Dpcom (Norway)

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) (100-3,000 mumol/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 mumol/L and 1580 mumol/L; DPDP--, less than 100 mumol/L and 1000 mumol/L; MnCl2, 30 mumol/L and 250 mumol/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 mumol/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--.

A new particulate magnetic resonance (MR) contrast agent was prepared by controlled precipitation of iron oxide in an aqueous starch solution. The potential of the magnetic starch microspheres (MSM) as a hepatosplenic contrast enhancer was studied by MR spectroscopy and MR imaging. Intravascular administration of MSM to rodents showed an effective blood clearance and a tissue-specific localization of the substance. MSM doses in a range of 0.3-1.5 mg Fe/kg caused a 50% alteration in sensitive contrast parameters (ED50 doses) of liver and spleen. The contrast effect of MSM in liver and spleen was halved within 2 to 5 days. The approximated lethal MSM dose in mice was 150-200 mg Fe/kg. MSM is a tissue-specific MR contrast substance with high efficacy, rapid bioelimination, and low acute toxicity.