PMID- 24107555
OWN - NLM
STAT- MEDLINE
DCOM- 20140707
LR  - 20240117
IS  - 1532-429X (Electronic)
IS  - 1097-6647 (Print)
IS  - 1097-6647 (Linking)
VI  - 15
IP  - 1
DP  - 2013 Oct 9
TI  - 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.
PG  - 94
LID - 10.1186/1532-429X-15-94 [doi]
AB  - BACKGROUND: Patients 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). METHODS: In 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. RESULTS: Serum 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 (R(2) = 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, 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.
FAU - Chang, Henry
AU  - Chang H
AD  - Dorothy M, Davis Heart and Lung Research Institute, The Ohio State University, 
      473 W 12th Ave, Suite 200, Columbus, OH 43210, USA. raman.1@osu.edu.
FAU - Tran, Tam
AU  - Tran T
FAU - Billman, George E
AU  - Billman GE
FAU - Julian, Mark W
AU  - Julian MW
FAU - Hamlin, Robert L
AU  - Hamlin RL
FAU - Simonetti, Orlando P
AU  - Simonetti OP
FAU - Ambrosio, Giuseppe
AU  - Ambrosio G
FAU - Baker, Peter B 3rd
AU  - Baker PB 3rd
FAU - Shao, Guohong
AU  - Shao G
FAU - Crouser, Elliott D
AU  - Crouser ED
FAU - Raman, Subha V
AU  - Raman SV
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
DEP - 20131009
PL  - England
TA  - J Cardiovasc Magn Reson
JT  - Journal of cardiovascular magnetic resonance : official journal of the Society 
      for Cardiovascular Magnetic Resonance
JID - 9815616
RN  - 0 (Biomarkers)
RN  - 0 (Troponin I)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
SB  - IM
MH  - Acute Coronary Syndrome/blood/*diagnosis/genetics/pathology/physiopathology
MH  - Animals
MH  - Biomarkers/blood
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
MH  - Cell Respiration
MH  - Disease Models, Animal
MH  - Dogs
MH  - Gene Expression Regulation
MH  - Genes, Mitochondrial
MH  - *Magnetic Resonance Imaging
MH  - Myocardium/metabolism/*pathology
MH  - Necrosis
MH  - Organs at Risk
MH  - Oxygen Consumption
MH  - Predictive Value of Tests
MH  - Reproducibility of Results
MH  - Stroke Volume
MH  - Time Factors
MH  - Tissue Survival
MH  - Troponin I/blood
MH  - Ventricular Function, Left
PMC - PMC3852225
EDAT- 2013/10/11 06:00
MHDA- 2014/07/08 06:00
PMCR- 2013/10/09
CRDT- 2013/10/11 06:00
PHST- 2013/07/08 00:00 [received]
PHST- 2013/10/01 00:00 [accepted]
PHST- 2013/10/11 06:00 [entrez]
PHST- 2013/10/11 06:00 [pubmed]
PHST- 2014/07/08 06:00 [medline]
PHST- 2013/10/09 00:00 [pmc-release]
AID - S1097-6647(23)00810-4 [pii]
AID - 1532-429X-15-94 [pii]
AID - 10.1186/1532-429X-15-94 [doi]
PST - epublish
SO  - J Cardiovasc Magn Reson. 2013 Oct 9;15(1):94. doi: 10.1186/1532-429X-15-94.