title: Effect of hydrogen sulfide on myocardial protection in the setting of cardioplegia and cardiopulmonary bypass.
abstract: We investigated the impact of hydrogen sulfide (H(2)S) on myocardium in the setting of cold crystalloid cardioplegia and cardiopulmonary bypass (CP/CPB). Eighteen male Yorkshire pigs underwent 1 h CP/CPB followed by 2 h of reperfusion. Pigs received either: placebo (control, n=9), or H(2)S (as NaHS) as a bolus/infusion (bolus/infusion, n=6), or as an infusion (infusion, n=6). The expression pattern of various myocardial effector pathways was investigated. Coronary microvascular relaxation to endothelium-dependent and -independent agonists was assessed. No differences in cardiac function were observed among groups. Endothelium-dependent microvascular relaxation to adenosine diphosphate was improved in the H(2)S bolus/infusion group only (P<0.05). The expression of hemeoxygenase-1, phospho-heat shock proteins27 and phospho-p44/42 MAPK extracellular signal-regulated kinase were higher in H(2)S-treated groups (P<0.05). Phospho-endothelial nitric oxide synthase (P=0.08), phospho-B-cell lymphoma 2 (P=0.09), and phospho-Bad (P=0.06) all displayed a trend to be higher with H(2)S treatment. The expressions of apoptosis inducing factor and Bcl 2/adenovirus E1B 19 kDa-interacting protein were lower in H(2)S treated groups (P<0.05). The microtubule-associated protein 1 light chain 3 ratio was lower in the infusion group vs. control animals (P<0.05). There was a trend for lower phospho-mammalian target of rapamycin expression in the infusion group (P=0.07), whereas phosphorylation of p70S6K1 was higher with H(2)S-treatment (P=0.09). This study demonstrates that H(2)S-treatment may offer biochemical myocardial protection via attenuation of caspase-independent apoptosis and autophagy in the setting of CP/CPB.
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, DANA 801, Boston, MA 02215, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Osipov
authors.forename: Michael P
authors.initials: MP
authors.lastname: Robich
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.forename: Vincent
authors.initials: V
authors.lastname: Chan
authors.forename: Richard T
authors.initials: RT
authors.lastname: Clements
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Deyo
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabo
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000097:blood; D002470:Cell Survival; D003326:Coronary Circulation / Q000187:drug effects; D006324:Heart Arrest, Induced / Q000009:adverse effects; D006360:Heat-Shock Proteins / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006862:Hydrogen Sulfide / Q000008:administration & dosage* / Q000097:blood; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D017680:Potassium Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013552:Swine; D013997:Time Factors; D019210:Troponin I / Q000097:blood; D014664:Vasodilation / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D002316:Cardiotonic Agents; D006360:Heat-Shock Proteins; D017680:Potassium Compounds; D019210:Troponin I; C018369:potassium cardioplegic solution; D006862:Hydrogen Sulfide