title: Hemodynamic and metabolic effects of hydrogen sulfide during porcine ischemia/reperfusion injury.
abstract: In awake spontaneously breathing mice, inhaling gaseous hydrogen sulfide (H2S) produced a "suspended animation-like" metabolic status with hypothermia and reduced O2 demand, thus protecting from lethal hypoxia. Murine models may be questioned, however, because due to their large surface area/mass ratio, rodents can rapidly drop their core temperature. Therefore, we investigated whether intravenous H2S (Na2S, sodium sulfide) would induce a comparable metabolic response in anesthetized and mechanically ventilated pigs. Because H2S was reported to improve heart function after myocardial ischemia, we also investigated whether sulfide would influence the noradrenaline responsiveness during reperfusion after aortic occlusion. After 2 h of i.v. sulfide (0.2 mg.kg followed by 2 mg.kg.per h; n=8) or vehicle (n=8), animals underwent 30 minutes of aortic occlusion with nitroglycerine, esmolol, and adenosine-5'-triphosphate adjusted to maintain MAP at 80% to 120% of baseline. During reperfusion, noradrenaline was titrated to keep MAP greater than or equal to 80% of this level. Sulfide reduced heart rate and cardiac output without affecting stroke volume, markedly decreased the time and dose of noradrenaline required to maintain hemodynamic targets, and caused a drop in core temperature concomitant with lower O2 uptake and CO2 production. Although arterial PCO2 and acid-base status were comparable, arterial PO2 was lower in the sulfide group at the end of the experiment. Sulfide attenuated the reperfusion-related hyperlactatemia, although glycemia was higher at the end of the experiment. The parameters of inflammation and oxidative stress did not differ. Intravenous sulfide allowed reducing energy expenditure in an anesthetized large-animal model and improved the noradrenaline responsiveness during reperfusion after aortic occlusion. Investigations are warranted, hence, whether it may also protect other organs after I/R injury.
authors.affiliation: Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Abteilung für Thorax- und Gefäbetachirurgie, Universitätsklinikum, Ulm, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Simon
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giudici
authors.forename: Cuong Nguyen
authors.initials: CN
authors.lastname: Duy
authors.forename: Hubert
authors.initials: H
authors.lastname: Schelzig
authors.forename: Sükrü
authors.initials: S
authors.lastname: Oter
authors.forename: Michael
authors.initials: M
authors.lastname: Gröger
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wachter
authors.forename: Josef
authors.initials: J
authors.lastname: Vogt
authors.forename: Günter
authors.initials: G
authors.lastname: Speit
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabó
authors.forename: Peter
authors.initials: P
authors.lastname: Radermacher
authors.forename: Enrico
authors.initials: E
authors.lastname: Calzia
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000737:chemistry; D006439:Hemodynamics; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007773:Lactates / Q000737:chemistry; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010101:Oxygen Consumption; D015427:Reperfusion Injury; D012769:Shock / Q000473:pathology; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007773:Lactates; D014409:Tumor Necrosis Factor-alpha; D002245:Carbon Dioxide; D005947:Glucose; D006862:Hydrogen Sulfide