At-risk but viable myocardium in a large animal model of non ST-segment elevation acute coronary syndrome: cardiovascular magnetic resonance with ex vivo validation

Abstract

BackgroundPatients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) have varying degrees of salvageable myocardium at risk of irreversible injury. We hypothesized that a novel model of NSTE-ACS produces acute myocardial injury, measured by increased T2 cardiovascular magnetic resonance (CMR), without significant necrosis by late gadolinium enhancement (LGE).MethodsIn a canine model, partial coronary stenosis was created and electrodes placed on the epicardium. Myocardial T2, an indicator of at-risk myocardium, was measured pre- and post-tachycardic pacing.ResultsSerum troponin-I (TnI) was not detectable in unoperated sham animals but averaged 1.97 ± 0.72 ng/mL in model animals. Coronary stenosis and pacing produced significantly higher T2 in the affected vs. the remote myocardium (53.2 ± 4.9 vs. 43.6 ± 2.8 ms, p < 0.01) with no evident injury by LGE. Microscopy revealed no significant irreversible cellular injury. Relative respiration rate (RRR) of affected vs. remote myocardial tissue was significantly lower in model vs. sham animals (0.72 ± 0.07 vs. 1.04 ± 0.07, p < 0.001). Lower RRR corresponded to higher final TnI levels (R2 = 0.83, p = 0.004) and changes in CaMKIID and mitochondrial gene expression.ConclusionsA large animal NSTE-ACS model with mild TnI elevation and without ST elevation, similar to the human syndrome, demonstrates signs of acute myocardial injury by T2-CMR without significant irreversible damage. Reduced tissue respiration and associated adaptations of critical metabolic pathways correspond to increased myocardial injury by serum biomarkers in this model. T2-CMR as a biomarker of at-risk but salvageable myocardium warrants further consideration in preclinical and clinical studies of NSTE-ACS.

Elastin-like recombinamers-based hydrogel modulates post-ischemic remodeling in a non-transmural myocardial infarction in sheep

“…So far, different methods are currently used to induce transmural (STEMI) infarction in large animals, including the permanent ligation of the left anterior descending coronary artery (LAD) (14,15). Only recently, the reproduction of non-ST elevation (NSTE)-acute coronary syndrome (ACS) has been developed in a canine model (16). However, the observed damage was not irreversible cardiac damage (16), which means that no infarct (i.e., NSTEMI) was produced.…”

“…Only recently, the reproduction of non-ST elevation (NSTE)-acute coronary syndrome (ACS) has been developed in a canine model (16). However, the observed damage was not irreversible cardiac damage (16), which means that no infarct (i.e., NSTEMI) was produced. With this in mind, we developed an NSTEMI model that enabled the investigation of the efficacy of customized ELRs-hydrogel in the modulation of post-ischemic remodeling.…”

T‐Wave Abnormality as Electrocardiographic Signature of Myocardial Edema in Non‐ST‐Elevation Acute Coronary Syndromes

“…We subsequently showed that myocardial edema by T2 CMR delineates at‐risk but salvageable myocardium in a large‐animal model of NSTE‐ACS 10. Thus, T2 CMR before angiography can delineate at‐risk but salvageable myocardium in NSTE‐ACS 11.…”

Review of Journal of Cardiovascular Magnetic Resonance 2014

“…CMR is invaluable to the study of patients with ischaemic heart disease and has made a major impact on this field and is now widely used to delineate myocardial infarction, [ 161 , 162 ] and scarring, [ 163 ] although more recently non-contrast techniques to detect infarction have been described. The use of techniques to define myocardial edema, [ 164 – 166 ] myocardium at risk, [ 167 ] myocardial hemorrhage, and microvascular obstruction, [ 168 ] has also grown greatly. Work has moved on to evaluating the relation between myocardial damage and aspects of myocardial function such as dyssynchrony, remodelling, healing, and determining outcomes, [ 169 ] and the indication for novel treatments [ 170 – 172 ].…”