title: Role of Na(+)-H+ exchange on reperfusion related myocardial injury and arrhythmias in an open-chest swine model.
abstract: The inhibition of Na(+)-H+ exchange (NHE) with amiloride analogues in vitro has been shown to prevent reperfusion arrhythmias and additional cell necrosis. Inhibition of intracellular Ca2+ overload via NHE inhibition has been suggested as a mechanism of these protective effects. The aim of this study was to examine whether treatment with amiloride analogues reduces the incidence of reperfusion arrhythmias and limits infarct size in vivo. Open-chest swine were exposed to a 30-minute left anterior descending artery (LAD) occlusion and 180 minutes of reperfusion during atrial pacing at 150 ppm. Intravenous 5-(N,N-dimethyl)-amiloride (AML, 5 micrograms/kg per min) was administered in the treatment group (n = 7) and intravenous saline in the control group (n = 7), starting 10 minutes before coronary occlusion. The infusion was continued during ischemia and reperfusion. The area at risk was defined by monastral blue dye and infarct size by triphenyltetrazolium chloride staining. Limb leads ECG and monophasic action potentials (MAPs) from the epicardium in the ischemic area were recorded. There was no significant difference in the size of the area at risk and hemodynamic parameters between the groups. However, the infarcted area was 0.4% +/- 1.0% of the area at risk in the treatment group, whereas it was 62% +/- 29% in the control group (P < 0.05). Pathological examination (Hematoxylin-eosin and Mallory's phosphotungstic acid-hematoxylin staining) revealed that all of the infarcted area consisted of contraction band necrosis. MAP duration in both groups was significantly shortened during ischemia. After reperfusion, MAP duration in the treatment group recovered earlier than that of control group. However, there was no significant difference in the incidence of ventricular tachyarrhythmia between the groups. Inhibition of NHE with AML prevented reperfusion related cell necrosis in the in vivo swine model, but did not reduce the incidence of ventricular tachyarrhythmia.
authors.affiliation: Third Department of Internal Medicine, Aichi Medical University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fukuta
authors.forename: Y
authors.initials: Y
authors.lastname: Wakida
authors.forename: T
authors.initials: T
authors.lastname: Iwa
authors.forename: M
authors.initials: M
authors.lastname: Uesugi
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000584:Amiloride / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D004396:Coloring Agents; D004195:Disease Models, Animal; D004232:Diuretics / Q000008:administration & dosage / Q000627:therapeutic use*; D004562:Electrocardiography / Q000187:drug effects; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin; D006439:Hemodynamics / Q000187:drug effects; D006859:Hydrogen / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007262:Infusions, Intravenous; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D009336:Necrosis; D010496:Pericardium / Q000187:drug effects; D010772:Phosphotungstic Acid; D012964:Sodium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013552:Swine; D017180:Tachycardia, Ventricular / Q000209:etiology; D013778:Tetrazolium Salts
chemical_list: D004396:Coloring Agents; D004232:Diuretics; D013778:Tetrazolium Salts; D010772:Phosphotungstic Acid; C039465:5-dimethylamiloride; D000584:Amiloride; C009591:triphenyltetrazolium; D006859:Hydrogen; D012964:Sodium; D002118:Calcium; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin