목적 : Nitric oxide (NO)는 간경변증 환자에서 혈관 리모델링과 맥관형성에 의한 문맥 순환의 재분배를 통해 과역동 혈액순환를 초래하는 혈관이완제 중의 하나로 nitric oxide synthase (NOS)에 의해 유도된다. 간경변증에서 NO는 간내 순환계, 문맥과 내장 순환계 및 전신 순환계 등 유래하는 위치에 따라 그 활성도에 다소의 차이가 있는 것으로 알려져 있다. 본 연구에서는 간경변증 환자의 말초혈액에서 NO의 활성도를 측정하여 간기능 이상이 없는 대조군과 비교하고, 문맥압 항진증과 관련된 과역동 혈액순환 및 잔여 간기능에 따른 NO의 활성도를 비교분석하여 간경변증에서 비교적 쉽게 접근할 수 있는 말초혈액에서의 NO 활성도 측정의 의의를 알아보고자 하였다. 방법 : 2004년 3월부터 2005년 2월까지 본원에 내원한 환자 중 임상적으로 의미있는 문맥압 항진증의 합병증이 동반된 61명의 간경변증 환자와 동반되지 않은 34명의 간경변증 환자를 대상으로 하였으며 32명의 건강검진자를 대조군으로 하였다. NO 활성도는 Griess 시약을 이용한 Nitrate/Nitrite Colorimetric Assay Kit (Cayman Chemical Co., Ann Arbor, USA)를 이용하여 대상 환자들의 말초혈액에서 측정하였다. 결과 : 간경변증 환자에서의 말초혈액 NO 활성도는 임상적 문맥압 항진증이 동반된 경우에 86.1±40.6 μmol/L, 동반되지 않은 경우에 83.5±47.2 μmol/L로 측정되어 대조군에서의 52.3±38.4 μmol/L에 비해 의미있게 높았으나(p<0.05), 임상적 문맥압 항진증 동반유무에 따른 차이는 관찰되지 않았다. Child-Pugh 분류 A, B, C에 따른 말초혈액 NO 활성도는 각각 84.9±45.5, 81.9±53.2, 86.4±39.8 μmol/L로 각 분류 간의 차이는 관찰할 수 없었으며, albumin, bilirubin, prothrombin time 등 생화학적 검사에 따른 NO 활성도의 차이도 관찰되지 않았다. 결론 : 간경변증 환자의 말초혈액에서 NO 활성도는 정상 대조군에 비해 증가되었으나 임상적 문맥압 항진증이나 잔여 간기능의 정도는 반영하지 못하였다. 향후 NO 활성도와 혈관 리모델링 및 맥관형성과 같은 과역동 혈액순환, 문맥압 항진증 및 잔여 간기능과의 정확한 상관관계의 분석을 위해서는 말초 혈액순환에서 보다는 간내 혈액순환이나 문맥 및 내장 혈액순환에서의 직접적인 NO 활성도 측정이 도움이 될 것으로 생각된다.

Background : Nitric Oxide (NO) induced by NO synthase is known to be associated with hyperdynamic circulation and collateralization by vascular remodeling in patients with cirrhosis. Methods : To assess the significance of peripheral NO activity in patients with cirrhosis, we measured the production of NO metabolites, nitrate and nitrite, using the nitrate/nitrite colorimetric assay with Griess reagents in the peripheral venous blood of 95 cirrhotic patients with or without clinical portal hypertension (PHT), and in the peripheral venous blood of 32 control patients without liver disease. Results : The peripheral NO activities in cirrhotic patients with clinical PHT, cirrhotic patients without clinical PHT, and non-liver disease control patients were 86.1±40.6 μmol/L, 83.5±47.2 μmol/L and 52.3±38.4 μmol/L, respectively. NO activity was significantly higher in cirrhotic patients than in non-liver disease control patients (p<0.05), while there was no significant difference of NO activity between the cirrhotic patients with or without clinical PHT. Peripheral NO activities in cirrhotic patients with Child-Pugh classification A, B, and C were 84.9±45.5 μmol/L, 81.9±53.2 μmol/L and 86.4±39.8 μmol/L, respectively; these results were not significantly different. A significant correlation of NO activity with the biochemical profiles of the serum albumin level, bilirubin level and prothrombin time were not defined. Conclusions : Peripheral NO activity was increased in cirrhotic patients, but it did not reflect the degree of clinical portal hypertension and the function of the hepatic reserve in this study. For a precise analysis of the association of NO and hyperdynamic circulation with collateralization in cirrhosis, intrahepatic or portal NO activity might be considered rather than peripheral NO activity.(Korean J Med 73:251-257, 2007)

Background : Nitric Oxide (NO) induced by NO synthase is known to be associated with hyperdynamic circulation and collateralization by vascular remodeling in patients with cirrhosis. Methods : To assess the significance of peripheral NO activity in patients with cirrhosis, we measured the production of NO metabolites, nitrate and nitrite, using the nitrate/nitrite colorimetric assay with Griess reagents in the peripheral venous blood of 95 cirrhotic patients with or without clinical portal hypertension (PHT), and in the peripheral venous blood of 32 control patients without liver disease. Results : The peripheral NO activities in cirrhotic patients with clinical PHT, cirrhotic patients without clinical PHT, and non-liver disease control patients were 86.1±40.6 μmol/L, 83.5±47.2 μmol/L and 52.3±38.4 μmol/L, respectively. NO activity was significantly higher in cirrhotic patients than in non-liver disease control patients (p<0.05), while there was no significant difference of NO activity between the cirrhotic patients with or without clinical PHT. Peripheral NO activities in cirrhotic patients with Child-Pugh classification A, B, and C were 84.9±45.5 μmol/L, 81.9±53.2 μmol/L and 86.4±39.8 μmol/L, respectively; these results were not significantly different. A significant correlation of NO activity with the biochemical profiles of the serum albumin level, bilirubin level and prothrombin time were not defined. Conclusions : Peripheral NO activity was increased in cirrhotic patients, but it did not reflect the degree of clinical portal hypertension and the function of the hepatic reserve in this study. For a precise analysis of the association of NO and hyperdynamic circulation with collateralization in cirrhosis, intrahepatic or portal NO activity might be considered rather than peripheral NO activity.(Korean J Med 73:251-257, 2007)

Liver cirrhosis, Portal hypertension, Nitric oxide