Jones J L, Jones R E
Crit Care Med. 1980 Mar;8(3):172-6. doi: 10.1097/00003246-198003000-00017.
Postcountershock arrhythmias are potentiated in patients receiving digitalis; and these arrhythmias frequently lead to irreversible ventricular fibrillation and death. The mechanisms underlying this potentiation are largely unknown. The purpose of this study was to determine whether an accentuation of electric shock induced arrhythmias was produced in in vitro myocardial cells by ouabain, a fast-acting digitalis glycoside. Such an accentuation would suggest that the in vivo potentiation occurred in the individual myocardial cell rather than through some secondary mechanism such as action on the nervous system as had been previously suggested. Myocardial cells grown in vitro were subjected to 5 msec square wave electric field stimulation of varying intensity. Pre- and postshock arrhythmias were evaluated using a photovoltaic cell mounted on a closed-circuit television monitor. The photocell converted the change in light intensity produced by cellular contraction to an electrical signal which was then processed and displayed on a strip chart recorder. Fibrillation of the cell sheet and of portions of individual myocardial cells could be observed visually on the television monitor. "Therapeutic" (antiarrhythmic) concentrations of ouabain were observed in the range of 1 x 10(-6)M to 5 x 10(-6)M; "toxic" (arrhythmia producing) concentrations were above 1 x 10(-5)M. Electric shocks of intensities which produced a short postshock arrest in nondigitalized cells, produced an increased duration of arrest proportional to the ouabain concentration in the range of 5 x 10(-8)M to 7 x 10(-6)M. Cellular fibrillation has been previously observed in in vitro myocardial cells after extremely high shock intensities in the absence of ouabain or after toxic concentrations of ouabain in the absence of electric shock. Similar cellular fibrillation was observed in this study after low intensity electric shocks in cells exposed to low concentrations of ouabain, neither of which produced cellular fibrillation alone. Because this cellular fibrillation in vitro appears to be related to "irreversible" fibrillation in vivo, these results suggest that the deleterious interactions between digitalis and electric countershock occur directly in the myocardial cell and that postshock cellular fibrillation may be the basis for the "unmasking" of digitalis toxicity by electric countershock which has been of clinical concern.
接受洋地黄治疗的患者，电击后心律失常会增强；这些心律失常常常会导致不可逆的心室颤动和死亡。这种增强作用的潜在机制在很大程度上尚不清楚。本研究的目的是确定快速起效的洋地黄苷类药物哇巴因是否会在体外心肌细胞中导致电击诱发的心律失常加重。这种加重表明体内的增强作用发生在单个心肌细胞中，而非如之前所认为的那样，是通过某些诸如作用于神经系统的继发机制。体外培养的心肌细胞接受不同强度的5毫秒方波电场刺激。使用安装在闭路电视监视器上的光电管评估电击前后的心律失常情况。光电管将细胞收缩产生的光强度变化转换为电信号，然后进行处理并显示在带状图表记录仪上。在电视监视器上可以直观地观察到细胞片层和单个心肌细胞部分的颤动。观察到哇巴因的“治疗性”（抗心律失常）浓度范围为1×10⁻⁶M至5×10⁻⁶M；“毒性”（产生心律失常）浓度高于1×10⁻⁵M。在未用洋地黄治疗的细胞中，能产生短暂电击后停搏的强度的电击，在5×10⁻⁸M至7×10⁻⁶M范围内，会使停搏持续时间增加，且与哇巴因浓度成正比。先前在无哇巴因时极高电击强度后或无电击时哇巴因毒性浓度下，已在体外心肌细胞中观察到细胞颤动。在本研究中，在暴露于低浓度哇巴因的细胞中，低强度电击后也观察到了类似的细胞颤动，单独的低浓度哇巴因或低强度电击均不会产生细胞颤动。由于这种体外细胞颤动似乎与体内“不可逆”颤动有关，这些结果表明洋地黄与电击除颤之间的有害相互作用直接发生在心肌细胞中，且电击后细胞颤动可能是临床上关注的电击除颤使洋地黄毒性“暴露”的基础。
