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An Improved Monkey Model of Myocardial Ischemic Infarction for Cardiovascular Drug Development

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Abstract

Non-human primate monkey model of myocardial ischemic infarction is precious for translational medicine research. Ligation of the left anterior descending (LAD) artery is a common procedure to induce myocardial ischemic infarction. However, the consistency of the myocardial infarction thus generated remains problematic. The present study was undertaken to critically evaluate the monkey model of myocardial ischemic infarction to develop a procedure for a consistent cross-study comparison. Forty male Rhesus monkeys were divided into 4 groups and subjected to LAD artery ligation at different levels along the artery. In addition, the major diagonal branch was selectively ligated parallel to the ligation site of the LAD artery according to the diagonal branch distribution. Analyses of MRI, echocardiography, cardiac hemodynamics, electrocardiography, histopathology, and cardiac injury biomarkers were undertaken to characterize the monkeys with myocardial infarction. Ligation at 40% of the total length of the artery, measured from the apex end, produced variable infarct areas with inconsistent functional alterations. Ligation at 60% or above coupled with selective ligation of diagonal branches produced a consistent myocardial infarction with uniform dysfunction. However, ligation at 70% caused a lethal threat. After a thorough analysis, it is concluded that ligation at 60% of the total length coupled with selective ligation of diagonal branches, enables standardization of the location of occlusion and the subsequent ischemic area, as well as avoids the influence of the diagonal branches, are ideal to produce a consistent monkey model of myocardial ischemic infarction.

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All data generated or analyzed during this study are included in this published article.

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Funding

This work was financially supported by the National Natural Science Foundation of China (NSFC 81230004 and 81300109) and West China Hospital.

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Authors and Affiliations

  1. Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, 610041, Sichuan, China

    Keke Wang, Pengfei Han, Lu Huang, Ying Xiao, Jianglong Hou, Pingliang Yang, Yuping Xie, Jindan Cai, Hongge Wang & Y. James Kang

  2. Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

    Jianglong Hou

  3. Department of Anesthesiology, First Affiliated Hospital of Chengdu Medical College, Xindu, 610050, Sichuan, China

    Pingliang Yang

  4. Department of Oncology, Chengdu First People’s Hospital, Chengdu, 610041, Sichuan, China

    Yuping Xie

  5. Department of Cardiology, Affiliated Renhe Hospital, China Three Gorges University, Yichang, 443001, Hubei, China

    Jindan Cai

  6. Tennessee Institute of Regenerative Medicine, University of Tennessee Health Science Center, Memphis, TN, USA

    Y. James Kang

Authors
  1. Keke Wang
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  2. Pengfei Han
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  9. Hongge Wang
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Contributions

YJK conceptualized the study, and KW, PH, KW and YJK designed the experiments; KW, PH, LH, YX, JH, PY, YP, JC, and HW carried out the experiments. KW, PH, and LH analyzed the data and interpreted the results; YJK and PH drafted the manuscript; YJK revised the draft and approved the final version of the manuscript.

Corresponding author

Correspondence to Y. James Kang.

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The authors declare no potential conflicts of interest.

Research Involving Human and Animal Studies

No human studies were carried out by the authors of this article. All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the Institutional Animal Care and Use Committee (IACUC) of Sichuan University West China Hospital (2015017A).

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Handling Editor: Yu-Ming Kang.

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Wang, K., Han, P., Huang, L. et al. An Improved Monkey Model of Myocardial Ischemic Infarction for Cardiovascular Drug Development. Cardiovasc Toxicol 22, 787–801 (2022). https://doi.org/10.1007/s12012-022-09754-6

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