氟乙酸钠(1080)对Sprague-Dawley大鼠的心肺作用

Bryan J. McCranor, Talearia D. Young, Justin Tressler, Laura Jennings, J. Irwin, N. Alli, Marilynda K. Abilez, Samuel Stone, M. Racine, Jennifer L. Devorak, A. Sciuto, Benjamin Wong
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引用次数: 2

摘要

氟乙酸钠(1080)是一种高毒性代谢性毒物,由于其缺乏明确的色、香、味和高水溶性,有可能通过食品掺假被有意或无意地摄入。虽然自20世纪50年代以来,1080的作用机制就已为人所知,但目前还没有已知的解药。为了更好地了解1080对心肺的影响,我们使用了全身容积描记仪和Sprague-Dawley大鼠遥测仪,使用无创辅助饮酒方法实时测量暴露后的呼吸和心脏参数。总体而言,这些动物在暴露后24小时内表现出明显的呼吸参数下降和肺组织出血。暴露24 h后,潮气量雄性减少30%,雌性减少60%,呼吸频率也显著降低。在遥测雌性大鼠中,我们观察到严重的心脏异常,在24小时的过程中,心率降低50%,收缩压降低75%,QRS间隔延长3.5倍。我们还观察到核心体温降低近15°C。我们的研究能够描述氟乙酸钠中毒对心肺功能的严重和显著影响,其结果表明,组织特异性和系统性缺陷都有助于1080中毒的毒理学进展,在制定任何潜在的1080中毒对策时需要考虑到这一点。
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The cardiopulmonary effects of sodium fluoroacetate (1080) in Sprague-Dawley rats
Abstract Sodium fluoroacetate (1080) is a highly toxic metabolic poison that has the potential because of its lack of defined color, odor, and taste and its high water solubility to be intentionally or unintentionally ingested through food adulteration. Although the mechanism of action for 1080 has been known since the 1950s, no known antidote exists. In an effort to better understand the cardiopulmonary impacts of 1080, we utilized whole-body plethysmography and telemeterized Sprague-Dawley rats which allowed for the real-time measurement of respiratory and cardiac parameters following exposure using a non-invasive assisted-drinking method. Overall, the animals showed marked depression of respiratory parameters over the course of 24 h post-exposure and the development of hemorrhage in the lung tissue. Tidal volume was reduced by 30% in males and 60% in females at 24 h post-exposure, and respiratory frequency was significantly depressed as well. In telemeterized female rats, we observed severe cardiac abnormalities, highlighted by a 50% reduction in heart rate, 75% reduction in systolic blood pressure, and a 3.5-fold lengthening of the QRS interval over the course of 24 h. We also observed a reduction in core body temperature of nearly 15°C. Our study was able to describe the severe and pronounced effects of sodium fluoroacetate poisoning on cardiopulmonary function, the results of which indicate that both tissue specific and systemic deficits contribute to the toxicological progression of 1080 intoxication and will need to be accounted for when developing any potential countermeasure for 1080 poisoning.
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Cogent Biology
Cogent Biology MULTIDISCIPLINARY SCIENCES-
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