Production of Swine Myocardial Infarction and Ischemic Heart Failure Models Using a Three-Dimensional Bioprinted Occluder

Abstract

Objectives: Clinical reproducibility of large animal models is important for developing new therapies for myocardial infarction (MI) and ischemic heart failure (IHF). This study aimed to induce MI and IHF in a swine model by using 3D bioprinted occluders to interrupt intravascular blood flow permanently. Methods: The 3D bioprinted occluder was placed in the proximal left anterior descending artery using a guide wire and a balloon catheter. Echocardiography was performed at the baseline, post MI (day 7-14), and at 28 days follow-up after the placement of the occluder to evaluate cardiac function. Quantitative coronary angiography was performed at baseline, post MI (immediately after the procedure) and at 42 days follow-up. Histopathology confirmed the deformation of the heart tissue and hypoxic damage.Results: Luminal diameter distal to the 3D bioprinted occluder was significantly reduced from the baseline to 42 days follow-up and left ventricular (LV) ejection fraction gradually decreased from the baseline to 28 days follow-up after the induction of MI. Tetrazolium staining showed firm and white area of the infarction in the LV apex and LV anterior wall. Hematoxylin and eosin stained section samples showed loss of normal architecture and morphology of myocytes in the LV myocardium. In addition, HIF-1 alpha was expressed in the ischemic myocardium area by immunohistochemistry staining. Conclusions: The customized occluder via 3D bioprinting technology could induce a stable, consistent and reproducible swine MI and IHF model.