Effects of MnDPDP, DPDP--, and MnCl2 on cardiac energy metabolism and manganese accumulation. An experimental study in the isolated perfused rat heart.
OBJECTIVE
Recent studies indicate that manganese dipyridoxyl diphosphate (MnDPDP) may function as a slow release agent for manganese ions (Mn++) and that MnDPDP is approximately 10 times less potent than manganese chloride (MnCl2) in depressing cardiac function. The authors examined the possibility that MnDPDP and MnCl2 may influence cardiac metabolism and enzyme release and lead to a tissue accumulation of Mn.


METHODS
Manganese DPDP, DPDP--, or MnCl2 (1000 microM) was infused in isolated rat hearts, which were freeze-clamped at various time intervals during infusion (5 minutes) and recovery (14-minute washout). Enzyme (lactate dehydrogenase) release, tissue high energy phosphates, Mn contents, and physiologic indices were measured at various time intervals.


RESULTS
No significant differences were noted for: lactate dehydrogenase in the treated groups; tissue creatine phosphate (CrP) and adenosine triphosphate in MnDPDP, DPDP--, and control groups; and tissue Mn in DPDP-- and control groups. Manganese-chloride and MnDPDP-treated hearts accumulated and retained Mn in an 8:1 ratio. Manganese chloride depressed cardiac function more effectively than MnDPDP.


CONCLUSIONS
The study has shown that: heart tissue uptake and retention of Mn++ is rapid and effective; MnCl2 is approximately eight times more potent than MnDPDP in promoting these effects; and a rise in tissue Mn content to eight to nine times (MnDPDP) or 60 to 70 times (MnCl2) the normal level does not lead to acute side effects on cardiac energy metabolism, function, and enzyme release. The study indicates that MnDPDP may act like a slow release compound for Mn++ ions.
Brurok
H
H
Department of Physiology and Biomedical Engineering, Faculty of Medicine, Norwegian University of Science and Technology, Oslo, Norway.
Schjøtt
J
J
Berg
K
K
Karlsson
J O
JO
Jynge
P
P
D000818:Animals; D002712:Chlorides / Q000493:pharmacokinetics / Q000494:pharmacology*; D003287:Contrast Media / Q000493:pharmacokinetics / Q000494:pharmacology*; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D008297:Male; D008345:Manganese / Q000493:pharmacokinetics / Q000494:pharmacology*; D017895:Manganese Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010477:Perfusion; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
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