Chronic Thromboembolic Pulmonary Hypertension – What Have We Learned From Large Animal Models

Stam, Kelly; Clauß, Sebastian; Taverne, Yannick J.H.J.; Merkus, Daphne

doi:10.3389/fcvm.2021.574360

Cited by 7 publications

(4 citation statements)

References 140 publications

(217 reference statements)

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“…On the other hand, Stephenson et al reported the feasibility of the usage of Holstein calves in developing a robotically assisted microsurgical system to perform coronary artery anastomoses [20]. In another review, studies on the pathophysiology Large Animal Models in Cardiovascular Research DOI: http://dx.doi.org/10.5772/intechopen.105754 of chronic thromboembolic pulmonary hypertension using large animal models such as dogs and pigs using either indwelling or Swan Ganz catheters are summarized [21]. An important translational feature of pig models is the possibility of percutaneous coronary intervention using human clinical equipment, and the procedures using metallic stents or angioplasty balloons [22,23].…”

Section: Advantages Of Large Animal Models For Cardiovascular Researc...mentioning

confidence: 99%

Large Animal Models in Cardiovascular Research

Osada¹,

Murata²,

Masumoto³

2023

Animal Models and Experimental Research in Medicine

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Studies of not only preclinical cardiovascular research but also those of life science, medical, and pharmacological fields commonly utilize small animal models. However, for the advancement of cardiovascular medicine, researches using large animal models are important step for preclinical validation of therapeutic efficacy and safety by virtue of having models with a body and heart size comparable with that of a human, providing clinically relevant experiments without the concern of over- or under-estimating therapeutic effects and risks. In particular, pigs are considered as a suitable animal model for research in cardiovascular medicine because of the similarities in physiology, metabolism, genomics, and proteomics to those in humans. Another advantage of pigs is the availability of various heart disease models such as myocardial infarction and genetically established cardiomyopathy. The present review updates the contributions of large animal model-based research to the development of cardiovascular medicine, especially focusing on the utility of pig models.

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Section: Advantages Of Large Animal Models For Cardiovascular Researc...mentioning

confidence: 99%

Large Animal Models in Cardiovascular Research

Osada¹,

Murata²,

Masumoto³

2023

Animal Models and Experimental Research in Medicine

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“…However, there are few studies exploring the aforementioned pathological and physiological mechanisms of CTEPD, mainly due to the difficulty in establishing animal models for CTEPD. Previous attempts by researchers to establish animal models through repeated thrombus embolization have been unsuccessful [6,7], primarily due to the strong fibrinolytic capacity of animals, which leads to rapid dissolution of injected thrombi, preventing chronic remodeling. Some researchers have ligated the left pulmonary artery in piglets and repeatedly injected non-dissolvable microspheres through the external jugular vein to induce right pulmonary embolism and establish a CTEPD model.…”

Section: Introductionmentioning

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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“…Large animal models of CTEPH have advanced our understanding of the pathophysiology of CTEPH (Mulchrone et al 2019;Stam et al 2021), but typically do not report local mechanical stimuli for disease progression such as WSS. Image-based computational uid dynamics (CFD) modeling can compute pulmonary artery blood ow with high spatial resolution (Burrowes et al 2017;Bordones et al 2018; Wang et al 2020), from which WSS can be calculated.…”

Section: Introductionmentioning

confidence: 99%

Subject-specific one-dimensional fluid dynamics model of chronic thromboembolic pulmonary hypertension

Kachabi,

Colebank,

Chesler

2023

Preprint

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Chronic thromboembolic pulmonary hypertension (CTEPH) develops due to the accumulation of blood clots in the lung vasculature that obstruct flow and increase pressure. The mechanobiological factors that drive progression of CTEPH are not understood, in part because mechanical and hemodynamic changes in the pulmonary vasculature due to CTEPH are not easily measurable. Using previously published hemodynamic measurements and imaging from a large animal model of CTEPH, we developed a subject-specific one-dimensional (1D) computational fluid dynamic (CFD) models to investigate the impact of CTEPH on pulmonary artery stiffening, time averaged wall shear stress (TAWSS), and oscillatory shear index (OSI). Our results demonstrate that CTEPH increases pulmonary artery wall stiffness and decreases TAWSS in extralobar (main, right and left pulmonary arteries) and intralobar vessels. Moreover, CTEPH increases the percentage of the intralobar arterial network with both low TAWSS and high OSI. This subject-specific experimental-computational framework shows potential as a predictor of the impact of CTEPH on pulmonary arterial hemodynamics and pulmonary vascular mechanics. By leveraging advanced modeling techniques and calibrated model parameters, we predict spatial distributions of flow and pressure, from which we can compute potential physiomarkers of disease progression, including the combination of low mean wall shear stress with high oscillation. Ultimately, this approach can lead to more spatially targeted interventions that address the needs of individual CTEPH patients.

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Chronic Thromboembolic Pulmonary Hypertension – What Have We Learned From Large Animal Models

Cited by 7 publications

References 140 publications

Large Animal Models in Cardiovascular Research

Large Animal Models in Cardiovascular Research

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

Subject-specific one-dimensional fluid dynamics model of chronic thromboembolic pulmonary hypertension

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