Middle cerebral artery function after stroke: the threshold duration of reperfusion for myogenic activity

Abstract

Background and purpose: Myogenic activity of the cerebral arteries is an important contributor to autoregulation of cerebral blood flow. Previous studies have demonstrated that increasing periods of ischemia diminished the amount of myogenic tone in cerebral arteries. In the present study, we investigated the effect of different periods of postischemic reperfusion on the myogenic behavior of middle cerebral arteries (MCAs). We measured both the amount of spontaneous myogenic tone that developed at 75 mm Hg and the contractile response to increased transmural pressure (TMP), ie, myogenic reactivity.

Methods: The MCA occlusion model was used in male Wistar rats (n=45) to induce 30 minutes of temporary ischemia, followed by different periods of reperfusion (0 or sham; 30 minutes; and 6, 12, 18, 20, and 22 hours), confirmed by laser Doppler flowmetry. MCAs were studied in vitro using an arteriograph system that allowed control of TMP and measurement of lumen diameter. After equilibration for 1 hour at 75 mm Hg, TMP was increased stepwise in 25-mm Hg increments to 125 mm Hg and lumen diameter measured at each pressure. The amount of spontaneous myogenic tone was determined in both ischemic and contralateral arteries for each reperfusion period and compared with the right and left MCAs in the sham group. Arteries were then fixed with 10% formalin pressurized in the arteriograph bath and stained for filamentous (F)-actin with fluorescently labeled phalloidin, a specific probe for F-actin. The amount of F-actin was quantified using confocal microscopy.

Results: MCAs from the sham-operated control group possessed considerable myogenic tone (35%). However, the amount of tone in ischemic MCAs progressively diminished as the reperfusion duration increased. In addition, sham-operated control arteries responded myogenically to increases in TMP, decreasing diameter as pressure increased. There was a similar response in arteries exposed to 30 minutes and 6 hours of reperfusion, all producing a negative slope on the pressure-diameter curve; however, myogenic reactivity was diminished at the longer periods of reperfusion, producing a positive slope of the graph. The slopes of the pressure-diameter curves were as follows: -0.10+/--0.06 (sham), -0.07+/--0.12 (30 minutes), -0.08+/--0.11 (6 hours), +0.09+/-0.09 (12 hours), +0.25+/-0.16 (18 hours), +0.38+/-0.09 (20 hours), and +0.57+/-0.09 (22 hours). F-actin content was significantly less only in ischemic MCAs at 6 and 12 hours of reperfusion.

Conclusions: These results demonstrate that longer periods of reperfusion significantly diminish myogenic activity of MCAs. Understanding how different periods of ischemia and reperfusion affect the function of the cerebral circulation may promote more effective treatment of ischemic stroke.