Model of chronic thromboembolic pulmonary hypertension in rats, caused by repeated intravenous administration of biodegradable microspheres from sodium alginate

Introduction. Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the most severe complications of pulmonary embolism (PE), characterized by poor prognosis and insuffcient effectiveness of standard treatment approaches. A small number of representative models of CTEPH make it diffcult to conduct preclinical studies of promising pharmacological substances.

Objective – development and validation of the experimental model of CTEPH in rats by embolization of the distal branches of the pulmonary artery with biodegradable microspheres.

Material and methods. Male Wistar rats were used for the experiments. Biodegradable microspheres (MS) based on sodium alginate and autologous blood clots (AT) were used as embolizing particles. The animals were divided into groups: control: saline solution was injected 4 times with an interval of 8 days into the tail vein; AT: according to the above protocol, 50 μL of AT was injected; MS was administered intravenously in a volume of 50 μl of MS according to two protocols: MS4: 4 times with an interval of 8 days; MS8: 8 times with an interval of 4 days. After 2 and 6 weeks after the last injection, a histological examination of the lungs was performed; after 6 weeks: echocardiographic study (TTE), right ventricular catheterization (RV) with measurement of right ventricular systolic pressure (RVSP), treadmill test, assessment of serum endothelin­1 levels by the immunoassay method.

Results. During the experiments, the survival rate in the MS8 group was 50 %. In the other groups, there were no animal losses. According to the treadmill test 6 weeks after the modeling of PE, exercise tolerance was signifcantly reduced in the MC4 and MC8 groups compared with the control group. TTE data indicate a signifcant increase in the diameter of the pulmonary trunk and the right ventricular outflow tract in the MC8 compared with the control and AT. There were signifcant increase in RVSP and the level of endothelin­1 compared with the control only in the MS8. After 6 weeks, the index of hypertrophy of vessel wall of the pulmonary artery in the MC4 and MC8 was signifcantly higher compared with the control and AT groups.

Conclusion. Based on the use of MS, administered under the MS 8 protocol, a new representative model of CTEPH has been created, which can be used to test promising pharmacological substances.

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