Effect of N-nitroso-N-methylurethane on gas exchange, lung compliance, and surfactant function of rabbits.
OBJECTIVE
To define the effect of N-nitroso-N-methyl-urethane (NNNMU) on pulmonary gas exchange, compliance and the biochemical and functional properties of the lung surfactant system.


METHODS
Four days after inducing lung injury, gas exchange and pulmonary compliance were studied and a bronchoalveolar lavage was taken.


METHODS
Experimental laboratory of a university department of medicine, division of pulmonary and critical care medicine.


METHODS
Ten rabbits after they had received an injection of NNNMU and five control animals.


METHODS
Controlled mechanical ventilation and bronchoalveolar lavage.


RESULTS
Measurements of gas exchange (using the multiple inert gas elimination technique), hemodynamics and pulmonary compliance were performed during ventilatory and hemodynamic steady state. A bronchoalveolar lavage (BAL) was taken after sacrificing the animal. BAL samples were processed for cell count and biochemical and functional surfactant analysis. Animals injected with NNNMU developed mild, but significant reduction in PaO2, while maintaining eucapnia during spontaneous air breathing. V/Q distributions and arterial blood gases were similar in all animals when ventilated mechanically with a fixed tidal volume. Compliance of the lung and phospholipid levels in lavage of NNNMU animals was significantly lower than in control animals (CON). Function of surfactant recovered from animals receiving NNNMU was decreased significantly where compared to CON. Thus, NNNMU resulted in a lowered lavage surfactant phospholipid content, impaired surfactant function, decreased compliance and hypoxemia during spontaneous ventilation. However, gas exchange was similar to that of control animals during mechanical ventilation.


CONCLUSIONS
We conclude that NNNMU-induced gas exchange abnormalities present after 4 days are mild and are reversed by fixed volume mechanical ventilation despite marked alteration in surfactant function and lung compliance. These observations further define properties of a lung injury model that is of value in the study of surfactant replacement.
Pappert
D
D
Klinik für Anaesthesiologie, und operative Intensivmedizin, WE01 Universitätsklinikum, Rudolf Virchow, Freie Universität Berlin, Germany.
Gilliard
N
N
Heldt
G
G
Merritt
T A
TA
Wagner
P D
PD
Spragg
R G
RG
D000818:Animals; D001784:Blood Gas Analysis; D018893:Bronchoalveolar Lavage; D006439:Hemodynamics / Q000187:drug effects; D008170:Lung Compliance / Q000187:drug effects*; D009605:Nitrosomethylurethane / Q000494:pharmacology; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D011663:Pulmonary Surfactants / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000503:physiopathology*
D011663:Pulmonary Surfactants; D009605:Nitrosomethylurethane