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O-013 Hypertension Decreases the Number and Duration of Collateral Openings during Middle Cerebral Artery Occlusion (MCAO) and Impairs Reperfusion
  1. M Cipolla,
  2. J Sweet,
  3. K Chan
  1. Neurological Sciences, University of Vermont, Burlington, VT


Introduction Hypertension is associated with large ischemic cores and little penumbral tissue that is thought to contribute to poor outcome from ischemic stroke. Pial collaterals (leptomeningeal anastomoses; LMA) are thought to perfuse the penumbra during MCAO by promoting retrograde flow from the anterior cerebral artery (ACA) to the MCA territory. We recently demonstrated that pial collaterals are vasoconstricted in spontaneously hypertensive rats (SHR) that likely contributes to poor collateral flow and increased infarction. Here, we developed methodology to measure collateral openings in SHR (n = 6) compared to normotensive Wistar (n = 6) rats during MCAO. We hypothesized that SHR have fewer collateral openings and/or shorter duration openings during MCAO, and impaired reperfusion.

Materials and methods Dual laser Doppler probes were used to simultaneously measure changes in relative cerebral blood flow (rCBF) in the MCA (probe 1: Bregma −2, lateral +4) and ACA collateral (probe 2: Bregma +2, lateral +3) vascular territories during 2 hours of MCAO by filament occlusion (Figure 1). Collateral openings were defined as increased collateral flow that did not correspond to changes in blood pressure. The number and duration of collateral openings were quantified off rCBF tracings blinded to group. Animals were mechanically ventilated during MCAO to maintain blood gases within physiologic ranges and body temperature at 37°C. Chloral hydrate anesthesia was used. Data are presented as mean ± SEM.

Results The overall drop in CBF during ischemia was similar between Wistar and SHR (−73 ± 1% and −78 ± 4%; p > 0.05). The average number collateral openings during 2 hours of ischemia was decreased in SHR compared to Wistar (0.8 ± 0.6 vs. 2.2 ± 0.3; p = 0.06), as was the total duration of collateral opening (4 ± 4 vs. 26 ± 8 min; p < 0.05). After 2 hours of reperfusion, rCBF was decreased in the MCA territory in both SHR and Wistar compared to baseline (−43 ± 6% and −24 ± 4%; p < 0.05) demonstrating incomplete microcirculatory perfusion; however, rCBF in the collateral perfusion territory was decreased in SHR and increased in Wistar (although variable) compared to baseline (−26 ± 7% vs. 70 ± 63%).

Conclusions These results demonstrate that collateral flow during ischemia, and reperfusion, was impaired in hypertension likely due to vasoconstriction of LMAs. Understanding the function of pial collaterals under conditions such as hypertension, that is associated with little penumbral tissue, may provide targeted therapies to prevent collateral failure and extend the time window for treatment in these patients.

Disclosures M. Cipolla: 1; C; NIH grants. J. Sweet: None. K. Chan: None.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work noncommercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

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