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Journal of Zhejiang University. Science. B2024; 25(2); 135-152; doi: 10.1631/jzus.B2300285

Therapeutic advances in atrial fibrillation based on animal models.

Abstract: Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia among humans, with its incidence increasing significantly with age. Despite the high frequency of AF in clinical practice, its etiology and management remain elusive. To develop effective treatment strategies, it is imperative to comprehend the underlying mechanisms of AF; therefore, the establishment of animal models of AF is vital to explore its pathogenesis. While spontaneous AF is rare in most animal species, several large animal models, particularly those of pigs, dogs, and horses, have proven as invaluable in recent years in advancing our knowledge of AF pathogenesis and developing novel therapeutic options. This review aims to provide a comprehensive discussion of various animal models of AF, with an emphasis on the unique features of each model and its utility in AF research and treatment. The data summarized in this review provide valuable insights into the mechanisms of AF and can be used to evaluate the efficacy and safety of novel therapeutic interventions. 心房颤动（Atrial fibrillation, AF）是人类最常见的由持续性心律失常导致的心脏疾病，其发病率随着年龄增长而显著增加。尽管房颤在临床实践中很常见，但其病因和治疗尚不清晰。为了制定有效的治疗策略，必须了解房颤的基本机制，因此建立房颤的动物模型对于探索其发病机制至关重要。虽然自发性房颤在大多数动物中罕见，但近年来一些大型动物模型，特别是猪、狗和马模型，已被证明在推进我们对房颤发病机制认识和开发新的治疗方案方面非常宝贵。本综述旨在对房颤的各种动物模型进行全面讨论，重点介绍每种模型的特征及其在房颤研究和治疗中的效用。本综述为房颤机制提供了宝贵的见解，并可用于评估新型治疗干预措施的有效性和安全性。. 心房颤动（Atrial fibrillation, AF）是人类最常见的由持续性心律失常导致的心脏疾病，其发病率随着年龄增长而显著增加。尽管房颤在临床实践中很常见，但其病因和治疗尚不清晰。为了制定有效的治疗策略，必须了解房颤的基本机制，因此建立房颤的动物模型对于探索其发病机制至关重要。虽然自发性房颤在大多数动物中罕见，但近年来一些大型动物模型，特别是猪、狗和马模型，已被证明在推进我们对房颤发病机制认识和开发新的治疗方案方面非常宝贵。本综述旨在对房颤的各种动物模型进行全面讨论，重点介绍每种模型的特征及其在房颤研究和治疗中的效用。本综述为房颤机制提供了宝贵的见解，并可用于评估新型治疗干预措施的有效性和安全性。
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Publication Date: 2024-02-02 PubMed ID: 38303497PubMed Central: PMC10835209DOI: 10.1631/jzus.B2300285Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This research article discusses the use of various animal models to study atrial fibrillation (AF), a common and complex heart rhythm disorder.
  • The paper focuses on how these models help to understand AF’s underlying mechanisms and aid in developing new treatment options.

Introduction to Atrial Fibrillation and the Need for Animal Models

  • Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans, with an increased incidence as people age.
  • Despite its prevalence in clinical settings, the exact causes (etiology) of AF and effective management strategies remain unclear.
  • Understanding the mechanisms that lead to AF is critical for developing better therapeutic interventions.
  • Animal models are essential research tools that allow scientists to study AF’s pathogenesis (origin and development) in a controlled environment.
  • Direct studies on humans can be limited by ethical, technical, and feasibility issues; thus, animal models serve as important substitutes.

Challenges in Animal Modeling of AF

  • Spontaneous atrial fibrillation is rare in most animal species, limiting natural models of the disease.
  • This rarity necessitates the development of experimental or induced models that simulate AF in animals.

Key Animal Models Discussed

  • Pigs:
    • Physiologically, pig hearts are quite similar to human hearts in size, anatomy, and electrophysiological properties, making them excellent models for AF research.
    • Pig models help in studying AF mechanisms and testing catheter ablation and other interventional treatments.
  • Dogs:
    • Canine models have been widely used due to their relatively large heart size and well-characterized cardiac physiology.
    • They allow studies on electrical remodeling (changes in electrical properties), structural remodeling, and the progression of AF.
    • Dogs have been instrumental in testing pharmaceutical therapies and device-based interventions.
  • Horses:
    • Horses naturally develop AF, especially those involved in high-performance activities, providing a naturally occurring large animal model.
    • This model is valuable to study exercise-induced AF and evaluate long-term physiological consequences.

Unique Features and Utility of Each Model

  • Each animal model has unique physiological and anatomical attributes that influence how AF develops and responds to treatments.
  • The pig model’s cardiac anatomy closely mimics human hearts, useful for surgical and catheter-based therapeutic research.
  • Dog models allow examination of cardiac electrical properties and pharmacological testing due to their electrophysiological similarities.
  • Horses provide insights into naturally occurring AF and how prolonged high-intensity exercise affects arrhythmia progression.
  • Hence, combining insights from different models gives a more comprehensive picture of AF pathophysiology.

Contributions to Therapeutic Advances

  • These animal models have shed light on the multifactorial mechanisms involved in AF, such as electrical remodeling, inflammation, fibrosis, autonomic nervous system roles, and genetic factors.
  • By replicating human AF conditions, these models facilitate testing the efficacy and safety of novel pharmacological agents and interventional techniques like ablation.
  • They help identify potential targets for therapy and optimize treatment protocols before clinical application in humans.
  • Novel therapies derived from these studies include new antiarrhythmic drugs, improved ablation strategies, and potentially gene or cell-based interventions.

Conclusion and Future Perspectives

  • The review underscores the importance of animal models in understanding AF pathogenesis and advancing treatment options.
  • It emphasizes selecting appropriate models depending on the research goals due to differences in anatomy, physiology, and disease progression between species.
  • Continued refinement of animal models and integration with emerging technologies will enhance the translational impact of research findings.
  • The ultimate goal is to develop safe, effective, and personalized therapies for AF patients, reducing the disease burden worldwide.

Cite This Article

APA
Gong Q, LE X, Yu P, Zhuang L. (2024). Therapeutic advances in atrial fibrillation based on animal models. J Zhejiang Univ Sci B, 25(2), 135-152. https://doi.org/10.1631/jzus.B2300285

Publication

Journal of Zhejiang University. Science. B
ISSN: 1862-1783
NlmUniqueID: 101236535
Country: China
Language: English
Volume: 25
Issue: 2
Pages: 135-152

Researcher Affiliations

Gong, Qian
  • Institute of Genetics and Reproduction, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
  • Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
LE, Xuan
  • Institute of Genetics and Reproduction, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Yu, Pengcheng
  • Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
Zhuang, Lenan
  • Institute of Genetics and Reproduction, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. zhuangln@zju.edu.cn.
  • Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China. zhuangln@zju.edu.cn.

MeSH Terms

  • Humans
  • Animals
  • Dogs
  • Horses
  • Swine
  • Atrial Fibrillation / drug therapy
  • Disease Models, Animal
  • Treatment Outcome

Grant Funding

  • 2021YFA0805902 / the National Key Research and Development Program of China
  • 32270884 / the National Natural Science Foundation of China

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