title: Prolonged transient acidosis during early reperfusion contributes to the cardioprotective effects of postconditioning.
abstract: We have previously reported that the prolonged transient acidosis during early reperfusion mediates the cardioprotective effects in canine hearts. Recently, postconditioning has been shown to be one of the novel strategies to mediate cardioprotection. We tested the contribution of the prolonged transient acidosis to the cardioprotection of postconditioning. Open-chest anesthetized dogs subjected to 90-min occlusion of the left anterior descending coronary artery and 6-h reperfusion were divided into four groups: 1) control group; no intervention after reperfusion (n = 6); 2) postconditioning (Postcon) group; four cycles of 1-min reperfusion and 1-min reocclusion (n = 7); 3) Postcon + sodium bicarbonate (NaHCO(3)) group; four cycles of 1-min reperfusion and 1-min reocclusion with the administration of NaHCO(3) (n = 8); and 4) NaHCO(3) group; administration of NaHCO(3) without postconditioning (n = 6). Infarct size, the area at risk (AAR), collateral blood flow during ischemia, and pH in coronary venous blood were measured. The phosphorylation of Akt and extracellular signal-regulated kinase (ERK) in ischemic myocardium was assessed by Western blot analysis. Systemic hemodynamic parameters, AAR, and collateral blood flow were not different among the four groups. Postconditioning induced prolonged transient acidosis during the early reperfusion phase. Administration of NaHCO(3) completely abolished the infarct size-limiting effects of postconditioning. Furthermore, the phosphorylation of Akt and ERK in ischemic myocardium induced by postconditioning was also blunted by the cotreatment of NaHCO(3). In conclusion, postconditioning mediates its cardioprotective effects possibly via prolonged transient acidosis during the early reperfusion phase with the activation of Akt and ERK.
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asanuma
authors.forename: Akio
authors.initials: A
authors.lastname: Hirata
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Wakeno
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahama
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Jiyoong
authors.initials: J
authors.lastname: Kim
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashima
authors.forename: Osamu
authors.initials: O
authors.lastname: Tsukamoto
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Shinozaki
authors.forename: Hitonobu
authors.initials: H
authors.lastname: Tomoike
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
mesh_terms: D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D003097:Collateral Circulation / Q000502:physiology; D003326:Coronary Circulation / Q000502:physiology; D004285:Dogs; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D009203:Myocardial Infarction / Q000378:metabolism / Q000517:prevention & control; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000401:mortality / Q000517:prevention & control*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017693:Sodium Bicarbonate / Q000494:pharmacology; D014680:Veins / Q000502:physiology
chemical_list: D017693:Sodium Bicarbonate; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases