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

Abstract

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.

Influenza A Virus Causes Histopathological Changes and Impairment in Functional Activity of Blood Vessels in Different Vascular Beds

“…In the present study, the experimental influenza virus infection of Wistar rats was conducted for two reasons: (1) the possibility of studying non-lethal influenza infection [21]; (2) rats of this stock are the main animal model of various cardiovascular disorders [22][23][24], which is an essential factor for our further studies.…”

“…To study this mechanism, we developed an experimental model of non-lethal influenza virus infection in mature Wistar rats [21]. These laboratory animals are also one of the main experimental models for the study of various cardiovascular disorders [22][23][24]. The study was carried out for the first time on both pulmonary and mesenteric blood vessels in order to analyze local and possible systemic effects on the cardiovascular system in non-lethal and clinically non-severe experimental influenza virus infection.…”

Rodent models of pulmonary embolism and chronic thromboembolic pulmonary hypertension

“…Most researchers agree that the isolated use of native thrombi prepared in vitro in healthy small laboratory rodents cannot cause the formation of CTEPH [ 50 , 84 ] because the blood plasma of rodents has great fibrinolytic activity.…”

Approaches to modeling pulmonary embolism and chronic thromboembolic pulmonary hypertension in rodents and medium-sized laboratory animals

“…Большинство исследователей сходятся во мнении, что изолированное применение приготовленных in vitro нативных тромбов у здоровых мелких лабораторных грызунов не может вызвать формирование ХТЭЛГ [44,65].…”

“…В ранее проведенном нами исследовании [65] был предложен метод моделирования ХТЭЛГ с помощью частично биодеградирующих микросфер из альгината натрия. Альгинат натрия -естественный биополимер из бурых водорослей, который обладает высокой биосовместимостью.…”