Our aim was to develop an easy-to-induce, reproducible, and low mortality clinically relevant closed-chest model of chronic myocardial infarction in swine using intracoronary ethanol and characterize its evolution using MRI and pathology. We injected 3-4？mL of 100% ethanol into the mid-LAD of anesthetized swine. Heart function and infarct size were assessed serially using MRI. Pigs were euthanized on days 7, 30, and 90 ( at each timepoint). Postoperative MRI revealed compromised contractility and decreased ejection fraction, from 53.8% ± 6.32% to 43.79% ± 7.72% ( ). These values remained lower than baseline thorough the followup (46.54% ± 11.12%, 44.48% ± 7.77%, and 40.48% ± 6.40%, resp., ). Progressive remodeling was seen in all animals. Infarcted myocardium decreased on the first 30 days (from 18.09% ± 7.26% to 9.9% ± 5.68%) and then stabilized (10.2% ± 4.21%). Pathology revealed increasing collagen content and fibrous organization over time, with a rim of preserved endocardial cells. In conclusion, intracoronary ethanol administration in swine consistently results in infarction. The sustained compromise in heart function and myocardial thinning over time indicate that the model may be useful for the preclinical evaluation of and training in therapeutic approaches to heart failure. 1. Introduction Cardiovascular diseases are a major cause of death and disability in developed countries. Myocardial infarction has an estimated annual incidence in the US of 525.000 new and 190.000 recurrent attacks. Approximately 15% of patients who suffer a coronary attack will die as a result of it [1]. Patients who survive a heart attack have an increased prevalence of heart failure (HF) [2]. Research in animal models is mandatory to assess safety and efficacy of any new therapy prior to clinical translation [3, 4]. Large animal models are essential to test new interventional, surgical, or electrophysiological procedures that cannot be performed in small animals, thus providing a platform for training specialists in optimal techniques involving new procedures, another highly important role of animal models of disease [5]. Current models for myocardial infarct creation are suboptimal for a variety of reasons, including a high mortality and inconsistent infarct creation [6–9]. Clinically, intracoronary ethanol has been used for the management of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) [10, 11] and in the therapy of arrhythmias. Studies using intracoronary ethanol administration in animals are limited and generally focused on refining HOCM therapies
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