Sezaki K, Murakawa Y, Inoue H, Nakajima T, Usui M, Yamashita T, Ajiki K, Oikawa N, Iwasawa K, Omata M
Second Department of Internal Medicine, University of Tokyo, Japan.
J Cardiovasc Pharmacol. 1995 Mar;25(3):393-6. doi: 10.1097/00005344-199503000-00007.
To determine whether isoproterenol could reverse enhancement of electrical defibrillation effectiveness by class III antiarrhythmic agents, we measured the internal defibrillation threshold (DFT) in 12 anesthetized dogs during infusion of (a) saline (baseline), (b) isoproterenol, (c) isoproterenol + E4031 (a new class III antiarrhythmic agent), and (d) E4031 alone. The isoproterenol infusion was adjusted so that heart rate (HR) was at least 30 beats/min greater than baseline. E4031 was given as a 40-micrograms/kg bolus at the beginning of the third stage of the study, followed by constant infusion at 2 micrograms/kg/min. Eight dogs completed the study. Although the energy-based DFT was not affected by isoproterenol (from 6.1 +/- 1.5 to 6.0 +/- 1.7 J), it was decreased to 3.7 +/- 1.6 J in the third stage by infusion of E4031 and isoproterenol (p < 0.01 vs. baseline and vs. isoproterenol). After the discontinuation of isoproterenol in the fourth stage, i.e., during infusion of E4031 alone, DFT was 3.4 +/- 1.6 J (p < 0.01 vs. baseline and vs. isoproterenol). Therefore, isoproterenol did not antagonize the effect of E4031 on the DFT, suggesting the possible clinical usefulness of class III agents for facilitating defibrillation even in the presence of augmented sympathetic activity.
为了确定异丙肾上腺素是否能够逆转Ⅲ类抗心律失常药物对电除颤有效性的增强作用，我们在12只麻醉犬输注以下药物期间测量了体内除颤阈值（DFT）：（a）生理盐水（基线）、（b）异丙肾上腺素、（c）异丙肾上腺素 + E4031（一种新型Ⅲ类抗心律失常药物）和（d）单独使用E4031。调整异丙肾上腺素的输注量，使心率（HR）比基线至少快30次/分钟。在研究的第三阶段开始时，以40微克/千克的剂量静脉推注E4031，随后以2微克/千克/分钟的速度持续输注。8只犬完成了研究。虽然基于能量的DFT不受异丙肾上腺素的影响（从6.1±1.5焦耳降至6.0±1.7焦耳），但在第三阶段，通过输注E4031和异丙肾上腺素，DFT降至3.7±1.6焦耳（与基线和异丙肾上腺素相比，p<0.01）。在第四阶段停止输注异丙肾上腺素后，即在单独输注E4031期间，DFT为3.4±1.6焦耳（与基线和异丙肾上腺素相比，p<0.01）。因此，异丙肾上腺素并未拮抗E4031对DFT的作用，这表明即使在交感神经活动增强的情况下，Ⅲ类药物在促进除颤方面可能具有临床应用价值。
