title: Antioxidant properties of pyruvate mediate its potentiation of beta-adrenergic inotropism in stunned myocardium.
abstract: This study tested the hypothesis that pyruvate's antioxidant actions, particularly its enhancement of the endogenous glutathione system, mediate its potentiation of beta-adrenergic inotropism in stunned myocardium. Isolated working guinea pig hearts, metabolizing 10 m M glucose and stunned by 45 min of low flow ischemia, were treated with 5 m M pyruvate, 5 m M N-acetylcysteine (NAC) and/or 2 n M isoproterenol beginning 15 min after reperfusion. The antioxidant NAC alone did not increase cardiac power (mJ/min/g wet: 11 +/- 1 in untreated and 15 +/- 2 in NAC treated stunned hearts), but NAC potentiated the increase in power produced by 2 n M isoproterenol (isoproterenol alone: 50+/-10; NAC plus isoproterenol: 133 +/- 24). Addition of NAC doubled cyclic AMP content but lowered cytosolic phosphorylation potential by 32% in isoproterenol-stimulated hearts. Stunning decreased the glutathione antioxidant ratio (GSH/GSSG) by 68%. The antioxidant ratio was completely restored by pyruvate alone or in combination with isoproterenol, but only partially restored by isoproterenol alone. Combining isoproterenol and NAC increased the GSH/GSSG ratio by an additional 36%. The combined treatment of pyruvate and isoproterenol increased the NADPH/NADP(+) ratio almost three-fold, and produced the greatest accumulation of glucose-6-phosphate of any treatment.
  
  
  CONCLUSIONS
  like pyruvate, the antioxidant NAC potentiated beta-adrenergic inotropism of stunned myocardium. Unlike pyruvate, NAC did not increase cellular energy reserves, thus effectively limiting its potentiation of beta-adrenergic stimulation. Thus, pyruvate's potentiation of beta-adrenergic stimulation in stunned myocardium is most likely the result of the combined effects of its antioxidant and energetic properties.
authors.affiliation: Department of Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, Texas 76107-2699, USA.
authors.forename: M I
authors.initials: MI
authors.lastname: Tejero-Taldo
authors.forename: J L
authors.initials: JL
authors.lastname: Caffrey
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: R T
authors.initials: RT
authors.lastname: Mallet
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004357:Drug Synergism; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D019289:Pyruvic Acid / Q000494:pharmacology*
chemical_list: D000318:Adrenergic beta-Agonists; D000975:Antioxidants; D019289:Pyruvic Acid; D005978:Glutathione; D005947:Glucose; D007545:Isoproterenol; D019803:Glutathione Disulfide; D000111:Acetylcysteine