Effects of Manganese Dipyridoxyl Diphosphate, Dipyridoxyl Diphosphate?? ??, and Manganese Chloride on Cardiac Function

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Abstract
Manganese dipyridoxyl diphosphate (MnDPDP) is a promising contrast agent for magnetic resonance imaging of the liver. The authors explored the possibility that high concentrations of MnDPDP may cause manganese ion (Mn++)-induced side effects on cardiac function. Potential cardiodepression by MnDPDP, DPDP– –, and manganese chloride (MnCl2) (100-3,0000 µmol/ L) was investigated in the isolated rat heart, with left ventricular developed (systolic—end-diastolic) pressure and heart rate as the primary indices of cardiac function. During 5-minute exposures, 10% and 50% decreases in left ventricular developed pressure were observed for MnDPDP, 250 µmol/L and 1580 /µmoI/L; DPDP– –, less than 100 µmol/L and 1000 /µmoI/L; MnCl2, 30 /µmol/L and 250 /µmol/L. Heart rate changes were not observed with MnDPDP. Cardiodepression was reversed within 2 minutes during a 14- minute recovery period for all investigated concentrations of MnDPDP and was less rapid for the highest concentrations of MnCl2. Manganese dipyridoxyl diphosphate is well tolerated in the rat heart at concentrations as high as 200 to 250 limol/L and is approximately 10 times less cardiotoxic than MnCl2. Cardiodepressive effects of MnDPDP in the present rat heart model, perfused in the absence of blood and proteins, are related primarily to the release of free Mn++ions and in part to the simultaneous release of DPDP¯ ¯.

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