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梭曼和沙林对狒狒的急性吸入毒性

Acute inhalation toxicity of soman and sarin in baboons.

作者信息

Anzueto A, deLemos R A, Seidenfeld J, Moore G, Hamil H, Johnson D, Jenkinson S G

机构信息

Department of Medicine, University of Texas Health Science Center, San Antonio.

出版信息

Fundam Appl Toxicol. 1990 May;14(4):676-87. doi: 10.1016/0272-0590(90)90293-s.

Abstract

Adult baboons (Papio sp.; 8-12 kg) were anesthesized with sodium pentobarbital (20 mg/kg iv). The animals were instrumented for measurement of mean blood pressure (MBP), pulmonary artery pressure (PAP), ECG, arterial and mixed venous blood gases, lung volumes, lung pressures, and efferent phrenic nerve activity. Bronchoalveolar lavage (BAL) was performed. Studies were done prior to exposure, at intervals during the first 4 hr postexposure, and at 4 and 28 days after exposure. Control animals received a sham exposure to 2-propanol (N = 5). Soman (pinacolyl methylphosphonofluoridate) at 13.14 micrograms/kg (2 X LD50) was vaporized into the upper airway in a second group of animals (N = 5), and sarin (isopropyl methylphosphonofluoride) 30 micrograms/kg (2 X LD50) was vaporized into a third group of animals (N = 4). Controls showed no change in any parameter either immediately after diluent exposure or during the monitoring period. Soman and sarin produced a decline in MBP and bradyarrhythmias that were reversed with atropine. Apnea occurred in all soman- and sarin-exposed animals within 5 min postexposure, and was associated with absence of phrenic nerve signal. Ventilation was mechanically supported until the animal could maintain normal arterial blood gases during spontaneous breathing. BAL studies revealed an increase in total white cell population and neutrophils at 4 hr in all three groups. There were signs of impaired hemodynamics and persistent lung injury for 4 days that resolved by 28 days after exposure. In conclusion, inhalation of soman and sarin in the baboon is associated with cardiac arrhythmias, development of apnea, and a significant decrease in MBP. Inhalation exposure also resulted in a persistent influx of neutrophils and hypoxemia.

摘要

成年狒狒(狒属;8 - 12千克)用戊巴比妥钠(20毫克/千克静脉注射)麻醉。对这些动物进行仪器安装,以测量平均血压(MBP)、肺动脉压(PAP)、心电图、动脉血和混合静脉血气、肺容量、肺压以及传出膈神经活动。进行支气管肺泡灌洗(BAL)。在暴露前、暴露后最初4小时内的不同时间间隔以及暴露后4天和28天进行研究。对照动物接受假暴露于2 - 丙醇(N = 5)。在第二组动物(N = 5)中,将13.14微克/千克(2倍半数致死剂量)的梭曼(频那基甲基膦酰氟)蒸发到上呼吸道,在第三组动物(N = 4)中,将30微克/千克(2倍半数致死剂量)的沙林(异丙基甲基膦酰氟)蒸发到上呼吸道。对照组在暴露于稀释剂后立即或在监测期间任何参数均无变化。梭曼和沙林导致平均血压下降和缓慢性心律失常,这些情况可被阿托品逆转。所有暴露于梭曼和沙林的动物在暴露后5分钟内出现呼吸暂停,并伴有膈神经信号缺失。进行机械通气支持,直到动物在自主呼吸时能够维持正常动脉血气。支气管肺泡灌洗研究显示,所有三组在4小时时总白细胞数量和中性粒细胞增加。有血流动力学受损和持续性肺损伤的迹象,持续4天,在暴露后28天恢复。总之,狒狒吸入梭曼和沙林与心律失常、呼吸暂停的发生以及平均血压显著下降有关。吸入暴露还导致中性粒细胞持续流入和低氧血症。

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