Skip to main content
SpringerLink
Log in

Sulfide Intoxication-Induced Circulatory Failure is Mediated by a Depression in Cardiac Contractility

  • Published:
Cardiovascular Toxicology Aims and scope Submit manuscript

Abstract

Hydrogen sulfide (H2S) intoxication produces a rapid cardio-circulatory failure leading to cardiac arrest. In non-lethal forms of sulfide exposure, the presence of a circulatory shock is associated with long-term neurological sequelae. Our aim was to clarify the mechanisms of H2S-induced circulatory failure. In anesthetized, paralyzed, and mechanically ventilated rats, cardiac output, arterial pressure and ventricular pressures were determined while NaHS was infused to increase arterial concentration of soluble H2S (CgH2S) from undetectable to levels leading to circulatory failure. Compared to control/saline infusion, blood pressure started to decrease significantly along with a modest drop in peripheral vascular resistance (−19 ± 5 %, P < 0.01), when CgH2S reached about 1 μM. As CgH2S exceeded 2–3 μM, parameters of ventricular contractility diminished with no further reduction in peripheral resistance. Whenever H2S exposure was maintained at a higher level (CgH2S over 7 μM), a severe depression of cardiac contractility was observed, leading to asystole within minutes, but with no evidence of peripheral vasoplegia. The immediate and long-term neurological effects of specifically counteracting sulfide-induced cardiac contractility depression following H2S exposure remain to be investigated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Reiffenstein, R. J., Hulbert, W. C., & Roth, S. H. (1992). Toxicology of hydrogen sulfide. Annual Review of Pharmacology and Toxicology, 32, 109–134.

    Article  PubMed  CAS  Google Scholar 

  2. Arnold, I. M., Dufresne, R. M., Alleyne, B. C., & Stuart, P. J. (1985). Health implication of occupational exposures to hydrogen sulfide. Journal of Occupational and Environmental Medicine, 27, 373–376.

    Article  CAS  Google Scholar 

  3. Bott, E., & Dodd, M. (2013). Suicide by hydrogen sulfide inhalation. American Journal of Forensic Medicine and Pathology, 34, 23–25.

    Article  PubMed  Google Scholar 

  4. Tvedt, B., Skyberg, K., Aaserud, O., Hobbesland, A., & Mathiesen, T. (1991). Brain damage caused by hydrogen sulfide: A follow-up study of six patients. American Journal of Industrial Medicine, 20, 91–101.

    Article  PubMed  CAS  Google Scholar 

  5. Baldelli, R. J., Green, F. H., & Auer, R. N. (1993). Sulfide toxicity: Mechanical ventilation and hypotension determine survival rate and brain necrosis. Journal of Applied Physiology, 75, 1348–1353.

    PubMed  CAS  Google Scholar 

  6. Yang, G., Wu, L., Jiang, B., Yang, W., Qi, J., Cao, K., et al. (2008). H2S as a physiologic vasorelaxant: Hypertension in mice with deletion of cystathionine gamma-lyase. Science, 322, 587–590.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  7. Zhao, W., Zhang, J., Lu, Y., & Wang, R. (2001). The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener. EMBO Journal, 20, 6008–6016.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  8. Hosoki, R., Matsuki, N., & Kimura, H. (1997). The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. Biochemical and Biophysical Research Communications, 237, 527–531.

    Article  PubMed  CAS  Google Scholar 

  9. Klingerman, C. M., Trushin, N., Prokopczyk, B., & Haouzi, P. (2013). H2S concentrations in the arterial blood during H2S administration in relation to its toxicity and effects on breathing. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 305, R630–R638.

    PubMed Central  PubMed  CAS  Google Scholar 

  10. Haouzi, P., Sonobe, T., Torsell-Tubbs, N., Prokopczyk, B., Chenuel, B., & Klingerman, C. M. (2014). In vivo interactions between cobalt or ferric compounds and the pools of sulphide in the blood during and after H2S poisoning. Toxicological Sciences, 141, 493–504.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  11. Zhang, R., Sun, Y., Tsai, H., Tang, C., Jin, H., & Du, J. (2012). Hydrogen sulfide inhibits L-type calcium currents depending upon the protein sulfhydryl state in rat cardiomyocytes. PLoS One, 7, e37073.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Sun, Y. G., Cao, Y. X., Wang, W. W., Ma, S. F., Yao, T., & Zhu, Y. C. (2008). Hydrogen sulphide is an inhibitor of L-type calcium channels and mechanical contraction in rat cardiomyocytes. Cardiovascular Research, 79, 632–641.

    Article  PubMed  CAS  Google Scholar 

  13. Olson, K. R. (2009). Is hydrogen sulfide a circulating “gasotransmitter” in vertebrate blood? Biochimica et Biophysica Acta, 1787, 856–863.

    Article  PubMed  CAS  Google Scholar 

  14. Olson, K. R. (2012). A practical look at the chemistry and biology of hydrogen sulfide. Antioxidants & Redox Signaling, 17, 32–44.

    Article  CAS  Google Scholar 

  15. Szabo, C. (2007). Hydrogen sulphide and its therapeutic potential. Nature Reviews Drug Discovery, 6, 917–935.

    Article  PubMed  CAS  Google Scholar 

  16. Millero, F. J. (1986). The thermodynamics and kinetics of the hydrogen-sulfide system in natural-waters. Marine Chemistry, 18, 121–147.

    Article  CAS  Google Scholar 

  17. Tang, G., Wu, L., Liang, W., & Wang, R. (2005). Direct stimulation of K(ATP) channels by exogenous and endogenous hydrogen sulfide in vascular smooth muscle cells. Molecular Pharmacology, 68, 1757–1764.

    PubMed  CAS  Google Scholar 

  18. Coletta, C., Papapetropoulos, A., Erdelyi, K., Olah, G., Modis, K., Panopoulos, P., et al. (2012). Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation. Proceedings of the National Academy of Sciences of the United States of America, 109, 9161–9166.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Bucci, M., Papapetropoulos, A., Vellecco, V., Zhou, Z., Zaid, A., Giannogonas, P., et al. (2012). CGMP-dependent protein kinase contributes to hydrogen sulfide-stimulated vasorelaxation. PLoS One, 7, e53319.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  20. Timmers, H. J., Rongen, G. A., Karemaker, J. M., Wieling, W., Marres, H. A., & Lenders, J. W. (2004). The role of carotid chemoreceptors in the sympathetic activation by adenosine in humans. Clinical Science, 106, 75–82.

    Article  PubMed  CAS  Google Scholar 

  21. Marshall, J. M. (1994). Peripheral chemoreceptors and cardiovascular regulation. Physiological Reviews, 74, 543–594.

    PubMed  CAS  Google Scholar 

  22. Winder, C. V., & Winder, H. O. (1933). The seat of action of sulfide on pulmonary ventilation. American Journal of Physiology, 105, 337–352.

    Google Scholar 

  23. Haouzi, P. (2012). Ventilatory and metabolic effects of exogenous hydrogen sulfide. Respiratory Physiology & Neurobiology, 184, 170–177.

    Article  CAS  Google Scholar 

  24. Abboud, F. M., & Thames, M. D. (2011). Interaction of cardiovascular reflexes in circulatory control. Comprehensive Physiology, Supplement 8, 675–753.

    Google Scholar 

  25. Ariyaratnam, P., Loubani, M., & Morice, A. H. (2013). Hydrogen sulphide vasodilates human pulmonary arteries: A possible role in pulmonary hypertension? Microvascular Research, 90, 135–137.

    Article  PubMed  CAS  Google Scholar 

  26. Sun, Y., Tang, C. S., Jin, H. F., & Du, J. B. (2011). The vasorelaxing effect of hydrogen sulfide on isolated rat aortic rings versus pulmonary artery rings. Acta Pharmacologica Sinica, 32, 456–464.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  27. Cooper, C. E., & Brown, G. C. (2008). The inhibition of mitochondrial cytochrome oxidase by the gases carbon monoxide, nitric oxide, hydrogen cyanide and hydrogen sulfide: Chemical mechanism and physiological significance. Journal of Bioenergetics and Biomembranes, 40, 533–539.

    Article  PubMed  CAS  Google Scholar 

  28. Eberhardt, M., Dux, M., Namer, B., Miljkovic, J., Cordasic, N., Will, C., et al. (2014). H2S and NO cooperatively regulate vascular tone by activating a neuroendocrine HNO-TRPA1-CGRP signalling pathway. Nature Communications, 5, 4381.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  29. Altaany, Z., Yang, G., & Wang, R. (2013). Crosstalk between hydrogen sulfide and nitric oxide in endothelial cells. Journal of Cellular and Molecular Medicine, 17, 879–888.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  30. Paciullo, C. A., McMahon Horner, D., Hatton, K. W., & Flynn, J. D. (2010). Methylene blue for the treatment of septic shock. Pharmacotherapy, 30, 702–715.

    Article  PubMed  CAS  Google Scholar 

  31. Preiser, J. C., Lejeune, P., Roman, A., Carlier, E., De Backer, D., Leeman, M., et al. (1995). Methylene blue administration in septic shock: A clinical trial. Critical Care Medicine, 23, 259–264.

    Article  PubMed  CAS  Google Scholar 

  32. Zima, A. V., & Blatter, L. A. (2006). Redox regulation of cardiac calcium channels and transporters. Cardiovascular Research, 71, 310–321.

    Article  PubMed  CAS  Google Scholar 

  33. Bouillaud, F., & Blachier, F. (2011). Mitochondria and sulfide: A very old story of poisoning, feeding, and signaling? Antioxidants & Redox Signaling, 15, 379–391.

    Article  CAS  Google Scholar 

  34. Haouzi, P., & Klingerman, C. M. (2013). Fate of intracellular H2S/HS(-) and metallo-proteins. Respiratory Physiology & Neurobiology, 188, 229–230.

    Article  CAS  Google Scholar 

  35. Wintner, E. A., Deckwerth, T. L., Langston, W., Bengtsson, A., Leviten, D., Hill, P., et al. (2010). A monobromobimane-based assay to measure the pharmacokinetic profile of reactive sulphide species in blood. British Journal of Pharmacology, 160, 941–957.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  36. Geng, B., Yang, J., Qi, Y., Zhao, J., Pang, Y., Du, J., & Tang, C. (2004). H2S generated by heart in rat and its effects on cardiac function. Biochemical and Biophysical Research Communications, 313, 362–368.

    Article  PubMed  CAS  Google Scholar 

  37. Khan, A. A., Schuler, M. M., Prior, M. G., Yong, S., Coppock, R. W., Florence, L. Z., & Lillie, L. E. (1990). Effects of hydrogen sulfide exposure on lung mitochondrial respiratory chain enzymes in rats. Toxicology and Applied Pharmacology, 103, 482–490.

    Article  PubMed  CAS  Google Scholar 

  38. Dorman, D. C., Moulin, F. J., McManus, B. E., Mahle, K. C., James, R. A., & Struve, M. F. (2002). Cytochrome oxidase inhibition induced by acute hydrogen sulfide inhalation: Correlation with tissue sulfide concentrations in the rat brain, liver, lung, and nasal epithelium. Toxicological Sciences, 65, 18–25.

    Article  PubMed  CAS  Google Scholar 

  39. Brenneman, K. A., Meleason, D. F., Sar, M., Marshall, M. W., James, R. A., Gross, E. A., et al. (2002). Olfactory mucosal necrosis in male CD rats following acute inhalation exposure to hydrogen sulfide: Reversibility and the possible role of regional metabolism. Toxicologic Pathology, 30, 200–208.

    Article  PubMed  CAS  Google Scholar 

  40. Lopez, A., Prior, M. G., Reiffenstein, R. J., & Goodwin, L. R. (1989). Peracute toxic effects of inhaled hydrogen sulfide and injected sodium hydrosulfide on the lungs of rats. Fundamental and Applied Toxicology, 12, 367–373.

    Article  PubMed  CAS  Google Scholar 

  41. Li, L., Whiteman, M., Guan, Y. Y., Neo, K. L., Cheng, Y., Lee, S. W., et al. (2008). Characterization of a novel, water-soluble hydrogen sulfide-releasing molecule (GYY4137): New insights into the biology of hydrogen sulfide. Circulation, 117, 2351–2360.

    Article  PubMed  CAS  Google Scholar 

  42. Evans, C. L. (1967). The toxicity of hydrogen sulphide and other sulphides. Experimental Physiology, 52, 231–248.

    Article  CAS  Google Scholar 

  43. Mustafa, A. K., Gadalla, M. M., Sen, N., Kim, S., Mu, W., Gazi, S. K., et al. (2009). H2S signals through protein S-sulfhydration. Science signaling, 2, ra72.

    PubMed Central  PubMed  Google Scholar 

  44. Haouzi, P., Chenuel, B., & Sonobe, T. (2015). High-dose hydroxocobalamin administered after H2S exposure counteracts sulfide-poisoning-induced cardiac depression in sheep. Clinical Toxicology, 53, 28–36.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work has been supported in part by the CounterACT Program, National Institutes of Health Office of the Director (NIH OD) and the National Institute of Neurological Disorders and Stroke (NINDS), Grant No. 1R21NS080788-01 and 1R21NS090017-01.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Pennsylvania State University, College of Medicine, 500 University Drive, H041, Hershey, PA, 17033, USA

    Takashi Sonobe & Philippe Haouzi

Authors
  1. Takashi Sonobe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Philippe Haouzi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Philippe Haouzi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sonobe, T., Haouzi, P. Sulfide Intoxication-Induced Circulatory Failure is Mediated by a Depression in Cardiac Contractility. Cardiovasc Toxicol 16, 67–78 (2016). https://doi.org/10.1007/s12012-015-9309-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12012-015-9309-z

Keywords

Search

Navigation