Mechanisms of pulmonary edema induced by an organophosphorus compound in anesthetized dogs.
To determine the mechanism governing pulmonary edema induced by an organophosphorus compound, S-(2-diisopropylaminoethyl)-O-ethylmethyl phosphonothiolate (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 6 micrograms/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 microliters/min, p less than 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 less than 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.
Laboratoire de Pharmacodynamie, Centre d'Etudes du Bouchet, Vert-Le-Petit, France.
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Lainee
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Robineau
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Guittin
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Benchetrit
D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D001784:Blood Gas Analysis; D001834:Body Water / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D006863:Hydrogen-Ion Concentration; D008168:Lung / Q000378:metabolism; D008208:Lymphatic System / Q000187:drug effects; D008297:Male; D009943:Organophosphorus Compounds / Q000633:toxicity*; D009946:Organothiophosphorus Compounds / Q000633:toxicity; D011652:Pulmonary Circulation / Q000187:drug effects; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000503:physiopathology
D000110:Acetylcholinesterase; D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D009946:Organothiophosphorus Compounds; C009680:VX-agent