Prolonged transient acidosis during early reperfusion contributes to the cardioprotective effects of postconditioning

Masashi Fujita, Hiroshi Asanuma, Akio Hirata, Masakatsu Wakeno, Hiroyuki Takahama, Hideyuki Sasaki, Jiyoong Kim, Seiji Takashima, Osamu Tsukamoto, Tetsuo Minamino, Yoshiro Shinozaki, Hitonobu Tomoike, Masatsugu Hori, Masafumi Kitakaze

Research output: Contribution to journalArticlepeer-review

87 Citations (Scopus)

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 (NaHCO3) group; four cycles of 1-min reperfusion and 1-min reocclusion with the administration of NaHCO3 (n = 8); and 4) NaHCO3 group; administration of NaHCO3 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 NaHCO3 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 NaHCO3. In conclusion, postconditioning mediates its cardioprotective effects possibly via prolonged transient acidosis during the early reperfusion phase with the activation of Akt and ERK.

Original languageEnglish
Pages (from-to)H2004-H2008
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number4
DOIs
Publication statusPublished - 2007 Apr
Externally publishedYes

Keywords

  • Acidosis
  • Postconditioning
  • Reperfusion
  • Reperfusion injury salvage kinase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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