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

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.

SUBMITTER: Longchamp A

PROVIDER: S-EPMC8574965 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Circadian rhythms are essential in a myriad of physiological processes to maintain homeostasis, especially the redox homeostasis. However, little is known about whether plasma H2S exhibits the physiological diurnal variation. The present study was performed to investigate the diurnal fluctuations of plasma H2S and explore the potential mechanisms. We found that the plasma H2S of the C57BL/6J mice was significantly higher at 19 o'clock than those at 7 o'clock which was not affected by the blood-collecting sequence and the concentrations of plasma cysteine (a precursor of H2S). No significant differences in mRNA or protein expression of the CSE, CBS, or MPST were observed between 7: 00 and 19: 00. There were also no significant differences in the CSE and CBS activities, while the activities of MPST in tissues were significantly higher at 19 o'clock. After treatment with AOAA (a CBS inhibitor) or PPG (a CSE inhibitor) for 14 days, plasma H2S concentrations at 19 o'clock were still significantly higher than those at 7 o'clock, although they were both significantly decreased as compared with controls. Identical findings were also observed in CSE KO mice. We also found the plasma H2O2 concentrations were significantly higher at 19 o'clock than those at 7 o'clock. However, H2O2 concentrations were significantly decreased at 19 o'clock than those at 7 o'clock when mice were exposed to continuous light for 24 h. Meanwhile, the diurnal fluctuations of plasma H2S levels and MPST activities in tissues were disappeared. After treatment with DTT for 14 days, there was no significant difference in plasma H2O2 concentrations between 7 o'clock and 19 o'clock. Meanwhile, the diurnal fluctuations of plasma H2S levels and MPST activities in tissues were disappeared. Identical findings were also observed in SOD2+/- mice. When heart tissues were incubated with increasing concentrations of H2O2in vitro, H2O2 could dose-dependently increase the activity of MPST within a certain concentration range. In conclusion, our studies revealed that plasma H2S concentration and tissue MPST activity exhibited diurnal fluctuations. Modulated by plasma H2O2 concentration, changes of MPST activity probably led to the diurnal fluctuations of plasma H2S.

Project description:BackgroundRecognising pain in donkeys is challenging because they are stoic.ObjectivesTo identify the responses of donkeys before and after surgical pain.Study designProspective, short-term longitudinal pre- and post-intervention observations.MethodsForty adult donkeys underwent surgical castration after sedation with intravenous (IV) xylazine, induction with guaiphenesin/thiopental IV and maintenance of anaesthesia with isoflurane and local anaesthetic blockade. Four hours after recovery from anaesthesia, flunixin meglumine 1.1 mg/kg, dipyrone 10 mg/kg and morphine 0.2 mg/kg IV were administered. Behavioural responses exhibited by the animals housed in individual stalls were recorded in four 30-min videos: before castration (M0), and 3.5-4.0 hours (M1), 5.5-6.0 hours (M2) and 23.5-24.0 hours after recovery from anaesthesia (M3). To exclude the influence of insects, the behaviour of six apparently pain-free donkeys was compared with and without the presence of faeces and urine in the stall.ResultsWhen compared with presurgical baseline behaviours (M0), after surgery (M1) donkeys raised their pelvic limbs more (P = .003). When compared with M1, after analgesia (M2), the median frequencies of ear movements (44 vs 16; P < .001), head shaking (7 vs 1; P < .001), head turning (5 vs 0; P < .001) and lifting of the both limbs (7 vs 0; P = .008) decreased; feeding (0 vs 29; P < .001) and water intake (0 vs 0, range 0-1 vs 0-7; P = .05) increased. The dirty stall increased tail (53 vs 80; P = .03), head (16 vs 30; P = .03) and ear movements (50 vs 78; P = .04).Main limitationsThe dirty stall and presence of insects possibly contributed to the expression of behaviours unrelated to pain.ConclusionLifting the pelvic limbs was the only specific pain behaviour after castration in donkeys. Analgesia restored appetite and water intake and reduced the frequency of head shaking and turning, ear movement and lifting the limbs. Tail, head and ear movements are unspecific responses related both to pain and a dirty stall, and are confounding factors when pain is assessed in donkeys in the presence of insects.

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

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