The sodium-calcium exchanger (NCX) is one of the transporters contributing to 
the control of intracellular calcium (Ca(2+)) concentration by normally 
mediating net Ca(2+) efflux. However, the reverse mode of the NCX can cause 
intracellular Ca(2+) concentration overload, which exacerbates the myocardial 
tissue injury resulting from ischemia. Although the NCX inhibitor SEA0400 has 
been shown to therapeutically reduce myocardial injury, no in vivo technique 
exists to monitor intracellular Ca(2+) fluctuations produced by this drug. 
Cardiac manganese-enhanced MRI (MEMRI) may indirectly assess Ca(2+) efflux by 
estimating changes in manganese (Mn(2+)) content in vivo, since Mn(2+) has been 
suggested as a surrogate marker for Ca(2+). This study used the MEMRI technique 
to examine the temporal features of cardiac Mn(2+) efflux by implementing a 
T(1)-mapping method and inhibiting the NCX with SEA0400. The change in (1)H(2)O 
longitudinal relaxation rate, Delta R(1), in the left ventricular free wall, was 
calculated at different time points following infusion of 190 nmol/g manganese 
chloride (MnCl(2)) in healthy adult male mice. The results showed 50% MEMRI 
signal attenuation at 3.4 +/- 0.6 h post-MnCl(2) infusion without drug 
intervention. Furthermore, treatment with 50 +/- 0.2 mg/kg of SEA0400 
significantly reduced the rate of decrease in Delta R(1). At 4.9-5.9 h 
post-MnCl(2) infusion, the average Delta R(1) values for the two groups treated 
with SEA0400 were 2.46 +/- 0.29 and 1.72 +/- 0.24 s(-1) for 50 and 20 mg/kg 
doses, respectively, as compared to the value of 1.27 +/- 0.28 s(-1) for the 
control group. When this in vivo data were compared to ex vivo absolute 
manganese content data, the MEMRI T(1)-mapping technique was shown to 
effectively quantify Mn(2+) efflux rates in the myocardium. Therefore, combining 
an NCX inhibitor with MEMRI may be a useful technique for assessing Mn(2+) 
transport mechanisms and rates in vivo, which may reflect changes in Ca(2+) 
transport.