https://orcid.org/0000-0002-1573-5793
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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.
PUBLIC INTEREST STATEMENT
The U.S. Army Medical Research Institute of Chemical Defense (USAMRICD) is the United States’ leading science and technology laboratory in the development of medical chemical countermeasures. At USAMRICD, the Inhalation Toxicology Team aims to support military and civilian populations through research in toxicology aimed at discovering and developing medical products and knowledge solutions. This group has used its expertise in the fields of toxic chemical toxicology and physiology to investigate the effects of sodium fluoroacetate (1080) on lung and heart function. Using real-time physiological measurements in a rat model, the team was able to visualize the significant impact of 1080 on both heart and lung function over the course of 24 h. In developing future treatments against 1080 intoxication, investigators will have to account for this severe weakening of heart and lung function.
Competing Interests
The authors declares no competing interests.
Acknowledgements
We would like to thank Dr. Rebecca J. Lewandowski for her input and assistance in the development of our in vivo model. We would also like to thank MAJ William L. Wilkins and the Comparative Pathology team at USAMRICD for help with the tissue histology analysis.
Disclaimers
The views expressed are solely those of the authors and do not necessarily represent the official views of the CCRP, NIAID, NIH, or HHS and do not reflect official policy of the Department of the Army, Department of Defense, or the U.S. Government. The experimental protocol was approved by the Animal Care and USE Committee at the United States Army Medical Research Institute of Chemical Defense, and all procedures were conducted in accordance with the principles stated in the Guide for the Care and Use of Laboratory Animals (National Research Council, 2011), and the Animal Welfare Act of 1966 (P.L. 89-544), as amended. N.A.A, M.K.A., and M.R. were supported in part by an appointment to the Research Participation Program for the U.S. Army Medical Research and Materiel Command administered by the Oak Ridge Institute for Science and Education through an agreement between the U.S. Department of Energy and U.S. Army Medical Research and Materiel Command.
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Bryan J. McCranor
Bryan J. McCranor is a research biochemist at the US Army Medical Research Institute of Chemical Defense where he is a principal investigator with the Inhalation Toxicology Team. Overall, his research focuses on the development of novel prophylactic, therapeutic and medical countermeasure treatments for exposure to chemical threat agents and toxic industrial compounds. His work centers on the identification of toxicological characteristics of toxic chemicals, investigation of potential novel therapeutic targets, and advancement of medical countermeasures.
