title: Protection of the myocardial cell during ischemia.
abstract: Prevention of myocardial necrosis in acute coronary syndromes is the immediate goal of therapy. Decreasing myocardial oxygen needs is of marginal value. Improving oxygen delivery by mechanical or thrombolytic reperfusion is more successful but still leaves much to be desired in terms of time to reperfusion before damage occurs due to reperfusion itself. During ischemia, there is a metabolic mismatch between glycolysis and glucose oxidation that results in accumulation of hydrogen ions, which, in turn, activates the Na+/H+ exchange system (NHE-1), leading to Na+ and Ca2+ overload and cell death. Blocking NHE-1 is a new strategy designed to prevent or delay cell death. Cariporide, a potent inhibitor of the NHE-1 system, is currently under investigation. Other agents under investigation are designed to modify proton generation, modify proton effects, and attenuate necrosis progression. Also under study are agents designed to mediate preconditioning (adenosine agonists and adenosine triphosphate-sensitive potassium channel openers). Other approaches to minimize cell injury include use of antioxidants and free-radical scavengers, complement inhibitors, selectin blockers, and glycoprotein (GP) IIb/IIIa antagonists.
authors.affiliation: Department of Medicine, Montreal Heart Institute and University of Montreal, Quebec, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Théroux
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects*; D006146:Guanidines / Q000627:therapeutic use*; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D010101:Oxygen Consumption / Q000187:drug effects; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000627:therapeutic use*
chemical_list: D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide