Worek F, Kleine A, Falke K, Szinicz L
Institut für Pharmakologie und Toxikologie, Sanitätsakademie der Bundeswehr, Garching, Germany.
Arch Int Pharmacodyn Ther. 1995 May-Jun;329(3):418-35.
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.
在急性神经性毒剂中毒的豚鼠中研究了阿托品及双吡啶肟类化合物HI6和HLö 7对心电图模式的影响。在雌性氨基甲酸乙酯麻醉的Pirbright - white豚鼠中记录心电图、循环和呼吸参数。在进行基线测量后,动物接受吡啶斯的明(0.05 μmol/kg),30分钟后接受塔崩(5倍半数致死剂量)、沙林(5倍半数致死剂量)、梭曼(5倍或10倍半数致死剂量)或VX(10倍或20倍半数致死剂量),2分钟后再给予生理盐水、阿托品(10 mg/kg)或阿托品加HI6或HLö 7(30 μmol/kg)。在未治疗的动物中,神经性毒剂中毒导致2 - 3分钟内呼吸停止,几分钟后循环停止。解毒剂治疗迅速恢复了心率和平均动脉压,并在不同程度上改善了呼吸功能。注射神经性毒剂在1 - 2分钟内引起明显的窦性心动过缓及随后的完全性房室传导阻滞,继而出现心室自主节律。在这些组中,死前未观察到室性快速性心律失常。给予阿托品及阿托品加肟立即恢复了窦性节律,在整个观察期(60分钟)内,呼吸功能足够(>基线的50%)的动物中窦性节律持续存在。在呼吸功能降低(<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,尤其是在塔崩和梭曼(10倍半数致死剂量)中毒时,治疗后1分钟内窦性节律转变为有害的室性心动过速。这些结果表明,含阿托品的解毒剂组合在神经性毒剂中毒时可能诱发致命性心律失常,这在重度吸入性中毒的静脉治疗期间可能具有临床重要性。