Heart injury in the calcium paradox: the effect of manganese

Prevention by manganese ions of heart injury induced by the calcium paradox was studied in isolated perfused rat heart. Lactate dehydrogenase (LDH) release, ATP and glycogen content, and 45Ca2+ accumulation were used as markers of the injury. If Mn2+ substituted Ca2+ in the perfusion buffer after Ca2+-free perfusion, LDH release from the heart was inhibited but the inhibition was eliminated by Ca2+ readmission. However, Mn2+ (0.2-2.5 mM), added from the beginning of Ca2+-free perfusion, prevented heart injury at the time of Ca2+ repletion. LDH release and 45Ca2+ accumulation in the myocardium were reduced by 90-99%; ATP, glycogen and water content in the heart as well as perfusion pressure and heart rate remained within control values. The observed protective effect of Mn2+ was proportional to its concentration, and to the duration of Ca2+-free perfusion. A possible explanation for the protective effect of Mn2+ ions can be competition with Ca2+ binding sites related to sarcolemma integrity.