Cardioprotective effects of hydrogen sulfide

Gábor Szabó, Gábor Veres, Tamás Radovits, Domokos Ger, Katalin Módis, Christiane Miesel-Gröschel, Ferenc Horkay, Matthias Karck, Csaba Szabó

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86 Scopus citations

Abstract

The gaseous mediator hydrogen sulfide (H 2S) is synthesized mainly by cystathionine γ-lyase in the heart and plays a role in the regulation of cardiovascular homeostasis. Here we first overview the state of the art in the literature on the cardioprotective effects of H 2S in various models of cardiac injury. Subsequently, we present original data showing the beneficial effects of parenteral administration of a donor of H 2S on myocardial and endothelial function during reperfusion in a canine experimental model of cardiopulmonary bypass. Overview of the literature demonstrates that various formulations of H 2S exert cardioprotective effects in cultured cells, isolated hearts and various rodent and large animal models of regional or global myocardial ischemia and heart failure. In addition, the production of H 2S plays a role in myocardial pre- and post-conditioning responses. The pathways implicated in the cardioprotective action of H 2S are multiple and involve K ATP channels, regulation of mitochondrial respiration, and regulation of cytoprotective genes such as Nrf-2. In the experimental part of the current article, we demonstrate the cardioprotective effects of H 2S in a canine model of cardiopulmonary bypass surgery. Anesthetized dogs were subjected hypothermic cardiopulmonary bypass with 60 min of hypothermic cardiac arrest in the presence of either saline (control, n = 8), or H 2S infusion (1 mg/kg/h for 2 h). Left ventricular hemodynamic variables (via combined pressure - volume-conductance catheter) as well as coronary blood flow, endothelium-dependent vasodilatation to acetylcholine and endothelium- independent vasodilatation to sodium nitroprusside were measured at baseline and after 60 min of reperfusion. Ex vivo vascular function and high-energy phosphate contents were also measured. H 2S led to a significantly better recovery of preload recruitable stroke work (p < 0.05) after 60 min of reperfusion. Coronary blood flow was also significantly higher in the H 2S group (p < 0.05). While the vasodilatory response to sodium nitroprusside was similar in both groups, acetylcholine resulted in a significantly higher increase in coronary blood flow in the H 2S-treated group (p < 0.05) both in vivo and ex vivo. Furthermore, high-energy phosphate contents were better preserved in the H 2S group. Additionally, the cytoprotective effects of H 2S were confirmed also using in vitro cell culture experiments in H9c2 cardiac myocytes exposed to hypoxia and reoxygenation or to the cytotoxic oxidant hydrogen peroxide. Thus, therapeutic administration of H 2S exerts cardioprotective effects in a variety of experimental models, including a significant improvement of the recovery of myocardial and endothelial function in a canine model of cardiopulmonary bypass with hypothermic cardiac arrest.

Original languageEnglish (US)
Pages (from-to)201-210
Number of pages10
JournalNitric Oxide - Biology and Chemistry
Volume25
Issue number2
DOIs
StatePublished - Aug 1 2011

Keywords

  • Cardiac function
  • Cardiopulmonary bypass
  • Hydrogen sulfide
  • Ischemia/reperfusion
  • Myocardial protection
  • Vascular reactivity

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cancer Research

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  • Cite this

    Szabó, G., Veres, G., Radovits, T., Ger, D., Módis, K., Miesel-Gröschel, C., Horkay, F., Karck, M., & Szabó, C. (2011). Cardioprotective effects of hydrogen sulfide. Nitric Oxide - Biology and Chemistry, 25(2), 201-210. https://doi.org/10.1016/j.niox.2010.11.001