Early complete recanalization in internal carotid artery embolism treated with high-dose t-PA. A sequential angiographic study in a novel model of embolism in rats

Abstract

Complete early recanalization rate of human internal carotid artery embolic occlusion treated with thrombolytic drugs is low. To study factors related with this difficulty to recanalize we have developed a novel model of rat ica embolism using a fragment of human embolus. In 50 male Wistar rats the ica was embolized through the external carotid artery with a fragment of an embolus obtained from a human embolectomy passed through a catheter of 0.8 mm diameter. Recanalization was assessed by sequential angiograms from 15 to 120 min after embolization. Reperfusion was classified according to TIMI grades. Emboli of either 1 (group 1) or 2 mm (group 2) in length were cut. In group 1, four groups of nine animals each were treated, 15 min after embolization, with i.v. t-PA at doses of 1 mg/kg, 10 mg/kg and 20 mg/kg or saline. In group 2 there was one control group of seven animals treated with saline and another of seven animals treated with 10 mg/kg t-PA. Complete recanalization (TIMI grade 3) within the first 30 min was present in two animals treated with 10 and 20 mg/kg. Complete recanalization within the first 60 min was present in 0% of controls and animals treated with 1 mg/kg and in 44% of the 10 and 20 mg/kg groups ( P<0.05 in chi-square test). Incomplete recanalization (TIMI grades 0,1 and 2) occurred in 33%. In group 2 total recanalization occurred in 1/7 controls and in 3/7 animals receiving 10 mg/kg of t-PA. Early (60 min) complete i.v. t-PA induced internal carotid artery embolic recanalization is low with standard doses and increases moderately when high doses are used. Further increases in the dose do not improve recanalization rate, which is not clearly influenced by embolus size. Complete recanalization within 30 min, the period after which infarction develops in the rat, is uncommon in our model.