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Developing and evaluating a chronic ischemic cardiomyopathy in swine model by rest and stress CMR

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Abstract

A large animal model of chronic coronary artery disease (CAD) is crucial for the understanding the underlying pathophysiological processes of chronic CAD and consequences for cardiac structure and function. The goal of this study was to develop a chronic model of CAD in a swine model and to evaluate the changes of myocardial structure, myocardial motility, and myocardial viability during coronary stenosis. A total of 30 swine (including 24 experimental animals and 6 controls) were enrolled. The chronic ischemia model was constructed by using Ameroid constrictor in experimental group. The 24 experimental animals were further divided into 4 groups (6 animals in each group) and were sacrificed at 1, 2, 3 and 4 weeks after operation for pathological examination, respectively. Cardiac magnetic resonance (CMR) was performed preoperatively and weekly postoperatively until sacrificed both in experimental and control group. CMR cine images, rest/adenosine triphosphate (ATP) stress myocardial contrast perfusion and LGE were performed and analyzed. The rest wall thickening (WT) score was calculated from rest cine images. The MPRI (myocardial perfusion reserve index) and MPR (myocardial perfusion reserve) were calculated based on rest and stress perfusion images. Pathology staining including triphenyltetrazolium chloride, HE and picrosirus red staining were performed after swine were sacrificed and collagen volume fraction (CVF) was calculated. The time to formation of ischemic, hibernating, and infarcted myocardium was recorded. In experimental group, from 1w to 4w after surgery, the rest WT score decreased gradually from 35.2 ± 2.0%, 32.0 ± 2.9% to 30.5 ± 3.0% and finally 29.06 ± 1.78%, p < 0.001. Left ventricular ejection fraction was gradually impaired after modeling (58.9 ± 12.6%, 56.3 ± 10.1%, 55.3 ± 9.0%, 53.8 ± 9.9%, respectively). And the MPR and MPRI also decreased stepwise with extent of surgery time (MPRI dropped from 2.1 ± 0.4, 2.0 ± 0.2 to 1.8 ± 0.3 and finally 1.7 ± 0.1, p = 0.004; MPR dropped from 2.3 ± 0.4, 2.1 ± 0.2 to 1.9 ± 0.4 and finally 1.8 ± 0.1, p < 0.001). Stronger associations between MPR, MPRI and CVF were paralleled lower wall thickening scores in fibrosis-affected areas. The ischemic myocardium was first appeared in the first week after surgery (involving ten segments), hibernated myocardium was first appeared in the second week after surgery (involving seventeen segments). LGE was first appeared in eight swine in the third weeks after surgery (16 segments). At 4w after surgery, average 9.6 g scar tissue was found among 6 swine. At the same time, histological analysis established the presence of fibrosis and ongoing apoptosis in the infarcted area. In conclusion, our study provided valuable insights into the pathophysiological processes of chronic CAD and its consequences for cardiac structure and function in a large animal model through combining myocardial motion and stress perfusion.

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Funding

This study was supported in part by research grants from the National Natural Science Foundation of China (No. 81971588), the Construction Research Project of Key Laboratory (Cultivation) of the Chinese Academy of Medical Sciences (No. 2019PT310025), the Clinical and Translational Fund of the Chinese Academy of Medical Sciences (No. 2019XK320063), Capital’s Funds for Health Improvement and Research (CFH 2020-2-4034) and the Clinically Characteristic Applied Research Fund (No. Z191100006619021).

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Author notes

  1. Baiyan Zhuang

    Present address: Department of Radiology, Beijing Anzhen Hospital, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Capital Medical University, Beijing, 100029, People’s Republic of China

Authors and Affiliations

  1. Department of Magnetic Resonance Imaging, Cardiovascular imaging and intervention Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China

    Baiyan Zhuang, Chen Cui, Jian He, Jing Xu, Shuang Li, Di Zhou, Wenjing Yang, Yining Wang, leyi zhu, Shihua Zhao & Minjie Lu

  2. Department of Animal Experimental Center, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Xin Wang & Liujun Jia

  3. Department of Pathology, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Li Li

  4. Department of Echocardiography, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Weichun Wu

  5. Key Laboratory of Cardiovascular Imaging (cultivation), Chinese Academy of Medical Sciences, Beijing, China

    Xiaoxin Sun & Minjie Lu

  6. National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, Maryland, USA

    Arlene Sirajuddin

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Contributions

Guarantors of integrity of entire study, B.Z., C.C., J.H., J.X., XS., X.D., L.L., S.L., X.W., M.L.; study concepts/study design or data acquisition or data analysis/interpretation, J.H., S.Z., W.Y., L.Z. D.Z., M.L.; experimental studies, B.Z., C.C., J.X., W.W., X.W., M.L.; statistical analysis, B.Z.; and manuscript editing, B.Z., X.D., A.S., M.L.

Corresponding author

Correspondence to Minjie Lu.

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Zhuang, B., Cui, C., He, J. et al. Developing and evaluating a chronic ischemic cardiomyopathy in swine model by rest and stress CMR. Int J Cardiovasc Imaging 40, 249–260 (2024). https://doi.org/10.1007/s10554-023-02999-4

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