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Inhibition of the sodium–calcium exchanger via SEA0400 altered manganese‐induced T1 changes in isolated perfused rat hearts
Authors:Ya Chen  Kevin Payne  Vindya S. Perara  Songping Huang  Akemichi Baba  Toshio Matsuda  Xin Yu
Affiliation:1. Department of Biomedical Engineering, Case Western Reserve University, , Cleveland, OH, USA;2. Case Center for Imaging Research, Case Western Reserve University, , Cleveland, OH, USA;3. Department of Chemistry, Kent State University, , Kent, OH, USA;4. Graduate School of Pharmaceutical Sciences, Osaka University, , Osaka, Japan;5. Department of Radiology, Case Western Reserve University, , Cleveland, OH, USA;6. Department of Physiology and Biophysics, Case Western Reserve University, , Cleveland, OH, USA
Abstract:Manganese (Mn2+)‐enhanced MRI (MEMRI) provides the potential for the in vivo evaluation of calcium (Ca2+) uptake in the heart. Recent studies have also suggested the role of the sodium–calcium (Na+–Ca2+) exchanger (NCX) in Mn2+ retention, which may have an impact on MEMRI signals. In this study, we investigated whether MEMRI with fast T1 mapping allowed the sensitive detection of changes in NCX activity. We quantified the dynamics of the Mn2+‐induced T1 changes in isolated perfused rat hearts in response to SEA0400, an NCX inhibitor. The experimental protocol comprised 30 min of Mn2+ perfusion (wash‐in), followed by a 30‐min wash‐out period. There were three experimental groups: 1, NCX inhibition by 1 µ m SEA0400 during Mn2+ wash‐in only (SEAin, n = 6); 2, NCX inhibition by 1 µ m SEA0400 during Mn2+ wash‐out only (SEAout, n = 6); 3, no NCX inhibition during both wash‐in and wash‐out to serve as the control group (CNTL, n = 5). Rapid T1 mapping at a temporal resolution of 3 min was performed throughout the perfusion protocol using a triggered saturation–recovery Look–Locker sequence. Our results showed that NCX inhibition during Mn2+ wash‐in caused a significant increase in relaxation rate (R1) at the end of Mn2+ perfusion. During the wash‐out period, NCX inhibition led to less reduction in R1. Further analysis of Mn2+ content in myocardium with flame atomic absorption spectroscopy was consistent with the MRI findings. These results suggest that Mn2+ accumulation and retention in rat hearts are, in part, dependent on NCX activity. Hence, MEMRI may provide an imaging method that is also sensitive to changes in NCX activity. Copyright © 2012 John Wiley & Sons, Ltd.
Keywords:manganese‐enhanced MRI  calcium uptake  sodium–  calcium exchanger  T1 mapping
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