萘普生对心肌电生理与收缩功能的影响

Effects of naproxen on electrophysiological and contraction functions of myocardium

目的观察非甾体消炎药萘普生对心脏电生理特征性的影响,探讨其对心脏的潜在不良反应及机制。方法采用Langendorff离体心脏灌流方法和细胞内微电极技术,观察萘普生对心肌细胞快、慢反应动作电位和离体心脏心肌收缩力、离体及整体心脏心电图的影响。结果萘普生呈浓度依赖地使豚鼠心室乳头肌快反应动作电位的时程（APD50和APD90）和有效不应期缩短,0期上升速率（Vmax）减慢;可使家兔窦房结慢反应动作电位4期自动除极速率（SDVP4）、窦房结自律性兴奋频率和动作电位0期上升幅值减小。在离体心脏心电图实验中,萘普生减慢窦性心率,明显延长RR间期和QRS波群的时程,当浓度在1×10-5mol/L时能引起严重的房室传导阻滞;同时,使心肌收缩力显著下降,且呈剂量依赖性变化。心率变异性（HRV）分析显示,萘普生显著增强低频段（0.04~0.15 Hz）功率（LF）、高频段（0.15~0.4 Hz）功率（HF）,但其LF/HF比值显著减小,且呈浓度依赖性。结论萘普生可能通过抑制Na＋、Ca2＋离子通道,促进K＋离子通道或通过对自主神经系统的调节,尤其是对副交感神经的调节而影响心功能。

Objective To observe the effects of nonsteroidal anti-inflammatory drug, naproxen, on the cardiac electrophysiological characteristics and explore its potential adverse effects and mechanisms. Methods Langendorff isolated heart perfusion method and intracellular microelectrode technique were employed to observe the effects of naproxen on the fast and slow response action potentials of cardiac muscle cell, myocardial contractility of isolated heart, and electrocardiograms of isolated heart and whole heart. Results Naproxen shortened the duration of action potential （APD50 and APD90 ） and effective refractory period of ventricular papillary muscle of guinea pigs in a concentration dependant way, slowed down the rise speed of phase zero （ Vmax）, and decreased the phase 4 automatic depolarization rate （SDVP4） of slow response action potential, self exciting frequency, and rising amplitude of phase 0 action potential of rabbit sinoatrial node. In isolated heartelectrocardiogram tests, naproxen reduced the sinus heart rate, while prolonged the RR interval and the duration of Q RS complex waves. Naproxen of 10-5 mol/L caused serious atrioventricular block and weakened the myocardial contraction force in a dose dependant way. The heart rate variability analysis showed that naproxen siguificandy increased both values at low frequency （LF, 0.04 -0.15 Hz） and high frequency （HF, 0.15 -0.4 Hz）, but the value of LF/HF decreased remarkably in a concentration dependant way. Conclusion Naproxen may affect the cardiac function by inhibiting Na ＋ and Ca2＋ channels and promoting K ＋ channel or regulating the autonomic nervous system, especially the parasympathetic system.