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

1年摘要：许多抗心律失常药物可引起心室除颤阈值（DFT）升高。虽然美西汀也被报道为可能导致DFT显著升高的原因，但没有先前的研究；因此，本研究探讨了美西汀对DFT的影响。实验是在10只杂种狗身上进行的。以美西汀1、2、4、6或8 mg/kg作为负荷剂量，随后以相同剂量/kg / h给药。在这五组中，每10分钟重复进行纤颤/除颤（F/D）试验，直到开始维持剂量后60分钟。F/D试验也在美西汀输注完成后30,45和60分钟进行。在心脏上施加内部电桨，最大能量为2、3、5、7、10、20和30 J。各组美西汀浓度变化范围为0 ~ 6.11 mg /ml， DFE变化范围为2 ~ 10 J，美西汀浓度与DFT之间无统计学相关性。我们得出结论，美西汀不会导致狗的DFT增加。第2年摘要：研究连续给药氟卡奈期间美西汀对DFT的影响。动物的准备与第一年相同。以氟氯胺2 mg/kg为负荷剂量，随后以相同剂量/kg / h给药。然后连续给予美西汀1、2、3、4、5 mg/kg，直至除颤失败。在每个阶段进行F/D试验。引起除颤的最小能量冲击（DFT）随美西汀剂量的增加而增加。总之，在给药氟卡奈的患者中，我们必须谨慎使用美西汀治疗心室颤动。

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.