• 作者： 蘇銘嘉; 林雪娥; 王志行; 曾淵如; 曾春典
• 作者服務機構： 臺大醫學院藥理研究所; 臺大醫院內科
• 中文摘要： 本實驗在單一大鼠心室細胞比較Amiodarone，Lidocaine與Quinidine對動作電位與膜電流之影響，在低頻刺激下（每10秒1次），20μM Quinidine會抑制動作電位去極化速率而且會使動作電位持續時間延長。相同濃度Lidocaine則使動作電位持續時間縮短，但去極化速率不變。Amiodarone則對動作電位持續時間及去極化速率均無影響。在膜電位鉗定時發現Amiodarone對心肌鈉電流之抑制與Lidocaine相似，但與Quinidine則有如下差異。第一點差異是在較低之鉗定頻率時（每10秒1次），Quinidine對鈉電流有明顯抑制，而Amiodarone與Lidocaine則無抑制效果。第二點差異是Quinidine之鈉電流抑制作用在每秒1次連續刺激時有明顯增強，而Amiodarone或Lidocaine則須每秒3次以上之連續刺激時有明顯增強效果。第三點差異是在海葵毒素(0.2μM)處理後，持續存在之鈉電流（即不活化速率很慢之鈉電流）會被Quinidine抑制，但不受Amiodarone抑制，另外在每秒鐘1次之連續刺激下，Quinidine之鈉電流抑制作用會被增強，這些結果與Quinidine會對抗海葵毒素之動作電位延長作用一致，此結果表示，Quinidine可能對開啟狀態之鈉管道也有很好之抑制作用，而Amiodarone對開啟狀態之鈉管道可能無抑制作用。 除了鈉電流抑制作用外，Quinidine對內流鈣電流及外流之鉀電流也有很強之抑制作用，而Amiodarone僅對內流鈣電流有輕微抑制，對外流鉀電流則無明顯抑制作用。至於Lidocaine，反而使瞬間外流鉀電流增加。由上述結果可知，Amiodarone在短期給予時可能經由鈉電流及鈣電流之抑制作用而產生抗心律不整效果。Quinidine則除了上述作用外，亦可經由對外流鉀電流抑制而產生抗心律不整效果。
• 英文摘要： The effects of 20 μM each of amiodarone, lidocaine and quinidine on action potential and membranecurrents were studied in rat ventricular cells. At a stimulation frequency of 0.1 Hz, quinidine prolongedthe action potential duration (APD ) from 120±26 to 660±8 msec and increased the time to peak (T )amplitude from 7±1 msec to 32±6 msec. Lidocaine shortened APD from 123±15 to 83±6 msecwithout altering T . Amiodarone changed neither APD nor T . Voltage clamp study revealed thatqumldine inhibited sodium inward current (I ) even when this current was elicited by aepolarlzirig pulsesat 0.1 Hz from a holding potential of -90 mV. For amiodarone and lidocaine, the inhibition was observedwhen I was elicited from a holding potential of -70 mV. A frequency-dependent inhibition of I by amiodarone and lidocaine was observed at frequencies higher than 1 Hz. Quinidine showed thisinhibition even at 1 Hz. In correlation with the stronger frequency dependent inhibition of I , a greaterdelay of the recovery and increase of the non-recovery fraction of I was induced by quinidine. Forlidocaine and amiodarone, only the recovery time constant was delayed. In cells treated with sea anemonetoxin (ATX, 0.2 μM), APD was prolonged to 4-5 sec in 5 min. Quinidine, but not amiodarone, com-pletely reversed the effect of ATX. Quinidine showed use-dependent inhibition of I in these ATX-treated cells Amiodarone, however, did not show this inhibition. It is likely that amiodarone suppressesI by delaying the recovery of I instead of blocking the open-state Na -channels. For quinidine, bothmechanisms are possible. In addition to the effect on I , the slight inhibition of I (calcium inwardcurrent) by amiodarone and the inhibition of both I and I (potassium outward current) by quinidinemay also contribute to their antiarrhythmic action.
• 中文關鍵字： amiodarone; lidocaine; quinidine; sea anemone toxin; antiarrhythmic agents; ventri-cular cells
• 英文關鍵字： --