Development of a closed chest model of chronic myocardial infarction in Swine: magnetic resonance imaging and pathological evaluation

Abstract

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 (n = 5 at each timepoint). Postoperative MRI revealed compromised contractility and decreased ejection fraction, from 53.8% ± 6.32% to 43.79% ± 7.72% (P = 0.001). These values remained lower than baseline thorough the followup (46.54% ± 11.12%, 44.48% ± 7.77%, and 40.48% ± 6.40%, resp., P < 0.05). 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.

Figure 1

Coronary angiogram obtained immediately after balloon inflation to assess correct occlusion of the artery prior to ethanol injection.

Figure 2

Cardiac MR images obtained during the study. Cine images obtained in short axis and four chamber views at all timepoints are shown in the first two rows. The third row depicts delayed enhanced acquisitions. (a) and (b) Baseline examinations showing normal swine cardiac anatomy. (c), (d) and (e) Images acquired immediately after infarct induction. The infarcted area can be identified by a density change in the cine images, which correspond to the enhanced area on the viability study. (f), (g) and (h) Images obtained 7 days after infarction. Little changes were evidenced in the cine images at this timepoint (apart from akinesia of the septum), but the DE view shows the typical hyperenhancement appearance of the infarct. (i), (j) and (k) Study performed on the 30-day followup. Wall thickness is clearly decreased in the infarcted area (anteroseptal), corresponding with the hyperenhanced septum in the viability study. (l), (m) and (n): 90-day followup. The infarcted area is clearly identified as a very thin wall in the cine acquisitions and as a highly enhanced area in the viability study.