title: Cardiac and metabolic effects of hypothermia and inhaled  hydrogen sulfide in anesthetized and ventilated mice.
abstract: OBJECTIVE
  To test the hypothesis whether inhaled hydrogen sulfide amplifies the effects of deliberate hypothermia during anesthesia and mechanical ventilation as hypothermia is used to provide organ protection after brain trauma or circulatory arrest. Awake mice inhaling hydrogen sulfide exhibit reduced energy expenditure, hypothermia, and bradycardia despite unchanged systolic heart function. In rodents, anesthesia alone causes decreased metabolic rate and thus hypothermia and bradycardia.
  
  
  METHODS
  Prospective, controlled, randomized study.
  
  
  METHODS
  University animal research laboratory.
  
  
  METHODS
  Male C57/B6 mice.
  
  
  METHODS
  After surgical instrumentation (central venous, left ventricular pressure-conductance catheters, ultrasound flow probes on the portal vein and superior mesenteric artery), normo- or hypothermic animals (core temperature = 38 degrees C and 27 degrees C) received either 100 ppm hydrogen sulfide or vehicle over 5 hrs (3 hrs hydrogen sulfide during normothermia).
  
  
  RESULTS
  During normothermia, hydrogen sulfide had no hemodynamic or metabolic effect. With or without hydrogen sulfide, hypothermia decreased blood pressure, heart rate, and cardiac output, whereas stroke volume, ejection fraction, and end-diastolic pressure remained unaffected. Myocardial and hepatic oxidative deoxyribonucleic acid damage (comet assay) and endogenous glucose production (rate of appearance of 1,2,3,4,5,6-13C6-glucose) were similar in all groups. Hypothermia comparably decreased CO2 production with or without inhaled hydrogen sulfide. During hypothermia, inhaled hydrogen sulfide increased the glucose oxidation rate (derived from the expiratory 13CO2/12CO2 ratio). This shift toward preferential carbohydrate utilization coincided with a significantly attenuated responsiveness of hepatic mitochondrial respiration to stimulation with exogenous cytochrome-c-oxidase (high-resolution respirometry).
  
  
  CONCLUSIONS
  In anesthetized and mechanically ventilated mice, inhaled hydrogen sulfide did not amplify the systemic hemodynamic and cardiac effects of hypothermia alone. The increased aerobic glucose oxidation together with the reduced responsiveness of cellular respiration to exogenous cytochrome-c stimulation suggest that, during hypothermia, inhaled hydrogen sulfide improved the yield of mitochondrial respiration, possibly via the maintenance of mitochondrial integrity. Hence, inhaled hydrogen sulfide may offer metabolic benefit during therapeutic hypothermia.
authors.affiliation: Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Klinik für Anästhesiologie, Universitätsklinikum Ulm, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Baumgart
authors.forename: Florian
authors.initials: F
authors.lastname: Wagner
authors.forename: Michael
authors.initials: M
authors.lastname: Gröger
authors.forename: Sandra
authors.initials: S
authors.lastname: Weber
authors.forename: Eberhard
authors.initials: E
authors.lastname: Barth
authors.forename: Josef A
authors.initials: JA
authors.lastname: Vogt
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wachter
authors.forename: Markus
authors.initials: M
authors.lastname: Huber-Lang
authors.forename: Markus W
authors.initials: MW
authors.lastname: Knöferl
authors.forename: Gerd
authors.initials: G
authors.lastname: Albuszies
authors.forename: Michael
authors.initials: M
authors.lastname: Georgieff
authors.forename: Pierre
authors.initials: P
authors.lastname: Asfar
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabó
authors.forename: Enrico
authors.initials: E
authors.lastname: Calzia
authors.forename: Peter
authors.initials: P
authors.lastname: Radermacher
authors.forename: Vladislava
authors.initials: V
authors.lastname: Simkova
mesh_terms: D000280:Administration, Inhalation; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D019069:Cell Respiration / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000494:pharmacology*; D007036:Hypothermia, Induced; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D012121:Respiration, Artificial; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology
chemical_list: D005947:Glucose; D006862:Hydrogen Sulfide