title: Prevention of ischemic rigor contracture during coronary occlusion by inhibition of Na(+)-H+ exchange.
abstract: OBJECTIVE
  To determine the effect of Na(+)-H+ exchange blockade on ischemic rigor contracture and reperfusion-induced hypercontracture.
  
  
  METHODS
  Thirty-six pigs were submitted to 55 min of coronary occlusion and 5 h reperfusion. Myocardial segment length analysis with ultrasonic microcrystals was used to detect ischemic rigor (reduction in passive segment length change) and hypercontracture (reduction in end-diastolic length).
  
  
  RESULTS
  Pretreatment with the new, highly selective Na(+)-H+ exchange inhibitor HOE642 before occlusion reduced ischemic rigor (P < 0.05), attenuated segment shrinkage (P < 0.05) during subsequent reperfusion, dramatically reduced infarct size (P < 0.0001) and attenuated arrhythmias (P < 0.01). Inhibition of Na(+)-H+ exchange only during reperfusion by means of direct intracoronary infusion of HOE642 into the area at risk prevented reperfusion arrhythmias but had no effect on final infarct size, while treatment with intravenous HOE642 immediately before reperfusion had no detectable effects.
  
  
  CONCLUSIONS
  These results indicate that inhibition of Na(+)-H+ exchange during ischemia is necessary to limit myocardial necrosis secondary to transient coronary occlusion, and that this action could by mediated by a protective effect against ischemic contracture. Inhibition of Na(+)-H+ exchange only during reperfusion has a partial and transient beneficial effect, but only when the inhibitor reaches the area at risk before reflow.
authors.affiliation: Servicio de Cardiología, Hospital General Universitari Vall d'Hebron, Barcelona, Spain. dgdorado@ar.vhebron.es
authors.forename: D
authors.initials: D
authors.lastname: Garcia-Dorado
authors.forename: M A
authors.initials: MA
authors.lastname: González
authors.forename: J A
authors.initials: JA
authors.lastname: Barrabés
authors.forename: M
authors.initials: M
authors.lastname: Ruiz-Meana
authors.forename: J
authors.initials: J
authors.lastname: Solares
authors.forename: R M
authors.initials: RM
authors.lastname: Lidon
authors.forename: J
authors.initials: J
authors.lastname: Blanco
authors.forename: Y
authors.initials: Y
authors.lastname: Puigfel
authors.forename: H M
authors.initials: HM
authors.lastname: Piper
authors.forename: J
authors.initials: J
authors.lastname: Soler-Soler
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D006146:Guanidines / Q000627:therapeutic use*; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000648:ultrastructure; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000627:therapeutic use*; D013552:Swine
chemical_list: D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide