In swine models, there are well-established protocols for creating a closed-chest myocardial infarction (MI) as well as protocols for characterization of cardiac function with cardiac magnetic resonance (CMR). This methods manuscript outlines a novel technique in CMR data acquisition utilizing smart-signal gradient recalled echo (GRE)-based array sequences in a free-breathing swine heart failure model allowing for both high spatial and temporal resolution imaging. Nine male Yucatan mini swine weighing 48.7 ± 1.6 kg at 58.2 ± 3.1 weeks old underwent the outlined imaging protocol before and 1-month after undergoing closed chest left anterior descending coronary artery (LAD) occlusion/reperfusion. The left ventricular ejection fraction (LVEF) at baseline was 59.3 ± 2.4% and decreased to 48.1 ± 3.7% 1-month post MI (P = 0.029). The average end-diastolic volume (EDV) at baseline was 55.2 ± 1.7 ml and increased to 74.2 ± 4.2 ml at 1-month post MI (P = 0.001). The resulting images from this novel technique and post-imaging analysis are presented and discussed. In a Yucatan swine model of heart failure via closed chest left anterior descending coronary artery (LAD) occlusion/reperfusion, we found that CMR with GRE-based array sequences produced clinical-grade images with high spatial and temporal resolution in the free-breathing setting.
PurposeCurrently, the American Heart Association (AHA) 17-segment model is the preferred clinical method to define and quantify left ventricle (LV) myocardial infarction (MI) size. This method is subjective and can be inaccurate given that segmental approximation assumes a specific percent of infarcted tissue when compared to reference standard post-mortem histopathology. To improve the accuracy and reproducibility of infarct volume quantification we propose a novel measurement technique based on cardiac MRI images from a porcine model of myocardial infarction. Data were collected from serial MRI exams of Yucatan mini swine over 6 months and endpoint organ harvesting for histopathologic analysis. MethodsTwo observers evaluated four infarct sizing methods: myocardial contouring of post-mortem heart slices, contouring using cardiac MRI, AHA 17-segment model analysis and novel long-axis MRI infarct sizing. ResultsLV infarct sizes ranges were 1.6% - 25.8% (n=10) using reference standard histopathologic infarct sizing. Intraclass correlations (ICC) were calculated between two observers and averaged due to high similarity, ICC > .900. A t-test of .0006 and Bland-Altman plots show statistically significant differences in 17-segment model infarct size compared to histopathologic analysis while no significant difference was found when compared to our new novel method with 0.8198. Linear correlation showed an R 2 of 0.9111 between MRI contoured infarct size and our novel MRI infarct sizing model to predict infarct size as a percentage while the R 2 of the 17-Seg model is 0.8197. ConclusionsThe 17-sgement model provides an inferior quantitative assessment of LV infarct size compared to the proposed long-axis infarct sizing suggesting it maybe a robust and easily implementable quantitative assessment of LV infarct size in advanced imaging.
Background: We tested a tissue engineered (TE) patch composed of a biodegradable mesh embedded with human neonatal fibroblasts and seeded with human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) to treat heart failure in Yucatan mini swine receiving no immune suppression. Methods: Swine (N=12) underwent a 90-minute balloon occlusion/reperfusion of the left anterior descending coronary artery to create a myocardial infarction (MI). Following a 4-week recovery, the TE patch was implanted via a mini median sternotomy. The following were obtained: Cardiac Magnetic Resonance (CMR) imaging, cardiac catheterization, activity monitoring with FitBark collars, treadmill testing, 24/7 ECGs with implanted loop recorders. Results: At 4 weeks after MI, swine had increased left ventricular (LV) volumes, decreased end-systolic elastance (Ees), a shift of the diastolic pressure/volume (P/V) to the right of baseline and an increase in the LV mass/volume. After 6 months of treatment, the TE treated swine (N=7) compared to inert tissue treated swine (N=5): End-systolic volume (2% decrease vs 18% increase); End-diastolic volume (7% decrease vs 26% increase): Ees (1.0±0.2 vs 1.9±0.2 mmHg/mL, P=0.006); the diastolic P/V loops shifted back toward baseline with no change in slope, and LV mass decreased. There was no mortality related to treatment; the TE patch was well tolerated as assessed by CMR and histology. The loop recorders showed TE treated animals remained in sinus rhythm throughout with no ventricular arrhythmias, no change in heart rate and a 20% increase in daily activity levels and a 20% increase in exercise tolerance. Conclusions: This TE patch with human neonatal fibroblasts and hiPSC-CMs improves LV function, partially reverses LV remodeling and improves exercise in non-immune suppressed swine with heart failure after 6 months of treatment.
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