HYDROPEROXIDE-INDUCED NUCLEOTIDE DEGRADATION AND ADENOSINE FORMATION IN ISOLATED RAT CARDIOMYOCYTES

The effect of tert-butyl hydroperoxide (tBH) on the nucleotide level i n isolated cardiomyocytes from adult rats was examined. Incubation of myocytes with the hydroperoxide resulted in loss of both ATP and NAD f rom mitochondria and cytosol. In contrast, only the cytosolic level of NADP was increased. The effect on myocyte content of ADP and AMP was less pronounced. A significant increase in formation and release of ad enosine also occurred in tBH-exposed cells. Treatment of cardiomyocyte s with tBH resulted in a progressive decline of rod-shaped and viable cells, which was accompanied by an increase in numbers of hypercontrac ted and round myocytes in the incubation mixture. Electron microscopic examination showed an intense contraction of the cells. In summary ou r results demonstrate that plasma membrane damage and hypercontraction are early manifestations of tBH-induced injury to isolated cardiomyoc ytes. The depletion of ATP and formation of adenosine also suggest tha t degradation of adenine nucleotides may contribute to the cytotoxicit y caused by tBH. Possible mechanisms involved in the ATP depletion are discussed.