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

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.