Aerosolized and instilled surfactant therapies for acute lung injury caused by intratracheal endotoxin in rats.
OBJECTIVE
To compare the effects of surfactant replacement by aerosol inhalation and bolus instillation on acute lung injury caused by the intratracheal injection of endotoxin in rats.


METHODS
Prospective, randomized study.


METHODS
University Laboratory.


METHODS
Male Wistar rats weighing 368 +/- 31 (SD) g.


METHODS
Escherichia coli endotoxin (57 +/- 20 mg/kg) was injected into the tracheas of 36 anesthetized and mechanically ventilated rats (FIO of 1.0). When the PaO2 had decreased to <200 torr (<26.7 kPa), the rats were randomly assigned to one of three groups: a control group (n=12)given no material; a bolus group (n=12) given a modified natural surfactant suspension (100 mg/kg in 2.0 mL/kg saline) by bolus instillation into the trachea; and an aerosol group (n=12) given surfactant aerosolized with an ultra-sonic nebulizer for 60 mins.


RESULTS
Bolus instillation transiently decreased the mean blood pressure by approximately 30%. However, aerosol inhalation did not. The PaO2 values of the control group remained <90 torr (<12.0 kPa) until the end of the experiment (180 mins). In contrast, the PaO2 of the bolus group increased to 387 +/- 134 torr (51.6 +/- 17.9 kPa; p<.05 vs. other groups) 15 mins after surfactant replacement, and remained at approximately 400 torr (approximately 53.3 kPa) throughout the experiment. The PaO2 values of the aerosol group increased slowly, peaked at 240 +/- 109 torr (32.0 +/- 14.5 kPa; p<.05 vs. the control group) 60 mins after the start of surfactant replacement, and remained at approximately 200 torr (approximately 26.7 kPa).


CONCLUSIONS
Bolus instillation was superior to aerosol inhalation concerning maximum efficacy, the rapid onset of therapeutic effects, and the necessary dose of surfactant. However, aerosol that does not cause hypotension may be of use in the treatment of adult respiratory distress syndrome in patients with circulatory instability.
Tashiro
K
K
Department of Anesthesiology and Intensive Care Medicine, School of Medicine, Kanazawa University, Japan.
Yamada
K
K
Li
W Z
WZ
Matsumoto
Y
Y
Kobayashi
T
T
D000336:Aerosols; D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004731:Endotoxins; D004926:Escherichia coli; D007322:Instillation, Drug; D008297:Male; D011663:Pulmonary Surfactants / Q000008:administration & dosage* / Q000302:isolation & purification; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology
D000336:Aerosols; D004731:Endotoxins; D011663:Pulmonary Surfactants