Cardiac metal contents after infusions of manganese - An experimental evaluation in the isolated rat heart

RATIONALE AND OBJECTIVES. Manganese dipyridoxyl diphosphate (MnDPDP), a contrast agent for liver MRI, releases free Mn2+ in a graded manner. The aim of the study was to compare the effects of brief versus prolonged infusions of MnDPDP and manganese chloride (MnCl2) on cardiac function, metabolism, Mn accumulation, and tissue metal content. METHODS. Isolated perfused rat hearts received 1-minute or 10-minute infusions of MnDPDP (100 mu M, 1000 mu M) Or of MnCl2 (10 mu M, 100 mu M). Physiologic indices were measured intermittently, and tissue high-energy phosphate compounds and Ca/Fe/Mg/Mn/Zn contents were measured after a standardized Mn washout. RESULTS. One-minute and 10-minute infusions induced, respectively, minor and marked depressions of contractile function and corresponding elevations in myocardial Mn content. MnCl2 was markedly more potent than MnDPDP. Ten-minute infusions of the highest concentration of MnDPDP and MnCl2 lowered tissue Mg and elevated tissue Ca (MnCl2), whereas high-energy phosphates were unaffected. CONCLUSIONS. Mn uptake after Mn infusion is strongly related to the duration, concentration, and dose of free Mn ions. Differences in Mn accumulation between MnDPDP and MnCl2 were more pronounced after the 10-minute infusion.