Skip to main content
Top
Published in: Indian Journal of Gastroenterology 3/2018

01-05-2018 | Original Article

Raised plasma levels of H2S and nitrate predict intrapulmonary vascular dilations: A preliminary report in patients with cryptogenic cirrhosis

Authors: Chinmay Bera, Kavitha Thangaraj, Purendra Kumar Pati, Jeyamani Ramachandran, K A Balasubramanian, Anup Ramachandran, Uday Zachariah, K G Sajith, Ashish Goel, C E Eapen

Published in: Indian Journal of Gastroenterology | Issue 3/2018

Login to get access

Abstract

Background and Aims

The role of vasoactive chemicals in the pathogenesis of hepatopulmonary syndrome (HPS), a disorder characterized by intrapulmonary vascular dilation (IPVD), is only vaguely elucidated. We aimed to study the association between plasma H2S, nitrate levels, and presence and severity of IPVD and HPS.

Methods

Consecutive adult patients with cryptogenic cirrhosis were evaluated for IPVD (by contrast echocardiography) and for hypoxemia (by arterial blood gas analysis). Plasma H2S and nitrate levels were measured in these patients.

Results

Fifty-eight patients with cryptogenic cirrhosis (male, 45; median age, range, 45, 16–74 years; Child’s class; A, 30; B, 18; C, 10) were enrolled in this study. Thirty-four of the 58 (59%) patients had IPVD and 13 (22%) had HPS (mild, 4; moderate, 5; severe, 2; very severe, 2). Plasma H2S levels were significantly higher in patients with IPVD (19.6, 5.7–83 μmol/L) as compared to patients who had no IPVD (12.3, 0–47 μmol/L; p-value 0.03) with an area under receiver operating characteristic curve of 0.68 (95% CI 0.53–0.84). Plasma H2S levels were higher in patients with IPVD irrespective of liver disease severity. There was a trend for higher plasma nitrate levels in patients with IPVD (47, 15.8–126.4 nmol/mL) as compared to patients who had no IPVD (32.3, 6.9–51.4 nmol/mL; p-value 0.1). Raised plasma H2S and nitrate levels had an additive effect on the presence of IPVD. Neither plasma H2S nor plasma nitrate levels correlated with the degree of hypoxemia.

Conclusion

Raised plasma H2S and nitrate levels predict the presence of IPVD in patients with cryptogenic cirrhosis.
Literature
2.
go back to reference Raevens S, Geerts A, Steenkiste CV, Verhelst X, Vlierberghe HV, Colle I. Hepatopulmonary syndrome and portopulmonary hypertension: recent knowledge in pathogenesis and overview of clinical assessment. Liver Int. 2015;35:1646–60.CrossRefPubMed Raevens S, Geerts A, Steenkiste CV, Verhelst X, Vlierberghe HV, Colle I. Hepatopulmonary syndrome and portopulmonary hypertension: recent knowledge in pathogenesis and overview of clinical assessment. Liver Int. 2015;35:1646–60.CrossRefPubMed
3.
go back to reference Zhang M, Luo B, Chen SJ, Abrams GA, Fallon MB. Endothelin-1 stimulation of endothelial nitric oxide synthase in the pathogenesis of hepatopulmonary syndrome. Am J Phys. 1999;277:G944–52. Zhang M, Luo B, Chen SJ, Abrams GA, Fallon MB. Endothelin-1 stimulation of endothelial nitric oxide synthase in the pathogenesis of hepatopulmonary syndrome. Am J Phys. 1999;277:G944–52.
4.
go back to reference Zhang XJ, Katsuta Y, Aikmoto T, Ohsuga M, Aramaki T, Takano T. Intrapulmonary vascular dilatation and nitric oxide in hypoxemic rats with chronic bile duct ligation. J Hepatol. 2003;39:724–30.CrossRefPubMed Zhang XJ, Katsuta Y, Aikmoto T, Ohsuga M, Aramaki T, Takano T. Intrapulmonary vascular dilatation and nitric oxide in hypoxemic rats with chronic bile duct ligation. J Hepatol. 2003;39:724–30.CrossRefPubMed
5.
go back to reference Arquedas MR, Drake BB, Kapoor A, Fallon MB. Carboxyhemoglobin levels in cirrhotic patients with and without hepatopulmonary syndrome. Gastroenterology. 2005;128:328–33.CrossRef Arquedas MR, Drake BB, Kapoor A, Fallon MB. Carboxyhemoglobin levels in cirrhotic patients with and without hepatopulmonary syndrome. Gastroenterology. 2005;128:328–33.CrossRef
6.
go back to reference Rabiller A, Nunes H, Lebrec D, et al. Prevention of gram-negative translocation reduces the severity of hepatopulmonary syndrome. Am J Respir Crit Care Med. 2002;166:514–7.CrossRefPubMed Rabiller A, Nunes H, Lebrec D, et al. Prevention of gram-negative translocation reduces the severity of hepatopulmonary syndrome. Am J Respir Crit Care Med. 2002;166:514–7.CrossRefPubMed
7.
go back to reference Zhang J, Luo B, Tang L, et al. Pulmonary angiogenesis in a rat model of hepatopulmonary syndrome. Gastroenterology. 2009;136:1070–80.CrossRefPubMed Zhang J, Luo B, Tang L, et al. Pulmonary angiogenesis in a rat model of hepatopulmonary syndrome. Gastroenterology. 2009;136:1070–80.CrossRefPubMed
8.
go back to reference Cheng Y, Ndisang JF, Tang G, Cao K, Wang R. Hydrogen sulphide-induced relaxation of resistance mesenteric beds of rats. Am J Physiol Heart Circ Physiol. 2004;287:H2316–23.CrossRefPubMed Cheng Y, Ndisang JF, Tang G, Cao K, Wang R. Hydrogen sulphide-induced relaxation of resistance mesenteric beds of rats. Am J Physiol Heart Circ Physiol. 2004;287:H2316–23.CrossRefPubMed
10.
go back to reference Aller R, Moya JL, Moreira V, et al. Diagnosis of hepatopulmonary syndrome with contrast transesophageal echocardiography. Advantages over contrast transtoracic echocardiography. Dig Dis Sci. 1999;44:1243–8.CrossRefPubMed Aller R, Moya JL, Moreira V, et al. Diagnosis of hepatopulmonary syndrome with contrast transesophageal echocardiography. Advantages over contrast transtoracic echocardiography. Dig Dis Sci. 1999;44:1243–8.CrossRefPubMed
11.
go back to reference Ahmad FD, Sattar MA, Rathore HA, et al. Exogenous hydrogen sulfide (h2s) improves the endothelial and renal excretory functions in streptozotocin induced wky diabetic rats. IJPSR. 2012;3:101–10. Ahmad FD, Sattar MA, Rathore HA, et al. Exogenous hydrogen sulfide (h2s) improves the endothelial and renal excretory functions in streptozotocin induced wky diabetic rats. IJPSR. 2012;3:101–10.
12.
go back to reference Sastry KVH, Moudgal RP, Mohan J, Tyagi JS, Rao GS. Spectrophotometric determination of serum nitrite and nitrate by copper-cadmium alloy. Anal Biochem. 2002;306:79–82.CrossRefPubMed Sastry KVH, Moudgal RP, Mohan J, Tyagi JS, Rao GS. Spectrophotometric determination of serum nitrite and nitrate by copper-cadmium alloy. Anal Biochem. 2002;306:79–82.CrossRefPubMed
13.
go back to reference Beltowski J. Hydrogen sulphide in pharmacology and medicine—an update. Pharmacol Rep. 2015;67:647–58.CrossRefPubMed Beltowski J. Hydrogen sulphide in pharmacology and medicine—an update. Pharmacol Rep. 2015;67:647–58.CrossRefPubMed
14.
go back to reference Yang G, Wu L, Jiang B, et al. H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase. Science. 2008;322:587–90.CrossRefPubMedPubMedCentral Yang G, Wu L, Jiang B, et al. H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase. Science. 2008;322:587–90.CrossRefPubMedPubMedCentral
15.
go back to reference Fiorucci S, Antonelli E, Mencarelli A, et al. The third gas: H2S regulates perfusion pressure in both the isolated and perfused normal rat liver and in cirrhosis. Hepatology. 2005;42:539–48.CrossRefPubMed Fiorucci S, Antonelli E, Mencarelli A, et al. The third gas: H2S regulates perfusion pressure in both the isolated and perfused normal rat liver and in cirrhosis. Hepatology. 2005;42:539–48.CrossRefPubMed
16.
go back to reference Rey FE, Gonzalez MD, Cheng J, Wu M, Ahern PP, Gordon JI. Metabolic niche of a prominent sulfate-reducing human gut bacterium. Proc Natl Acad Sci U S A. 2013;110:13582–7.CrossRefPubMedPubMedCentral Rey FE, Gonzalez MD, Cheng J, Wu M, Ahern PP, Gordon JI. Metabolic niche of a prominent sulfate-reducing human gut bacterium. Proc Natl Acad Sci U S A. 2013;110:13582–7.CrossRefPubMedPubMedCentral
17.
go back to reference Ritz NL, Burnett BJ, Setty P, et al. Sulfate-reducing bacteria impairs working memory in mice. Physiol Behav. 2016;157:281–7.CrossRefPubMed Ritz NL, Burnett BJ, Setty P, et al. Sulfate-reducing bacteria impairs working memory in mice. Physiol Behav. 2016;157:281–7.CrossRefPubMed
18.
go back to reference Beaumont M, Andriamihaja M, Lan A, et al. Detrimental effects for colonocytes of an increased exposure to luminal hydrogen sulfide: the adaptive response. Free Radic Biol Med. 2016;93:155–64.CrossRefPubMed Beaumont M, Andriamihaja M, Lan A, et al. Detrimental effects for colonocytes of an increased exposure to luminal hydrogen sulfide: the adaptive response. Free Radic Biol Med. 2016;93:155–64.CrossRefPubMed
19.
21.
22.
go back to reference Song K, Li Q, Yin XY, Lu Y, Liu CF, Hu LF. Hydrogen sulfide: a therapeutic candidate for fibrotic disease? Oxidative Med Cell Longev. 2015;2015:458720. Song K, Li Q, Yin XY, Lu Y, Liu CF, Hu LF. Hydrogen sulfide: a therapeutic candidate for fibrotic disease? Oxidative Med Cell Longev. 2015;2015:458720.
23.
go back to reference Wu D, Wang J, Li H, Xue M, Ji A, Li Y. Role of hydrogen sulfide in ischemia-reperfusion injury. Oxidative Med Cell Longev. 2015;2015:186908. Wu D, Wang J, Li H, Xue M, Ji A, Li Y. Role of hydrogen sulfide in ischemia-reperfusion injury. Oxidative Med Cell Longev. 2015;2015:186908.
25.
go back to reference Iwakiri Y, Kim YM. Nitric oxide in liver diseases. Trends Pharmacol Sci. 2015;6:524–36.CrossRef Iwakiri Y, Kim YM. Nitric oxide in liver diseases. Trends Pharmacol Sci. 2015;6:524–36.CrossRef
26.
go back to reference Ames PR, Guardascione M, Batuca JR, Arcaro A, Gentile F, Amitrano L. Nitric oxide metabolites, nitrative stress, and paraoxonase activity in hepatopulmonary syndrome. Scand J Gastroenterol. 2016;51:73–7.CrossRefPubMed Ames PR, Guardascione M, Batuca JR, Arcaro A, Gentile F, Amitrano L. Nitric oxide metabolites, nitrative stress, and paraoxonase activity in hepatopulmonary syndrome. Scand J Gastroenterol. 2016;51:73–7.CrossRefPubMed
27.
go back to reference Feng G, Rong H. The role of hemodynamic and vasoactive substances on hepatopulmonary syndrome. Eur Rev Med Pharmacol Sci. 2014;18:380–6.PubMed Feng G, Rong H. The role of hemodynamic and vasoactive substances on hepatopulmonary syndrome. Eur Rev Med Pharmacol Sci. 2014;18:380–6.PubMed
Metadata
Title
Raised plasma levels of H2S and nitrate predict intrapulmonary vascular dilations: A preliminary report in patients with cryptogenic cirrhosis
Authors
Chinmay Bera
Kavitha Thangaraj
Purendra Kumar Pati
Jeyamani Ramachandran
K A Balasubramanian
Anup Ramachandran
Uday Zachariah
K G Sajith
Ashish Goel
C E Eapen
Publication date
01-05-2018
Publisher
Springer India
Published in
Indian Journal of Gastroenterology / Issue 3/2018
Print ISSN: 0254-8860
Electronic ISSN: 0975-0711
DOI
https://doi.org/10.1007/s12664-018-0862-9

Other articles of this Issue 3/2018

Indian Journal of Gastroenterology 3/2018 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.