title: The mitochondria as a target for cardioprotection in acute myocardial ischemia.
abstract: The ischemic heart suffers from nutrient deprivation, lack of oxygen, metabolic acidosis, hyperkalemia and Ca(2+) overload as well as high level of reactive oxygen species (ROS) generation; these risk factors endanger the cardiomyoctes and may cause their demise. Nevertheless, the treatment of acute myocardial infarction includes reperfusion, although it can exacerbate the effects of ischemia since resumption of blood supply to the ischemic myocardium is associated with increased ROS production. In the past 20 years, preconditioning and postconditioning were revealed, directing research efforts at finding pharmacological agents that can mimic these techniques. Soon thereafter, the involvement of several molecular pathways such as the reperfusion injury salvage kinase, the ATP-sensitive K(+) channel, the survivor-activating factor enhancement and the adenosine mono phosphate activated protein kinase pathways were discovered. Further, studies have shown that these pathways convey the adverse effects of ischemia, reperfusion and the combination thereof to the mitochondria, suggesting that the death signals during ischemia and reperfusion are controllable, and can therefore be partially inhibited or even reversed. Hence, the aim of this review is to describe these signaling pathways, the established pre-clinical means to manipulate them, and their current application status in the clinic.
authors.affiliation: The Eliachar Research Laboratory, Western Galilee Medical Center, Nahariya, Israel.
authors.forename: Offir
authors.initials: O
authors.lastname: Ertracht
authors.affiliation: The Department of Physiology and Biophysics, Technion - Israel Institute of Technology, Haifa, Israel; The Rappaport Faculty of Medicine and Research Institute, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Assaf
authors.initials: A
authors.lastname: Malka
authors.affiliation: Division of Cardiology, Western Galilee Medical Center, Nahariya, Israel; The Faculty of Medicine in the Galilee, Bar-Ilan University, Israel.
authors.forename: Shaul
authors.initials: S
authors.lastname: Atar
authors.affiliation: The Department of Physiology and Biophysics, Technion - Israel Institute of Technology, Haifa, Israel; The Rappaport Faculty of Medicine and Research Institute, Technion - Israel Institute of Technology, Haifa, Israel. Electronic address: binah@tx.technion.ac.il.
authors.forename: Ofer
authors.initials: O
authors.lastname: Binah
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D054086:KATP Channels / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D054086:KATP Channels; D009569:Nitric Oxide; D055372:AMP-Activated Protein Kinases
keywords: Biochemical pathways; Ischemia-reperfusion; Mitochondria; Myocardial infarction