Göransson-Nyberg A, Cassel G, Jeneskog T, Karlsson L, Larsson R, Lundström M, Persson S A
Division of Biomedicine, National Defense Research Establishment, Umea, Sweden.
Arch Toxicol. 1995;70(1):20-7. doi: 10.1007/s002040050244.
The therapeutic effectiveness of a new binary autoinjector containing 500 mg HI-6 and 2 mg atropine sulphate was tested in anesthetized pigs poisoned by a lethal dose of soman i.v. (9 micrograms/kg per 20 min). Pharmacokinetics and pharmacodynamics of HI-6 were studied concomitantly on administration of HI-6 alone, together with atropine sulphate, or together with atropine sulphate during soman intoxication. Cardiopulmonary parameters were monitored and serum concentrations of oxime and acetylcholinesterase (AChE) were measured in blood samples taken at intervals over a 6-h period postinjection. Five minutes after the start of soman infusion, mean AChE activity was decreased to 27 +/- 4.3% of baseline and signs of poisoning appeared. The antidotes, HI-6 and atropine sulphate, were then administered i.m. One minute after this injection there was a transient significant increase in AChE activity of 76 +/- 8.2% of baseline (p < 0.01). It then again decreased and remained suppressed throughout the experiment. Mean respiratory rate was significantly decreased (p < 0.01) to 20 +/- 3.2% of baseline after 20 min of soman infusion and remained low during the rest of the experiment. The poisoning signs were counteracted 15-20 min after antidote therapy and all pigs survived soman intoxication without ventilatory assistance. Administration of either atropine or atropine and soman had no significant effect on the pharmacokinetics of HI-6 in anesthetized pigs.
一种新型二元自动注射器,含有500毫克HI - 6和2毫克硫酸阿托品,其治疗效果在静脉注射致死剂量梭曼(9微克/千克,每20分钟)中毒的麻醉猪身上进行了测试。在单独给予HI - 6、与硫酸阿托品一起给予或在梭曼中毒期间与硫酸阿托品一起给予时,同时研究了HI - 6的药代动力学和药效学。在注射后6小时内,每隔一段时间采集血样,监测心肺参数并测量肟和乙酰胆碱酯酶(AChE)的血清浓度。梭曼输注开始5分钟后,平均AChE活性降至基线的27±4.3%,中毒症状出现。然后肌肉注射解毒剂HI - 6和硫酸阿托品。注射后1分钟,AChE活性短暂显著增加至基线的76±8.2%(p<0.01)。然后它再次下降,并在整个实验过程中一直受到抑制。梭曼输注20分钟后,平均呼吸频率显著降低(p<0.01)至基线的20±3.2%,并在实验的其余时间保持较低水平。解毒剂治疗15 - 20分钟后,中毒症状得到缓解,所有猪在没有通气辅助的情况下从梭曼中毒中存活下来。单独给予阿托品或阿托品与梭曼对麻醉猪体内HI - 6的药代动力学没有显著影响。