Exhaled nitric oxide and oxygenation abnormalities in hepatic cirrhosis

Abstract

Impaired arterial oxygenation, ranging from increased alImpaired 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 anIncreased circulation of a pulmonary vasodilator seems abnormally increased (ú15 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 õ .0001; and 47.5 { 29.4 vs. 32.9NO is a powerful local vasodilator of endothelial origin, { 10.1 mmol/L, P õ .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 Å .78, P õ .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 ú 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 t...

Genetic Risk Factors for Hepatopulmonary Syndrome in Patients With Advanced Liver Disease

“…Increased production of the gaseous vasodilators nitric oxide and carbon monoxide has also been associated with vascular dilatation in HPS,30,44,45 and, thus, we tested variants in the inducible and endothelial forms of nitric oxide synthase (NOS) as well as heme oxygenase 1 ( HMOX1 ), the rate-limiting enzyme in the production of carbon monoxide. A recent report found that the Glu298Asp (rs1799983) variant in NOS3 was associated with risk of HPS in 20 subjects with pediatric (predominately anatomic or metabolic) liver disease.…”

Hepatopulmonary syndrome: prevalence and predictive value of various cut offs for arterial oxygenation and their clinical consequences

“…Also, the contrast agent used may have contributed to the different prevalence data. Krowka and colleagues 7 and Stoller and colleagues 13 in part used indocyanine green dye solution which provides microbubbles with diameters of up to 90 µm, while we and others (Hopkins and colleagues, 8 Abrams and colleagues, 5 Rolla and colleagues, 15 and Aller and colleagues 6 ) used saline solution which creates microbubbles of 15-180 µm. Vedrinne and colleagues 10 used a modified fluid gelatine solution which creates microbubbles of 10±2 µm.…”

Pharmacological Treatment for Hepatopulmonary Syndrome

“…The crucial role of NO pathway has been suggested in the development of HPS in experimental and human studies. Cirrhotic patients with HPS have higher levels of exhaled NO compared to cirrhotic patients without HPS [10]. NOS isoforms are upregulated in rat model of cirrhosis with HPS [11].…”