羟苯氨酮对心肌生理特性及细胞内游离钙的影响

Effects of oxyphenamone on physiological characteristics and intracellular free calcium of myocardium

目的了解羟苯氨酮(oxyphenamone)对心肌基本生理特性的影响及正性肌力作用机制。方法测定豚鼠离体乳头肌和心房肌张力与动作电位,Fura2/AM法测细胞内游离钙。结果羟苯氨酮剂量依赖性地增加心肌收缩力,延长收缩时程,减慢右房自发频率,减低心肌自律性,延长功能不应期和动作电位时程,不影响心肌兴奋性。它不增加心肌细胞内[Ca2+],甚至还能明显地对抗缺氧复氧所致的细胞内钙超载。结论除增强心肌收缩性外,羟苯氨酮对心肌的其他生理特性及细胞内[Ca2+]的影响不同于磷酸二酯酶抑制剂(PDEI)等正性肌力药,有希望发展成为一种不易导致心律失常的、不良反应较低的新型强心药。

OBJECTIVE: To investigate the effect of oxyphenamone on the physiological characteristics of myocardium and the mechanism of its positive inotropic effect. METHODS: The preparations of isolated papillary muscles and atria of guinea pigs were used for recording the myocardial tension and the technique of Fura-2/AM was used for measuring the concentration of free calcium in myocytes. RESULTS: At the concentration range of 1 ∼ 100 μmol&middotL -1, oxyphenamone dose-dependently increased the contractive force of guinea pig myocardium, decreased the spontaneous pulse rate of right atrium, diminished the myocardial automaticity, and prolonged the myocardial contractive period, the active refractory period and the action potential duration, and not affect myocardial excitability. Oxyphenamone did not increase the concentration of free calcium in myocytes, but did antagonize the calcium overload induced by anoxia-reoxygenation. CONCLUSION: Except the positive inotropic effect, there are some differences in myocardial physiological characteristics and in the influence on intracellular calcium concentration between oxyphenamone and the known cardiotonics including phosphodiesterase inhibitors. It indicates that oxyphenamone is a hopeful new cardiotonic agent without the risk of arrhythmia in the treatment of cardiovascular diseases.