Total plasma sulfide in mild to moderate diastolic heart dysfunction

mechanisms of diastolic dysfunction are not understood well. Hydrogen sulfide is an important endogenous gaseous trans-mitter that can influence heart remodeling. The aim was to determine total plasma sulfide (TPS) levels, as a surrogate marker of hydrogen sulfide, in patients with mild diastolic dysfunction.

Methods. Total plasma sulfide and N-ter-minal pro brain-type natriuretic peptide (NT-proBNP) levels were determined in ambulatory patients with arterial hyper-tension or diabetes mellitus and echocar-diographically mild to moderate diastolic dysfunction.

Results. Twenty-four patients were in-cluded: nine with normal diastolic func-tion (Grade 0), eight with an impaired relaxation pattern (Grade 1), and seven with a pseudo-normalized pattern (Grade 2). TPS levels were highest in patients with normal diastolic function (Grade 0), and lowest in patients with Grade 2 diastolic dysfunction, with this difference between Grade 0 and Grade 2 showing statistical significance (p = 0.017). NT-proBNP lev-els showed the reverse behavior, with this difference again showing statistical signifi-cance (p = 0.042).

Conclusions. Total plasma sulfide levels decrease with worsening of diastolic func-tion from normal to moderate diastolic dysfunction. 

total plasma sulfide, hydrogen sulfide, arterial hypertension, diastolic dys-function, echocardiography

1. Cleland JGF, Pellicori P. Defining diastolic heart failure and identifying effective therapies. JAMA 2013;309:825-6.

2. Levy D, Larson MG, Vasan RS, Kannel WB, Ho KK. The progression of hyptertension to congestive heart failure. JAMA 1996;275:1557.

3. Reiffenstein RJ, Hulbert WC, Roth SH. Toxicology of hydrogen sulfide. Annu Rev Pharmacol Toxicol 1992;32:109-34.

4. Zhang Z, Huang H, Liu P, Tang C, Wang J. Hydrogen sulfide contributes to cardioprotection during ischemia-reperfusion injury by opening K ATP channels. Can J Physiol Pharmacol 2007;85:1248-53.

5. Szabo C. Hydrogen sulphide and its therapeutic potential. Nat Rev Drug Discov 2007;6:917-35.

6. Shibuya N, Tanaka M, Yoshida M, Ogasawara Y, Togawa T, Ishii K et al. 3-Mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain. Antioxid Redox Signal 2009;4:703-14.

7. Whitfield NL, Kreimier EL, Verdial FC, Skovgaard N, Olson KR. Reappraisal of H2S/ sulfide concentration in vertebrate blood and its potential significance in ischemic preconditioning and vascular signaling. Am J Physiol Regul Integr Comp Physiol 2008;6:1930-37.

8. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Car-diovascular Imaging. Eur Heart J Cardiovasc Imaging 2015;16:233-70.

9. Nauget SF, Applwton CP, Gillbert TC, Marino PN, Oh JK, Smiseth OA. Recommendation for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr 2009;10:165-93.

10. Lawrence NS, Davis J, Compton RG. Analytical strategies for the detection of sulfide: a review. Talanta 2000;52:771-84.

11. Fogo JK, Poposky M. Spectrophotometric determination of hydrogen sulfide. Anal Chem 1949;21:732-4.

12. Siegel LM. A direct microdetermination for sulfide. Anal Biochem 1965;11:126-32.

13. Collin M, Anuar FB, Murch O, Bhatia M, Moore PK, Thiemermann C. Inhibition of endogenous hydrogen sulfide formation re-duces the organ injury caused by endotoxemia. Br J Pharmacol 2005;146:498-505.

14. Zhang H, Zhi L, Moore PK, Bhatia M. Role of hydrogen sulfide in cecal ligation and puncture-induced sepsis in the mouse. Am J Physiol Lung Cell Mol Physiol 2006;290:1193-201.

15. Mok YY, Atan MS, Yoke Ping C, Zhong Jing W, Bhatia M, Moochhala S et al. Role of hydrogen sulphide in haemorrhagic shock in the rat: protective effect of inhibitors of hydrogen sulphide biosynthesis. Br J Pharmacol 2004;143:881-9.

16. Stipanuk MH, Beck PW. Characterization of the enzymic capacity for cysteine desulphhydration in liver and kidney of the rat. Biochem J 1982;206:267-77.

17. Abe K, Kimura H. The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci 1996;16:1066-71.

18. Martinez DA, Guhl DJ, Staley WC, Vailas AC. Extracellular matrix maturation in the left ventricle of normal and diabetic swine. Diabet Res Clin Pract 2003;59:1-9.

19. Atisha D, Bhalla MA, Morrison LK, Felicio L, Clopton P, Gardetto N et al. A prospective study in search of an optimal B-natriuretic peptide level to screen patients for cardiac dysfunction. Am Heart J 2012;148:518-23.

20. Plehn G, Vormbrock J, Christ M, Prull M, Lefringhausen L, Trappe HJ et al. Masked diastolic dysfunction caused by exercise test-ing in hypertensive heart failure patients with normal ejection fraction and normal or mildly increased LV mass. Acta Cardiol 2009;64:617-26.

21. Bhalla V, Willis S, Maisel AS. B-type natriuretic peptide: the level and the drug partners in the diagnosis of heart failure. Congest Heart Fail 2004;10:3-27.

22. Liang F, Gardner DG. Mechanical strain activates BNP gene transcription through a p38/NF-κB–dependent mechanism. J Clin Invest 1999;104:1603-12.

23. Maeder MT, Staub D, Surnier Y, Reichlin T, Noveanu M, Breidthardt T et al. Determinants of absolute and relative exercise-induced changes in B-type natriuretic peptides. I J Card 2011;147:409-15.

24. Bielecka-Dabrowa A, Michalska-Kasiczak M, Gluba A, Ahmed A, Gerdts E, von Haehlinh S et al. Biomarkers and echocardio-graphic predictors of myocardial dysfunction in patients with hypertension. Sci Rep 2015;5:8916.

25. Zhang Z, Huang H, Liu P, Tang C, Wang J. Hydrogen sulfide contributes to cardioprotection during ischemia-reperfusion injury by opening K ATP channels. Can J Physiol Pharmacol 2007;85:1248-53.

26. Al-Magableh MR, Kemp-Harper BK, Ng HH, Miller AA, Hart JL. Hydrogen sulfide protects endothelial nitric oxide function un-der conditions of acute oxidative stress in vitro. Naunyn-Schmiedeberg Arch Pharmacol 2014;387:67-74.

27. Jin HF, Sun Y, Liang ML, Tang CS, Du JB. Hypotensive effects of hydrogen sulfide via attenuating vascular inflammation in spon-taneously hypertensive rats. Zhonghua Xin Xue Guan Bing Za Zhi 2008;36:541-5.

28. Predmore BL, Julian D, Cardounel AJ. Hydrogen sulfide increases nitric oxide production from endothelial cells by an Akt-depend-ent mechanism. Front Physiol 2011;2:104.

29. Tsuda T, Gao E, Evangelisti L, Markova D, Ma X, Chu ML. Post-ischemic myocardial fibrosis occurs independent of hemodynamic changes. Cardiovasc Res 2003;59:926-33.

30. Opie LH, Commerford PJ, Gersh BJ, Pfeffer MA. Controversies in ventricular remodelling. Lancet 2006;367:356-67.

31. Sun L, Jin H, Sun L, Chen S, Huang Y, Liu J et al. Hydrogen sulfide alleviates myocardial collagen remodeling in association with inhibition of TGF-β/Smad signaling pathway in spontaneously hypertensive rats. MolMed 2014;20:503-15

32. Drachuk KO, Dorofeyeva NA, Sagach VF. The role of hydrogen sulfide in diastolic function restoration during aging. Physiol J 2016;6:62.

33. King AL, Polhemus DJ, Bhushan S, Otsuka H, Kondo K, Nicholson CK et al. Hydrogen sulfide cytoprotective signaling is endothe-lial nitric oxide synthase-nitric oxide dependent. Proc Natl Acad Sci USA 2014;11:3182-87.

34. Xiao l, Dong JH, Jin S, Xue HM, Guo Q, Teng X et al. Hydrogen sulfide improves endothelial dysfunction via downregulating BMP4/COX-2 pathway in rats with hypertension. Oxidat Med Cell Longev 2016:1-10.

35. Bradley JM, Organ CL, Lefer DJ. Garlic-derived organic polysulfides and myocardial protection. J Nutr 2016;146:403-9.

36. Yan H, Du J, Tang C. The possible role of hydrogen sulfide on the pathogenesis of spontaneous hypertension in rats. Biochem Biophys Res Comm 2004;313:22-7.

37. Gu Q, Wang B, Zhang XF, Ma YP, Liu JD, Wang XZ. Contribution of hydrogen sulfide and nitric oxide to exercise-induced at-tenuation of aortic remodeling and improvement of endothelial function in spontaneously hypertensive rats. Mol Cell Biochem 2013;375:199-206.

38. Kovačić D, Glavnik N, Marinšek M, Zagozen P, Rovan K, Goslar T et al. Total plasma sulfide as prognostic indicator for patients with congestive heart failure. J Card Fail 2012;18:541-8.

39. Wintner EA, Deckwerth TL, Langston W, Bengtsson A, Leviten D, Hill P et al. A monobromobimane-based assay to measure the pharmacokinetic profile of reactive sulphide species in blood. Br J Pharmacol 2010;160:941-57.