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 ABOUT THE AUTHOR 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.

Methylene blue and monosodium glutamate improve neurologic signs after fluoroacetate poisoning

“…11 Metabolic panels run on blood collected 24 h postexposure have been consistent with hepatic, renal, and cardiac damage. 48 In this study, treatment with a combination of 5 mg/kg MB and 250 mg/kg MSG, at 0.5 and 2 h postexposure, seemed to reduce markers of organ damage. Concentrations of enzymes indicative of multiorgan damage were similar in treated animals and control animals but elevated in sham-treated animals ( Fig.…”

“…Prior data have shown that 1080 diminishes respiratory function in exposed animals; however, as administered, MB and MSG did not improve respiratory parameters. 48 Minute volume, the product of tidal volume multiplied by the respiratory rate, was tracked for 24 h to evaluate the effects of therapeutics on respiration. Consistent with previously published data, animals exposed to 1080 showed signs of respiratory distress.…”

“…Previous publications quantifying concentrations of cytokines in blood serum have shown elevated concentrations of the proinflammatory cytokine IL-17 in animals exposed to 1080. 48 Transcriptomic analysis revealed changes in gene expression associated with the generation of an inflammatory response in multiple organs following 1080 exposure. The expression of genes regulating the acute phase response pathway was found to be altered in cardiac tissue at 2 and 3 h postexposure ( Fig.…”

“…After baseline, animals were removed and administered either 1080 or water via a noninvasive assisteddrinking method. 48,49 To mimic real-world conditions, animals were not fasted prior to experiments. Control animals not exposed to 1080 were used to establish a baseline for healthy animals.…”

“…Exposure concentrations of 1080 were calculated based on an LD 50 of 2.08 mg/kg. 48 Doses of 1080 and therapeutics were scaled to preexposure animal weight, and liquid volumes administered were normalized. Animals were then returned to WBP chambers, where respiratory function was tracked for 24 hours.…”