HYPEROXIC LUNG INJURY REDUCES EXOGENOUS SURFACTANT CLEARANCE IN-VIVO

We studied the rate of clearance of treatment doses of radiolabeled ca lf lung surfactant extract, which was instilled into the lungs of youn g adult rabbits exposed to air (control) or 100% oxygen for 64 h. More than 75% of the instilled surfactant remained lung-associated at all time points up to 24 h post-instillation in both groups; however, sign ificantly more of the labeled phosphatidylcholine (PC) remained in the alveolar wash of oxygen-exposed rabbits (44 +/- 9% in 100% O-2 versus 27 +/- 5% in controls at 6 h and 27 +/- 2% in 100% O-2 versus 6 +/- 1 % in control rabbits at 24 h, p < 0.05). Less of the labeled PC could be found in type II pneumocytes isolated from the oxygen exposed anima ls than in control animals, both at 6 h (24 +/- 2 cpm/10(6) cells in O -2 versus 38 +/- 7 cpm/10(6) cells in control) and 24 h (42 +/- 5 cpm/ 10(6) cells in O-2 versus 70 +/- 12 cpm/10(6) cells in control) post-i nstillation. Type II cells from animals exposed to 100% oxygen also de monstrated significantly lower PC synthesis rates than cells from lung s of control animals. interestingly, clearance of exogenous surfactant in rabbits exposed to 100% oxygen for 48 h, an exposure that does not cause significant type It pneumocyte dysfunction, was not different f rom control. We concluded that injury to type II pneumocytes may resul t in decreased clearance of instilled surfactant from the alveolar spa ce and may be important in determining dosing regimens for the use of surfactant therapy in adult respiratory distress syndrome.