title: Gaseous hydrogen sulfide protects against myocardial ischemia-reperfusion injury in mice partially independent from hypometabolism.
abstract: BACKGROUND
  Ischemia-reperfusion injury (IRI) is a major cause of cardiac damage following various pathological processes. Gaseous hydrogen sulfide (H2S) is protective during IRI by inducing a hypometabolic state in mice which is associated with anti-apoptotic, anti-inflammatory and antioxidant properties. We investigated whether gaseous H2S administration is protective in cardiac IRI and whether non-hypometabolic concentrations of H2S have similar protective properties.
  
  
  METHODS
  Male C57BL/6 mice received a 0, 10, or 100 ppm H2S-N2 mixture starting 30 minutes prior to ischemia until 5 minutes pre-reperfusion. IRI was inflicted by temporary ligation of the left coronary artery for 30 minutes. High-resolution respirometry equipment was used to assess CO2-production and blood pressure was measured using internal transmitters. The effects of H2S were assessed by histological and molecular analysis.
  
  
  RESULTS
  Treatment with 100 ppm H2S decreased CO2-production by 72%, blood pressure by 14% and heart rate by 25%, while treatment with 10 ppm H2S had no effects. At day 1 of reperfusion 10 ppm H2S showed no effect on necrosis, while treatment with 100 ppm H2S reduced necrosis by 62% (p<0.05). Seven days post-reperfusion, both 10 ppm (p<0.01) and 100 ppm (p<0.05) H2S showed a reduction in fibrosis compared to IRI animals. Both 10 ppm and 100 ppm H2S reduced granulocyte-influx by 43% (p<0.05) and 60% (p<0.001), respectively. At 7 days post-reperfusion both 10 and 100 ppm H2S reduced expression of fibronectin by 63% (p<0.05) and 67% (p<0.01) and ANP by 84% and 63% (p<0.05), respectively.
  
  
  CONCLUSIONS
  Gaseous administration of H2S is protective when administered during a cardiac ischemic insult. Although hypometabolism is restricted to small animals, we now showed that low non-hypometabolic concentrations of H2S also have protective properties in IRI. Since IRI is a frequent cause of myocardial damage during percutaneous coronary intervention and cardiac transplantation, H2S treatment might lead to novel therapeutical modalities.
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. p.m.snijder@umcg.nl
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Snijder
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.forename: Eelke M
authors.initials: EM
authors.lastname: Bos
authors.forename: Joost C
authors.initials: JC
authors.lastname: van den Born
authors.forename: Willem-Peter T
authors.initials: WP
authors.lastname: Ruifrok
authors.forename: Inge
authors.initials: I
authors.lastname: Vreeswijk-Baudoin
authors.forename: Marcory C R F
authors.initials: MC
authors.lastname: van Dijk
authors.forename: Jan-Luuk
authors.initials: JL
authors.lastname: Hillebrands
authors.forename: Henri G D
authors.initials: HG
authors.lastname: Leuvenink
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D002460:Cell Line; D004195:Disease Models, Animal; D015870:Gene Expression; D006339:Heart Rate / Q000187:drug effects; D006862:Hydrogen Sulfide / Q000008:administration & dosage*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D032386:Myoblasts, Cardiac / Q000187:drug effects / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats
chemical_list: D008562:Membrane Glycoproteins; D002245:Carbon Dioxide; D009320:Atrial Natriuretic Factor; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; D006862:Hydrogen Sulfide