Intrapulmonary vascular dilatation and nitric oxide in hypoxemic rats with chronic bile duct ligation

Zhang, Xuejun; Katsuta, Yasumi; Akimoto, Toshio; Ohsuga, Masaru; Aramaki, Takumi; Takano, Teruo

doi:10.1016/s0168-8278(03)00430-6

Cited by 51 publications

(45 citation statements)

References 35 publications

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“…(20) In our study, we demonstrated significant differences between the experimental and control groups in terms of these parameters. Experimental studies have shown that control animals present PaO 2 values of 90-99 mmHg and PaCO 2 values of ≈40 mmHg, (21,22) values comparable to those seen in the IN CCl 4 -Co group animals evaluated in the present study. We observed that PaO 2 and SaO 2 were significantly lower the IN CCl 4 -Ex group than in the IN CCl 4 -Co group, whereas PaCO 2 was higher, although not significantly so.…”

Section: Discussionsupporting

confidence: 85%

Modelos experimentais para avaliação das alterações pulmonares na síndrome hepatopulmonar

et al. 2008

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Objective: The aim of this study was to identify the best experimental model in which to observe the pulmonary alterations characterizing hepatopulmonary syndrome (HPS). Methods: Male Wistar rats, with mean weight of 250 g, were used in four experimental models: inhaled carbon tetrachloride; intraperitoneal carbon tetrachloride; partial portal vein ligation; and bile duct ligation (BDL). The animals in all groups were divided into control and experimental subgroups. The following variables were measured: transaminase levels; blood gases; lipoperoxidation, using thiobarbituric acid reactive substances (TBARS) and chemiluminescence; and levels of superoxide dismutase (SOD) anti-oxidant activity. Anatomopathological examination of the lung was also performed. Results: There were statistically significant differences between the BDL control and BDL experimental groups: aspartate aminotransferase (105.3 ± 43 vs. 500.5 ± 90.3 IU/L); alanine aminotransferase (78.75 ± 37.7 vs. 162.75 ± 35.4 IU/L); alkaline phosphatase (160 ± 20.45 vs. 373.25 ± 45.44 IU/L); arterial oxygen tension (85.25 ± 8.1 vs. 49.9 ± 22.5 mmHg); and oxygen saturation (95 ± 0.7 vs. 73.3 ± 12.07%). Lipoperoxidation and antioxidant activity also differed significantly between the two BDL groups (control vs. experimental): TBARS (0.87 ± 0.3 vs. 2.01 ± 0.9 nmol/mg protein); chemiluminescence (16008.41 ± 1171.45 vs. 20250.36 ± 827.82 cps/mg protein); and SOD (6.66 ± 1.34 vs. 16.06 ± 2.67 IU/mg protein). The anatomopathological examination confirmed pulmonary vasodilatation in the BDL model. In the other models, there were no alterations that were characteristic of HPS. Conclusions: The data obtained suggest that the BDL model can be used in future studies involving hepatic alterations related to oxidative stress and HPS.Keywords: Hepatopulmonary syndrome; Lung; Oxidative stress; Rats. ResumoObjetivo: O objetivo deste trabalho foi avaliar o melhor modelo experimental para observar alterações pulmonares que caracterizam a síndrome hepatopulmonar (SHP). Métodos: Ratos machos Wistar, com peso médio de 250 g foram usados em quatro modelos experimentais:tetracloreto de carbono inalatório; tetracloreto de carbono intraperitoneal; ligadura parcial de veia porta; e ligadura de ducto biliar (LDB). Em todos os grupos os animais foram divididos em controle e experimental. Foram avaliadas as seguintes variáveis: transaminases; gasometria; lipoperoxidação por substâncias que reagem ao ácido tiobarbitúrico (TBARS) e por quimiluminescência; e atividade antioxidante da enzima superóxido dismutase (SOD). Foi feito também o exame anatomopatológico do pulmão. Resultados: Observou-se diferenças significativas entre os grupos LDB controle e experimental: aspartato amino transferase (105,3 ± 43 vs. 500,5 ± 90,3 UI/L); alanino aminotransferase (78,75 ± 37,7 vs. 162,75 ± 35,4 UI/L); fosfatase alcalina (160 ± 20,45 vs. 373,25 ± 45,44 UI/L); pressão parcial de oxigênio (85,25 ± 8,1 vs. 49,9 ± 22,5 mmHg); e saturação de hemoglobina (95 ± 1,4 vs. 73,3 ± 24,14%). A lipoperoxid...

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Section: Discussionsupporting

confidence: 85%

Modelos experimentais para avaliação das alterações pulmonares na síndrome hepatopulmonar

et al. 2008

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“…In addition, ROS cause oxidation of cellular proteins and extensive damage to mitochondrial DNA and mitochondrial synthesis by liver damage (8,24,34) . When we evaluated lipid peroxidation in the two models of cirrhosis, animals in the EX group had significantly higher values compared to those in the CO group, and the level of TBARS and QL were elevated in the lung and liver in both groups.…”

Section: Discussionmentioning

confidence: 99%

Lung and Liver Changes Due to the Induction of Cirrhosis in Two Experimental Models

Ferrari

Tieppo

Rosa

et al. 2013

Arq. Gastroenterol.

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-Context -To evaluate lung and liver changes in two experimental models using intraperitoneal carbon tetrachloride (CCl 4 ) and bile duct ligation (BDL). Methods -Twenty-four male Wistar rats were divided into a control group (CO) and an experimental group (EX). We evaluated the liver transaminases (AST, ALT, AP), arterial blood gases (PaO 2 , PCO 2 and SpO 2 ) and lipid peroxidation by TBARS (substances that react to thiobarbituric acid) and chemiluminescence. We also evaluated the antioxidant enzyme superoxide dismutase (SOD) and histology of lung tissue and liver. Results -There were significant differences in AST, ALT, ALP and PaO 2 between CO group and EX group (P<0.05). The levels of TBARS, chemiluminescence and activity of enzyme superoxide dismutase were increased to different degrees in the CCl 4 groups: CO and in the BDL -EX (P<0.05, respectively). In the lung histology, an increase in the wall thickness of the pulmonary artery and a diameter reduction in the CCl 4 animal model were observed: comparing CO group with EX group, we observed a reduction in thickness and an increase in the diameter of the artery wall lung. Conclusion -Both experimental models have caused liver damage and alterations in the artery wall that are associated with major changes in pulmonary gas exchange.

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“…4,6,10,23 In a rat HPS model, pulmonary vascular remodeling, gas exchange abnormalities, and blunted pulmonary vasopressor response were all linked to increased expression and activities of both pulmonary endothelial 4,23 and inducible NO synthase. 6 Moreover, it has been shown that intravenous L-NAME acutely improved arterial hypoxemia, 10 thereby suggesting that NO-dependent pulmonary vasodilatation actively contributes to V A /Q imbalance in HPS.…”

Section: Discussionmentioning

confidence: 99%

“…2 Few experimental and clinical evidences in HPS suggest that enhanced pulmonary production of nitric oxide (NO) plays a key role in the development of intrapulmonary vascular dilatations. [3][4][5][6][7][8][9][10] Morphologically, the striking feature in HPS is widespread dilatation and increased number of pulmonary capillaries in alveolar regions 11 that suggest a vasculogenic rather than a vasoactive pathobiological process. 12 Studies with NO inhibitors in HPS, however, have highlighted that active NO-dependent pulmonary vasodilatation may contribute to the persistence of gas exchange abnormalities.…”

Section: See Editorial On Page 912mentioning

confidence: 99%

“…12 Studies with NO inhibitors in HPS, however, have highlighted that active NO-dependent pulmonary vasodilatation may contribute to the persistence of gas exchange abnormalities. 10,13,14 In patients with HPS, there was a transient improvement in arterial oxygenation after intravenous methylene blue, an inhibitor of soluble guanylate cyclase and cyclic guanosine monophosphate production, a final molecular step for NO-mediated vasorelaxation. 13,14 Similarly, inhibition of NO synthase with nebulized N G -nitro-L-arginine methyl ester (L-NAME) in a patient with HPS improved arterial oxygen tension, 15 suggesting that the selective inhibition of pulmonary NO through the inhaled route could be of potential therapeutic benefit.…”

Section: See Editorial On Page 912mentioning

confidence: 99%

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Effects of nebulized N G-nitro-L-arginine methyl ester in patients with hepatopulmonary syndrome

et al. 2006

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Enhanced pulmonary production of nitric oxide (NO) has been implicated in the pathogenesis of hepatopulmonary syndrome (HPS). NO inhibition with N G -nitro-L-arginine methyl ester (L-NAME) in both animals and humans with HPS has improved arterial hypoxemia. We assessed the role of enhanced NO production in the pathobiology of arterial deoxygenation in HPS and the potential therapeutic efficacy of selective pulmonary NO inhibition. We investigated the effects of nebulized L-NAME (162.0 mg) at 30 and 120 minutes on all intrapulmonary and extrapulmonary factors governing pulmonary gas exchange in 10 patients with HPS (60 ؎ 7 [SD] yr; alveolar-arterial oxygen gradient, range 19-76 mm Hg; arterial oxygen tension, range 37-89 mm Hg). Nebulized L-NAME maximally decreased exhaled NO (by ؊55%; P < .001), mixed venous nitrite/nitrate (by ؊12%; P ‫؍‬ .02), and cardiac output (by ؊11%; P ‫؍‬ .002) while increased systemic vascular resistance (by 11%; P ‫؍‬ .008) and pulmonary vascular resistance (by 25%; P ‫؍‬ .03). In contrast, ventilation-perfusion mismatching, intrapulmonary shunt and, in turn, arterial deoxygenation remained unchanged. In conclusion, gas exchange disturbances in HPS may be related to pulmonary vascular remodeling rather than to an ongoing vasodilator effect of enhanced NO production. ( H epatopulmonary syndrome (HPS) is defined as an arterial oxygenation defect induced by intrapulmonary vascular dilatations associated with hepatic disease. 1 Arterial deoxygenation in HPS is caused by ventilation-perfusion mismatching and intrapulmonary shunt along with a diffusion-perfusion defect in most advanced cases. 2 Few experimental and clinical evidences in HPS suggest that enhanced pulmonary production of nitric oxide (NO) plays a key role in the development of intrapulmonary vascular dilatations. [3][4][5][6][7][8][9][10] Morphologically, the striking feature in HPS is widespread dilatation and increased number of pulmonary capillaries in alveolar regions 11 that suggest a vasculogenic rather than a vasoactive pathobiological process. 12 Studies with NO inhibitors in HPS, however, have highlighted that active NO-dependent pulmonary vasodilatation may contribute to the persistence of gas exchange abnormalities. 10,13,14 In patients with HPS, there was a transient improvement in arterial oxygenation after intravenous methylene blue, an inhibitor of soluble guanylate cyclase and cyclic guanosine monophosphate production, a final molecular step for NO-mediated vasorelaxation. 13,14 Similarly, inhibition of NO synthase with nebulized N G -nitro-L-arginine methyl ester (L-NAME) in a patient with HPS improved arterial oxygen tension, 15 suggesting that the selective inhibition of pulmonary NO through the inhaled route could be of potential therapeutic benefit. Nevertheless, the precise role of a NO-dependent pulmonary vasodilatation involved in the pathogenesis of abnormal pulmonary gas exchange in HPS remains far from clear.To shed further light into the pathogenesis of HPS and to explore the potential therapeutic a...

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Intrapulmonary vascular dilatation and nitric oxide in hypoxemic rats with chronic bile duct ligation

Cited by 51 publications

References 35 publications

Modelos experimentais para avaliação das alterações pulmonares na síndrome hepatopulmonar

Modelos experimentais para avaliação das alterações pulmonares na síndrome hepatopulmonar

Lung and Liver Changes Due to the Induction of Cirrhosis in Two Experimental Models

Effects of nebulized N G-nitro-L-arginine methyl ester in patients with hepatopulmonary syndrome

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