title: Pre-treatment with the Na+/H+ exchange inhibitor cariporide delays cell-to-cell electrical uncoupling during myocardial ischemia.
abstract: OBJECTIVE
  Inhibition of Na(+)-H(+) exchange (NHE) delays the onset of myocardial rigor contracture during ischemia. The aim of this study was to analyse the effects of NHE inhibition on cell-to-cell electrical uncoupling during myocardial ischemia/reperfusion.
  
  
  METHODS
  Twenty-six isolated rat hearts and 23 in situ porcine hearts were submitted to no-flow ischemia followed by reperfusion, with or without pre-treatment with cariporide (7 microM in rats and 3 mg/kg in pigs). Ischemic rigor and hypercontracture, conduction velocity and myocardial electrical impedance were monitored.
  
  
  RESULTS
  Pre-treatment with cariporide delayed ATP depletion (luminescence assay in rat myocardium) and onset of rigor contracture (tension recordings or ultrasonic crystals) during ischemia both in rat and pig hearts (P<0.05). In addition, cariporide delayed the onset of sharp changes in tissue resistivity and phase angle in impedance recordings (four-electrode probes) from 10+/-1 to 13+/-1 min (P<0.001) in rat hearts, and from 22+/-1 to 38+/-2 min (P<0.001) in pigs. Blockade of impulse propagation (transmembrane action potentials in rat hearts) was also markedly delayed by cariporide (from 14+/-1 to 20+/-1 min, P<0.001). Reperfusion-induced LDH release in rat hearts and infarct size in pigs were markedly reduced by pre-treatment with cariporide.
  
  
  CONCLUSIONS
  Inhibition of NHE with cariporide slows the progression of ischemic injury during myocardial ischemia, and delays the onset of cell-to-cell electrical uncoupling.
authors.affiliation: Laboratorio de Investigación Cardiovascular, Servicio de Cardiología, Hospitals Vall d'Hebron, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez-Sinovas
authors.forename: David
authors.initials: D
authors.lastname: García-Dorado
authors.forename: Ferran
authors.initials: F
authors.lastname: Padilla
authors.forename: Javier
authors.initials: J
authors.lastname: Inserte
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Barrabés
authors.forename: Marisol
authors.initials: M
authors.lastname: Ruiz-Meana
authors.forename: Luis
authors.initials: L
authors.lastname: Agulló
authors.forename: Jordi
authors.initials: J
authors.lastname: Soler-Soler
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D006146:Guanidines / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000494:pharmacology*; D013552:Swine
chemical_list: D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase