Reperfusion Decreases Myogenic Reactivity and Alters Middle Cerebral Artery Function After Focal Cerebral Ischemia in Rats

Abstract

Background and Purpose After focal cerebral ischemia, the function of cerebral arteries is critical to maintain cerebrovascular resistance and minimize damage to ischemic brain regions during reperfusion. In this study we examined the contractile function of isolated and pressurized middle cerebral arteries (MCAs) after 2 hours of occlusion with either 1 to 2 minutes or 24 hours of reperfusion using the intraluminal suture model of transient focal ischemia in rats. Methods MCAs were dissected after 2 hours of occlusion with either 1 to 2 minutes (OCC, n=8) or 24 hours (RPF, n=5) of reperfusion and compared with those of controls that did not have surgery (n=5). Isolated MCAs were mounted on two glass cannulas in an arteriograph chamber that allowed control over transmural pressure (TMP) and measurement of lumen diameter. Responses to changes in TMP (including myogenic reactivity, basal tone, and passive distensibility) and sensitivity to serotonin and acetylcholine were compared. Results Increasing TMP from 25 to 75 mm Hg caused vasoconstriction and development of tone that was similar in control and OCC arteries: percent tone was 33±5% versus 25±7% ( P >.05). In contrast, tone was severely diminished in RPF MCAs after 24 hours of reperfusion: percent tone=8±4% ( P <.01). Sensitivity to serotonin was reduced in OCC arteries, increasing the EC 50 value from 0.04±0.1 to 0.11±0.02 μmol/L ( P <.05); after 24 hours of reperfusion, sensitivity of RPF MCAs was similar to control. Vasodilation to 10.0 μmol/L acetylcholine was significantly impaired only in RPF arteries: percent increased lumen diameter was 19±3% (control) and 13±4% (OCC, P >.05) versus 9±2% (RPF, P <.01). Passively, OCC MCAs were more distensible, which was reversed after 24 hours of reperfusion; RPF vessels had distensibility similar to that of control arteries but thicker arterial walls. Conclusions Abnormal structure and function of MCAs occur after 2 hours of ischemia, with diminished myogenic reactivity and tone associated with longer reperfusion.