Paraquat poisoning: an experimental model of dose-dependent acute lung injury due to surfactant dysfunction.
Since the most characteristic feature of paraquat poisoning is lung damage, a prospective controlled study was performed on excised rat lungs in order to estimate the intensity of lesion after different doses. Twenty-five male, 2-3-month-old non-SPF Wistar rats, divided into 5 groups, received paraquat dichloride in a single intraperitoneal injection (0, 1, 5, 25, or 50 mg/kg body weight) 24 h before the experiment. Static pressure-volume (PV) curves were performed in air- and saline-filled lungs; an estimator of surface tension and tissue works was computed by integrating the area of both curves and reported as work/ml of volume displacement. Paraquat induced a dose-dependent increase of inspiratory surface tension work that reached a significant two-fold order of magnitude for 25 and 50 mg/kg body weight (P < 0.05, ANOVA), sparing lung tissue. This kind of lesion was probably due to functional abnormalities of the surfactant system, as was shown by the increase in the hysteresis of the paraquat groups at the highest doses. Hence, paraquat poisoning provides a suitable model of acute lung injury with alveolar instability that can be easily used in experimental protocols of mechanical ventilation.
Laboratório de Poluição Atmosférica Experimental, Faculdade de Medicina, Universidade de São Paulo, Brasil. pepino@usp.br
M F
MF
Silva
P H
PH
Saldiva
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006540:Herbicides / Q000506:poisoning*; D007320:Inspiratory Capacity; D008297:Male; D010269:Paraquat / Q000506:poisoning*; D011663:Pulmonary Surfactants / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000139:chemically induced*
D006540:Herbicides; D011663:Pulmonary Surfactants; D010269:Paraquat