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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, T1 and T2, 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 wash‐out to remove extracellular (ec) Mn2+ MnCl2, 25 and 100 µM, elevated tissue Mn content to six and 12 times the level of control (0 µM 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 T1 data yielded results in parallel to, but also differing from, results reported with an ec contrast agent. The calculated lifetime of ic water (τic) 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 © 2003 John Wiley & Sons, Ltd.