Pathophysiology and Treatment of Chronic Thromboembolic Pulmonary Hypertension

Otani, Naoyuki; Watanabe, Ryo; Tomoe, Takashi; Toyoda, Shigeru; Yasu, Takanori; Nakamoto, Takaaki

doi:10.3390/ijms24043979

Cited by 14 publications

(16 citation statements)

References 117 publications

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“…Firstly, fragmented small thrombi directly obstruct the arterioles and undergo organization, leading to secondary remodeling. Secondly, proximal pulmonary artery obstruction causes redistribution of blood flow and changes in neurohumoral factors and shear forces, resulting in remodeling of the pulmonary arterioles [20]. The latter can be simulated in the proximal pulmonary artery remodeling model, so our distal pulmonary arteriole remodeling model primarily focuses on simulating remodeling caused by fragmented small thrombi.…”

Section: Discussionmentioning

confidence: 99%

Construction of Animal Models Based on Exploring Pathological Features and Mechanisms of Different Locations in the Progression of DVT-APTE-CTEPD/CTEPH

Lin,

Wang,

Chen

et al. 2024

Preprint

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Background: Chronic thromboembolic pulmonary disease (CTEPD) and chronic thromboembolic pulmonary hypertension (CTEPH) are sequelae of acute pulmonary embolism (APE) and severely affect patients' health and quality of life. The treatment of these conditions is challenging, and their underlying mechanisms remain unclear. The main reason for this is the lack of an animal model that can fully simulate the entire chain of DVT-APTE-CTEPD/CTEPH progression. The objective of this study is to construct an ideal animal model that simulates the major pathological changes of DVT-APTE-CTEPD/CTEPH and can be used for mechanistic exploration. We aim to compare the advantages and disadvantages of different modeling approaches and provide an experimental basis for investigating the mechanisms of pulmonary embolism chronicization at different stages of evolution. Methods and Materials: We first evaluated the pathological changes in the pulmonary arterial intima stripping tissue of CTEPH patients. Animal models were established by multiple injections of thrombus columns through the internal jugular vein to simulate distal remodeling of the pulmonary artery. To simulate significant remodeling and fibrosis in the middle and distal segments of the pulmonary artery, thrombus columns were injected along with splenectomy. A CTEPD model with intimal fibrosis remodeling was successfully established by selectively injecting large thromboemboli into the pulmonary artery sites in large animals (dogs). A rat model with pathological manifestations of intimal fibrosis remodeling in the proximal end of the pulmonary artery was constructed using large thrombi combined with nitric oxide synthase inhibitors. An animal model of DVT was established using the inferior vena cava ligation method. Results: According to the different pathological features and mechanisms observed in the progression of human DVT-APTE-CTEPD/CTEPH, we constructed animal models that conform to these pathological manifestations and mechanisms, each with its own advantages. Furthermore, the different methods used to construct animal models can be integrated and applied together. Conclusion: Animal models constructed using different modeling methods can effectively simulate the pathological and physiological manifestations of the corresponding stages of chronic pulmonary embolism. Researchers can select the aforementioned models according to their specific research purposes, directions, and requirements.

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Section: Discussionmentioning

confidence: 99%

Construction of Animal Models Based on Exploring Pathological Features and Mechanisms of Different Locations in the Progression of DVT-APTE-CTEPD/CTEPH

Lin,

Wang,

Chen

et al. 2024

Preprint

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“…In recent years, research on CTEPH has largely centered on these two items. The risk factors that have been demonstrated include inflammation and infection, abnormalities of the coagulation system, abnormalities of fibrinolysis, abnormalities of platelet function, cancer, blood group, myofibroblasts, impaired angiogenesis, and impaired small vessels [ 16 ]. Therefore, the therapeutic regimens developed around the pathological features and related risk factors are constantly being updated, and their treatments mainly include basic therapy (long-term anticoagulation and home oxygen therapy, etc.…”

Section: Discussionmentioning

confidence: 99%

Analysis of genes characterizing chronic thrombosis and associated pathways in chronic thromboembolic pulmonary hypertension

Zhan,

Wang,

Wang

et al. 2024

PLoS ONE

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Purpose In chronic thromboembolic pulmonary hypertension (CTEPH), fibrosis of thrombi in the lumen of blood vessels and obstruction of blood vessels are important factors in the progression of the disease. Therefore, it is important to explore the key genes that lead to chronic thrombosis in order to understand the development of CTEPH, and at the same time, it is beneficial to provide new directions for early identification, disease prevention, clinical diagnosis and treatment, and development of novel therapeutic agents. Methods The GSE130391 dataset was downloaded from the Gene Expression Omnibus (GEO) public database, which includes the full gene expression profiles of patients with CTEPH and Idiopathic Pulmonary Arterial Hypertension (IPAH). Differentially Expressed Genes (DEGs) of CTEPH and IPAH were screened, and then Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) functional enrichment analyses were performed on the DEGs; Weighted Gene Co-Expression Network Analysis (WGCNA) to screen the key gene modules and take the intersection genes of DEGs and the key module genes in WGCNA; STRING database was used to construct the protein-protein interaction (PPI) network; and cytoHubba analysis was performed to identify the hub genes. Results A total of 924 DEGs were screened, and the MEturquoise module with the strongest correlation was selected to take the intersection with DEGs A total of 757 intersecting genes were screened. The top ten hub genes were analyzed by cytoHubba: IL-1B, CXCL8, CCL22, CCL5, CCL20, TNF, IL-12B, JUN, EP300, and CCL4. Conclusion IL-1B, CXCL8, CCL22, CCL5, CCL20, TNF, IL-12B, JUN, EP300, and CCL4 have diagnostic and therapeutic value in CTEPH disease, especially playing a role in chronic thrombosis. The discovery of NF-κB, AP-1 transcription factors, and TNF signaling pathway through pivotal genes may be involved in the disease progression process.

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“…PEA is a procedure performed under very hypothermic (16–18 °C) intermittent circulatory arrest. The left and right main pulmonary arteries are incised, an appropriate dissection surface between the internal elastic plate and tunica media is found, and then one proceeds to the regional artery and removes the organizing thrombus [ 4 ]. However, PEA is not indicated in patients presenting with heart failure because they may not be able to maintain their circulatory status; therefore, transcatheter therapy or pharmacotherapy is more likely to be used [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

“…In the present case, both PAP and PVR remained stable and could be managed without any circulatory disturbance. Common immediate postoperative complications of PEA are reperfusion lung injury and intratracheal hemorrhage, which require attention [ 4 ]. On searching PubMed for case reports of anesthetic management with remimazolam for PEA in patients with CTEPH, no such report was found.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of total intravenous anesthesia with remimazolam in general anesthesia for pulmonary endarterectomy of chronic thromboembolic pulmonary hypertension: a case report

et al. 2023

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Background Pulmonary endarterectomy (PEA) is a treatment modality for chronic thromboembolic pulmonary hypertension (CTEPH). PEA requires anesthesia management to prevent an increase in pulmonary vascular resistance (PVR) and circulatory failure. Therefore, it is necessary to select an anesthetic agent that can achieve these goals as much as possible. On the other hand, remimazolam, a short-acting sedative, was launched in Japan in 2020, and its use in various cases has been increasingly reported. This report demonstrates that remimazolam can be used safely in the anesthetic management of PEA. Case presentation A 57-year-old man was scheduled to undergo PEA for CTEPH. Remimazolam was used for sedation from induction of anesthesia. Hemodynamics were stable during surgery without circulatory failure. Anesthesia was managed intraoperatively without any particular increase in PVR. Discussion Anesthesia was successfully managed without any complications. This case suggests that remimazolam is one of the options for anesthetic management in PEA.

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Pathophysiology and Treatment of Chronic Thromboembolic Pulmonary Hypertension

Cited by 14 publications

References 117 publications

Construction of Animal Models Based on Exploring Pathological Features and Mechanisms of Different Locations in the Progression of DVT-APTE-CTEPD/CTEPH

Construction of Animal Models Based on Exploring Pathological Features and Mechanisms of Different Locations in the Progression of DVT-APTE-CTEPD/CTEPH

Analysis of genes characterizing chronic thrombosis and associated pathways in chronic thromboembolic pulmonary hypertension

Evaluation of total intravenous anesthesia with remimazolam in general anesthesia for pulmonary endarterectomy of chronic thromboembolic pulmonary hypertension: a case report

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