Microbubble administration accelerates thrombolysis in occlusion of the middle cerebral artery of rabbits during 2 MHz ultrasound monitoring

Abstract

Objective To evaluate the efficacy ofmicrobubbles-assisted urokinase thrombolysis under transcranial Doppler ultrasound (TCD) in rabbits with cerebral infarctions.Methods Male New Zealand white rabbits (n=32) were randomly divided into two groups,a urokinase group and a combined urokinase and microbubble group (n=16).The middle cerebral artery (MCA) was occluded by injecting autologous blood clots through the carotid artery.In the combined urokinase and microbubble group,sulfur hexafluoride (SonoVue) microbubbles were injected intravenously immediately after intravenous injection of urokinase.The animals in these two groups were monitored by TCD within 2 h of thrombolysis,and the hemodynamic changes were recorded and the recanalization was noted according to the TCD spectral morphology and blood flow velocity.Results The average blood flow velocity of the middle cerebral artery before performing thrombolysis showed no significant difference between the 2 groups (P＜0.05).One rabbit in the urokinase group had complete recanalization and 4 partial mecanalization with a recanalization rate of 31.3％.Three rabbits in the combined urokinase and microbubble group had complete recanalization and 6 partial recanalization with a recanalization rate of 56.3％.Pathological examination showed no cerebral hemorrhage in either group.The average size of the infarction foci was 13.9％ in the urokinase group and 9.3％ in the combined urokinase and microbubble group with significant difference (P=0.025).Conclusion The addition of microbubbles to urokinase treatment increases vascular recanalization and decreases infarct size,and does not cause side effect of cerebral hemorrhage.During 2 MHz ultrasound monitoring,microbubble can assist urokinase thrombolysis for acute cerebral infarctions. Key words: Tran-cranial Doppler ultrasound; Cerebral infarction; Urokinase; Microbubble; Thrombolysis