Effects of single intratracheal exposure to chlorhexidine gluconate on the rat lung.
ABSTRACT Chlorhexidine gluconate (CHX) is an antiseptic that has been widely used for disinfection of cutaneous wound and gingivae. Recently, a patient who inhaled CHX solution died from acute respiratory distress syndrome (ARDS). Although it is highly possible that direct pulmonary damage might be the cause of ARDS, there is no preclinical information about the pulmonary toxicity of CHX. In the current study, the acute direct action of CHX to the lung was evaluated in rats. We successfully exposed the left but not the right lung either to CHX at concentrations of 1%, 0.1%, and 0.01% or to saline using a curved-tip administration tube. At the higher concentrations of CHX (0.1% and 1%), severe congestion to the alveoli and capillaries and perivascular and intra-alveolar hemorrhages were observed 1 day after exposure. Aniline blue-stained collagen fibers with an infiltration of inflammatory cells were present 7 days after exposure. The fibrotic changes and intra-alveolar inflammatory cells had decreased but were still observed sporadically 28 and 84 days after exposure. These detrimental effects were more severe at 1% than at 0.1% CHX. No remarkable effect was observed after exposures to 0.01% CHX and saline. We were able to evaluate the time-course changes in the pulmonary toxicity of CHX by exposures limited to the left lung. It is highly possible that CHX at a concentration of more than 0.1% might directly induce ARDS when aspirated and reaching to the alveoli.
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ABSTRACT: An understanding of the epidemiology of ALI/ARDS and the effects of treatment have been hampered by the lack of a uniform definition of the syndrome. Various definitions have been proposed, and these are reviewed with particular attention to how changes in definition have affected our understanding of the natural history and treatment options for the condition.Thorax 06/2002; 57(5):452-8. · 8.38 Impact Factor
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ABSTRACT: The time course of histopathological changes in a rat lung lavage model of the acute respiratory distress syndrome (ARDS) was analyzed by sacrificing animals 10, 30, 60, 180, and 210 min after the last lung parenchyma lavage which was performed with physiological saline solution. This lavage depleted the lung from its natural surfactant resources leading into a pathophysiological cascade similar to that of the acute respiratory distress syndrome. Tracheotomized rats (12 animals per time point) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths/min, inspiration–expiration ratio of 1:2, peak inspiratory pressure of 28 cm H2O at positive end-expiratory pressure (PEEP) of 8 cm H2O. During the whole experimental period, the ventilation was not changed. Blood gases (partial arterial oxygen pressures [PaO2, mmHg] and partial arterial carbon dioxide pressures [PaCO2, mmHg]) were estimated before, directly after, and 10, 30, 60, 90, 120, 150, 180, and 210 min after the last lavage.For grading lung lavage-induced histopathological changes associated with the time-dependent development of ARDS, slides were coded and evaluated without any knowledge of the sacrifice time. A semiquantitative grading was performed with respect to the severity of the following parameters: hyaline membrane formation (HM), interstitial and intraalveolar edema edema (E), and margination and infiltration of polymorphonuclear neutrophil leukocytes (PMNL) into the lung alveoli. The severity of these parameters showed a time-dependent increase after the last lavage. This was accompanied by a time-dependent decrease in partial arterial oxygen pressure (PaO2) values during the early postlavage period (up to 30 min). Thereafter, PaO2 levels remained fairly stable. The severity of intraalveolar and/or perivascular hemorrhages within the lung was not time dependent. The rat lavage model shows similarities to the pathophysiological sequelae occuring during the acute phase of the acute respiratory distress syndrome in humans. Most of the characteristic pathognomic histological changes seen in humans can be observed in this lung lavage model. This ARDS model is brief and easy in its experimental design, showed a good and homogeneous reproducibility of pathophysiological and histopathological parameters, and is therefore a useful model to estimate the influence of therapeutic pharmacological treatments of ARDS.Journal of Pharmacological and Toxicological Methods 09/1998; · 2.15 Impact Factor
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ABSTRACT: The safety evaluation of chlorhexidine (Hibitane) in animal species will be briefly reviewed. The relevance of these studies to human use will be discussed, and species comparisons made where possible. Animal studies with chlorhexidine were begun more than two decades ago and the evaluation of its safety has been under continual review ever since. Chlorhexidine is poorly absorbed after oral administration, well tolerated after parenteral administration and its percutaneous absorption is abolutely minimal. No clinical or histological effects have been obtained in any animal study to cause hesitation in the light of proliferating applications of chlorhexidine in human use. The various toxicological studies in animals will be described and in particular the results of a 2-year study in rats will be outlined. In this, as an in earlier long-term study, there were no effects whatsoever to suggest that chlorhexidine treatment could give rise to any kind of tumourigenic effect or any other toxic sign.Journal Of Clinical Periodontology 01/1978; 4(5):66-,2. · 3.69 Impact Factor