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.

The Intrapericardial Delivery of Extracellular Vesicles from Cardiosphere-Derived Cells Stimulates M2 Polarization during the Acute Phase of Porcine Myocardial Infarction

“…Although it was not the purpose of the study, the long-term effect of these treatments (in terms of cardiac functionality) could be determined at 10 weeks. Unfortunately these results were not conclusive, more especially since these healthy and young animal models are characterized by an early regenerative potential which could mask the therapeutic effect of the treatments [46]. In any case, our results did not show any significant difference between groups (Ejection Fraction: 29.6 ± 8.0 in Placebo, 29.8 ± 17.2 in EV-CDCs, 32.0 ± 6.7 in CDCs; % Infarct: 12.4 ± 3.5 in Placebo, 10.6 ± 1.7 in EV-CDCs, 9.2 ± 4.0 in CDCs).…”

Microencapsulated Insulin-Like Growth Factor-1 therapy improves cardiac function and reduces fibrosis in a porcine acute myocardial infarction model

“…Nevertheless, a statistically significant decrease over time in this parameter was observed in the three groups. This reduction in the percentage of infarction, including CON and MSPs groups, could be attributed to an overestimation in that parameter in the earliest phases of infarction due to the presence of inflammation, haemorrhage and edema 44,[50][51][52] . Likewise, the decrease in IS at 10 weeks could be explained by the degree of LV wall thinning due to ventricular remodelling resulting in a loss of cardiomyocytes, destruction of the extracellular matrix of the necrotic area and its replacement by a fibrotic scar 53,54 .…”

Misinterpretation of the mouse ECG: ‘musing the waves of Mus musculus’

“…In experimental models, ischaemia is usually generated by occlusion of the left anterior descending artery (LAD). This leads to an average infarct size of approximately 25% of the left ventricular mass in large animal models, comparable to that of humans (Coronel et al 2007;Crisostomo et al 2013). In mice, however, the average size of the ischaemic myocardium is much larger and represents up to 50% of the left ventricular mass (Elrod et al 2007;Pol et al 2011;Marsman et al 2013;Methner et al 2013).…”

“…; Crisostomo et al . ). In mice, however, the average size of the ischaemic myocardium is much larger and represents up to 50% of the left ventricular mass (Elrod et al .…”