Publication details

Vývoj nových trombolytik – strategie testování efektivity trombolýzy na in vivo modelu u potkana .

Title in English Development of new thrombolytics - a strategy for testing the effectiveness of thrombolysis in an in vivo rat model


Year of publication 2022
Type Appeared in Conference without Proceedings
MU Faculty or unit

Faculty of Pharmacy

Description In-vivo testing of thrombolytics must primarily meet the ability to evaluate thrombolysis as a dynamic process. This criterion can be met by direct monitoring of thrombolysis with a fluoroscopy or computed tomography. Objective: To develop an experimental model of systemic embolism (SE) allowing direct monitoring of thrombolysis in an in vivo rat model. Methodology: The model uses artificial clots (AC) prepared from human fibrin-based tissue glue and barium sulfate was added for radiographic visualization. SE was induced by applying AC (3 pieces, length 10 mm) retrograde from the common carotid to the aortic arch. Animals were imaged simultaneously with initiation of thrombolytic therapy. Fluoroscopy (permanent live image, recording every 5 minutes) and microCT (recording every 10 minutes) were used to detect lysis. The model was used successfully in 144 fluoroscopy and 25 microCT examinations. Fluoroscopy images were analyzed using ImageJ software, mikroCT using Bruker CTan software. Results: The SE model is safe and has zero mortality in case of successful AC application. When using mikroCT, the number of evaluated AC is equal to or higher than that applied (possibility of fragmentation of AC during application). In skiagraphy, the number of analyzed ACs was 309, the average number of measured ACs was 2.15±0.74. The limit of skiagraphy is 1/ the 2D image (the measured shadow is affected by the projection angle) and 2/ the relative limit is the number of displayed ACs is lower than the number of applied ACs, 3/ the lower quality of displaying ACs in cerebral vessels. The limit of microCT is 1/ motion blur in the case of AC in the mesenteric arteries, 2/ a relatively small scanned part of the animal, during which a maximum of 2 clots in the abdominal area can be observed simultaneously. The advantage of fluoroscopy is a "real-time" image, the possibility of performing catheterization procedures including angiography, very low radiation exposure. The advantage of microCT is high accuracy in measuring changes in clot volume in 3D visualization and excellent imaging of small ACs in cerebral vessels. The SE model only monitors the effectiveness of thrombolysis, the safety can be assessed indirectly. Conclusion: The use of artificial clots with a contrast agent based on barium sulfate allows radiologically quantifying the rate of clot disintegration and constructing a lytic curve. The simplicity, repeatability and robustness of the model will allow comparison of the thrombolytic effect of new potential thrombolytics or their combinations. The application of more AC allows the multiplication of lytic curves and thus ultimately reduces the number of laboratory animals used.
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