To determine the effect of delayed administration of inhaled nitric oxide (NO) on acute lung injury after the onset of gram-negative sepsis.
Nonrandomized controlled study.
University medical center laboratory.
Five groups of swine were anesthetized, mechanically ventilated, and studied for 5 hours. After surgical preparation, control (n=10) and NO-treated control (n=6) animals received a 1-hour infusion of sterile saline solution. Sepsis was induced with a 1-hour intravenous infusion of live Pseudomonas aeruginosa. Untreated animals with sepsis (n=10) received no treatment. Inhaled NO at 20 ppm was administered to NO30-treated animals with sepsis (n=7) and NO60-treatedanimals with sepsis (n=8) beginning at 30 and 60 minutes after bacterial infusion was begun, respectively.
Main Outcome Measures:
Systemic and pulmonary hemodynamics, arterial blood gas determination, bronchoalveolar lavage protein and neutrophil content, neutrophil oxidant burst, lung myeloperoxidase content, and scanning electron micrographic studies.
A progressive, significant (P<.05) decline in Pao2 developed in untreated animals with sepsis, which was prevented in NO30- and NO60-treated animals with sepsis. A significant (P<.05) increase in bronchoalveolar lavage protein and neutrophil counts compared with baseline values was observed in untreated animals with sepsis, indicating acute lung injury. These variables exhibited no notable increase in NO30- and NO60-treated animals with sepsis and were significantly (P<.05) reduced compared with untreated animals with sepsis. The lung myeloperoxidase content was significantly (P<.05) elevated at 5 hours in all groups with sepsis compared with baseline values and the control and NO-treated control groups. The total phorbol myristate acetate—induced polymorphonuclear leukocyte oxidant burst at 5 hours was significantly (P<.05) decreased in the NO30-and NO60-treated animals with sepsis compared with untreated animals with sepsis. Untreated and NO30- and NO60-treated animals with sepsis showed a significant (P<.05) increase in pulmonary artery pressure at 30 minutes, followed by a progressive decline. These changes were significant (P<.05) compared with baseline values and the control groups. No significant (P<.05) difference in pulmonary artery pressure or systemic arterial pressure was found at any time between untreated and NO30- and NO60-treated animals with sepsis.
The delayed administration of inhaled NO preserves alveolar-capillary membrane integrity in this porcine model of gram-negative sepsis. The inhibition of neutrophil transendothelial migration, rather than neutrophil rolling or tight adhesion, may be a critical mechanism by which inhaled NO produces this effect. Decreased oxidant production by activated neutrophils may be a secondary mechanism by which inhaled NO reduces acute lung injury.Arch Surg. 1997;132:65-75