经颅多普勒超声监护下超声微泡剂对尿激酶溶栓治疗作用的影响

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

目的 评价经颅多普勒超声（TCD）监护下超声微泡剂辅助尿激酶溶栓治疗的有效性。方法 将雄性新西兰大白兔32只按随机数字表法分为单用尿激酶组和尿激酶联合超声微泡剂组，每组各16只。采用兔颈外动脉插管注入自体血栓方法制备成大脑中动脉栓塞模型，并应用TCD监测血栓溶解过程。尿激酶联合超声微泡剂组静注尿激酶后立即静注六氟化硫超声微泡剂（声诺维）。2组动物均在溶栓治疗后2h内持续TCD监测并记录溶栓治疗后不同时间点大脑中动脉血流动力学变化，并根据TCD频谱形态及血流速度判断血管再通情况。结果 2组动物溶栓治疗前大脑中动脉的平均血流速度比较差异无统计学意义（P〉0．05）。溶栓治疗后单用尿激酶组完全再通1例，部分再通4例，血管再通率为31．3％；尿激酶联合超声微泡剂组完全再通3例，部分再通6例，血管再通率为56.3％。2组动物病理检查均未见脑出血。单用尿激酶组梗死灶大小占梗死半球的百分率平均为13．9％，尿激酶联合超声微泡剂组梗死灶大小占梗死半球的百分率平均为9．1％，比较差异有统计学意义（P=0．025）。结论 TCD监测下应用超声微泡剂有助于增强尿激酶的溶栓治疗效果，初步证明TCD联合超声微泡剂可辅助尿激酶溶栓治疗脑梗死。

Objective To evaluate the efficacy of microbubbles-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 recanalization 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 ofmicrobubbles 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.