Volume 1 • Issue 3 • 1000115 J Cardiovasc Dis Diagn ISSN: 2329-9517 JCDD, an open access journal Research Article Open Access Iqbal and Garcia, J Cardiovasc Dis Diagn 2013, 1:3 DOI: 10.4172/2329-9517.1000115 Review Article Open Access Keywords: Acute Myocardial Infarction; Clinical trials; Congestive Heart Failure; Percutaneous Coronary Intervention Introduction Morbidity and mortality from chronic coronary artery disease and Acute Myocardial Infarction (AMI) represents a signifcant public health burden in the United States and is the leading cause of death throughout the world [1]. Despite advances on multiple fronts to reduce ischemic injury from AMI such as thrombolytic therapy, primary Percutaneous Coronary Intervention (PCI) and establishment of regional networks for AMI transfer and care, many patients will develop post-AMI Lef Ventricular (LV) dysfunction and Congestive Heart Failure (CHF), which is the leading hospital admission diagnosis in this country [2-6]. Additionally, many patients will also require placement of cardiac defbrillators and bi-ventricular pacemakers highlighting the critical need for identifcation and implementation of novel forms of cardioprotection in the setting of AMI [7-9]. Although the rapid restoration of coronary blood fow is the most efective means of reducing infarct size and preserving lef-ventricular (LV) function, reperfusion may also be associated with further injury to the myocardium and vasculature [10]. Reperfusion injury may increase infarct size to a degree that is similar to the initial ischemic insult by increasing myocyte cell death, activation of apoptosis and promotion of endothelial dysfunction [11-13] (Figure 1). Unfortunately, reducing reperfusion injury replicating methods previously used in animal models has largely been unsuccessful in clinical trials [9]. To date, clinical trials to limit reperfusion injury have targeted many areas including Reactive Oxygen Species (ROS), reductions in calcium overload and Na + - H + exchange inhibitors and the infammation. Reasons for disappointing results in the majority of trials may include the much longer duration of ischemia in humans with AMI compared to animals and failure to deliver the therapy at the immediate onset of reperfusion. Tis point is essential since even a delay of several minutes following reperfusion may render these therapies inefective [14]. Te objective of this review is to summarize current knowledge on myocardial protection through pre- and post-conditioning with emphasis on mechanisms of action and clinical trials. Historical Notes on Myocardial Pre-conditioning Murry and coauthors were the frst to demonstrate the concept of myocardial protection through pre-conditioning (PreC) [15]. Te authors observed that repetitive episodes of ischemia, applied prior to a complete 40-minute duration circumfex artery occlusion, could beget protection (75% reduction in infarct size was reported in this frst experiment) instead of the logically anticipated myocardial damage. Tese authors were also the frst to notice the time-dependence of PreC. *Corresponding author: Santiago Garcia, Assistant Professor of Medicine, One Veterans Drive (111-C), Minneapolis, MN 55417, USA, Tel: 612-467-3670; Fax: 612-727-5668; E-mail: garci205@umn.edu Received June 29, 2013; Accepted July 20, 2013; Published July 27, 2013 Citation: Iqbal Q, Garcia S (2013) Myocardial Protection through Pre- and Post- Conditioning: A Review of Mechanisms, Clinical Trials and Future Directions. J Cardiovasc Dis Diagn 1: 115. doi:10.4172/2329-9517.1000115 Copyright: © 2013 Iqbal Q, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Although the benefts of pre- and post-conditioning have been extensively documented in animal models, the translation from “bench to bedside” has been disappointing and slow. In this article we review the mechanisms of action and potential pharmacological targets of pre and post-conditioning, discuss key fndings of clinical trials and provide a summary of ongoing clinical trials. Myocardial protection before planned myocardial ischemia and during reperfusion has the potential to signifcantly impact clinical outcomes. Industry and government support are critical to validate the fndings of small-scale studies to the broader population with cardiovascular disease. Myocardial Protection through Pre- and Post-Conditioning: A Review of Mechanisms, Clinical Trials and Future Directions Qamar Iqbal 1 and Santiago Garcia 2,3 * 1 Department of Medicine, HealthEast Care System, St. Paul, MN, USA 2 Department of Medicine, Minneapolis VA Healthcare System, Minneapolis, MN, USA 3 Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA Figure 1: Quantifcation of reperfusion and ischemic injury in relationship to fnal infarct size in acute myocardial infarction. Reproduced from N Engl J Med 2007; 357: 1121-1135 with permission of Massachusetts medical Society. Journal of Cardiovascular Diseases & Diagnosis J o u r n a l o f C a r d i o v a s c u l a r D i s e a s e s & D i a g n o s i s ISSN: 2329-9517