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Aim: To test the effect on pulmonary gas exchange and mechanics of multiple small doses of exogenous surfactant as an alternative to bolus delivery in experimental respiratory failure induced by lung lavage., Method: After anesthesia, tracheostomy and constant volume ventilation, respiratory failure was induced by lung lavage in 20 rats. Animals were randomly assigned to an untreated control group or two experimental groups. Equal total doses of modified porcine surfactant (200 mg.kg-1 body weight), were given by tracheal instillation, either as a single bolus or in four (50 mg.kg-1 b.w.) fractional doses at 10-min intervals. Arterial pH and blood gases, and peak inspiratory pressure (PIP) were measured., Results: After lavage, a rapid decrease in arterial pH and PaO2, and an increase in PaCO2 and PIP were observed in all animals. In both surfactant-treated groups, PaO2 increased after surfactant instillation, and remained significantly higher than controls throughout the experiment. Arterial pH was significantly higher and PaCO2 significantly lower only in the single bolus group. In the multiple dose group, these levels were similar to those of controls., Conclusion: In surfactant-depleted rats with respiratory failure, instillation of four fractional surfactant doses did not result in the same enhancement on gas exchange and PIP, in the following 60 min, as same total dose given by a single bolus.