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The lung, by virtue of its anatomy and position, is uniquely designed to facilitate exchange of oxygen and waste gases. Although the metabolic functions of the lung have been appreciated for more than 70 years, these same characteristics make it an important organ in the processing of biologic compounds and drugs. In 1925, Starling and Verney 94 reported that only when the lungs were included in the circuit could an isolated kidney be perfused adequately. Without the lungs in the circuit, defibrinated blood reaching the kidney caused the vessels to constrict. They concluded that the blood was "detoxicated" in the lungs. In 1948, the vasoconstrictor was identified as serotonin (5-HT). 82 However, it was not until 1953 that Gaddum et al 28 confirmed that 5-HT was metabolized in the lung. It was subsequently proposed that an important function of the lung is to serve as a chemical filter, protecting the systemic circulation from exposure to high levels of circulating vasoactive compounds 12,25,26,32,37,38,57,90,98 and regulating systemic arterial concentrations of exogenous substances. Because of its ultrastructure and position in the circulation, the lung is uniquely suited for this role. The lung receives the total cardiac output, as opposed to other organs that receive only fractional output. In the lung, the circulating blood is exposed to the largest capillary endothelial surface in the body (70 square meters). These two factors combine to make the lung an effective biochemical filter. With a cardiac output of 5 L/min and 30% removal of a substance, pulmonary clearance is 1.5 L/min (5 × 0.3). Although the liver is often perceived to be the primary metabolic organ, the maximal clearance of a substance completely metabolized by the liver reflects resting hepatic blood flow (i.e., 1.6 L/min). 38 Initial studies of 5-HT suggested that the lungs were capable of removing or inactivating toxic substances as they traversed the pulmonary circulation. Subsequent research has established a more complex role for this organ. Some compounds, such as 5-HT or norepinephrine, are totally or partially eliminated or inactivated in the pulmonary circulation. Some closely related compounds (epinephrine, histamine) pass through the lungs unchanged. Other hormones are activated by the lungs or released into the pulmonary circulation (Table 1). The selectivity of the lung in differentially processing closely related compounds and its multiple actions suggest that it serves as more than a general filter. Whether injury can precipitate a pathophysiologic process by interfering with the lung's metabolic functions is an important question. Additionally, the potential exists to use the metabolic processing of the lung to assess the severity of lung injury. Thus, a picture of the lung emerges in which it acts not only as a chemical filter but also as an active processor of hormones and xenobiotics (Table 1). This article emphasizes the various metabolic functions of the lung and the clinically important pharmacokinetic effects it has on a large number of endogenous and exogenous substances of special interest to anesthesiologists. 32,61,97 We also describe some important drug-drug interactions at the pulmonary level that impact on clinical practice. |
