title: Na+/H+ exchange inhibition in hypertrophied myocardium subjected to cardioplegic arrest: an effective cardioprotective approach.
abstract: OBJECTIVE
  This study was designed to assess whether the protective effects of Na+/H+ exchange (NHE) inhibition, which have been largely demonstrated in normal hearts, are also manifest in a more surgically relevant model of hypertrophied myocardium subjected to cardioplegic arrest.
  
  
  METHODS
  Left ventricular hypertrophy was created in 3-week-old rats by coarctation of the ascending thoracic aorta with a hemoclip. Eight weeks later, hearts were excised, isovolumetrically perfused and subjected to 1 h of potassium cardioplegic arrest followed by 2 h of reperfusion. Hearts were allocated to one of the following four groups: sham-operated and aortic banding hearts without any treatment or treated with the NHE inhibitor cariporide (1 micromol/L) given as an additive to cardioplegia and over the first 15 min of reperfusion.
  
  
  RESULTS
  The major effect of cariporide was to reduce ischemic peak contacture and to improve post-ischemic diastolic function in both sham-operated and hypertrophied hearts. Total creatine kinase release over the first 45 min of reperfusion was significantly reduced in hypertrophied hearts treated with cariporide. The endothelium-dependent coronary vasodilation to 5-hydroxytryptamine was observed in all sham-operated hearts before cardiac arrest, however, it was significantly impaired following cardioplegic ischemia and reperfusion. Hypertrophied hearts demonstrated markedly impaired endothelium-dependent and -independent coronary vasodilations during both pre- and post-ischemic period that were not affected by the treatment with cariporide.
  
  
  CONCLUSIONS
  The cardioprotective effects of the NHE inhibitor cariporide are also manifest in hypertrophied myocardium, which supports the potential usefulness of NHE inhibition in the setting of cardiac surgery.
authors.affiliation: Department of Physiology and Heart Centre, Kaunas University of Medicine, Kaunas, Lithuania.
authors.forename: Egidijus
authors.initials: E
authors.lastname: Kevelaitis
authors.forename: Aasim A
authors.initials: AA
authors.lastname: Qureshi
authors.forename: Christian
authors.initials: C
authors.lastname: Mouas
authors.forename: Francoise
authors.initials: F
authors.lastname: Marotte
authors.forename: Sigita
authors.initials: S
authors.lastname: Kevelaitiene
authors.forename: Metin
authors.initials: M
authors.lastname: Avkiran
authors.forename: Philippe
authors.initials: P
authors.lastname: Menasché
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003402:Creatine Kinase / Q000032:analysis; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006324:Heart Arrest, Induced / Q000379:methods*; D006352:Heart Ventricles / Q000503:physiopathology; D009200:Myocardial Contraction / Q000187:drug effects; D015425:Myocardial Reperfusion / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D002316:Cardiotonic Agents; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C069139:growth factor-activatable Na-H exchanger NHE-1; C093373:cariporide; D003402:Creatine Kinase