Nagasawa Hidehiko, Fujiki Akira, Fujikura Naoki, Matsuda Tomoyuki, Yamashita Toru, Inoue Hiroshi
The Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
Circ J. 2002 Feb;66(2):185-91. doi: 10.1253/circj.66.185.
The effects of a new benzopyran derivative, NIP-142, on atrial fibrillation (AF) and flutter (AFL) and on electrophysiological variables were studied in the dog. NIP-142 (3mg/kg) was administered intravenously to pentobarbital-anesthetized beagles during vagally-induced AF and during AFL induced after placement of an intercaval crush. Isolated canine atrial tissues were studied using standard microelectrode technique. NIP-142 terminated AF in 5 of 6 dogs after an increase in fibrillation cycle length (CL) and prevented reinitiation of AF in all 6 dogs. NIP-142 terminated AFL in all 6 dogs without any appreciable change in flutter CL, and prevented reinitiation of AFL in all 6 dogs. NIP-142 prolonged atrial effective refractory periods (11+/-5%, 3+/-3%, 12+/-3%, and 10+/-5% from the baseline value at basic CLs of 150, 200, 300, and 350ms, respectively) without changes in intraatrial conduction time. The prolongation of the atrial effective refractory period was greater in the presence of vagal stimulation. NIP-142 decreased action potential phase-1 notch and increased phase-2 plateau height without making any changes in the action potential duration, although it did reverse carbachol-induced shortening of the action potential duration. In conclusion, NIP-142 is effective in treating AFL and vagally-induced AF by prolonging atrial refractoriness.
在犬类动物中研究了一种新型苯并吡喃衍生物NIP - 142对心房颤动（AF）和心房扑动（AFL）以及电生理变量的影响。在戊巴比妥麻醉的比格犬诱发迷走神经介导的AF期间以及在腔静脉间挤压后诱发AFL期间，静脉注射NIP - 142（3mg/kg）。使用标准微电极技术研究离体犬心房组织。NIP - 142使6只犬中的5只在颤动周期长度（CL）增加后终止AF，并防止所有6只犬再次发生AF。NIP - 142使所有6只犬的AFL终止，扑动CL无明显变化，并防止所有6只犬再次发生AFL。NIP - 142延长心房有效不应期（在基础CL分别为150、200、300和350ms时，相对于基线值分别延长11±5%、3±3%、12±3%和10±5%），而心房内传导时间无变化。在迷走神经刺激存在的情况下，心房有效不应期的延长更大。NIP - 142降低动作电位1期切迹并增加2期平台高度，而动作电位持续时间无任何变化，尽管它确实逆转了卡巴胆碱诱导的动作电位持续时间缩短。总之，NIP - 142通过延长心房不应期有效治疗AFL和迷走神经介导的AF。
