Imaging characterization of myocardial function, fibrosis, and perfusion in a nonhuman primate model with heart failure-like features

Xing-Li Liu; Guan-Zhong Wang; Mao-Ping Rui; Dong Fan; Jie Zhang; Zheng-Hua Zhu; Rosario Perez; Tony Wang; Li-Chuan Yang; Liang Lyu; Jie Zheng; Gang Wang

doi:10.3389/fcvm.2023.1214249

Imaging characterization of myocardial function, fibrosis, and perfusion in a nonhuman primate model with heart failure-like features

Front Cardiovasc Med. 2023 Aug 17:10:1214249. doi: 10.3389/fcvm.2023.1214249. eCollection 2023.

Authors

Xing-Li Liu^{1

2}, Guan-Zhong Wang³, Mao-Ping Rui^{1

2}, Dong Fan^{1

2}, Jie Zhang³, Zheng-Hua Zhu³, Rosario Perez³, Tony Wang³, Li-Chuan Yang³, Liang Lyu^{1

2}, Jie Zheng⁴, Gang Wang^{1

2}

Affiliations

¹ Department of Radiology, The First People's Hospital of Yunnan Province, Kunming, China.
² Department of Radiology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.
³ Department of Pharmocolgy, Kunming Biomed International of TriApex Group, Kunming, China.
⁴ Mallinckrodt Institute of Radiology, Washington University in Saint Louis, St. Louis, MO, United States.

Abstract

Introduction: The availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close physiology relatedness to humans, the non-human primate (NHP) HF model would be valuable to better understand the pathophysiology and pharmacology of HF. The purpose of this work was to present preliminary cardiac image findings using echocardiography and cardiovascular magnetic resonance (CMR) in a HF-like cynomolgus macaque model.

Methods: The NHP diet-induced model developed cardiac phenotypes that exhibited diastolic dysfunction with reduced left ventricular ejection fraction (LVEF) or preserved LVEF. Twenty cynomolgus monkeys with cardiac dysfunction were selected by echocardiography and subsequently separated into two groups, LVEF < 65% (termed as HFrEF, n = 10) and LVEF ≥ 65% with diastolic dysfunction (termed as HFpEF, n = 10). Another group of ten healthy monkeys was used as the healthy control. All monkeys underwent a CMR study to measure global longitudinal strain (GLS), myocardial extracellular volume (ECV), and late gadolinium enhancement (LGE). In healthy controls and HFpEF group, quantitative perfusion imaging scans at rest and under dobutamine stress were performed and myocardial perfusion reserve (MPR) was subsequently obtained.

Results: No LGE was observed in any monkey. Monkeys with HF-like features were significantly older, compared to the healthy control group. There were significant differences among the three groups in ECV (20.79 ± 3.65% in healthy controls; 27.06 ± 3.37% in HFpEF group, and 31.11 ± 4.50% in HFrEFgroup, p < 0.001), as well as for stress perfusion (2.40 ± 0.34 ml/min/g in healthy controls vs. 1.28 ± 0.24 ml/min/g in HFpEF group, p < 0.01) and corresponding MPR (1.83 ± 0.3 vs. 1.35 ± 0.29, p < 0.01). After adjusting for age, ECV (p = 0.01) and MPR (p = 0.048) still showed significant differences among the three groups.

Conclusion: Our preliminary imaging findings demonstrated cardiac dysfunction, elevated ECV, and/or reduced MPR in this HF-like NHP model. This pilot study laid the foundation for further mechanistic research and the development of a drug testing platform for distinct HF pathophysiology.

Keywords: cardiovascular magnetic resonance; extracellular volume; fibrosis; heart failure; nonhuman primate; perfusion.

Grants and funding

This work was supported by the Yunnan “Ten thousand people plan” famous doctor special project [grant number: YNWR-MY-2019-011] and the clinical medical center open project of the first People's hospital of Yunnan province [grant number: 2022LCZXKF-HX06].