Treatment with low dose fasudil for acute ischemic stroke in chronic hypertension

Abstract

We investigated the effect of Rho kinase inhibition on changes in cerebral blood flow (CBF), brain injury and vascular function after ischemic stroke in spontaneously hypertensive rats (SHR). Changes in core MCA and collateral perfusion were measured by a validated laser Doppler method. Animals underwent 2 h tMCAO and 2 h reperfusion. Fasudil (0.1 mg/kg, i.v.) or vehicle was given at 30 min ischemia (n = 9/group; mean (SD)). Brain injury was determined by 2,3,5-triphenyltetrazolium chloride staining. To determine the effect of fasudil on vascular function, fasudil was given 10 min before reperfusion and parenchymal arterioles studied isolated (n = 6/group; mean(SD)). Collateral perfusion was low in vehicle-treated SHR (−8(32)%) that changed minimally with fasudil (6(24)%, p > 0.05, effect size: 0.47;95% CI−0.49–1.39). Reperfusion CBF was below baseline in vehicle (−27(26)%) and fasudil (−32(25)%, p > 0.05, effect size: 0.19; 95% CI−0.74–1.11) groups, suggesting incomplete reperfusion in both groups. Fasudil had little effect on brain injury volume (28(13)% vs. 36(7)% in vehicle, p > 0.05, effect size: 0.75; 95% CI−0.24–1.66). In isolated parenchymal arterioles, myogenic tone was similar between groups (37(6)% vs. 38(10)% in vehicle, p > 0.05, effect size: 0.09; 95% CI−1.05–1.21). There were no differences with fasudil treatment vs. vehicle in perfusion, brain injury and vascular function that may be related to the low dose that had minimal blood pressure lowering effect.