Abstract 13116: Ex-vivo Signatures of Myocardial Edema by in-vivo T2-CMR in a Novel Large Animal Model of NSTE-ACS
BACKGROUND: Patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), the majority of all ACS, may have myocardium at risk of irreversible injury. We hypothesized that myocardial T2 increase without late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) detects reversible ischemic injury; that is, areas of the affected myocardium that remain viable. We tested this using a novel canine model of NSTE-ACS that combines reduced myocardial O2 supply with increased demand.
METHODS & RESULTS: In 7 dogs, a partial stenosis of the left circumflex coronary artery was created and electrodes placed on the epicardial surface of the right ventricle for tachycardic pacing (15 minutes at 180-200% of the resting heart rate). 6 other dogs served as shams. Serum troponin-I (TnI) was not detectable in shams but averaged 1.97±0.72ng/mL in model animals. Coronary stenosis and pacing resulted in significantly higher T2 in the circumflex distribution vs. the remote myocardium (53.2±4.9 vs. 43.6±2.8ms, p<0.01) with no evident injury by LGE imaging. Microscopy revealed no significant irreversible cellular injury. Relative respiration rate (RRR) measured by ex-vivo tissue O2 consumption between affected and remote myocardium was significantly lower in model vs. sham animals (0.72±0.07 vs. 1.04±0.07ms, 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.
CONCLUSIONS: A large animal NSTE-ACS model with mild TnI elevation and without ST elevation, similar to the human syndrome, exhibits 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 as a biomarker of at-risk but salvageable myocardium warrants further consideration in preclinical and clinical studies of NSTE-ACS.
- © 2013 by American Heart Association, Inc.