 25%-30% of control) was induced for 30 min by suture occlusion of the middle cerebral artery in rats untreated or pretreated with polyethylene glycol-conjugated superoxide dismutase (PEG-SOD, 10000 U/kg i.v.). During reperfusion the reactivity of microflow to N G-nitro-L-arginine methyl esther (L-NAME), indomethacin, and papaverine was tested. I/R did not affect the LDF response to L-NAME or papaverine but abolished the response to indomethacin. Although pretreatment with PEG-SOD resulted in a multifold increase of plasma SOD scavenging activity, it did not affect the severity of the ischemia or the time course of reperfusion. It also failed to restore the normal response of LDF to indomethacin. Our results demonstrate that shear stress-dependent control of the cerebral microcirculation is impaired following focal I/R in the rat due to the withdrawal of prostacyclin-dependent vasodilator tone. They also suggest that superoxide radicals are not responsible for this impairment.