INHALED NITRIC-OXIDE DOES NOT PREVENT ENDOTOXIN-INDUCED LUNG INJURY IN RABBITS

Background: Neutrophils, platelets, and cytokines are thought to play a pivotal role in the pathogenesis of endotoxin-induced lung injury wh ich resembles features of acute respiratory distress syndrome (ARDS). For initiation of this pathological process, neutrophils and platelets are activated and adhere to pulmonary endothelium. Nitric oxide (NO) inhibits adhesion and activation of these cells and decreases the cyto kine level in bronchoalveolar lavage (BAL) fluid obtained from patient s with ARDS. Limited data are available on the effect of NO treatment before and after endotoxin on the development and advance of ARDS. The aim of the current study was to determine whether NO inhalation preve nts acute lung injury. Methods: Thirty-two male anaesthetized rabbits were randomly assigned to receive one of four treatments (n = 8 each); Group S-N received saline with nitrogen (N-2), Group S-NO received sa line infusion with NO (20 p.p.m.) inhalation, Group E-N received an in fusion of Escherichia coli endotoxin 100 mu g/kg over 60 min with inha lation of N-2 and Group E-NO received endotoxin with NO (20 p.p.m.) in halation. The lungs of the rabbits were ventilated with 40% oxygen unt il 6 h after the start of endotoxin or saline administration. Haemodyn amics and PaO2 were recorded during the ventilation period. After obse rvation, the lung wet-to dry-(W/D) weight ratio, lung mechanics, and c ell fraction, activated complements, cytokines, arachidonic acid metab olites, and albumin concentrations in the BAL fluid were measured and analysed. Light microscopic findings were compared among the four grou ps. Results: Pulmonary hypertension and deterioration of oxygenation b y endotoxin were less pronounced in rabbits receiving NO. The lung com pliance after endotoxin was similar in Groups E-NO and E-N. The W/D we ight ratio and neutrophils and albumin concentrations in the BAL fluid increased in Groups E-NO and E-N. The BAL fluid concentrations of int erleukin-8, thromboxane A(2), and prostacyclin were similar in the two endotoxin-treated groups. Endotoxin caused extensive morphologic lung damage regardless of NO inhalation. Conclusions: The increase in pulm onary arterial pressure and deterioration of oxygenation were less in endotoxin-exposed rabbits receiving NO inhalation compared with those receiving N-2. Accumulation of neutrophils and platelets in the lung, morphological lung damage, and the release of cytokines and prostanoid s were observed in the E-NO group. However, we are unable to extrapola te these results directly to the human clinical setting because of the short observation period, the use of only one dose of NO, and the spe cies difference.