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Middle cerebral artery function after stroke: the threshold duration of reperfusion for myogenic activity
Marilyn J Cipolla1, Amy B Curry
1Department of Neurology, University of Vermont College of Medicine, Burlington, Vt 05405, USA. mcipolla@zoo.uvm.edu
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.
Insights
Prolonged reperfusion after cerebral ischemia significantly reduces myogenic tone in middle cerebral arteries (MCAs). This impaired myogenic reactivity, crucial for blood flow regulation, highlights the impact of reperfusion duration on cerebrovascular function.
Area of Science:
- Cerebrovascular physiology
- Vascular smooth muscle biology
- Ischemic stroke research
Background:
- Cerebral artery myogenic activity is key for regulating cerebral blood flow.
- Previous research indicates ischemia reduces myogenic tone.
- This study examines post-ischemic reperfusion effects on middle cerebral artery (MCA) myogenic behavior.
Purpose of the Study:
- To investigate how varying reperfusion durations impact MCA myogenic tone and reactivity.
- To quantify spontaneous myogenic tone and contractile responses to transmural pressure (TMP) changes.
- To assess F-actin content as a marker of myogenic activity.
Main Methods:
- Middle cerebral artery (MCA) occlusion model in rats (n=45) for 30 minutes ischemia, followed by diverse reperfusion periods (0-22 hours).
- In vitro arteriograph system to measure MCA diameter changes under controlled TMP.
- Assessment of spontaneous myogenic tone, myogenic reactivity (pressure-diameter slopes), and F-actin content via confocal microscopy.
Main Results:
- Ischemic MCAs showed progressively diminished myogenic tone with increased reperfusion duration.
- Myogenic reactivity was impaired at longer reperfusion periods (≥12 hours), indicated by positive pressure-diameter slopes.
- Reduced F-actin content was observed in ischemic MCAs at 6 and 12 hours of reperfusion.
Conclusions:
- Extended reperfusion periods significantly impair MCA myogenic activity.
- Understanding these effects is crucial for developing effective ischemic stroke treatments.
- Reperfusion duration is a critical factor influencing cerebrovascular autoregulation post-ischemia.