Thiermann Horst, Szinicz Ladislaus, Eyer Peter, Zilker Thomas, Worek Franz
Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstr. 11, 80937 Munich, Germany.
Chem Biol Interact. 2005 Dec 15;157-158:345-7. doi: 10.1016/j.cbi.2005.10.102. Epub 2005 Nov 2.
Assessment of effectiveness of oximes in severely organophosphate poisoned patients is hampered by sedation, artificial ventilation and other therapeutic measures as well as varying individual clinical courses due to, e.g. differences in type and amount of poison ingested or time elapsed before treatment starts. To evaluate oxime effects a suitable surrogate parameter would be helpful. Red blood cell acetylcholinesterase (RBC-AChE) is easily obtainable, shows a similar structure as synaptic enzyme and may be useful to reflect the AChE status at the synaptic site. Accordingly, it appeared rational to check whether RBC-AChE activity could be correlated with neuromuscular transmission (NMT), an easily accessible clinical parameter. The correlation was assessed in a clinical trial with severely OP-poisoned patients who were treated with obidoxime. The investigation revealed a good correlation between both parameters and showed, that a very low RBC-AChE activity (<10% of normal) was associated with a strongly impaired NMT marker, the so called decrement-phenomenon, RBC-AChE activity between 10 and 30% by impaired NMT with the decrement-increment-phenomenon and RBC activities above 30% generally by normal muscle function. Accordingly, RBC-AChE appears to be a suitable parameter for judgment of oxime effectiveness at the neuromuscular junction, one of the most important targets for therapy where atropine is ineffective in OP-poisoning.
对于重度有机磷中毒患者，肟类药物有效性的评估受到镇静、人工通气及其他治疗措施的阻碍，同时还受到个体临床病程差异的影响，例如摄入毒物的类型和数量不同，或治疗开始前经过的时间不同。为评估肟类药物的效果，一个合适的替代参数会有所帮助。红细胞乙酰胆碱酯酶（RBC - AChE）易于获取，其结构与突触酶相似，可能有助于反映突触部位的乙酰胆碱酯酶状态。因此，检查RBC - AChE活性是否与神经肌肉传递（NMT）相关是合理的，NMT是一个易于获取的临床参数。在一项使用双复磷治疗重度有机磷中毒患者的临床试验中评估了这种相关性。研究发现这两个参数之间存在良好的相关性，并且表明，极低的RBC - AChE活性（<正常的10%）与严重受损的NMT标志物即所谓的递减现象相关，RBC - AChE活性在10%至30%之间与伴有递减 - 递增现象的NMT受损相关，而RBC活性高于30%时通常肌肉功能正常。因此，RBC - AChE似乎是判断肟类药物在神经肌肉接头处有效性的合适参数，神经肌肉接头是有机磷中毒时阿托品无效的最重要治疗靶点之一。
