The oxygen paradox and the calcium paradox: Two facets of the same problem?

Abstract

An isolated rat heart preparation was used to study and compare the sudden tissue damage which may result from calcium repletion after a period of calcium-free perfusion with the effects of reoxygenation after a period of anoxic perfusion and with reperfusion after a period of ischaemia. Striking similarities in morphological and enzyme release characteristics exist for all three phenomena. Our results suggest that the primary lesion in the calcium paradox is the separation of the basement membrane from the sarcolemma and the energy-dependent loss of intracellular calcium to the extracellular space during the phase of calcium depletion. These changes, coupled with separation of opposing faces of the intercalated disc predispose the cell to the major damage which results from an energy independent, sudden, cellular influx of calcium during the phase of calcium repletion. In the case of the oxygen paradox the primary lesion would be the accumulation of cytoplasmic calcium and the loss of cellular and subcellular membrane control. While these anoxia or ischaemia-induced processes are related to the cellular availability of energy, the sudden damage induced by oxygen repletion would appear to be initiated by an energy-independent mitochondrial calcium uptake which is triggered by the reoxidation of the electron transport chain. Studies of such factors as the critical duration of calcium or oxygen depletion, the effects of stepwise calcium or oxygen repletion or the striking effects of hypothermia, reinforce the association between the calcium and oxygen paradoxes. While the basic principles underlying the cause of damage may be similar in both cases, fine differences exist in the progression, the nature and the extent of damage.