Effects of manganese dipyridoxyl diphosphate, dipyridoxyl diphosphate--, and manganese chloride on cardiac function. An experimental study in the Langendorff perfused rat heart.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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--.
Brurok
H
H
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Trondheim, Norway.
Schjøtt
J
J
Berg
K
K
Karlsson
J O
JO
Jynge
P
P
Schøjtt
J
J
D000818:Animals; D002712:Chlorides / Q000494:pharmacology*; D003287:Contrast Media / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D017895:Manganese Compounds / Q000494:pharmacology*; D010477:Perfusion / Q000379:methods; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; D008345:Manganese; D011732:Pyridoxal Phosphate; D004492:Edetic Acid; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid; C025340:manganese chloride