Magnetic Resonance Imaging/Magnetic Resonance Spectroscopy Biomarkers Evaluation of Stunned Myocardium in Canine Model

OBJECTIVES: To evaluate whether dynamic alterations in high-energy phosphate (HEP) occur in postischemic "stunned" myocardium (SM) in canine model and to investigate the correlation between HEP and cardiac function, using cine magnetic resonance imaging (cine-MRI) and phosphorus-31 magnetic resonance spectroscopy (31P-MRS). MATERIALS AND METHODS: Dogs (n = 13) underwent cine MRI and 31P-MRS at 60 minutes, 8 days after 10 minutes full left anterior descending occlusion followed by reperfusion. The same MRI/MRS experiments were repeated on 5 reference animals (dogs without ischemic reperfusion) at the same time points to serve as internal reference myocardium (RM). After MR data acquisitions, the SM dogs (n = 3 at 60 minutes; n = 10 at 60 minutes and day 8) and RM dogs (n = 5) were euthanized and myocardial tissues were sampled for histologic study by triphenyltetrazolium chloride staining, hematoxylin and eosin staining, and electron microscopic examination. RESULTS: The myocardial stunning at 60 minutes was confirmed by electron microscopy examinations from the 3 randomly chosen animals with SM. The phosphocreatine (PCr)/β- adenosine triphosphate (ATP) ratio of SM was significantly lower at 60 minutes than that at day 8 (1.07 ± 0.20 vs. 1.97 ± 0.28, P < 0.05). However, no significant difference was found between 60 minutes and day 8 in RM group (1.91 ± 0.14 at 60 minutes vs. 1.89 ± 0.16 at day 8, P > 0.05). At 60 minutes, the PCr/β-ATP ratio has significant difference between SM and RM groups; while at day 8, the ratio shows no significant difference between the 2 groups. The same results were obtained for left ventricle ejection fraction (LVEF). In SM group, LVEF has good correlation with myocardial PCr/β-ATP ratios at 60 minutes (R2 = 0.71, P < 0.05) and at day 8 (R2 = 0.73, P < 0.05), respectively. CONCLUSIONS: The HEP alterations were confirmed by 31P-MRS in SM and there is a good correlation between PCr/β-ATP ratio and LVEF for SM at 60 minutes and recovered myocardium at day 8. The combined MRS/MRI method offers the potential to systematically assess the cardiac function, morphology, and metabolism of SM. These MRS/MRI biomarker datasets could be used to dynamically monitor therapeutic efficiency and predict cardiac events.