Inhibition of the sodium-calcium exchanger via SEA0400 altered manganese-induced T1 changes in isolated perfused rat hearts.
Inhibition of the sodium-calcium exchanger via SEA0400 altered manganese-induced T1 changes in isolated perfused rat hearts.
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DOI：
10.1002/nbm.2799
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发表时间：
2012-11
影响因子：
2.9
通讯作者：
Yu, Xin
中科院分区：
文献类型：
--
作者：
Chen, Ya;Payne, Kevin;Perara, Vindya S.;Huang, Songping;Baba, Akemichi;Matsuda, Toshio;Yu, Xin
锰 (Mn2+) 增强 MRI (MEMRI) 为体内评估心脏钙 (Ca2+) 吸收提供了可能。最近的研究还表明钠钙 (Na+–Ca2+) 交换器 (NCX) 在 Mn2+ 保留中的作用，这可能对 MEMRI 信号产生影响。在本研究中，我们研究了具有快速 T1 映射的 MEMRI 是否可以灵敏地检测 NCX 活性的变化。我们量化了离体灌注大鼠心脏中 Mn2+ 诱导的 T1 变化的动态，以响应 NCX 抑制剂 SEA0400。实验方案包括 30 分钟的 Mn2+ 灌注（冲洗），然后是 30 分钟的冲洗期。实验分为三个组：1、仅在 Mn2+ 清洗过程中使用 1 μM SEA0400 抑制 NCX（SEAin，n = 6）； 2，仅在 Mn2+ 洗脱过程中 1 μM SEA0400 抑制 NCX（SEAout，n = 6）； 3、在洗入和洗出过程中没有NCX抑制作为对照组(CNTL，n = 5)。在整个灌注方案中，使用触发的饱和恢复 Look-Locker 序列以 3 分钟的时间分辨率进行快速 T1 映射。我们的结果表明，Mn2+ 冲洗期间的 NCX 抑制导致 Mn2+ 灌注结束时弛豫率 (R1) 显着增加。在清除期间，NCX 抑制导致 R1 减少较少。进一步用火焰原子吸收光谱分析心肌中Mn2+含量，与MRI结果一致。这些结果表明，大鼠心脏中 Mn2+ 的积累和保留部分取决于 NCX 活性。因此，MEMRI 可能提供一种对 NCX 活性变化也敏感的成像方法。
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 μM SEA0400 during Mn2+ wash-in only (SEAin, n = 6); 2, NCX inhibition by 1 μM 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.
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影响因子：
20.1
作者：
Pogwizd, SM;Schlotthauer, K;Bers, DM
通讯作者：
Bers, DM
影响因子：
7.3
作者：
Farkas, A. S.;Acsai, K.;Farkas, A.
通讯作者：
Farkas, A.
影响因子：
5
作者：
BASSANI, RA;BERS, DM
通讯作者：
BERS, DM
影响因子：
5.5
作者：
SHAM, JSK;HATEM, SN;MORAD, M
通讯作者：
MORAD, M
影响因子：
5.5
作者：
BASSANI, JWM;BASSANI, RA;BERS, DM
通讯作者：
BERS, DM