title: Electrical plasticity and cardioprotection in myocardial ischemia--role of selective sodium channel blockers.
abstract: The concept of electrical protection of the ischemic myocardium is in constant evolution and has recently been supported by experimental and clinical studies. Historically, antiplatelet agents, angiotensin-converting enzyme inhibitors, β-blockers, and statins have been all proposed as drugs conferring anti-ischemic cardioprotection. This was supported by the evidence consistently indicating that all these drugs were capable of reducing mortality and the risk of repeat myocardial infarction. The electrical plasticity paradigm is, however, a novel concept that depicts the benefits of improved sodium channel blockade with drugs such as ranolazine and cariporide. Although it has been hypothesized that the protective role of ranolazine depends on decreased fatty acid β-oxidation affecting preconditioning, we speculate against such a hypothesis, because inhibition of β-oxidation requires higher concentrations of the drug, above the therapeutic range. Rather, we discuss the key role of calcium overload reduction through inhibition of the late sodium current (I(Na)). Mechanisms driving cardioprotection involve the block of a cascade of complex ionic exchanges that can result in intracellular acidosis, excess cytosolic calcium, myocardial cellular dysfunction, and eventually cell injury and death. In this review we discuss the studies that demonstrate how electrical plasticity through sodium channel blockers can promote cardioprotection against ischemia in coronary heart disease.
authors.affiliation: Texas Heart Institute and St. Luke's Episcopal Hospital, Department of adult cardiiology, Houston, Texas, USA. rmadonna@unich.it
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Madonna
authors.forename: Cihan
authors.initials: C
authors.lastname: Cevik
authors.forename: Maher
authors.initials: M
authors.lastname: Nasser
mesh_terms: D000200:Action Potentials; D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004734:Energy Metabolism / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D026941:Sodium Channel Blockers / Q000627:therapeutic use*
chemical_list: D002316:Cardiotonic Agents; D026941:Sodium Channel Blockers