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

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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.