Contribution of delayed intracellular pH recovery to ischemic postconditioning protection

Antioxid Redox Signal. 2011 Mar 1;14(5):923-39. doi: 10.1089/ars.2010.3312. Epub 2010 Oct 6.

Abstract

Ischemic postconditioning (PoCo) has been proven to be a feasible approach to attenuate reperfusion injury and enhance myocardial salvage in patients with acute myocardial infarction, but its mechanisms have not been completely elucidated yet. Recent studies demonstrate that PoCo may delay the recovery of intracellular pH during initial reperfusion, and that its ability to limit infarct size critically depends on this effect. Prolongation of postischemic intracellular acidosis inhibits hypercontracture, mitochondrial permeability transition, calpain-mediated proteolysis, and gap junction-mediated spread of injury during the first minutes of reflow. This role of prolonged acidosis does not exclude the participation of other pathways in PoCo-induced cardioprotection. On the contrary, it may allow these pathways to act by preventing immediate reperfusion-induced cell death. Moreover, the existence of interactions between intracellular acidosis and endogenous protection signaling cannot be excluded and needs to be investigated. The role of prolonged acidosis in PoCo cardioprotection has important implications in the design of optimal PoCo protocols and in the translation of cardioprotective strategies to patients with on-going myocardial infarction receiving coronary reperfusion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acidosis / metabolism
  • Animals
  • Calpain / metabolism
  • Connexin 43 / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Intracellular Space / metabolism*
  • Ischemia / metabolism
  • Ischemia / prevention & control
  • Ischemic Postconditioning*
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Permeability Transition Pore
  • Myocardial Reperfusion Injury / metabolism*
  • Myocardial Reperfusion Injury / prevention & control*

Substances

  • Connexin 43
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Calpain