Impaired arterial oxygenation, ranging from increased al-Impaired arterial oxygenation, ranging from increased alveolar-arterial oxygen gradient (AaDo 2 ) to hypoxemia, is veolar-arterial oxygen gradient (AaDo 2 ) to hypoxemia, is comcommonly reported in patients with cirrhosis. 1 In the absence monly present in patients with cirrhosis. Nitric oxide (NO), of overt mechanical dysfunction of the lung, it has been through pulmonary vasodilatation, may play a major role in suggested that oxygenation abnormalities of cirrhotic pathe oxygen abnormalities of cirrhosis. Our aim was to study tients may be a consequence of ventilation/perfusion misthe relationship between NO production and O 2 abnormalities match and intrapulmonary shunting. 2-4 Intrapulmonary vasin 45 nonsmoking patients with cirrhosis and without major cular dilatations and artero-venous communications are cardiovascular and respiratory diseases. Intrapulmonary thought to be the pathological bases of the physiological shunting was detected by contrast-enhanced (CE) echocardimechanisms of oxygenation abnormalities. 5,6
ography. Lung volumes and diffusion, arterial blood gas analy-
The vascular dilatations can result in severe hypoxemia, sis, serum NO 0 2 /NO 0 3 , NO output in the exhaled air, and which, at variance from that caused by intrapulmonary cardiac index by the echocardiographic method were detershunts, may respond normally to supplemental oxygen. mined in all patients. Twenty-seven (60%) patients had an Increased circulation of a pulmonary vasodilator seems abnormally increased (ΓΊ15 mm Hg) AaDo 2 . The mean values to be the favored mechanism for intrapulmonary vascular of exhaled NO output and serum NO 0 2 /NO 0 3 were significantly dilatations in cirrhosis, and nitric oxide (NO) has recently higher in cirrhotic patients than in controls (252 { 117 vs.
ascended to the top of the list of possible substances. 6,7 75.2 { 19 nL/min/m 2 , P Γ΅ .0001; and 47.5 { 29.4 vs. 32.9
NO is a powerful local vasodilator of endothelial origin, { 10.1 mmol/L, P Γ΅ .02, respectively). In all patients, there which contributes to the normally low pulmonary vascular was a significant correlation between exhaled NO and AaDo 2 tone. 8 NO has been shown to play an important role in regulat-(r Γ
.78, P Γ΅ .0001). Twelve patients (26.6%) were found to ing the vasomotor tone in experimental cirrhosis. 9,10 It is now have CE-echocardiographic evidence of intrapulmonary possible to measure NO produced in the lung by measuring its shunting (positive CE-echo). Nine patients were considered concentration in exhaled air. 11,12 Recently, increased NO output to have hepatopulmonary syndrome (HPS) on the basis of an in exhaled air has been reported in patients with advanced AaDo 2 ΓΊ 15 mm Hg and positive CE-echo. These 9 patients cirrhosis, in whom exhaled NO was associated with systemic had a mean value of exhaled NO significantly higher than circulatory disturbances. 13 Exhaled NO was reported to be patients without HPS (331 { 73.2 vs. 223 { 118.4 nL/min/ raised almost threefold in three patients with hepatopulmonary m 2 , P Γ΅ .05). In all patients, cardiac index was positively syndrome (HPS), compared with normal volunteers and with correlated with exhaled NO (r Γ
.47, P Γ΅ .001) and with normoxemic cirrhotic patients. 14 We make the hypothesis that serum NO 0 2 /NO 0 3 (r Γ
.43, P Γ΅ .01). The results suggest an NO locally produced in the lung may play an important role important role of NO in the oxygenation and circulatory abin determining oxygenation abnormalities in patients with cirnormalities of patients with cirrhosis. (HEPATOLOGY rhosis. To this aim, we investigated the relationship between 1997;26:842-847.) NO produced in the lung, assessed by exhaled NO measurement, and oxygenation abnormalities in patients with advanced cirrhosis. All the patients were noninvasively investigated for the presence of intrapulmonary vascular dilatations by contrast-Abbreviations: AaDo2 alveolar-arterial oxygen gradient; HPS, hepatopulmonary synenhanced (CE) echocardiography 15 and Pao 2 on 100% oxygen drome; CE, contrast-enhanced; FEV1, forced expiratory volume at first second; VC, vital capacity; TLco, transfer factor for carbon monoxide; Kco, TLco Ο¬ alveolar volume; breathing. 16 Plasma nitrite/nitrate levels, NO stable metabolites, CI, cardiac index.