Cardiac rehabilitation in porcine models: Advances in therapeutic strategies for ischemic heart disease

Abstract

Ischemic heart disease (IHD) remains a leading contributor to cardiovascular disease (CVD) worldwide. Despite advances in diagnostic and therapeutic approaches, translational research demands robust large animal models to bridge the gap between experimental interventions and clinical application. Among these, porcine models have gained prominence due to their anatomical, physiological, immunological, and genomic similarities to humans. This review provides a comprehensive overview of current methodologies for establishing porcine IHD models, critically assesses emerging rehabilitative strategies, and outlines innovative therapeutic technologies, with the goal of guiding model selection and fostering the development of novel treatment strategies.

Keywords: Cardiovascular disease; Ischemic heart disease; Physical therapy modality; Porcine model; Rehabilitation.

Figure 1

Prevention and treatment strategies for IHD Management of IHD includes risk factor management, medication, and reperfusion therapy to fully control damage caused by disease progression. Illustration was created by BioRender.com. IHD: Ischemic heart disease.

Figure 2

Establishment of porcine AS model AS can be induced by a high-fat diet or endothelial damage. High-fat diet increases LDL in the blood and promotes its oxidation and foam cell formation. Endothelial injury triggers an inflammatory response, which accelerates LDL deposition and plaque development, leading to atherosclerotic lesions. Constructing gene-edited pigs or adding vitamin D3 or bovine serum albumin to a high-fat diet can shorten AS establishment time. Illustration was created by BioRender.com. ApoE: Apolipoprotein E; AS: Atherosclerosis; GOF: Gain-of-function; KO: Knockout; LDL: Low-density lipoprotein; LDLR: Low-density lipoprotein receptor.

Figure 3

Establishment of porcine MI, I/R injury, and HF models Permanent MI and I/R injury models can be established by coronary artery ligation via thoracotomy or interventional surgery to block the target coronary artery. Myocardial ischemia and hypoxia occur after coronary artery occlusion. Inflammatory cells rapidly infiltrate damaged myocardium to remove necrotic tissue. Granulation tissue subsequently forms, but excessive repair results in the progressive replacement of the myocardium by fibrotic tissue. As the disease progresses, the pumping function of the heart becomes severely impaired, leading to HF. An HF model can also be established by an ameroid constrictor, leading to chronic ischemia of coronary arteries. A hygroscopic ameroid constrictor ring is surgically placed around a coronary artery in pigs, where it gradually swells, causing chronic ischemia, myocardial dysfunction, and HF. Cardiac function is monitored via echocardiography and hemodynamic assessment, validating the model for ischemic HF research. Illustration was created by BioRender.com. HF: Heart failure; I/R: Ischemia-reperfusion; MI: Myocardial infarction.

Figure 4

Pathophysiological changes in porcine IHD models after application of cardiac rehabilitation A: Exercise training for porcine AS. Exercise training can regulate coronary vessels and improve inflammation and oxidative stress by regulating ion channels and expression of oxidative stress proteins, thus reducing formation of atherosclerotic plaques. B: Exercise training for porcine MI. Exercise training can regulate coronary artery blood vessels, improve inflammation and oxidative stress, reduce mitochondrial dysfunction, promote angiogenesis, and reduce fibrosis by regulating expression of ion channels and vasoactive factors to improve cardiac function and delay disease progression. C: ESWT for porcine MI. ESWT can improve cardiac function after MI by reducing inflammation, promoting angiogenesis, improving fibrosis, and reducing oxidative stress. Therapeutic mechanisms are summarized from studies based on porcine IHD models and do not cover all therapeutic mechanisms of rehabilitation modalities. Illustration was created by BioRender.com. AS: Atherosclerosis; EF: Ejection fraction; ESWT: Extracorporeal shock wave therapy; HF: Heart failure; IHD: Ischemic heart disease; I/R: Ischemia-reperfusion; MI: Myocardial infarction.