Adverse respiratory effects in rats following inhalation exposure to ammonia: respiratory dynamics and histopathology

Abstract

Acute respiratory dynamics and histopathology of the lungs and trachea following inhaled exposure to ammonia were investigated. Respiratory dynamic parameters were collected from male Sprague-Dawley rats (300-350 g) during (20 min) and 24 h (10 min) after inhalation exposure for 20 min to 9000, 20,000, and 23,000 ppm of ammonia in a head-only exposure system. Body weight loss, analysis of blood cells, and lungs and trachea histopathology were assessed 1, 3, and 24 h following inhalation exposure to 20,000 ppm of ammonia. Prominent decreases in minute volume (MV) and tidal volume (TV) were observed during and 24 h post-exposure in all ammonia-exposed animals. Inspiratory time (IT) and expiratory time (ET) followed similar patterns and decreased significantly during the exposure and then increased at 24 h post-exposure in all ammonia-exposed animals in comparison to air-exposed controls. Peak inspiratory (PIF) and expiratory flow (PEF) significantly decreased during the exposure to all ammonia doses, while at 24 h post-exposure they remained significantly decreased following exposure to 20,000 and 23,000 ppm. Exposure to 20,000 ppm of ammonia resulted in body weight loss at 1 and 3 h post-exposure; weight loss was significant at 24 h compared to controls. Exposure to 20,000 ppm of ammonia for 20 min resulted in increases in the total blood cell counts of white blood cells, neutrophils, and platelets at 1, 3, and 24 h post-exposure. Histopathologic evaluation of the lungs and trachea tissue of animals exposed to 20,000 ppm of ammonia at 1, 3, and 24 h post-exposure revealed various morphological changes, including alveolar, bronchial, and tracheal edema, epithelial necrosis, and exudate consisting of fibrin, hemorrhage, and inflammatory cells. The various alterations in respiratory dynamics and damage to the respiratory system observed in this study further emphasize ammonia-induced respiratory toxicity and the relevance of efficacious medical countermeasure strategies.

The physiology and toxicology of acute inhalation phosphine poisoning in conscious male rats

“…At the low dose, the effects of PH 3 inhalation on respiratory dynamics and clinical observations were markedly different from those observed at all other exposure doses, with only slight increases in MV n and no discernible signs and symptoms observed. However, the increase in net respiration was consistently observed at all PH 3 exposure doses, and this contrasts sharply with previous work using real-time plethysmography to examine the respiratory patterns of rats during exposure to chemical agents from different toxidromes, including diisopropylfluorophosphate (DFP) (Wong, Perkins, Santos, Rodriguez, Murphy and Sciuto 2013), soman (Perkins, Wong, Rodriguez, et al 2015), and ammonia (Perkins et al 2017), which found that agent exposure typically induced net decreases in respiration over the course of exposure. However, for PH 3 , the elevation of MV is primarily driven by increases in TV at the moderate and high doses, but by increases in f in the low-dose group.…”

A sex‐balanced rodent model for evaluating phosphine inhalation toxicity

“…This respiratory pattern differs from that commonly observed for respiratory irritants and various chem-ical agents, where animals exhibit MV reductions, likely in an attempt to lessen exposure or as a side effect of direct damages caused by caustic or corrosive chemicals. [35][36][37] Interestingly, animals exposed to PH 3 also showed signs and symptoms consistent with hypoxia (Table 1; e.g., lethargy) despite the absence of reduced ventilation. The apparent disparity between physiology and behavior suggests that oxygen transport or oxygen bioavailability may be hindered.…”

Alleviation of methyl isocyanate−induced airway obstruction and mortality by tissue plasminogen activator

“…However, animal monitoring was terminated at 8 h after MIC exposure and coagulation within the airways was not investigated during that study. Given the propensity of TICs to induce leakage of blood plasma, fibrinogen, and other clotting factors into the airways, [22][23][24][25][26] we hypothesized that extravascular coagulation in airways resulted from MIC inhalation. Furthermore, we supposed that the fibrinolytic agent tissue plasminogen activator (tPA) could mitigate airway obstruction and mortality after MIC inhalation.…”