Plasma Hydrogen Sulfide Is Positively Associated With Post-operative Survival in Patients Undergoing Surgical Revascularization

Alban Longchamp; Michael R MacArthur; Kaspar Trocha; Janine Ganahl; Charlotte G Mann; Peter Kip; William W King; Gaurav Sharma; Ming Tao; Sarah J Mitchell; Tamás Ditrói; Jie Yang; Péter Nagy; C Keith Ozaki; Christopher Hine; James R Mitchell

doi:10.3389/fcvm.2021.750926

Plasma Hydrogen Sulfide Is Positively Associated With Post-operative Survival in Patients Undergoing Surgical Revascularization

Front Cardiovasc Med. 2021 Oct 25:8:750926. doi: 10.3389/fcvm.2021.750926. eCollection 2021.

Authors

Alban Longchamp^{1

2}, Michael R MacArthur³, Kaspar Trocha⁴, Janine Ganahl⁵, Charlotte G Mann³, Peter Kip⁴, William W King⁴, Gaurav Sharma⁴, Ming Tao⁴, Sarah J Mitchell³, Tamás Ditrói⁶, Jie Yang⁷, Péter Nagy^{6

8}, C Keith Ozaki⁴, Christopher Hine⁷, James R Mitchell³

Affiliations

¹ Department of Vascular Surgery, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
² Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.
³ Department of Health Sciences and Technology, Eidgenössische Technische Hochschule (ETH) Zürich, Zurich, Switzerland.
⁴ Department of Surgery and the Heart and Vascular Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
⁵ Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Boston, MA, United States.
⁶ Department of Molecular Immunology and Toxicology, National Institute of Oncology, Budapest, Hungary.
⁷ Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, United States.
⁸ Department of Anatomy and Histology, University of Veterinary Medicine, Budapest, Hungary.

Abstract

Objective: Hydrogen sulfide (H₂S) is a gaseous signaling molecule and redox factor important for cardiovascular function. Deficiencies in its production or bioavailability are implicated in atherosclerotic disease. However, it is unknown if circulating H₂S levels differ between vasculopaths and healthy individuals, and if so, whether H₂S measurements can be used to predict surgical outcomes. Here, we examined: (1) Plasma H₂S levels in patients undergoing vascular surgery and compared these to healthy controls, and (2) the association between H₂S levels and mortality in a cohort of patients undergoing surgical revascularization. Methods: One hundred and fifteen patients undergoing carotid endarterectomy, open lower extremity revascularization or lower leg amputation were enrolled at a single institution. Peripheral blood was also collected from a matched control cohort of 20 patients without peripheral or coronary artery disease. Plasma H₂S production capacity and sulfide concentration were measured using the lead acetate and monobromobimane methods, respectively. Results: Plasma H₂S production capacity and plasma sulfide concentrations were reduced in patients with PAD (p < 0.001, p = 0.013, respectively). Patients that underwent surgical revascularization were divided into high vs. low H₂S production capacity groups by median split. Patients in the low H₂S production group had increased probability of mortality (p = 0.003). This association was robust to correction for potentially confounding variables using Cox proportional hazard models. Conclusion: Circulating H₂S levels were lower in patients with atherosclerotic disease. Patients undergoing surgical revascularization with lower H₂S production capacity, but not sulfide concentrations, had increased probability of mortality within 36 months post-surgery. This work provides insight on the role H₂S plays as a diagnostic and potential therapeutic for cardiovascular disease.

Keywords: biomarker; hydrogen sulfide; limb ischemia; peripheral artery disease (PAD); surgery.