Manganese ions as intracellular contrast agents: proton relaxation and calcium interactions in rat myocardium

Paramagnetic manganese (Mn) ions (Mn2+) are taken up into cardiomyocytes where they are retained for hours. Mn content and relaxation parameters, T-1 and T-2, were measured in right plus left ventricular myocardium excised from isolated perfused rat hearts. In the experiments 5 min wash-in of MnCl2 were followed by 15 min washout to remove extracellular (ec) Mn2+ MnCl2, 25 and 100 muM, elevated tissue Mn content to six and 12 times the level of control (0 muM MnCl2). Variations in perfusate calcium (Ca2+) during wash-in of MnCl2 and experiments including nifedipine showed that myocardial slow Ca2+ channels are the main pathway for Mn2+ uptake and that Mn2+ acts as a pure Ca2+ competitor and a preferred substrate for slow Ca2+ channel entry. Inversion recovery analysis at 20 MHz revealed two components for longitudinal relaxation: a short T1 - 1 and a longer T1 - 2. Approximate values for control and Mn-treated hearts were in the range 600-125 ms for T1 - 1 and 2200-750 ms for T1 - 2. The population fractions were about 59 and 41% for the short and the long component, respectively. The intracellular (ic) R1 - 1 and R2 - 1 correlated best with tissue Mn content. Applying two-site exchange analyses. on the obtained T-1 data yielded results in parallel to, but also differing from, results reported with an ec contrast agent. The calculated lifetime of ic water (tau(ic)) of about 10 s is compatible with a slow water exchange in the present excised cardiac tissue. The longitudinal relaxivity of Mn ions in ic water [60 (s mM)(-1)] was about one order of magnitude higher than that of MnCl2 in water in vitro [6.9 (s mM)(-1)], indicating that ic Mn-protein binding is an important potentiating factor in relaxation enhancement. Copyright (C) 2003 John Wiley Sons, Ltd.