Morbidity and mortality resulting from acute inhalation exposures to hydrogen fluoride and carbonyl fluoride in rats.

OBJECTIVE: Experiments were undertaken to compare morbidity and mortality from brief inhalation exposures to high levels of hydrogen fluoride (HF) and carbonyl fluoride (COF2). METHODS: Rats from both sexes were exposed for durations of 5 and 10 min to nominal concentrations of 10,000 to 57,000 ppm HF or 500 to 10,000 ppm COF2. Respiration was monitored before, during, and after exposure. Animals were observed up to 6 days post-exposure. Terminal blood samples were collected for routine clinical chemistry and hematology. Post-mortem lung fluoride concentrations and lung weights were measured, and gross pathology noted. RESULTS: Both gases produced respiratory depression independent of concentration or exposure duration with minute ventilation decreasing to approximately 50% of baseline. Estimated mixed-gender HF and COF2 10-min LC50's were 48,661 ppm and 1083 ppm, respectively. HF mortalities were generally delayed 3 to 4 days post-exposure, while COF2 mortalities occurred during or briefly after exposure. Lung fluoride levels increased with COF2 dose, though elevated lung weights occurred only at the mid-level exposures. Lung weights were unaffected in the HF-exposed animals, and their lung fluoride concentrations were variable. Clinical chemistry and hematology had few consistent trends with the exception of hemoconcentration primarily in HF-exposed males. These short-term exposure experiments conclude that COF2 is nearly 45 times more lethal than HF in rats. CONCLUSIONS: These experiments suggest that hydrolysis to HF cannot solely explain COF2 toxicity. Although HF and COF2 may have common injury mechanisms, they are expressed to markedly different degrees and temporal occurrence.

Prehospital Detection of Life-Threatening Intracranial Pathology: An Unmet Need for Severe TBI in Austere, Rural, and Remote Areas.

Severe traumatic brain injury (TBI) is a leading cause of death and disability worldwide, especially in low- and middle-income countries, and in austere, rural, and remote settings. The purpose of this Perspective is to challenge the notion that accurate and actionable diagnosis of the most severe brain injuries should be limited to physicians and other highly-trained specialists located at hospitals. Further, we aim to demonstrate that the great opportunity to improve severe TBI care is in the prehospital setting. Here, we discuss potential applications of prehospital diagnostics, including ultrasound and near-infrared spectroscopy (NIRS) for detection of life-threatening subdural and epidural hemorrhage, as well as monitoring of cerebral hemodynamics following severe TBI. Ultrasound-based methods for assessment of cerebrovascular hemodynamics, vasospasm, and intracranial pressure have substantial promise, but have been mainly used in hospital settings; substantial development will be required for prehospital optimization. Compared to ultrasound, NIRS is better suited to assess certain aspects of intracranial pathology and has a smaller form factor. Thus, NIRS is potentially closer to becoming a reliable method for non-invasive intracranial assessment and cerebral monitoring in the prehospital setting. While one current continuous wave NIRS-based device has been FDA-approved for detection of subdural and epidural hemorrhage, NIRS methods using frequency domain technology have greater potential to improve diagnosis and monitoring in the prehospital setting. In addition to better technology, advances in large animal models, provider training, and implementation science represent opportunities to accelerate progress in prehospital care for severe TBI in austere, rural, and remote areas.

Consequences of brief exposure to high concentrations of carbon monoxide in conscious rats.

Exposure to high-concentration carbon monoxide (CO) is of concern in military operations. Experimentally, the physiologic manifestations of a brief exposure to elevated levels of CO have not been fully described. This study investigated the development of acute CO poisoning in conscious male Sprague-Dawley rats (220-380 g). Animals were randomly grouped (n = 6) and exposed to either air or 1 of 6 CO concentrations (1000, 3000, 6000, 10,000, 12,000, or 24,000 ppm) in a continuous air/CO dynamic exposure chamber for 5 min. Respiration was recorded prior to and during exposures. Mixed blood carboxyhemoglobin (COHb) and pH were measured before and immediately after exposure. Before exposure the mean baselines of respiratory minute volumes (RMVs) were 312.6 +/- 43.9, 275.2 +/- 40.8, and 302.3 +/- 39.1 ml/min for the 10,000, 12,000 and 24,000 ppm groups, respectively. In the last minute of exposure RMVs were 118.9 +/- 23.7, 62.1 +/- 10.4, and 22.0 +/- 15.1% (p < .05) of their mean baselines in these 3 groups, respectively. Immediately after exposure, blood COHb saturations were elevated to 60.16, 63.42, and 69.37%, and blood pH levels were reduced to 7.43 +/- 0.09, 7.25 +/- 0.05, and 7.13 +/- 0.04 in the 3 groups, respectively. Mortality during exposure was 1/12 in the 12,000 ppm group and 4/12 in the 24,000 ppm group. Deaths occurred close to the end of 5 min exposure. In each animal that died by exposure, pH was <6.87 and COHb saturation was >82%. Blood pH was unaltered and no death occurred in rats exposed to CO at concentrations <6000 ppm, although COHb saturations were elevated to 14.52, 29.94, and 57.24% in the 1000, 3000, and 6000 ppm groups, respectively. These results suggest that brief exposure to CO at concentrations <10,000 ppm may produce some significant physiological changes. However, exposure to CO at concentrations >10,000 ppm for brief periods as short as 5 min may change RMV, resulting in acute respiratory failure, acidemia, and even death.

Significant pulmonary response to a brief high-level, nose-only nitrogen dioxide exposure: an interspecies dosimetry perspective.

Brief, high-level nitrogen dioxide (NO(2)) exposures are major hazards during fires and heat-generating explosions. To characterize the lung response to a brief high-level NO(2) exposure, we exposed two groups (n = 5) of 325-375 g, male, Sprague-Dawley rats to either 200 +/- 5 ppm (376 +/- 9 mg/m(3)) NO(2) or room air for 15 min. The rats were nose-only exposed in a multiport exposure chamber fitted with pressure transducers to monitor their respiration during exposure. One hour after exposure, we euthanized the rats, collected blood samples, lavaged the lungs with warm saline, and then excised them. One lung lobe was cooled to -196 degrees C and used for low-temperature electron paramagentic resonance (EPR) analysis. The remainder was homogenized and used for biochemical analyses. Inspired minute ventilation (V(i)) during exposure decreased 59% (p < 0.05). Calculated total inspired dose was 0.880 mg NO(2). In lung lavage, both total and alveolar macrophage cell counts declined (approximately 75%, p < 0.05), but epithelial cell count increased 8.5-fold. Lung weight increased 40% (p < 0.05) after exposure. In the blood, potassium and methemoglobin increased 45 and 18% (p < 0.05), respectively; glucose, lactate, and total hemoglobin were not altered significantly. EPR analysis of lung tissue revealed hemoglobin oxidation and carbon-centered radical formation. Vitamins E and C and uric acid were depleted, and lipid peroxidation measured by three different methods (TBARS, conjugated dienes, and fluorescent peroxidation end products) was elevated, but total protein, DNA, and lipid contents were unchanged. These observations combined demonstrate that a brief (15 min) high-level (200 ppm) NO(2) exposure of rats was sufficient to cause significant damage. However, comparison of the exposure dose normalized to rat body weight with previously reported sheep and estimated human values revealed significant differences. This raises a question about interspecies dosimetry and species-specific responses when animal data are extrapolated to humans and used for safety standard setting, particularly with high-level brief exposures.