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  

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

作　　者：李光[1] 龙超良[1] 慕邵峰[1] 崔文玉[1] 汪海[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国临床药理学与治疗学》2004年第2期149-152,共4页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：军队医药卫生"十五"重点项目 (№ 0 1Z0 2 5)

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 1 2～ 1 6kg。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 1 0∶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 1 5、60min等时点平均动脉压 (MAP)、心室内压最大上升速率 (+dp dtmax)、心室内压最大下降速率 (-dp dtmax)、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 dtmax、Vpm)和反映心脏舒张功能的指标 (-dp dtmax)均显著下降 (P <0 .0 1 ) ,此时NO、ET和 6 Keto PGF1α 等血管活性物质则显著升高(P <0 .0 1 ) ;美加明与阿托品合用治疗 1 5min时上述血流动力学指标及血管活性物质即显著好转 ,60min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?AIM: To investigate the changes of hemodynam ic parameters and plasma vascular active substances before and after treatment wit h neuronal nicotinic receptor antagonist mecamylamine or muscarinic receptor ant agonist atropine against the circulation failures induced by the cholinesterase inhibitor DDV in dogs. METHODS: 20 male dogs were randomized int o 4 groups: control; treatment with mecamylamine; treatment with atropine and tr eatment 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 hemodyna mic 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-PG 1α before and after treated 15 and 60 min were observ ed. RESULTS: In anesthetized dogs intoxicated with cholinesteras e inhibitor DDV, the circulation failure was characterized by the significant de creases in hemodynamic parameters MAP, +dp/dt max , Vpm and -dp/dt max . The plasma vascular active substances NO, ET and 6-Keto-PGF 1α were increased significantly. After treated with mecamylamine and atropine 15 min, al l the hemodynamic parameters were increased markedly and all the three vascular active substances were decreased significantly. After treated 60min,all the para meters were almost resumed to the normal level. The therapeutic effects of combi nation 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-PGF 1α in plasma can reflect the sev erity of circulation failure. There were synergic effects between mecamylamine a nd atropine against circulation failures induced by DDV.

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 

分 类 号：R971.92[医药卫生—药品] R965[医药卫生—药学]