Kieval R S, Butler V P, Derguini F, Bruening R C, Rosen M R
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
J Am Coll Cardiol. 1988 Mar;11(3):637-43. doi: 10.1016/0735-1097(88)91543-4.
Substances structurally and functionally similar to digitalis glycosides are produced by several vertebrate species. There also is evidence for a digitalis-like substance of human origin. Standard microelectrode techniques were used to study the direct effects on the cellular electrophysiology of canine Purkinje fibers of 1) bufalin, an unconjugated cardiotonic steroid molecule that is produced by the toad Bufo marinus, and 2) an extract of human bile that showed digitalis-like immunoreactivity on radioimmunoassay. The goal of this study was to determine whether these substances have arrhythmogenic effects comparable with those seen with toxic doses of digitalis glycosides. Bufalin, 2 x 10(-8) M, significantly (p less than 0.05) reduced maximal diastolic potential, action potential amplitude and duration and maximal rate of rise of phase 0 (Vmax) within 40 min of onset of exposure. All six fibers developed delayed afterdepolarizations and two developed triggered rhythms. Ouabain was less potent, in that a 2 x 10(-7) M concentration was required to comparably reduce maximal diastolic potential, action potential amplitude and duration and Vmax within 30 min. These Purkinje fibers also developed delayed afterdepolarizations and triggered rhythms. A sample of an extract of human bile that showed digitalis-like immunoreactivity with an antibufalin serum also reduced maximal diastolic potential, action potential amplitude and duration and Vmax, and produced delayed afterdepolarizations and triggered activity. In contrast, immunologically unreactive bile extracts had no appreciable effect on the action potential. In summary, the cardiac toxicity of digitalis substances produced by lower vertebrates is comparable with that induced by the glycosides. Moreover, it appears that humans may produce digitalis-like substances that may be cardiotoxic.
几种脊椎动物会产生结构和功能与洋地黄苷相似的物质。也有证据表明存在源自人类的类洋地黄物质。本研究采用标准微电极技术，研究了以下两种物质对犬浦肯野纤维细胞电生理的直接影响：1）蟾毒灵，一种由海蟾蜍Bufo marinus产生的未结合强心甾体分子；2）一种人胆汁提取物，该提取物在放射免疫分析中显示出类洋地黄免疫反应性。本研究的目的是确定这些物质是否具有与洋地黄苷中毒剂量时相当的致心律失常作用。2×10⁻⁸M的蟾毒灵在暴露开始后40分钟内，显著（p＜0.05）降低了最大舒张电位、动作电位幅度和时程以及0期最大上升速率（Vmax）。所有6根纤维均出现延迟后去极化，2根出现触发节律。哇巴因的作用较弱，需要2×10⁻⁷M的浓度才能在30分钟内同等程度地降低最大舒张电位、动作电位幅度和时程以及Vmax。这些浦肯野纤维也出现了延迟后去极化和触发节律。一份与抗蟾毒灵血清显示出类洋地黄免疫反应性的人胆汁提取物样本，也降低了最大舒张电位、动作电位幅度和时程以及Vmax，并产生了延迟后去极化和触发活动。相比之下，免疫无反应的胆汁提取物对动作电位没有明显影响。总之，低等脊椎动物产生的洋地黄类物质的心脏毒性与洋地黄苷诱导的毒性相当。此外，似乎人类可能产生具有心脏毒性的类洋地黄物质。
