Objective: The role of microtubules in ischemic preconditioning (PC) was investigated in isolated perfused rabbit hearts.
Methods: Myocardial infarction was induced by 30-min global ischemia and 2-h reperfusion, and infarct size was expressed as a percentage of the left ventricle (%IS/LV). Using separate groups of rabbits, ventricular biopsies were taken before and after PC for determination of protein kinase C (PKC) translocation and p38-mitogen-activated protein kinase (p38MAP kinase) activation. To depolymerize microtubules, we used two structurally different agents, colchicine (50 muM) and nocodazole (1 muM).
Results: PC with two cycles of 5-min ischemia/5-min reperfusion significantly reduced infarct size from 60.1 +/- 5.0% to 20.0 +/- 5.0%. Although neither colchicine nor nocodazole modified infarct size in nonpreconditioned hearts, these agents abolished the infarct size-limiting effects of PC (%IS/LV=56.1 +/- 6.0% and 53.5 +/- 2.5%, respectively). Colchicine prevented translocation of PKC-epsilon and p38MAP kinase activation by PC. PKC translocation by infusion of 1-oleyl-2-acetyl-sn-glycerol in nonischemic hearts was also prevented by colchicine.
Conclusion: Microtubules play a crucial role in the development of anti-infarct tolerance by PC as a mechanism supporting translocation of activated PKC. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.