Postconditioning via stuttering reperfusion limits myocardial infarct size in rabbit hearts: role of ERK1/2

UMMS Affiliation

Department of Emergency Medicine; Department of Anesthesiology

Publication Date


Document Type



1-Phosphatidylinositol 3-Kinase; Animals; Ischemic Attack, Transient; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Myocardial Infarction; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocardium; Rabbits


Life Sciences | Medicine and Health Sciences


Emerging evidence suggests that restoration of blood flow in a stuttering manner may limit lethal myocardial ischemia-reperfusion injury. However, the mechanisms contributing to this phenomenon, termed postconditioning (post-C), remain poorly defined. Our aim was to test the hypothesis that activation of classic "survival kinases," phosphatidylinositol 3-kinase (PI3-kinase) and/or extracellular signal-regulated kinase (ERK)1/2, may play a role in post-C-induced cardioprotection. In protocol 1, isolated buffer-perfused rabbit hearts underwent 30 min of sustained coronary artery occlusion and were randomized to receive abrupt reperfusion (controls) or four cycles of 30 s of reperfusion and 30 s of reocclusion before full restoration of flow (post-C). Protocol 2 was identical except control and postconditioned hearts received the PI3-kinase inhibitor LY-294002 (protocol 2A) or the ERK1/2 antagonist PD-98059 (protocol 2B) throughout the first 25 min of reperfusion, whereas in protocol 3, myocardial samples were obtained during the early minutes of reflow from additional control, postconditioned, and nonischemic sham hearts for the assessment, by standard immunoblotting, of phospho-Akt (downstream target of PI3-kinase) and phospho-ERK. Protocols 1 and 2 corroborated that infarct size (delineated by tetrazolium staining and expressed as a percent of risk region) was reduced in postconditioned hearts vs. control hearts and also revealed that post-C-induced cardioprotection was maintained despite LY-294002 treatment but was abrogated by PD-98059. These pharmacological data were supported by protocol 3, which showed increased immunoreactivity of phospho-ERK but not phospho-Akt with post-C. Thus our results implicate the involvement of ERK1/2 rather than PI3-kinase/Akt in the reduction of infarct size achieved with post-C.

DOI of Published Version



Am J Physiol Heart Circ Physiol. 2005 Oct;289(4):H1618-26. Epub 2005 Jun 3. Link to article on publisher's site

Journal/Book/Conference Title

American journal of physiology. Heart and circulatory physiology

Related Resources

Link to article in PubMed

PubMed ID