How to evaluate the efficacy of thrombolysis in vivo.
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| Year of publication | 2024 |
| Type | Conference abstract |
| MU Faculty or unit | |
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| Description | Background If a clot is visualized in an animal, then biological effect of thrombolytic drugs could be assessed directly by measuring thrombus size in thromboembolic animal models. Study validates a novel systemic embolization in vivo model using micro-fluoroscopy imaging for to evaluate the efficacy of thrombolysis in vivo. Aims 1/ To quantifying the thrombolytic efficacy of alteplase (rtPA); 2/ to verify the yield of multiple clots application; 3/ to describe the mortality rate and technical complication of the model. Methods Pilot validation study: Twenty-six outbreed Wistar rats, randomized into two groups, received three human-fibrin based clots (AC artificial clot) labelled with BaSO4 into the descending aorta. Using micro-fluoroscopy imaging for 60 minutes, the size of detected clots, after administration of rtPA (0.9 mg/kg/hour) in 16 rats (analysed 33 ACs) or saline solution (rats 10 analysed ACs 21) in an equivalent volume and time, were measured. For model validation, the relative change (%) in the clot area, lysis rates (%/min), and area under the curve (% ? min) were calculated. Validated models were used in next studies with different dose of rtPA (rats 19, ACs 40), tenecteplase (rats 27, ACs 47), plasminogen addition (rats 49, ACs 99), novel mutant of rtPA - ALT04 (rats 30, 54). Results Clots were detected in each animal (n=132), with the mean 2.136 clots per animal. No animal died. The relative change in clot area at 60 minutes from baseline in the treated vs. control group was -46±26% vs. -21±14%. The average lysis rate in the period 0-60 minutes was -0.9±0.5 %/min (95%CI [0.7 to 1.1]) in the treated group and -0.4±0.3 %/min (95%CI [0.3 to 0.6]) in the control group. The area under the thrombolytic curve in the time 0 to 60 minutes was -662 % ? min in the control group (95%CI [-866,6 to -456,5]) vs. -1433 % ? min in the treated group (95%CI [-180556 to -1232,9]). Conclusions The model with C-arm micro-fluoroscopy imaging visualized clots in animals, allowed measurement of clot size and was sensitive to detect thrombolytic activity of Alteplase. Such model holds promise to be used for translation of new thrombolytics in preclinical research into clinical practice. |
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