Background

Although oxygen free radicals have been shown to induce myocardial cell damage and cardiac dysfunction, the exact mechanism by which these radicals affect the heart function is not clear. Since the occurrence of intracellular Ca²⁺ overload is critical in the genesis of cellular damage and cardiac dysfunction, and since the sarcolemmal Na⁺–Ca²⁺ exchange is intimately involved in Ca²⁺ movements in myocardium, this study was undertaken to examine the effects of oxygen free radicals on the relationship between changes in cardiac contractile force development and sarcolemmal Na⁺–Ca²⁺ exchange activity.

Methods and Results

Isolated rat hearts were perfused with a medium containing xanthine plus xanthine oxidase for different times, and changes in contractile force as well as sarcolemmal Na⁺–Ca²⁺ exchange activity were monitored. Perfusion of the heart with xanthine plus xanthine oxidase resulted in a transient increase followed by a marked decrease in contractile activity; the resting tension was markedly increased. The xanthine plus xanthine oxidase-induced depression in developed tension, rate of contraction, and rate of relaxation, except the transient increase in contractile activity, was prevented by the addition of catalase, but not by superoxide dismutase, in the perfusion medium. A time-dependent depression in sarcolemmal Na⁺–Ca²⁺ was also evident upon perfusing the heart with xanthine plus xanthine oxidase. This depression in Na⁺-dependent Ca²⁺ uptake was associated with a decrease in the maximal velocity of reaction without any changes in the affinity of Na⁺–Ca²⁺ exchanger for Ca²⁺. The presence of catalase, unlike superoxide dismutase, prevented the decrease in sarcolemmal Na⁺–Ca²⁺ exchange activity in hearts perfused with xanthine plus xanthine oxidase.

Conclusion

The results support the view that a depression in the sarcolemmal Na⁺–Ca²⁺ exchange activity may contribute to the occurrence of intracellular Ca²⁺ overload and subsequent decrease in contractile activity. Furthermore, these actions of xanthine plus xanthine oxidase in the whole heart appear to be a consequence of H₂O₂ production rather than the ‘ generation of superoxide radicals.

中文翻译：

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氧自由基对心脏收缩活性和肌膜Na ⁺ -Ca ²⁺交换的影响

背景

尽管已证明氧自由基可引起心肌细胞损伤和心脏功能障碍，但这些自由基影响心脏功能的确切机制尚不清楚。由于细胞内Ca ²⁺超负荷的发生在细胞损伤和心脏功能障碍的发生中至关重要，并且由于肌膜Na ⁺ -Ca ²⁺交换与心肌中Ca ^2+的运动密切相关，因此本研究旨在研究氧自由基对心脏收缩力发展变化与肌膜Na ⁺ -Ca ²⁺交换活性之间关系的影响。

方法与结果

离体大鼠心脏灌注含有黄嘌呤加黄嘌呤氧化酶的培养基不同时间，并监测其收缩力的变化以及肌膜Na ⁺ -Ca ²⁺交换活性。黄嘌呤加黄嘌呤氧化酶对心脏的灌注会导致短暂的增加，然后收缩活动显着降低。静息张力明显增加。黄嘌呤加黄嘌呤氧化酶诱导的紧张性，收缩率和松弛率的降低，除了短暂的收缩活性增加外，通过在灌注培养基中添加过氧化氢酶来预防，但不能通过超氧化物歧化酶来预防。Na ⁺ –Ca ^2+的时间依赖性抑郁用黄嘌呤加黄嘌呤氧化酶灌注心脏也很明显。Na ⁺依赖性Ca ²⁺吸收的降低与最大反应速度的降低相关，而Na ⁺ -Ca ²⁺交换剂对Ca ²⁺的亲和力没有任何变化。与超氧化物歧化酶不同，过氧化氢酶的存在阻止了黄嘌呤加黄嘌呤氧化酶灌注的心脏肌膜Na ⁺ -Ca ²⁺交换活性的降低。

结论

结果支持这样一种观点，即肌膜Na ⁺ -Ca ²⁺交换活性的降低可能会导致细胞内Ca ²⁺超负荷的发生并随后降低收缩活性。此外，黄嘌呤加黄嘌呤氧化酶在整个心脏中的这些作用似乎是H ₂ O ₂产生的结果，而不是超氧化物自由基的产生。