Quantification of leptomeningeal collateral blood flow in hypertensive rats during ischemic stroke.

Abstract

OBJECTIVES: There is increasing evidence that poor leptomeningeal collateral blood flow in hypertensive animals is due to increased vascular myogenic tone, indicating that therapies to enhance collateral blood flow during ischemic stroke may be particularly effective. To develop such therapies, we need a greater understanding of the factors that regulate collateral blood flow in the setting of hypertension. Therefore, we aimed to quantify blood flow velocity, diameter and absolute blood flow in individual collateral vessels in an ischemic stroke model in spontaneously hypertensive rats (SHRs) and determine which factors had the greatest influence on blood flow. MATERIALS AND METHODS: We quantified collateral flow velocity and vessel diameter and calculated absolute collateral blood flow in SHRs (n = 5) during 70 min of middle cerebral artery occlusion (MCAO), using a fluorescent microsphere method. RESULTS: Average collateral blood flow significantly increased post-occlusion relative to baseline (pre-MCAO: 16.8 ± 7.1nL/min vs. post-MCAO: 146.4 ± 37.7nL/min, p = 0.02). Within animal linear regression analysis showed a strong positive correlation between changes in collateral blood flow versus changes in collateral diameter during stroke (r = 0.7-0.99, p = 0.3-0.002). In contrast, collateral blood flow was only weakly correlated with collateral blood flow velocity during stroke (r = -0.03-0.97, p = 0.9-0.1). CONCLUSIONS: Collateral blood flow and velocity significantly increased post-occlusion. Collateral flow was strongly influenced by vessel diameter, likely because of marked baseline vasoconstriction of collaterals which is flow-limiting.