title: Preconditioning tachycardia decreases the activity of the mitochondrial permeability transition pore in the dog heart.
abstract: Cardioprotection by preconditioning is a central issue of current research on heart function. Several reports indicate that preventing the assembly and opening of the mitochondrial permeability transition pore (mPTP) protects the heart against ischemia-reperfusion injury. We have previously reported that brief episodes of tachycardia decrease the infarct size produced by subsequent prolonged occlusion of a coronary artery, indicating that controlled tachycardia is an effective preconditioning manoeuvre. The effects of preconditioning tachycardia on mPTP activity have not been reported. Therefore, in this work we investigated if preconditioning tachycardia protects against calcium-induced mitochondrial swelling, a measure of mPTP activity. We found that tachycardia decreased by 2.5-fold the rate of mitochondrial calcium-induced swelling, a factor that presumably contributes to the cardioprotective effects of tachycardia. The oxidative status of the cell increased after tachycardia, as evidenced by the decrease in the cellular and mitochondrial GSH/GSSG ratio. We also observed increased S-glutathionylation of cyclophilin-D, an essential mPTP component, after tachycardia. This reversible redox modification of cyclophilin-D may account, al least in part, for the decreased mPTP activity produced by preconditioning tachycardia.
authors.affiliation: Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago 8389100, Chile. gisanchez@med.uchile.cl
authors.forename: Gina
authors.initials: G
authors.lastname: Sánchez
authors.forename: Carolina
authors.initials: C
authors.lastname: Fernández
authors.forename: Luis
authors.initials: L
authors.lastname: Montecinos
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Domenech
authors.forename: Paulina
authors.initials: P
authors.lastname: Donoso
mesh_terms: D000818:Animals; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism; D004285:Dogs; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006339:Heart Rate; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008929:Mitochondria, Heart / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D005082:Physical Exertion
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D021983:Cyclophilins; D005978:Glutathione; D019803:Glutathione Disulfide