胆碱酯酶抑制剂类神经性毒剂诱导的犬循环衰竭救治前后血流动力学及血液内血管活性物质的变化

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (2): 149-152.

胆碱酯酶抑制剂类神经性毒剂诱导的犬循环衰竭救治前后血流动力学及血液内血管活性物质的变化

李光, 龙超良, 慕邵峰, 崔文玉, 汪海

军事医学科学院毒物药物研究所, 北京 100850

收稿日期:2003-10-30 修回日期:2003-11-27 出版日期:2004-02-26 发布日期:2020-11-16
通讯作者: 汪海,男, 研究员, 博士生导师, 研究方向:分子药理学与心血管药物研究。Tel:010-66932651 　Fax:010-68211656 　E-mail: wh@nic.bmi.ac.cn
作者简介:李光, 男, 硕士研究生, 主治医师, 现在军事医学科学院附属医院。
基金资助:
军队医药卫生“ 十五” 重点项目(NO.01Z025)

Changes of hemodynamic parameters and plasma vascular active substances in dog circulation failures induced by cholinesterase inhibitor

LI Guang, LONG Chao-liang, MU Shao-Feng, CUI Wen-Yu, WANG Hai

Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China

Received:2003-10-30 Revised:2003-11-27 Online:2004-02-26 Published:2020-11-16

摘要/Abstract

摘要： 目的: 在胆碱酯酶抑制剂中毒诱发犬循环衰竭的模型上, 研究循环衰竭前后及N 受体拮抗剂美加明与M 受体拮抗剂阿托品救治后, 动物血流动力学及血液中血管活性物质的变化规律。方法: 健康成年雄性杂种犬, 体重12 ~ 16 kg 。随机分为4 组:对照组、美加明组、阿托品组、阿托品和美加明(剂量比10∶1) 联用组。肌肉注射敌敌畏诱发循环衰竭模型, 观察染毒前、循环衰竭时、救治15 、60 min 等时点平均动脉压(MAP) 、心室内压最大上升速率(+dp/dt_max) 、心室内压最大下降速率(-dp/dt_max) 、心肌纤维缩短速度(Vpm) 等血流动力学指标的变化及血液中一氧化氮(NO) 、内皮素(ET) 、6-酮-前列腺素F1α(6-Keto-PGF1α) 等血管活性物质的变化。结果: 与染毒前相比, 犬循环衰竭时, MAP 以及反映心脏收缩功能的指标(+dp/dt_max 、Vpm) 和反映心脏舒张功能的指标(-dp/dt_max) 均显著下降(P<0.01), 此时NO 、ET 和6-Keto-PGF1α等血管活性物质则显著升高(P<0.01) ;美加明与阿托品合用治疗15 min 时上述血流动力学指标及血管活性物质即显著好转,60 min 时基本恢复正常, 疗效均明显好于单用阿托品、美加明组。结论: 血浆NO 、ET 、6-Keto-PGF1α等血管活性物质的升高水平与胆碱酯酶抑制剂类神经性毒剂诱导的犬循环衰竭程度及病情转归相关, 美加明与阿托品之间存在协同增强作用。

关键词: 胆碱酯酶抑制剂, 循环衰竭, 美加明, 一氧化氮, 内皮素, 6-酮-前列腺素F1α

Abstract: AIM: To investigate the changes of hemodynamic parameters and plasma vascular active substances before and after treatment with neuronal nicotinic receptor antagonist mecamylamine or muscarinic receptor antagonist atropine against the circulation failures induced by the cholinesterase inhibitor DDV in dogs.METHODS: 20 male dogs were randomized into 4 groups:control ;treatment with mecamylamine ;treatment with atropine and treatment with mecamylamine and atropine at the dose ratio of 1 ∶10.Animals were given intramuscularly DDV, and when the mean blood pressure was decreased to 40-45 mmHg, the drugs were intramuscularly injected and the changes of hemodynamic parameters such as mean arterial pressure (MAP), +dp/dt_max, Vpm and-dp/dt_max and vascular active substances such as nitric oxide (NO), endothelin(ET) and 6-Keto-PG1αbefore and after treated 15 and 60 min were observed.RESULTS: In anesthetized dogs intoxicated with cholinesterase inhibitor DDV, the circulation failure was characterized by the significant decreases in hemodynamic parameters MAP, +dp/dt_max, Vpm and-dp dt max.The plasma vascular active substances NO, ET and 6-Keto-PGF1α were increased significantly.After treated with mecamylamine and atropine 15 min, all the hemodynamic parameters were increased markedly and all the three vascular active substances were decreased significantly.After treated 60min, all the parameters were almost resumed to the normal level.The therapeutic effects of combination of mecamylamine and atropine were much better than those of mecamylamine or atropine used separately.CONCLUSION: The levels of vascular active substances NO, ET and 6-Keto-PGF1αin plasma can reflect the severity of circulation failure.There were synergic effects between mecamylamine and atropine against circulation failures induced by DDV.

Key words: cholinesterase inhibitor, circulation failure, mecamylamine, NO, endothelin, 6-Keto-PGF1α

中图分类号:

R971.92
R965

李光, 龙超良, 慕邵峰, 崔文玉, 汪海. 胆碱酯酶抑制剂类神经性毒剂诱导的犬循环衰竭救治前后血流动力学及血液内血管活性物质的变化[J]. 中国临床药理学与治疗学, 2004, 9(2): 149-152.

LI Guang, LONG Chao-liang, MU Shao-Feng, CUI Wen-Yu, WANG Hai. Changes of hemodynamic parameters and plasma vascular active substances in dog circulation failures induced by cholinesterase inhibitor[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(2): 149-152.

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