Inhibition of the sodium–calcium exchanger via SEA0400 altered manganese‐induced T1 changes in isolated perfused rat hearts

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.