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Repeated Ca2+ depletion and repletion of short duration, termed Ca2+ preconditioning (CPC), is hypothesized to protect the heart from lethal injury after exposing it to the Ca2+ paradox (Ca2+ PD). Hearts were preconditioned with five cycles of Ca2+ depletion (1 minute) and Ca2+ repletion (5 minutes). These hearts were then subjected to Ca2+ PD, ie, one cycle of Ca2+ depletion (10 minutes) and Ca2+ repletion (10 minutes). Hearts subject to the Ca2+ PD underwent rapid necrosis, and myocytes were severely injured. CPC hearts showed a remarkable preservation of cell structure; ie, 65% of the cells were normal in CPC hearts compared with 0% in the Ca2+ PD hearts. LDH release was significantly reduced in CPC hearts compared with Ca2+ PD hearts (2.45 +/- 0.18 and 8.02 +/- 0.7 U.min-1 x g-1, respectively). ATP contents of CPC hearts were less depleted compared with the Ca2+ PD hearts (5.9 +/- 0.8 and …