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

抗心律失常药物治疗心律失常时提高除颤阈值的研究

• 批准号: 05454414
• 负责人: NAITO Hiroshi
• 金额: $ 4.16万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454414/
• 关键词: mexiletine; flecainide; defibrillation threshold; ventricular fibrillation; antiarrythmic drug; sudden cardiac arrest

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.

第一年摘要：许多抗心律失常药物会导致心室除颤阈值（DFT）升高。虽然美西律也被报道为 DFT 显着升高的可能原因，但之前没有研究；因此，本研究探讨了美西律对 DFT 的影响。实验在十只杂种狗身上进行。美西律 1、2、4、6 或 8 mg/kg 作为负荷剂量给药，随后每小时按相同剂量/kg 给药。在这五组中，每 10 分钟重复进行一次颤动/除颤 (F/D) 试验，直到开始维持剂量后 60 分钟。 F/D 试验也在美西律输注完成后 30、45 和 60 分钟进行。将内部桨应用于心脏，使用的最大能量为 2、3、5、7、10、20 和 30 J。各组的美西律浓度从0到6.11μg/ml变化，DFE范围为2-10J，并且美西律浓度与DFT之间没有发现统计相关性。我们得出结论，美西律不会引起狗的DFT增加。第2年摘要：第2年研究了氟卡尼连续给药期间美西律对DFT的影响。动物的准备与第一年相同。氟卡尼 2 mg/kg 作为负荷剂量给药，随后每小时以相同剂量/kg 给药。然后连续给予美西律1、2、3、4、5 mg/kg，直至除颤失败。每个阶段都进行了 F/D 试验。引起除颤的最小能量冲击（DFT）随着美西律剂量的增加而增加。总之，对于服用氟卡尼的患者，在治疗心室颤动时使用美西律时必须小心。

项目成果

佐藤 重仁: "Mexilletine Has No Effect on Defibrillation Energy Requirement in Dogs" Pacing and Cardioelectrophysiology. 17. 2279-2284 (1994)

Shigehito Sato：“Mexilletine 对狗的除颤能量需求没有影响”起搏和心脏电生理学 17. 2279-2284 (1994)。

佐藤重仁: "Mexiletine Has No Effect on Defibrillation Energy Requirement in Dogs" Pacing and Cardioelectrophysiology. 17. 2279-2284 (1994)

Shigehito Sato：“美西律对狗的除颤能量需求没有影响”起搏和心脏电生理学 17. 2279-2284 (1994)。