Model of Chronic Thromboembolic Pulmonary Hypertension in Rats Caused by Repeated Intravenous Administration of Partially Biodegradable Sodium Alginate Microspheres
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 p...
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| author | Andrei A. Karpov Nikita A. Anikin Aleksandra M. Mihailova Sergey S. Smirnov Dariya D. Vaulina Leonid A. Shilenko Dmitry Yu. Ivkin Alexei Y. Bagrov Olga M. Moiseeva Michael M. Galagudza |
| author_facet | Andrei A. Karpov Nikita A. Anikin Aleksandra M. Mihailova Sergey S. Smirnov Dariya D. Vaulina Leonid A. Shilenko Dmitry Yu. Ivkin Alexei Y. Bagrov Olga M. Moiseeva Michael M. Galagudza |
| author_sort | Andrei A. Karpov |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T03:48:33Z |
| format | Article |
| id | doaj.art-8ee3734636e14488922b1e29853e3c49 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T03:48:33Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8ee3734636e14488922b1e29853e3c492023-12-03T14:31:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01223114910.3390/ijms22031149Model of Chronic Thromboembolic Pulmonary Hypertension in Rats Caused by Repeated Intravenous Administration of Partially Biodegradable Sodium Alginate MicrospheresAndrei A. Karpov0Nikita A. Anikin1Aleksandra M. Mihailova2Sergey S. Smirnov3Dariya D. Vaulina4Leonid A. Shilenko5Dmitry Yu. Ivkin6Alexei Y. Bagrov7Olga M. Moiseeva8Michael M. Galagudza9Almazov National Medical Research Centre, 197341 St. Petersburg, RussiaAlmazov National Medical Research Centre, 197341 St. Petersburg, RussiaAlmazov National Medical Research Centre, 197341 St. Petersburg, RussiaAlmazov National Medical Research Centre, 197341 St. Petersburg, RussiaAlmazov National Medical Research Centre, 197341 St. Petersburg, RussiaAlmazov National Medical Research Centre, 197341 St. Petersburg, RussiaSaint Petersburg State Chemical Pharmaceutical University, 197376 St. Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 St. Petersburg, RussiaAlmazov National Medical Research Centre, 197341 St. Petersburg, RussiaAlmazov National Medical Research Centre, 197341 St. Petersburg, RussiaChronic 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.https://www.mdpi.com/1422-0067/22/3/1149chronic thromboembolic pulmonary hypertensionexperimental modelmicrospherespulmonary embolismratssodium alginate |
| spellingShingle | Andrei A. Karpov Nikita A. Anikin Aleksandra M. Mihailova Sergey S. Smirnov Dariya D. Vaulina Leonid A. Shilenko Dmitry Yu. Ivkin Alexei Y. Bagrov Olga M. Moiseeva Michael M. Galagudza Model of Chronic Thromboembolic Pulmonary Hypertension in Rats Caused by Repeated Intravenous Administration of Partially Biodegradable Sodium Alginate Microspheres International Journal of Molecular Sciences chronic thromboembolic pulmonary hypertension experimental model microspheres pulmonary embolism rats sodium alginate |
| title | Model of Chronic Thromboembolic Pulmonary Hypertension in Rats Caused by Repeated Intravenous Administration of Partially Biodegradable Sodium Alginate Microspheres |
| title_full | Model of Chronic Thromboembolic Pulmonary Hypertension in Rats Caused by Repeated Intravenous Administration of Partially Biodegradable Sodium Alginate Microspheres |
| title_fullStr | Model of Chronic Thromboembolic Pulmonary Hypertension in Rats Caused by Repeated Intravenous Administration of Partially Biodegradable Sodium Alginate Microspheres |
| title_full_unstemmed | Model of Chronic Thromboembolic Pulmonary Hypertension in Rats Caused by Repeated Intravenous Administration of Partially Biodegradable Sodium Alginate Microspheres |
| title_short | Model of Chronic Thromboembolic Pulmonary Hypertension in Rats Caused by Repeated Intravenous Administration of Partially Biodegradable Sodium Alginate Microspheres |
| title_sort | model of chronic thromboembolic pulmonary hypertension in rats caused by repeated intravenous administration of partially biodegradable sodium alginate microspheres |
| topic | chronic thromboembolic pulmonary hypertension experimental model microspheres pulmonary embolism rats sodium alginate |
| url | https://www.mdpi.com/1422-0067/22/3/1149 |
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