Acute effect of paraquat on lung fluid balance and prostanoid production in awake sheep.
Paraquat, a widely used herbicide, causes severe lung damage in humans and laboratory animals. Pulmonary edema is a common initial feature of paraquat toxicity, but its pathophysiology is not well understood. The purpose of this investigation was to determine the acute toxic effect of paraquat (30 mg/kg) on pulmonary transvascular protein and fluid fluxes, histologic features, and prostanoid production, using awake sheep with chronic lung lymph fistulas (n = 6). Lung lymph flow increased significantly 3.5 h after intravenous infusion of paraquat and rose to 2.6 times baseline within 8 h (from 4.4 +/- 0.4 to 11.4 +/- 1.5 ml/h, p less than 0.05). Lymph-plasma protein concentration ratio increased during the same time period (from 0.64 +/- 0.05 to 0.75 +/- 0.04, p less than 0.05). Lung lymph protein clearance also increased at 3.5 h and remained elevated throughout the duration of the experiment. Pulmonary arterial and left atrial pressure were only slightly altered. Plasma and lung lymph thromboxane A2 (as TXB2) concentrations were significantly increased at 30 min and continued so thereafter. Plasma and lung lymph prostacyclin (6-keto-PGF1 alpha) concentrations increased significantly at 3 h and were more than 5 times baseline by 7 h. The time course of the increase in 6-keto-PGF1 alpha concentrations seemed similar to that of lung lymph flow. The high flow of protein-rich lymph strongly suggested an increase in pulmonary vascular permeability, which may indicate pulmonary endothelial damage. Histologic studies of the lungs revealed only minor changes in perivascular cuffing, minimal alveolar hemorrhage, and slight neutrophilic alveolar wall infiltration.(ABSTRACT TRUNCATED AT 250 WORDS)
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D001826:Body Fluids / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D005402:Fistula / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008171:Lung Diseases / Q000503:physiopathology; D008196:Lymph / Q000032:analysis / Q000187:drug effects / Q000502:physiology; D008206:Lymphatic Diseases / Q000503:physiopathology; D010269:Paraquat / Q000633:toxicity*; D011453:Prostaglandins / Q000096:biosynthesis*; D012756:Sheep; D013929:Thromboxane B2 / Q000032:analysis; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects*
D011453:Prostaglandins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D010269:Paraquat