Large animal models of cardiac ischemia-reperfusion injury: Where are we now?

Zool Res. 2023 May 18;44(3):591-603. doi: 10.24272/j.issn.2095-8137.2022.487.

Abstract

Large animal models of cardiac ischemia-reperfusion are critical for evaluation of the efficacy of cardioprotective interventions prior to clinical translation. Nonetheless, current cardioprotective strategies/interventions formulated in preclinical cardiovascular research are often limited to small animal models, which are not transferable or reproducible in large animal models due to different factors such as: (i) complex and varied features of human ischemic cardiac disease (ICD), which are challenging to mimic in animal models, (ii) significant differences in surgical techniques applied, and (iii) differences in cardiovascular anatomy and physiology between small versus large animals. This article highlights the advantages and disadvantages of different large animal models of preclinical cardiac ischemic reperfusion injury (IRI), as well as the different methods used to induce and assess IRI, and the obstacles faced in using large animals for translational research in the settings of cardiac IR.

在临床转化为人体试验之前,心脏缺血-再灌注的大型动物模型对于评估心脏保护干预措施的效果至关重要。然而,现有的心脏保护策略/干预方法往往仅限于小型动物模型,由于不同的因素,这些方法无法转移到大型动物模型中重现,原因有:(i) 人类缺血性心脏病 (ICD) 的复杂多样的特征难以在动物模型中准确模拟。(ii) 目前所应用的外科手术技术存在显着差异。 (iii) 小型动物与大型动物在心血管解剖学和生理学方面存在差异。该文重点介绍了不同大型动物模型在前临床实验中心脏缺血再灌注损伤 (IRI) 的一些优点/缺点、用于诱导和评估 IRI 的不同方法,以及在利用这些大型动物进行转化研究时面临的障碍和挑战。.

Keywords: Cardiovascular disorder; Ischemic cardiac disease; Ischemic-reperfusion injury; Large animal model; Myocardial infarction; Translational gap.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Humans
  • Myocardial Reperfusion Injury* / veterinary

Grants and funding

This work was supported by the Early Career Scheme (ECS) 2022/23 (CUHK 24110822) from the Research Grants Council of Hong Kong, as well as the Direct Grant for Research 2020/21 (2020.035), Project Impact Enhancement Fund (PIEF) (PIEF/Ph2/COVID/08), and Improvement on Competitiveness in Hiring New Faculties Funding Scheme from CUHK as well as the Centre for Cardiovascular Genomics and Medicine (CCGM) of the Lui Che Woo Institute of Innovative Medicine CUHK (to S.B.O.). A.R. is a CUHK Department of Medicine & Therapeutics (MEDT)-funded PhD student. Y.L. is a CUHK Vice-Chancellor’s PhD Scholarship holder