Translational large animal model of coronary microvascular embolism: characterization by serial cardiac magnetic resonance and histopathology

This study aimed to construct a large animal model of coronary microvascular embolism, and investigate whether it could mimic the clinical imaging phenotypes of myocardial hypoperfusion in patients with ST-segment elevation myocardial infarction (STEMI). Nine minipigs underwent percutaneous coronary embolization with microspheres, followed by cardiac magnetic resonance (CMR) on week 1, 2 and 4 post operation. Microvascular obstruction (MVO) was defined as the isolated hypointense core within the enhanced area on late gadolinium enhancement images, which evolved during a 4-week follow-up. Fibrotic fraction of the segments was measured by Masson trichrome staining using a panoramic analysis software. Iron deposit and macrophage infiltration were quantified based on Perl’s blue and anti-CD163 staining, respectively. Seven out of 9 (77.8%) minipigs survived and completed all of the imaging follow-ups. Four out of 7 (57.1%) minipigs were identified as transmural infarct with MVO. The systolic wall thickening (SWT) of MVO zone was similar to that of infarct zone ( P = 0.762). Histopathology revealed transmural deposition of collagen, with microvessels obstructed by microspheres. The fibrotic fraction of infarct with MVO segments was similar to that of infarct without MVO segments ( P = 0.954). The fraction of iron deposit in infarct with MVO segments was higher than that of infarct without MVO segments ( P < 0.05), but the fraction of macrophage infiltration between these two segments did not show statistical difference ( P = 0.723). Large animal model of coronary microvascular embolism could mimic most clinical imaging phenotypes of myocardial hypoperfusion in patients with STEMI, demonstrated by serial CMR and histopathology.