Rodent models of pulmonary embolism and chronic thromboembolic pulmonary hypertension

Карпов, А. А.; Vaulina, D. D.; Smirnov, Sergey; Moiseeva, O. M.; Галагудза, М. М.

doi:10.1016/j.heliyon.2022.e09014

Cited by 14 publications

(11 citation statements)

References 130 publications

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“…Although as a representative APE model, it still has certain limitations. The SD rats have a highly efficient endogenous fibrinolysis system, and autologous blood clots do not produce permanently fixed pulmonary embolism model ( Karpov et al, 2022 ). Approximately 95% lysis of rat pulmonary artery autologous thrombi occurs within 24 h ( Karpov et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, finding better drugs for APE therapy is imperative. Karpov et al. (2022) pointed out that new approaches to studying improved prognosis in APE patients relied heavily on reliable animal models, including rat models.…”

Section: Introductionmentioning

confidence: 99%

“…(2022) pointed out that new approaches to studying improved prognosis in APE patients relied heavily on reliable animal models, including rat models. The construction of pulmonary artery autologous thrombus in Sprague-Dawley (SD) rats resulted in a rise in pulmonary artery resistance and pulmonary artery pressure within 24 h, which better mimicked changes in pulmonary artery pressure in APE humans during this period of time ( Karpov et al, 2022 ). Therefore, we made selection to construct APE rat model to complete our study.…”

Section: Introductionmentioning

confidence: 99%

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Recombinant hirudin attenuates pulmonary hypertension and thrombosis in acute pulmonary embolism rat model

Wei,

Zou,

Dong

et al. 2024

PeerJ

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Background Acute pulmonary embolism (APE) is classified as a subset of diseases that are characterized by lung obstruction due to various types of emboli. Current clinical APE treatment using anticoagulants is frequently accompanied by high risk of bleeding complications. Recombinant hirudin (R-hirudin) has been found to have antithrombotic properties. However, the specific impact of R-hirudin on APE remains unknown. Methods Sprague-Dawley (SD) rats were randomly assigned to five groups, with thrombi injections to establish APE models. Control and APE group rats were subcutaneously injected with equal amounts of dimethyl sulfoxide (DMSO). The APE+R-hirudin low-dose, middle-dose, and high-dose groups received subcutaneous injections of hirudin at doses of 0.25 mg/kg, 0.5 mg/kg, and 1.0 mg/kg, respectively. Each group was subdivided into time points of 2 h, 6 h, 1 d, and 4 d, with five animals per point. Subsequently, all rats were euthanized, and serum and lung tissues were collected. Following the assessment of right ventricular pressure (RVP) and mean pulmonary artery pressure (mPAP), blood gas analysis, enzyme-linked immunosorbnent assay (ELISA), pulmonary artery vascular testing, hematoxylin-eosin (HE) staining, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, immunohistochemistry, and Western blot experiments were conducted. Results R-hirudin treatment caused a significant reduction of mPAP, RVP, and Malondialdehyde (MDA) content, as well as H2O2 and myeloperoxidase (MPO) activity, while increasing pressure of oxygen (PaO2) and Superoxide Dismutase (SOD) activity. R-hirudin also decreased wall area ratio and wall thickness to diameter ratio in APE rat pulmonary arteries. Serum levels of endothelin-1 (ET-1) and thromboxaneB2 (TXB2) decreased, while prostaglandin (6-K-PGF1α) and NO levels increased. Moreover, R-hirudin ameliorated histopathological injuries and reduced apoptotic cells and Matrix metalloproteinase-9 (MMP9), vascular cell adhesion molecule-1 (VCAM-1), p-Extracellular signal-regulated kinase (ERK)1/2/ERK1/2, and p-P65/P65 expression in lung tissues. Conclusion R-hirudin attenuated pulmonary hypertension and thrombosis in APE rats, suggesting its potential as a novel treatment strategy for APE.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Recombinant hirudin attenuates pulmonary hypertension and thrombosis in acute pulmonary embolism rat model

Wei,

Zou,

Dong

et al. 2024

PeerJ

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“…The rats were infused with 20 autologous clots 1 × 1 × 2 mm in size slowly over 5 min. A right ventricular pressure increase exceeding 10 mmHg above baseline pressure after clots infusion was considered as acute PE 18,19 . For few rats, supplementary clots were infused to take the right ventricular pressure exceeding that level.…”

Section: Methodsmentioning

confidence: 99%

Pulmonary embolism induces pneumonia‐like lung injury beyond pulmonary infarction

Wang,

Liu,

Zhou

et al. 2023

Pulm. circ.

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Patients with pulmonary embolism (PE) commonly manifest concomitant “pneumonia,” which is generally believed to be either a cause (infection) or a consequence (infarction) of PE. This study aimed to clarify the relationship between PE and “pneumonia‐like” lesions beyond pulmonary infection and infarction. Chest computed tomography (CT) images of patients with PE and deep vein thrombosis (DVT) were retrospectively analyzed to compare the incidence of pneumonia lesions. The pathological damage and wet/dry ratio of lung tissues were observed in PE rats and PE plasma‐injected rats. In total, 793 and 914 inpatients were enrolled in the PE and DVT groups, respectively. Pneumonia lesions were observed in 36.9% and 26.3% of patients in the PE and DVT groups, respectively (p < 0.0001). Among PE rats, 33.3% exhibited focal severe lung injury, which closely resembled the pathological damage of community‐acquired pneumonia. The wet/dry ratio was significantly higher in the PE group than in the PE‐control group (4.98 ± 0.08 vs. 4.39 ± 0.06, p < 0.0001). Among PE plasma‐injected rats, individuals with focal proven lung injury were found at all experimental points, with an incidence of 27.6%. The lung wet/dry ratio was significantly higher in the PE plasma group than in the PE‐control plasma group at 1 and 2 h postinjection (5.02 ± 0.12 vs. 4.61 ± 0.06 and 4.76 ± 0.16 vs. 4.34 ± 0.09, respectively; p < 0.05). In conclusion, the manifestation of pneumonia lesions in chest CT images was higher among PE patients than among DVT patients. Plasma of PE rats could induce focal pneumonia‐like lung injury in healthy rats.

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“…Pulmonary embolism (PE) ranks third in prevalence among all cardiovascular diseases [ 1 , 2 ]. It is worth considering that the risk of venous thromboembolism in patients under 45 years varies in the range of 1.0–1.5 per 1000 people per year and almost doubles every decade.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of JAK1,2 Prevents Fibrotic Remodeling of Pulmonary Vascular Bed and Improves Outcomes in the Rat Model of Chronic Thromboembolic Pulmonary Hypertension

Карпов

Mihailova

Shilenko

et al. 2022

IJMS

Self Cite

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Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism with poor clinical outcomes. Therapeutic approaches to prevention of fibrotic remodeling of the pulmonary vascular bed in CTEPH are limited. In this work, we tested the hypothesis that Janus kinase 1/2 (JAK1/2) inhibition with ruxolitinib might prevent and attenuate CTEPH in a rat model. CTEPH was induced by repeated embolization of the pulmonary artery with partially biodegradable 180 ± 30 μm alginate microspheres. Two weeks after the last injection of microspheres, ruxolitinib was administered orally at doses of 0.86, 2.58, and 4.28 mg/kg per day for 4 weeks. Prednisolone (1.475 mg/kg, i.m.) was used as a reference drug. Ruxolitinib in all doses as well as prednisolone reduced pulmonary vascular wall hypertrophy. Ruxolitinib at a dose of 2.58 mg/kg and prednisolone reduced vascular wall fibrosis. Prednisolone treatment resulted in decreased right ventricular systolic pressure. Pulmonary vascular resistance was lower in the prednisolone and ruxolitinib (4.28 mg/kg) groups in comparison with the placebo group. The plasma level of brain natriuretic peptide was lower in groups receiving ruxolitinib at doses of 2.58 and 4.28 mg/kg versus placebo. This study demonstrated that JAK1/2 inhibitor ruxolitinib dose-dependently reduced pulmonary vascular remodeling, thereby preventing CTEPH formation in rats.

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Rodent models of pulmonary embolism and chronic thromboembolic pulmonary hypertension

Cited by 14 publications

References 130 publications

Recombinant hirudin attenuates pulmonary hypertension and thrombosis in acute pulmonary embolism rat model

Recombinant hirudin attenuates pulmonary hypertension and thrombosis in acute pulmonary embolism rat model

Pulmonary embolism induces pneumonia‐like lung injury beyond pulmonary infarction

Inhibition of JAK1,2 Prevents Fibrotic Remodeling of Pulmonary Vascular Bed and Improves Outcomes in the Rat Model of Chronic Thromboembolic Pulmonary Hypertension

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