哌替啶的心脏电生理效应

Effects of pethidine on cardiac electrophysiological properties

目的 :观察哌替啶对心脏电生理学特性的影响 ,探讨可能的离子机制。方法 :采用 L angendorff灌流心脏模型 ,观察哌替啶对大鼠心率和心律的影响 ;采用全细胞电流钳及电压钳技术 ,在酶解分离的心室肌细胞上观察哌替啶对动作电位和离子电流的影响。结果 :哌替啶呈浓度依赖地减慢窦性心率 ,当浓度≥ 2 5 0μmol/ L时 ,能引起严重的房室传导阻滞。哌替啶可浓度依赖地降低心室肌细胞动作电位的去极化速度和幅度 ,延长动作电位时程。哌替啶 10 0 μmol/ L孵育后 ,能分别抑制 INa、Ito、Ik 和 ICa.L到对照组的 (6 0 .7± 6 .9) %、(5 5 .4± 5 .6 ) %、(6 5 .1± 8.0 ) %和(6 7.4± 10 .1) % ,阿片受体阻断剂纳洛酮不能阻断上述效应。结论 :哌替啶可减慢心率 ,引起房室传导阻滞 ,可能与它抑制了心肌细胞多种跨膜离子电流有关 ,其抑制作用并不通过阿片受体介导。

Objective: To investigate the effects of pethidine on electrophysiological properties of the isolated ventricular myocytes and the underlying mechanism.Methods:Langendorff was applied to perfuse rat heart model and whole-cell current clamp and voltage clamp techniques were used.Results:Pethidine decreased heart rate (HR) in a concentration dependent manner and caused severe atrioventricular block (AVB) at ≥250 μmol/L.Pethidine reduced action potential amplitude and maximal rate of depolarization,prolonged action potential duration.Pethidine at 100 μmol/L decreased sodium currents (I Na),transient outward potassium currents (I to),delayed rectifier potassium currents (I k) and L-type calcium currents (I Ca.L) to (60.7±6.9)%,(55.4±5.6)%,(65.1±8.0)% and (67.4±10.1)% of control levels,respectively.These effects could be recovered by washout.Naloxone,an opioid receptor antagonist,could not abolish the effects of pethidine on ionic currents.Conclusion:Pethidine decreased HR and induced AVB,which may be related to the inhibition of I Na,I to,I k and I Ca-L of heart.The depression of cardiac currents is not mediated by opioid receptor.