Am J Cardiovasc Dis 2013;3(4):180-196

Review Article
Mechanisms of load dependency of myocardial ischemia reperfusion injury

Mahmood S Mozaffari, Jun Yao Liu, Worku Abebe, Babak Baban

Department of Oral Biology, College of Dental Medicine, Georgia Regents University, Augusta, Georgia 30912, USA

Received July 26, 2013; Accepted October 18, 2013; Epub November 1, 2013; Published November 15, 2013

Abstract: Coronary artery disease and associated ischemic heart disease are prevalent disorders worldwide. Further,
systemic hypertension is common and markedly increases the risk for heart disease. A common denominator of systemic
hypertension of various etiologies is increased myocardial load/mechanical stress. Thus, it is likely that high
pressure/mechanical stress attenuates the contribution of cardioprotective but accentuates the contribution of cardiotoxic
pathways thereby exacerbating the outcome of an ischemia reperfusion insult to the heart. Critical events which contribute
to cardiomyocyte injury in the ischemic-reperfused heart include cellular calcium overload and generation of reactive
oxygen/nitrogen species which, in turn, promote the opening of the mitochondrial permeability transition pore, an important
event in cell death. Increasing evidence also indicates that the myocardium is capable of mounting a robust inflammatory
response which contributes importantly to tissue injury. On the other hand, cardioprotective maneuvers of ischemic
preconditioning and postconditioning have led to identification of complex web of signaling pathways (e.g., reperfusion
injury salvage kinase) which ultimately converge on the mitochondria to exert cytoprotection. The present review is intended
to briefly describe mechanisms of cardiac ischemia reperfusion injury followed by a discussion of our work focused on
how pressure/mechanical stress modulates endogenous cardiotoxic and cardioprotective mechanisms to ultimately
exacerbate ischemia reperfusion injury. (AJCD1307005).

Keywords: Heart, ischemia-reperfusion, pressure, calcium overload, oxidative/nitrosative stress, signaling mechanisms,
inflammation, stem cells

Address correspondence to: Dr. Mahmood S Mozaffari, Department of Oral Biology, CL-2134, College of Dental Medicine,
Georgia Regents University, Augusta, Georgia 30912-1128, USA. Tel: 706-721-3163; Fax: 706-721-6252; E-mail:
Mmozaffa@gru.edu
AJCD Copyright © 2011-present, All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711, USA