INCREASED NITRIC-OXIDE IN EXHALED GAS IS AN EARLY MARKER OF HYPOVOLEMIC STATES

Acute hemorrhage is associated with a variety of physiologic and metab olic alterations, including vascular hyporeactivity and endothelial ce ll dysfunction. The lung is a major target organ during hemorrhagic sh ock. The effect of acute hemorrhage on NO production in the lung is no t well described. In the present study we examined the effect of acute hemorrhage on exhaled NO (NOe), and studied how changes in blood volu me and flow affect NOe. Anesthetized and mechanically ventilated rabbi ts were used. The effect of acute hemorrhage by slow exsanguination on NOe was examined using chemiluminescence. Because hemorrhagic shock i s associated with decreased pulmonary blood flow, we established an is olated lung preparation perfused with autologous blood (Hct = 17.4%) a nd studied the effect of pulmonary flow rate on NOe independent of met abolic changes. In order to separate the effect of how from the effect of changes in blood volume, we examined the effect of flow in isolate d lungs perfused with a blood-free albumin solution (PAS). In the isol ated lung, ventilation was similar to that used in the intact animal, and temperature, pH, pCO(2), and PO2 were kept normal. Prior to exsang uination, baseline NOe in the intact animal was 24 +/- 3 ppb. At 5, 10 , 15, and 20 min after initiating the hemorrhage, NOe rose to 31 +/- 3 , 51 +/- 7, 94 +/- 10, and 154 +/- 16 ppb, respectively (P < 0.05). Du ring baseline conditions in the blood-perfused isolated lungs (200 ml/ min), NOe was 35 +/- 3 ppb. When flow was decreased to 70 and 0 ml/ mi n, NOe increased to 37 +/- 3 and 56 +/- 6 ppb, respectively (P < 0.001 ). During baseline conditions in the PAS-perfused lungs (70 ml/min), N Oe was 94 +/- 13 ppb and was unaffected by changes in flow. The perfus ion pressure in the isolated lungs was in the normal range. Reduction in blood flow rate in the isolated lung was associated with less than twofold increase in NOe. This was attributed to reduction in red blood cell volume and not due to changes in blood flow rate. Reduction in f low in the intact animal during hemorrhage generated more than threefo ld increase in NOe, suggesting that neurohumoral mediators, in additio n to changes in flow, play an important role in determining NOe in the intact condition. NOe began to rise immediately after exsanguination began, and therefore may be a useful early marker of acute hemorrhagic shock and hypovolemia. This information may be useful in the intensiv e care setting. (C) 1997 Academic Press.