S418 INTRODUCTION: There is evidence that patients with hepatic cirrhosis have elevated levels of exhaled nitric oxide (NO). [1] This study was designed to examine the effect of orthotopic liver transplantation (OLT) on the perioperative concentrations of exhaled NO in patients with end-stage liver disease. METHODS: After IRB approval and informed consent, 4 patients undergoing orthotopic liver transplantation were studied. Exhaled NO concentrations were measured using a rapid response chemiluminescence analyzer (Sievers Instruments Inc. Boulder, Co). A restricted exhaled breath technique was utilized. Contamination by nasopharyngeal NO was excluded by using a constant exhalation pressure of 20 torr and 46 ml/s exhalation flow rate. Initial measurements were taken just prior to induction of anesthesia. Post-transplant measurements were taken daily after completion of surgery with the patient extubated. Laboratory data (PT, AST, ALT) were also obtained to determine if signs of graft dysfunction affected levels of exhaled NO. RESULTS: All patients maintained elevated levels of exhaled NO post-operatively, however, patients 1 and 3 displayed signs of acute cellular rejection. In both of these patients the exhaled NO concentrations peaked at a level above that measured in the preoperative period. Patient 1 increased from 38.4ppb to 49ppb and patient 3 increased from 35.3ppb to 42.3ppb, respectively. See Table 1.Table 1: Exhaled NO Concentrations in extubated OLT patients. (Normal exhaled NO value for a healthy individual [similar]10ppb.)DISCUSSION: Nitric oxide is hypothesized as being the mediator of peripheral vasodilation in patients with cirrhosis. Hepatocytes and Kuppfer cells have been shown to produce excessive amounts of NO in cirrhotic livers [2]. Because NO is thought to be rapidly inactivated by the circulating hemoglobin, it is likely that most of the exhaled NO is the result of excessive local production of NO by the lung, rather than the liver. Vascular and bronchial endothelial cells probably produce this NO and that would account for the maintained increased levels of exhaled NO after implantation of a new liver graft. Recent studies, however, have shown that some NO may not be deactivated by hemoglobin but is instead transported as s-nitrosyl hemoglobin [3-4]. This may then be circulated directly to the lungs where it is released as exhaled NO. If this is true, then the liver hepatocyte function could be a component of exhaled NO concentrations. This preliminary data does show some trends of an increase in exhaled NO with early signs of graft dysfunction. Further studies should be able to demonstrate if concentrations of exhaled NO are a reliable marker of graft dysfunction.

S122 INTRODUCTION: The concentration of nitric oxide (NO) in exhaled breath has been demonstrated to be at increased levels in patients with severe liver cirrhosis [1]. This prospective study investigates the variation in levels of exhaled NO in patients undergoing orthotopic liver transplantation. METHOD: After IRB approval and informed consent, 8 patients with severe liver cirrhosis undergoing orthotopic liver transplantation had intraoperative levels of exhaled NO monitored. A chemiluminecence analyzer (Sievers Inc. Boulder, Co) was utilized and samples were measured from the elbow connector attaching the breathing circuit to the endotracheal tube. Nasopharyngeal produced NO was excluded from the sample by the endotracheal tube. Peak concentrations of NO were recorded during exhalation. RESULTS: See Table 1.Table 1: Peak concentrations for exhaled nitric oxide in patients during three stages of orthotopic liver transplantation.DISCUSSION: The NO measured in the exhaled breath of patients with severe liver cirrhosis may be the result of an increased production of NO by hepatocytes and Kuppfer cells in the liver, where it is then transported to the lungs as s-nitrosyl hemoglobin and released, or it may have originated from the local production of NO in the lungs [2-4]. Both of these pathways may exist together. If the liver is a significant source of this NO production, then the anhepatic phase of the transplant procedure should result in a reduction of exhaled NO levels. In this preliminary study, the trend seen in some patients corroborates this hypothesis. If this finding is confirmed by further investigation then exhaled NO analysis may provide an early indication of liver graft function.