Influence of ATP or oxygen plus substrate on occurrence of the calcium paradox

Reperfusion of Ca2+-deprived rat hearts with Ca2+-containing medium results in irreversible cell damage (calcium paradox). In this study this type of cell damage was studied in the anoxic rat heart, in the presence and absence of glucose. Creatine kinase (CK) release was used to define cell damage. Hearts were perfused successively with Ca2+-containing medium (30 min), Ca2+-free medium (5 min), and Ca2+-containing medium (5 min). In the presence of glucose, myocardial ATP was maintained at a fairly high concentration. Reperfusion with Ca2+ resulted in an immediate and massive release of CK. In the absence of glucose, the ATP concentration was almost zero after 30 min. Reperfusion with Ca2+ did not result in release of CK. Massive release occurred as soon as these hearts were reoxygenated. It is concluded that this type of calcium-induced cell damage only occurs in the presence of ATP, or oxygen plus substrate. Mitochondria most likely play a major role in the occurrence of the calcium paradox because of their ability to accumulate huge amounts of Ca2+ under these conditions.