Plasma Hydrogen Sulfide Production Capacity is Positively Associated with Post-Operative Survival in Patients Undergoing Surgical Revascularization

ObjectiveHydrogen 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 examine: 1) Plasma H2S levels in patients undergoing vascular surgery and compare these to healthy controls, and 2) Associations between H2S levels and mortality in surgical revascularization patients. Approach & ResultsPatients undergoing carotid endarterectomy, open lower extremity revascularization or leg amputation were enrolled. Peripheral blood was also collected from a matched 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. 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 versus 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. ConclusionsCirculating 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. HIGHLIGHTSO_LIVascular disease patients have higher plasma hydrogen sulfide levels than controls without vascular disease as measured by two distinct methods, the lead acetate hydrogen sulfide release method and the HPLC-based monobromobimane method. C_LIO_LIOnly the lead acetate hydrogen sulfide release method robustly predicts survival after vascular surgery intervention over 35 months of follow up. C_LIO_LIThe lead acetate release method measures non-enzymatic hydrogen sulfide release from plasma which requires iron and is catalyzed by vitamin B6. C_LI