Srovnání bezpečnosti alteplázy a tenekteplázy při trombolýze provedené 4 hodiny po indukci ischemické cévní mozkové příhody u normotenzních potkanů.
| Title in English | Comparison of the safety of alteplase and tenecteplase in thrombolysis performed 4 hours after induction of ischemic stroke in normotensive rats. |
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| Authors | |
| Year of publication | 2024 |
| Type | Article in Proceedings |
| Conference | 51. pracovní konference Komise experimentální kardiologie |
| MU Faculty or unit | |
| Citation | |
| Keywords | thrombolytics safety comparation, |
| Description | In clinical trials, treatment with tenecteplase has been repeatedly studied in comparison with alteplase. Results according to study settings oscillate from the more successful tenecteplase to a neutral effect to the superiority of alteplase. In ours models of systemic embolism is both the relative change in the area of radiopaque labeled clot and the area under thrombolytic curve significantly smaller in rats treated with tenecteplase at a clinically relevant dose 0.25 mg/kg compared to a group of rats treated with a dose of alteplase 0.9 mg/kg in a 60-minute infusion after application of an initial bolus with a volume of 10% of the calculated dose. The aim of the work is to compare safety and efficiency identical treatments in a model of thromboembolic occlusion of the branches of the circle of Willis in rats 4 hours after induction occlusion. 52 rats were included in the study with the aim of having at least 21 included individuals in the group. The treatment was chosen at random by lottery. According to treatment, patients were assigned to the rtPA group treated with alteplase or the group TNK-tPA treated with tenecteplase at the above-mentioned clinically relevant doses. Occlusion of the branches of Willis circle (CoWBO – Circle of Wilis Branches Occlusion) was induced by the application of 2 pieces of artificial fibrin clots of size 0.3x1.5 mm introduced into the left internal carotid artery. Four hours after induction, CoWBO was included treatment. At the latest 24 hours after occlusion, the brain was taken for a microCT scan. Brain it was still photographed macroscopically using an operating microscope and a histological examination was performed brain processing for HE staining. The occurrence of cerebral infarction (BS), the occurrence of hemorrhagic events was evaluated transformation (HT) and % hemispheric asymmetry (% HA) as a recanalization parameter. Of the 52 subjects used, 7 were excluded for the absence of cerebral infarction, with not a single excluded brain did not have HT (3 treated with TNK-tPA, 4 treated with rtPA). Of the 24 rats in the rtPA group, 13 (54%) did not have HT, 6 (25%) individuals had HI1, 4 (17%) had HI2, and one rat (4%) had bleeding classified as PH1. In contrast, in a group TNK-tPA was of 21 subjects 8 (38%) without HT, 6 (29%) subjects had HI1, 3 (14%) had HI2 and 4 rats (19%) had bleeding classified as PH1. For the time being, 9 brains have been evaluated in the parameter % asymmetry of the hemispheres in the rtPA group and 12 brains in the TNK-tPA group. Partial results are as follows %HA is in the rtPA group vs. TNK-tPA (further always in this order) in brains without HT 3.31±1.07 vs. 2.24±1.98; in brains with HT it is 29.32±1.94 vs. 10.04±1.85. The average degree of bleeding was 1.75±0.83 vs. 2.00±0.71. Partial results suggest that consistent with clinical data, tenecteplase is more successful in recanalization and is associated with less swelling after reperfusion, but at the same time it is associated with a higher incidence of higher hemorrhagic grades transformation. |
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