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

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...

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Bibliographic Details
Published in:Cardiovascular toxicology 2022-09, Vol.22 (9), p.787-801
Main Authors: Wang, Keke, Han, Pengfei, Huang, Lu, Xiao, Ying, Hou, Jianglong, Yang, Pingliang, Xie, Yuping, Cai, Jindan, Wang, Hongge, Kang, Y. James
Format: Article
Language:English
Subjects:
Analysis
Biomarkers
Biomedical and Life Sciences
Biomedicine
Cardiology
Cardiovascular agents
Drug development
Echocardiography
EKG
Electrocardiography
Heart
Heart attack
Heart attacks
Hemodynamics
Histopathology
Injury analysis
Ischemia
Monkeys
Myocardial infarction
Occlusion
Pharmacology/Toxicology
Primates
Standardization
Veins & arteries
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Summary: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. Graphical abstract
ISSN:1530-7905
1559-0259
DOI:10.1007/s12012-022-09754-6