© 1991 Oxford University Press
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Mechanisms of Pulmonary Edema Induced by an Organophosphorus Compound in Anesthetized Dogs

*Laboratoire de Pharmacodynamie, Centre d'Etudes du Bouchet BP n°3, 91710 Vert-Le-Petit
Laboratoire de Physiologie Faaillé de Medecine de Grenoble, 38700 La Tronche, France
Received September 27, 1990; accepted February 13, 1991
Mechanisms of Pulmonary Edema Induced by an Organophosphorus Compound in Anesthetized Dogs. LAINEE, P., ROBINEAU, P., GUNTIN, P., COQ, H., AND BENCHETRIT, G. (1991). Fundam. Appl. Toxtcol. 17, 177-185. To determine the mechanism governing pulmonary edema induced by an organophosphorus compound, 5-{2-diisopropylaminoethyl)-O-ethvlmethyl phos-phonothiolate (VX), lung lymph flow and lymph-to-plasma protein concentration ratio were measured in six anesthetized, open-chest, mechanically ventilated beagle dogs before and after intravenous injection of 6µg/kg of VX. Systemic and pulmonary hemodynamic data (heart rate, aortic blood flow, and left atrial, systemic arterial, pulmonary arterial, and pulmonary capillary pressures) were continuously recorded. Arterial blood gases and pH were measured every 30 min. Histological examinations and lung water content measurements were also carried out. Following VX injection, lung lymph flow increased (from 109 ± 38 to 179 ± 66 jil/min, p < 0.05) while lymph-to-plasma protein concentration ratio remained unchanged (from 0.64 ± 0.14 to 0.62 ± 0.12, N.S.). Neither systemic nor pulmonary hemodynamics were changed. Lung water content expressed as blood-free wet-to-dry weight ratio increased from 4.31 ± 0.23 to 5.35 ± 0.26 (p < 0.05). Histological examinations revealed in many cases diffUse congestion of lungs and interstitial edema. These results suggest that VX injection induces an increase in pulmonary capillary permeability which may lead to a high-permeability edema.