A Lanyu Pig Model of Ischemia-Reperfusion Myocardial Infarction for Cardiac Regeneration

Abstract Background Myocardial infarction (MI) remains a leading cause of heart failure worldwide. Robust large animal models that mimic human physiology are necessary to develop regenerative therapies such as cell transplantation. However, conventional porcine models (e.g., Yorkshire and Göttingen minipigs) are limited by high perioperative mortality, primarily from lethal ventricular arrhythmias, and rapid somatic growth, which hinders long-term study. We hypothesized that the Lanyu pig, a genetically distinct miniature breed, would offer a superior translational platform with better survival and physiological stability than do the conventional models. Methods Catheter-based ischemia-reperfusion injury was induced in 17 adult Lanyu pigs through 90-min balloon occlusion of the midsegment of the left anterior descending artery. An insertable cardiac monitor was implanted 3 days before surgery for continuous rhythm tracking. Cardiac function was comprehensively assessed at baseline, immediately after MI, and on Day 14 after MI through transthoracic echocardiography and pressure-volume loop analysis. Intramyocardial injections were administered on Day 14 to simulate the subacute phase and validate the feasibility of therapeutic delivery. Results The Lanyu pig model achieved a procedural survival rate of 94.1% (16/17), significantly higher than the historical rates for other breeds. Post-MI assessments confirmed substantial functional decline: left ventricular ejection fraction decreased from 69.4% to 40.0% ( p < 0.001), and the slope of end-systolic pressure-volume relationship maximum rate of pressure rise decreased from 5.6 to 1.9 mmHg/mL ( p < 0.001). Although transient arrhythmias were observed, no sustained malignant arrhythmias occurred. Infarcts were consistent, and the animals tolerated the surgical and follow-up procedures well. Conclusion Our Lanyu pig MI model demonstrated high survival rates, reproducible cardiac dysfunction, and physiological similarity to humans. This model overcomes key limitations of conventional porcine models, offering a robust and ethically refined tool for preclinical evaluation of novel cardiac regenerative therapies.