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

Paramagnetic manganese (Mn) ions (Mn 2+ ) 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 MnCl 2 were followed by 15 min wash‐out to remove extracellular (ec) Mn 2+ MnCl 2 , 25 and 100 µ M , elevated tissue Mn content to six and 12 times the level of control (0 µ M MnCl 2 ). Variations in perfusate calcium (Ca 2+ ) during wash‐in of MnCl 2 and experiments including nifedipine showed that myocardial slow Ca 2+ channels are the main pathway for Mn 2+ uptake and that Mn 2+ acts as a pure Ca 2+ competitor and a preferred substrate for slow Ca 2+ channel entry. Inversion recovery analysis at 20 MHz revealed two components for longitudinal relaxation: a short T 1 − 1 and a longer T 1 − 2 . Approximate values for control and Mn‐treated hearts were in the range 600–125 ms for T 1 − 1 and 2200–750 ms for T 1 − 2 . The population fractions were about 59 and 41% for the short and the long component, respectively. The intracellular (ic) R 1 − 1 and R 2 − 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 (τ 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 m M ) −1 ] was about one order of magnitude higher than that of MnCl 2 in water in vitro [6.9 (s m M ) −1 ], indicating that ic Mn‐protein binding is an important potentiating factor in relaxation enhancement. Copyright © 2003 John Wiley & Sons, Ltd.