EFFECTS OF MNDPDP, DPDP--, AND MNCL2 ON CARDIAC ENERGY-METABOLISM ANDMANGANESE ACCUMULATION - AN EXPERIMENTAL-STUDY IN THE ISOLATED-PERFUSED RAT-HEART

RATIONALE AND OBJECTIVES. Recent studies indicate that manganese dipyr idoxyl diphosphate (MnDPDP) may function as a slow release agent for m anganese ions (Mn++) and that MnDPDP is approximately 10 times less po tent than manganese chloride (MnCl2) in depressing cardiac function, T he authors examined the possibility that MnDPDP and MnCl2 may influenc e cardiac metabolism and enzyme release and lead to a tissue accumulat ion of Mn, METHODS. Manganese DPDP, DPDP-, or MnCl2 (1000 mu M) was in fused in isolated rat hearts, which were freeze-clamped at various tim e intervals during infusion (5 minutes) and recovery (14-minute washou t), Enzyme (lactate dehydrogenase) release, tissue high energy phospha te, Mn contents, and physiologic indices were measured at various time intervals, RESULTS. NO significant differences were noted for: lactat e 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-t reated hearts accumulated and retained Mn in an 8:1 ratio, Manganese c hloride depressed cardiac function more effectively than MnDPDP, CONCL USIONS. 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 me tabolism, function, and enzyme release, The study indicates that MnDPD P may act like a slow release compound for Mn++ ions.