Tirofiban combined with rt-PA intraarterial thrombolysis improves the recanalization rate of acute middle cerebral artery occlusion in rabbits

Y.-J. Yu, W. Xiong

Department of Emergency, Affiliated Hospital of Weifang Medical University, Weifang, China. xiongwen1216@sina.com

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• Pharmacology

OBJECTIVE: To investigate the curative effect of tirofiban combined with recombinant tissue-plasminogen activator (rt-PA) selective intra-arterial thrombolysis on acute middle cerebral artery occlusion (MCAO).

MATERIALS AND METHODS: A total of 60 adult male Japanese white rabbits weighing 2.5-3.0 kg were selected, and the acute cerebral infarction model was established via autologous thromboembolism of middle cerebral artery. Rabbits were randomly divided into 4 groups: tirofiban group (Ti group, 5 μg/kg, n=15), rt-PA group (rt-PA group, 2 mg/kg, n=15), tirofiban + rt-PA group (Ti + rt-PA group, 3 μg/kg Ti + 1 mg/kg rt-PA, n=15), and control group (Co group, n=15). The vascular recanalization rate of intra-arterial thrombolysis was observed via digital subtraction angiography (DSA), relative apparent diffusion coefficient (rADC) was observed via diffusion-weighted imaging (DWI), and neurologic impairment was observed via modified Bederson’s scoring method. Rabbits were executed after 24 h, then the volume of cerebral infarction was measured via triphenyl tetrazolium chloride (TTC) staining, pathological examinations were performed using the optical microscope and electron microscope, and immunohistochemical examination was performed for brain-derived neurotrophic factor (BDNF).

RESULTS: In Ti + rt-PA group, the vascular recanalization rate was 91.7%, and there was no significant bleeding in pathological examination. The rADC value, neurologic impairment score and cerebral infarction area in Ti + rt-PA group were superior to those in Co group, Ti group and rt-PA group. Immunohistochemical results of BDNF showed that the expression of BDNF in Ti + rt-PA group was increased compared with those in Co group, Ti group and rt-PA group. In Ti group and rt-PA group, there were neuronal degeneration, moderate organelle swelling, moderate mitochondrial swelling, enlarged volume and decreased number of cristae, and rupture and disappearance of some mitochondrial cristae. In Co group, neuronal karyopyknosis, nuclear chromatolysis and disappearance of cellular structure could be seen. Results of electron microscopy showed that the shape of neuronal nuclei in Ti + rt-PA group was basically normal, and there were mild mitochondrial swelling and enlarged volume of cristae.

CONCLUSIONS: Early application of tirofiban combined with rt-PA in intra-arterial thrombolysis for ultra-early cerebral ischemia can improve the recanalization rate of cerebral artery. The time of cerebral ischemia and hypoxia is short, and the neuronal ischemia-reperfusion injury is mild, whose thrombolysis effect is better than the single application of tirofiban or rt-PA.

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