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Open AccessArticle

Model of Chronic Thromboembolic Pulmonary Hypertension in Rats Caused by Repeated Intravenous Administration of Partially Biodegradable Sodium Alginate Microspheres

1
Almazov National Medical Research Centre, 197341 St. Petersburg, Russia
2
First Pavlov State Medical University of Saint Petersburg, 197022 St. Petersburg, Russia
3
N.P. Bechtereva Institute of Human Brain, Russian Academy of Science, 197376 St. Petersburg, Russia
4
Saint Petersburg State Chemical Pharmaceutical University, 197376 St. Petersburg, Russia
5
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 St. Petersburg, Russia
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(3), 1149; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031149
Received: 17 December 2020 / Revised: 18 January 2021 / Accepted: 19 January 2021 / Published: 24 January 2021
(This article belongs to the Special Issue Cardiotonic Steroids: From Toxins to Hormones)
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and life-threatening complication of pulmonary embolism. As existing animal models of CTEPH do not fully recapitulate complex disease pathophysiology, we report a new rat model for CTEPH evoked by repetitive embolization of the distal pulmonary artery branches with partially biodegradable alginate microspheres (MSs). MSs (180 ± 28 μm) were intravenously administered eight times at 4-day intervals; control animals received saline. The validity of the model was confirmed using transthoracic echocardiography, exercise testing, catheterization of the right ventricle, and histological examination of the lung and heart. The animals in the CTEPH group demonstrated a stable increase in right ventricular systolic pressure (RVSP) and decreased exercise tolerance. Histopathological examination revealed advanced medial hypertrophy in the small pulmonary arteries associated with fibrosis. The diameter of the main pulmonary artery was significantly larger in the CTEPH group than in the control group. Marinobufagenin and endothelin-1 serum levels were significantly elevated in rats with CTEPH. In conclusion, repetitive administration of alginate MSs in rats resulted in CTEPH development characterized by specific lung vasculature remodeling, reduced exercise tolerance, and a persistent rise in RVSP. The developed model can be used for pre-clinical testing of promising drug candidates. View Full-Text
Keywords: chronic thromboembolic pulmonary hypertension; experimental model; microspheres; pulmonary embolism; rats; sodium alginate chronic thromboembolic pulmonary hypertension; experimental model; microspheres; pulmonary embolism; rats; sodium alginate
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MDPI and ACS Style

Karpov, A.A.; Anikin, N.A.; Mihailova, A.M.; Smirnov, S.S.; Vaulina, D.D.; Shilenko, L.A.; Ivkin, D.Y..; Bagrov, A.Y.; Moiseeva, O.M.; Galagudza, M.M. Model of Chronic Thromboembolic Pulmonary Hypertension in Rats Caused by Repeated Intravenous Administration of Partially Biodegradable Sodium Alginate Microspheres. Int. J. Mol. Sci. 2021, 22, 1149. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031149

AMA Style

Karpov AA, Anikin NA, Mihailova AM, Smirnov SS, Vaulina DD, Shilenko LA, Ivkin DY, Bagrov AY, Moiseeva OM, Galagudza MM. Model of Chronic Thromboembolic Pulmonary Hypertension in Rats Caused by Repeated Intravenous Administration of Partially Biodegradable Sodium Alginate Microspheres. International Journal of Molecular Sciences. 2021; 22(3):1149. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031149

Chicago/Turabian Style

Karpov, Andrei A.; Anikin, Nikita A.; Mihailova, Aleksandra M.; Smirnov, Sergey S.; Vaulina, Dariya D.; Shilenko, Leonid A.; Ivkin, Dmitry Y..; Bagrov, Alexei Y.; Moiseeva, Olga M.; Galagudza, Michael M. 2021. "Model of Chronic Thromboembolic Pulmonary Hypertension in Rats Caused by Repeated Intravenous Administration of Partially Biodegradable Sodium Alginate Microspheres" Int. J. Mol. Sci. 22, no. 3: 1149. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031149

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