INCREASED NITRIC-OXIDE IN EXHALED GAS AS AN EARLY MARKER OF LUNG INFLAMMATION IN A MODEL OF SEPSIS

Nitric Oxide (NO) has been implicated in the pathologic vasodilation o f sepsis. Because NO can be measured in the exhaled gas of animals and humans, we hypothesized that increases in exhaled NO would occur in a septic model. Using a blinded design, 10 male Sprague-Dawley rats (30 0 to 400 g) were anesthetized, paralyzed, tracheotomized, and randomiz ed (5/group) to receive an intravenous injection of either lipopolysac charide (LPS) (Salmonella typhosa, 20 mg/kg) or placebo (equal volume of saline). Thereafter exhaled gas was collected and measurements of N O concentration were made using chemiluminescence every 20 min for 300 min during ventilation (RR 40 breaths/min, VT 3 ml, PEEP 0, Fl(O2) 0. 21). Another group of 10 animals (5 LPS; 5 control) were treated in th e same fashion and then killed at 240 min and an arterial blood sample obtained for blood gas and TNF alpha determinations. Pressure volume (PV) curves were constructed and lungs removed, preserved, and submitt ed for histologic evaluation. LPS-treated rats had lower mean arterial pressures than the control group, p < 0.0001. No significant differen ces in static lung compliance and PV curves were found in the two grou ps. TNF alpha levels were greater in the LPS group (1.40 +/- 0.24 ng/m l) versus control group (0.09 +/- 0.04 ng/ml), p < 0.001. By contrast to the control group, exhaled NO concentration rose in all LPS-treated rats at approximately 100 min and at about 160 min reached a plateau that was 6 times greater than control levels (p < 0.0001). There was g reater interstitial, airspace, and total lung injury in the LPS group (p = 0.01). Hypotension alone was not responsible for the rise in exha led NO because no increase in NO was noted over 300 min in another two rats that did not receive LPS and that were slowly exsanguinated to m aintain mean systemic arterial pressure 40 to 60 mm Hg. In two rats th at were completely exsanguinated at 240 min we observed marked increas es in exhaled NO concentration compared with LPS-treated rats with int act circulation. We conclude that in this model of sepsis, increases i n exhaled NO concentration originate in the lungs and appear to be a r elatively early marker of lung inflammation.