A Novel Closed-Chest Porcine Model of Chronic Ischemic Heart Failure Suitable for Experimental Research in Cardiovascular Disease

Abstract

Cardiac pathologies are among the leading causes of mortality and morbidity in industrialized countries, with myocardial infarction (MI) representing one of the major conditions leading to heart failure (HF). Hitherto, the development of consistent, stable, and reproducible models of closed-chest MI in large animals, meeting the clinical realism of a patient with HF subsequent to chronic ischemic necrosis, has not been successful. We hereby report the design and ensuing application of a novel porcine experimental model of closed-chest chronic ischemia suitable for biomedical research, mimicking post-MI HF. We also emphasize the key procedural steps involved in replicating this unprecedented model, from femoral artery and vein catheterization to MI induction by permanent occlusion of the left anterior descending coronary artery through superselective deployment of platinum-nylon coils, as well as endomyocardial biopsy sampling for histologic analysis and cell harvesting. Our model could indeed represent a valuable contribution and tool for translational research, providing precious insights to understand and overcome the many hurdles concerning, and currently quenching, the preclinical steps mandatory for the clinical translation of new cardiovascular technologies for personalized HF treatments.

Cardiac Function in a Long-Term Follow-Up Study of Moderate and Severe Porcine Model of Chronic Myocardial Infarction

“…Again, therapeutic efficacy is easier to test in a model in which outcome is not affected by confounding factors such as spontaneous recovery that may exceed and hence mask the therapeutic effect. Importantly, our findings in both the LAD model and the LCx model on cardiac function and infarct size correspond to chronic myocardial ischemia models [ 15 , 16 ]. This indicates that 150-minute occlusion followed by reperfusion results in the same amount of myocardial damage but more closely resembles the clinical course and treatment of MI.…”

Novel porcine model of acute myocardial infarction using polyethylene terephthalate

“…Previous studies have used open chest surgery (amyloid constructor and surgical ligation) and cardiac intervention procedure (ethanol infusion, coil embolization, and balloon occlusion) to induce a porcine AMI [7,[21][22][23][24][25][26][27][28][29][30][31][32][33][34]. Our new model used interventional devices that are readily available and frequently used in clinical settings, and allows a simple and direct method to induce an ischemic lesion in the left ventricular myocardium without the need for non-biocompatible beads or invasive thoracotomy with coronary ligation [35,36].…”

Embolization of the first diagonal branch of the left anterior descending coronary artery as a porcine model of chronic trans-mural myocardial infarction

“…Previously reported porcine MI models have been associated with substantial challenges, which have limited their utility in assessment of therapeutic candidates. The most commonly used approaches to date have utilized surgical ligation [ 6 – 9 ] or coil embolization [ 10 – 12 ] of the left anterior descending (LAD) coronary artery, distal to the first and/or second diagonal branches as a standard for level of occlusion. Alternatively, ameroid constrictors [ 5 ], cryoinjury [ 13 ], ethanol infusion [ 14 ], autologous platelet embolization [ 3 ], balloon occlusion [ 15 – 17 ], and micro-bead LAD embolization [ 18 ] procedures have also been described.…”