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In This Article

  • Summary
  • Abstract
  • Introduction
  • Protocol
  • Representative Results
  • Discussion
  • Acknowledgements
  • Materials
  • References
  • Reprints and Permissions

Summary

A detailed methodology for establishing a minimally invasive rat model of pulmonary embolism using autologous blood clots is described. Additional methods for quantifying the infarcted area and visualizing the pulmonary arterial tree are also provided.

Abstract

Pulmonary embolism (PE) is one of the leading causes of cardiovascular death, resulting in a significant socioeconomic burden. Although current treatments primarily focus on anticoagulation and thrombolysis, there is an urgent need for a better understanding of its pathophysiology and the development of new treatment strategies. Animal models play a crucial role in understanding PE and developing new therapies for the disease, with rodents commonly used due to ethical and cost considerations. However, existing rodent models for PE are limited by a lack of standardized procedures, which hampers reproducibility and cross-study comparisons. This study aims to establish a minimally invasive rat model of PE using autologous blood clots. The model features a minimally invasive blood sampling technique, a standardized thrombus generation procedure, and minimally invasive vein access. Additionally, protocols for quantifying infarcted areas and visualizing the pulmonary arterial tree are provided. These procedures aim to improve the reliability of rodent models for studying PE progression and facilitate the development of novel treatments.

Introduction

Pulmonary embolism (PE) is a leading cause of in-hospital death and the third most frequent cause of cardiovascular death. Despite its high incidence, prevention and prompt diagnosis remain challenging1,2. Anticoagulation and thrombolytic therapies are critical in treating PE, yet a deeper understanding of disease progression and novel therapeutic approaches is essential for improving disease management3.

In modern biomedical research, animal models play a pivotal role in elucidating the mechanisms of human diseases and developing new therapies

Protocol

All animal experiments were conducted with the approval of the Animal Care and Use Committee of the Chinese Academy of Medical Sciences & Peking Union Medical College (approval number: IRM/2-1ACUC-2311-015). Male Sprague-Dawley rats, 6 weeks old and weighing around 250 g, were used in this study. The animals were housed in a specific pathogen-free environment with ad libitum access to a balanced chow diet and water. They were kept under a 12-h light/dark cycle at a room temperature of 22 °C ± 2 °C. The.......

Representative Results

Symptoms and pathology of the PE model
During embolization, the rats experienced shortness of breath, and the thorax showed widened fluctuations. Nearly all the animals survived the pulmonary embolism episode when fewer than 10 cm of blood clots were administered (14 out of 15 modeled animals). After being returned to their cages, the animals curled up in corners and showed reduced interest in food and water. However, these symptoms resolved quickly, and within several hours, the animals behaved no.......

Discussion

In this study, a minimally invasive rat model of PE using autologous blood clots was successfully established. Once mastered, this modeling procedure can be completed within 30 min. The model effectively captures key features of clinical PE, as confirmed by pathological examinations. Consequently, it offers a valuable tool for elucidating the hemodynamic changes and pathogenesis of complications following PE, developing new diagnostic biomarkers and therapeutic targets, and testing novel anti-thrombotic treatments.

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Acknowledgements

This study is supported by a grant from Wu Jieping Medical Foundation (320.6750.19089-36).

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Materials

NameCompanyCatalog NumberComments
Analytical balanceMETTLER TOLEDOMA55/ANone
Dispensing needleJinrong electronicsNone19 G and 18 G
Fine scissorsStrongerXGJ1300None
Heparin sodium saltSolarbio01-08-9041140U/mg
IsofluraneRWDR510-22-10None
Methyl salicylateMacklinM813577AR, 99%
Micro clampJZ W40160None
Micro tweezersStrongerXGN1310None
Silicone casting compoundFlow TechMV-130None
Sprague-Dawley ratsVital RiverSD-IGSNone
Stereo microscopeMurziderMSD204None

References

  1. Götzinger, F., et al. Interventional therapies for pulmonary embolism. Nat Rev Cardiol. 20 (10), 670-684 (2023).
  2. Falster, C., et al. Comparison of international guideline recommendations for the diagnosis o....

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