ABSTRACT
The measurement of exhaled gas compositions has proved to be an invaluable noninvasive technique for the detection of pathophysiological changes in the lung. Common techniques that assess lung volumes (multiple breath washouts, helium dilution), gas extraction, and pulmonary capillary blood flow (carbon monoxide diffusing capacity, measurement of ventilation/perfusion ratios) all rely on the collection and measurement of exhaled gas (1). However, most of these methods rely on the determination of changes in the composition of inspired gas mixtures that result from their inhalation. With the development of improved analytical techniques by the early 1970s, it became possible to detect and assay very low concentrations of endogenously generated exhaled gases, and these observations raised the possibility of using endogenous gas production as an indicator of lung injury. The utility of such measurements was demonstrated by Reily et al. (2), who showed that exhaled ethane could be used as a surrogate in the detection of the peroxidation of unsaturated lipids in the liver. Subsequent toxicological studies suggest that the measurements of the endogenously generated gases ethane or pentane can serve as sensitive indicators of lipid peroxidation (3). With the recent reports that nitric oxide (NO) can be detected in exhaled air,
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the possibility that exhaled breath contains additional markers that may serve as surrogate measurements of lung injury has received renewed attention (4). These more recent studies have examined the exhalation of gaseous substances such as NO and CO as well as compounds in breath condensates such as hydrogen peroxide and isoprostanes (5,6). Not surprisingly, some measurements have been made in patients with adult respiratory distress syndrome (ARDS), bronchiectasis, and asthma; however, the evolving complexity of these clinical conditions has made the interpretation of such results problematic (4,7-10). In the case of NO, for example, the measured exhaled concentration of NO actually represents “net” production (i.e., the difference between NO produced and NO removed). Since either or both of these parameters might change during evolving injury, methods that evaluate both NO production and NO extraction need to be employed if we are to understand the relationship between exhaled NO levels and the underlying pathology that causes them. In this chapter we describe a rat model of endotoxemia that augurs the events that lead to the development of acute lung injury (ALI), by measuring the appearance of NO in exhaled air after intravenous injection of an endotoxin, lipopolysaccharide (LPS). We propose that these results are relevant to the condition of septicemia and the subsequent development of ALI and ARDS in humans.
