Exercise potentiation of lung injury following inhalation of a pneumoedematogenic gas: perfluoroisobutylene.

Exercise performed after exposure to various pneumoedematogenic gases can increase the severity of pulmonary edema beyond that which occurs when exposure is followed by rest. The present study was performed to investigate the potential relationship between a preexisting breach in the lung's permeability status following exposure to an edematogenic gas (perfluoroisobutylene, PFIB) and the potentiating effects of postexposure exercise. Rats were exposed to a concentration of PFIB (100 mg/M3 for 10 min) that results in a unique postexposure latency period (approximately 8 h) prior to the occurrence of overt pulmonary edema. The study examined how exercise performed during and after the latency period affects the severity of the injurious response to this toxic gas. The initial results indicated that exercise performed during the post-PFIB exposure latency period does not potentiate the injurious response, as judged by conventional lung gravimetric and histopathological criteria, but when overt pulmonary edema was preexistent, exercise had a potentiating effect. Changes in lavageable protein were assessed as a more sensitive indicator of permeability changes that may occur during the latency period following PFIB exposure, and the study examined how exercise performed early during the latency period affects this index of pulmonary edema. The study also assessed whether PFIB-induced damage to lung cells is enhanced by exercise during the latency period by measuring lavageable lactate dehydrogenase activity. The results from these latter experiments suggest that a preexisting enhancement in lung permeability is not an absolute requirement for exercise to potentiate the pulmonary edematous response in lungs that are undergoing insidious injury, and that postexposure exercise does not enhance the cell-killing effects of PFIB as a mechanism underlying the exercise potentiating response. Conceivably, the ability of exercise to increase lavageable protein in the absence of a preexisting increase in lung permeability may be due to hyperventilation- and/or pulmonary hypertension-associated intercellular junctional changes that may occur during exercise. Additionally, it remains possible that exercise during PFIB-induced insideous lung injury results in an enhancement in the rate of transcellular transport of blood proteins onto the alveolar surface.

Lung injury following exposure of rats to relatively high mass concentrations of nitrogen dioxide.

Human inhalation exposures to relatively high mass concentrations of the oxidant gas nitrogen dioxide (NO2) can result in a variety of pulmonary disorders, including life-threatening pulmonary edema, pneumonia, and bronchiolitis obliterans. Inasmuch as most experimental studies to date have examined NO2-induced lung injury following exposures to near ambient or supra-ambient concentrations of NO2, e.g., < or = 50 ppm, little detailed information about the pulmonary injurious responses following the acute inhalation of higher NO2 concentrations that are more commensurate with some actual human exposure conditions is currently available. Described in this report are the results from a series of investigations in which various aspects of the inhalation toxicity of high concentrations of NO2 have been examined in laboratory rats. In the first component of our study, we characterized the kinetic course of development of lung injury following acute exposures to high concentrations of NO2 delivered over varying durations, and we assessed the relative importance of NO2 exposure concentration versus exposure time in producing lung injury. For a given exposure duration, the resulting severity of lung injury was found to generally scale proportionately with inhaled mass concentration, whereas for a given concentration of inhaled NO2, the magnitude of resulting injury was not directly proportional to exposure duration. Moreover, evidence was obtained that indicated exposure concentration is more important than exposure time when high concentrations of NO2 are inhaled. In a second component of our investigation, we assessed the pulmonary injurious response that occurs when NO2 is inhaled during very brief, 'high burst' exposures to very high concentrations of NO2. Such exposures resulted in significant lung injury, with the magnitude of such injury being directly proportional to exposure concentration. Comparisons of results obtained from this and the first component studies additionally revealed that brief exposures to the very high concentrations of NO2 are more hazardous than longer duration exposures to lower concentrations. In a third study series, we examined pre-exposure, exposure, and post-exposure modifiers of NO2-induced lung injury, including dietary taurine, minute ventilation, and post-exposure exercise. Results from these studies indicated: (i) dietary taurine does not protect the rat lung against high concentration NO2 exposure, (ii) the severity of acute lung injury in response to NO2 inhalation is increased by an increase in minute ventilation during exposure, and (iii) the performance of exercise after NO2 exposure can significantly enhance the injurious response to NO2.(ABSTRACT TRUNCATED AT 400 WORDS)