Multiparametric CMR imaging of infarct remodeling in a percutaneous reperfused Yucatan mini‐pig model

Abstract

Purpose To further understanding of the temporal evolution and pathophysiology of adverse ventricular remodeling over the first 60 days following a myocardial infarction (MI) in both the infarcted and remote myocardium, we performed multi-parametric cardiac magnetic resonance imaging (CMR) in a closed-chest chronic Yucatan mini-pig model of reperfused MI. Methods Ten animals underwent 90 minute left anterior descending artery occlusion and reperfusion. Three animals served as controls. Multiparametric CMR (1.5T) was performed at baseline, day-2, day-30 and in four animals at day-60 post-MI. Left ventricular volumes and infarct size were measured. T1 and T2 Mapping sequences were performed to measure values in the infarct and remote regions. Remote region collagen fractions were compared between infarcted animals and controls. Results Procedure success was 80%. The model created large infarcts (28 ± 5% of left ventricular mass on day-2), which led to significant adverse myocardial remodeling that stabilized beyond 30 days. Native T1 values did not reliably differentiate remote and infarct regions acutely. There was no evidence of remote fibrosis as indicated by partition coefficient and collagen fraction analyses. The infarct T2 values remained elevated up to 60 days post-MI. Conclusion Multiparametric CMR in this model showed significant adverse ventricular remodeling 30 days post-MI similar to that seen in humans. In addition, this study demonstrated that remote fibrosis is absent and that infarct T2 signal remains chronically elevated in this model. These findings need to be considered when designing pre-clinical trials using CMR endpoints.

Adenosine stress CMR perfusion imaging of the temporal evolution of perfusion defects in a porcine model of progressive obstructive coronary artery occlusion

“…Although the sample size was relatively small, and we were unable to obtain external validation of the measured perfusion values, our measured perfusion values and MPR agree with prior porcine studies using other modalities . The time frame of the study was only 6 weeks; however, results were stable between 3 and 6 weeks, and infarct remodeling is typically complete within the time frame that we studied …”

“…These infarcts were fairly small (1.9% of LV mass) and decreased from the 3 week to the 6 week time points due to infarct remodeling. 28 Three animals showed evidence of ischemia without myocardial infarction by 3 weeks. Figure 1 summarizes the differences in perfusion metrics among the different anesthetic agents at baseline.…”

“…17,18,36 The time frame of the study was only 6 weeks; however, results were stable between 3 and 6 weeks, and infarct remodeling is typically complete within the time frame that we studied. 28 One challenge with the ameroid occlusion model is that there is some heterogeneity in the presence of infarction versus ischemia. It is possible that in some animals the ameroid occluder closed abruptly due to the sizing of the ameroid or kinking of the vessel by the ameroid occluder, causing an abrupt occlusion and myocardial infarction.…”

MRI Brain Templates of the Male Yucatan Minipig

“…The limited number of pig templates that do exist include the domestic pig (Saikali et al, 2010), the neonatal piglet (Conrad et al, 2014), and the Göttingen minipig (Watanabe et al, 2001). The Yucatan is known to be gentle, has an adult weight ranging from approximately 70 to 90 kg (150 to 200 lbs), and has been used extensively for developing surgical and experimental techniques as well as models for metabolic syndrome, biocompatability, skin lesions, pharmacology, toxicology, and cardiovascular disease (Estrada et al, 2008;Eubanks et al, 2006;Curtasu et al, 2019;Mattern et al, 2007;Quesson et al, 2011;Montezuma et al, 2006;Pak et al, 2006;Lin et al, 1998;Hurtig et al, 2019;Swindle et al, 1990Swindle et al, , 2011Witczak et al, 2006;Lopez et al, 2017).…”

Evaluating Novel Targets of Ischemia Reperfusion Injury in Pig Models

“…Significant changes in the field have occurred since the initial histological, structural and immunohistological evaluation of cardiovascular events in the pig [40]. They have been combined with clinic-grade imaging tools, e.g., magnetic resonance imaging (MRI): in a longitudinal study on reperfusion injury, cardiovascular magnetic resonance (CMR) revealed the 2-amplitude course of T2 relaxation in ischemic tissue within the first seven days post reperfusion [41]; in an acute setting, CMR was used to monitor ischemia-induced scar formation [42]; Gadolinium (Gd)-enhanced MRI was used to examine the post-conditional application of cardiosphere-derived cells (CDC) [43]; magnetic resonance imaging was used to determine T1 and T2 mapping in combination with Gd-contrast enhancement, phase-sensitive inversion recovery (LGE), cine-balanced steady-state free precession (bSSFP) and cine displacement encoding with stimulated echoes (DENSE) to analyze ischemia reperfusion injuries [44]. Compressed sensing has been used to further improve 3D multicontrast late enhancement for better identification of low spatiotemporal MR signals [45].…”