Study for elevating effect of defibrillation threshold by antiarrythmic drugs during the treatment of arrythmia

第一年摘要：许多抗心律失常药物导致室性除颤阈值(DFT)升高。虽然美西律也被报道为DFT显著升高的可能原因，但以前没有研究；因此，本研究调查了美西律对DFT的影响。这些实验是在10只杂种狗身上进行的。负荷剂量为美西律1、2、4、6、8 mg/kg，后按相同剂量/kg/h给药。在这五组中，每10分钟重复进行一次纤颤/除颤(F/D)试验，直到开始维持剂量后60分钟。在美西律输注完成后30、45、60分钟进行F/D试验。对心脏施加内桨，最大能量为2，3，5，7，10，20和30J。各组美西律浓度变化范围为0~6.11µg/ml，DFE为2~10 J，与DFT之间无统计学相关性。结论：美西律不会引起犬DFT增加。动物的准备与1岁时相同。氟卡胺2 mg/kg为负荷量，后按相同剂量/kg/h给药。然后连续给予美西律1，2，3，4，5 mg/kg，直至除颤失败。每一阶段均进行F/D试验。引起除颤的最小能量休克(DFT)随美西律剂量的增加而增加。综上所述，在服用氟卡胺的患者中，在使用美西律治疗室颤时必须谨慎。

Abstract of 1st year : Many of the antiarrhythmic drugs produce a rise in the ventricular defibrillation threshold (DFT). Although mexiletine has also been reported as the probable cause of a significant elevation of DFT,there has been no previous study ; therefore, the effect of mexiletine on DFT was investigated in the present study. The experiments were performed on ten mongrel dogs. Mexiletine 1,2,4,6, or 8 mg/kg was administered as the loading dose, followed by the same dose/kg per hour. In these five groups, fibrillation/defibrillation (F/D) trials were performed repeatedly every 10 minutes, until 60 minutes after starting the maintenance dose. F/D trials were also performed at 30,45, and 60 minutes after the completion of mexiletine infusion. Applying internal paddles to the heart, energies of 2,3,5,7,10,20, and 30 J maximum were used. The mexiletine concentration in each group changed from 0 to 6.11 mug/ml, DFE ranged from 2-10 J,and no statistical correlation was found between mexiletine concentration and DFT.We conclude that mexiletine does not induce an increase in DFT in dogs.Abstract of 2nd year : The effect of mexiletine on DFT during continuous administration of flecainide was investigated in the 2nd year. The animals were prepared as same as 1st year. Flecainide 2 mg/kg was administered as the loading dose, followed by the same dose/kg per hour. Then, mexiletine 1,2,3,4,5 mg/kg was consecutively administered until the failure of defibrillation. F/D trials were performed in each phase. The minimal energy shock that caused defibrillation (DFT) increased according the increment dose of mexiletine. In conclusion, in a patient administered flecainide, we must be careful for administration of mexiletine in treating ventricular fibrillation.