Arrhythmias in organophosphate poisoning: effect of atropine and bispyridinium oximes.

F Worek, A Kleine, K Falke, L Szinicz
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Abstract

The effect of atropine and of the bispyridinium oximes, HI6 and HLö 7, on the electrocardiographic pattern was investigated in acutely nerve agent-poisoned guinea-pigs. The electrocardiographic, circulatory and respiratory parameters were recorded in female urethane-anaesthetized Pirbright-white guinea-pigs. After base line measurements, the animals received pyridostigmine (0.05 mumol/kg) and, 30 min later, tabun (5xLD50), sarin (5xLD50), soman (5xLD50 or 10xLD50) or VX (10xLD50 or 20xLD50), followed by saline or atropine (10 mg/kg) or atropine plus HI 6 or or HLö 7 (30 mumol/kg) 2 minutes later. Nerve agent poisoning resulted in respiratory arrest within 2-3 minutes, followed by circulatory arrest a few minutes later in nontreated animals. Antidote treatment rapidly restored heart rate and mean arterial pressure and improved the respiratory function to various extent. The nerve agent injection caused a marked sinus bradycardia and a subsequent complete atrioventricular block within 1-2 minutes, followed by idioventricular rhythm. No ventricular tachyarrhythmias were observed in these groups just before death. Atropine and atropine plus oxime administration immediately restored sinus rhythm which persisted in animals with sufficient respiration > 50% of base line) throughout the observation period (60 minutes). In guinea-pigs with depressed respiratory function ( < 50%), intermittent ST-T wave alterations and second degree atrioventricular block were observed. In some cases, especially in tabun and soman (10xLD50) poisoning, sinus rhythm converted to deleterious ventricular tachycardia within 1 minute after treatment. These results suggest that atropine-containing antidote combinations may induce lethal arrhythmias in nerve agent poisoning, which may be of clinical importance during intravenous treatment of severe inhalative intoxications.

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有机磷中毒引起的心律失常:阿托品和双吡啶肟的作用。
研究了阿托品和双吡啶肟、HI6、HLö 7对急性神经毒剂中毒豚鼠心电图的影响。记录雌性脲烷麻醉豚鼠的心电图、循环和呼吸参数。基线测量后,给药吡哆斯的明(0.05 μ mol/kg), 30分钟后给药他本(5xLD50)、沙林(5xLD50)、索曼(5xLD50或10xLD50)或VX (10xLD50或20xLD50), 2分钟后给药生理盐水或阿托品(10 mg/kg)或阿托品加HI 6或HLö 7 (30 μ mol/kg)。神经毒剂中毒在2-3分钟内导致呼吸停止,随后在未治疗的动物中几分钟后出现循环停止。解毒剂治疗可迅速恢复心率和平均动脉压,不同程度地改善呼吸功能。神经毒剂注射引起明显的窦性心动过缓,随后在1-2分钟内发生完全房室传导阻滞,随后出现室间节律。这些组在死亡前未观察到室性心动过速。在整个观察期间(60分钟),阿托品和阿托品加肟可立即恢复窦性心律(在呼吸充足>基线的50%的动物中持续存在)。在呼吸功能下降(< 50%)的豚鼠中,观察到间歇性ST-T波改变和二度房室传导阻滞。在某些情况下,特别是在他本和索曼(10xLD50)中毒的情况下,窦性心律在治疗后1分钟内转化为有害的室性心动过速。这些结果提示,含阿托品的解毒剂组合可引起神经毒剂中毒致死性心律失常,这可能对静脉治疗严重吸入性中毒具有重要的临床意义。
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