title: Intracellular sodium increase and susceptibility to ischaemia in hearts from type 2 diabetic db/db mice.
abstract: OBJECTIVE
  An important determinant of sensitivity to ischaemia is altered ion homeostasis, especially disturbances in intracellular Na(+) (Na(i)(+)) handling. As no study has so far investigated this in type 2 diabetes, we examined susceptibility to ischaemia-reperfusion in isolated hearts from diabetic db/db and control db/+ mice and determined whether and to what extent the amount of (Na(i)(+)) increase during a transient period of ischaemia could contribute to functional alterations upon reperfusion.
  
  
  METHODS
  Isovolumic hearts were exposed to 30-min global ischaemia and then reperfused. (23)Na nuclear magnetic resonance (NMR) spectroscopy was used to monitor[Formula: see text] and (31)P NMR spectroscopy to monitor intracellular pH (pH(i)).
  
  
  RESULTS
  A higher duration of ventricular tachycardia and the degeneration of ventricular tachycardia into ventricular fibrillation were observed upon reperfusion in db/db hearts. The recovery of left ventricular developed pressure was reduced. The increase in[Formula: see text] induced by ischaemia was higher in db/db hearts than in control hearts, and the rate of pH(i) recovery was increased during reperfusion. The inhibition of Na(+)/H(+) exchange by cariporide significantly reduced (Na(i)(+)) gain at the end of ischaemia. This was associated with a lower incidence of ventricular tachycardia in both heart groups, and with an inhibition of the degeneration of ventricular tachycardia into ventricular fibrillation in db/db hearts.
  
  
  CONCLUSIONS
  These findings strongly support the hypothesis that increased (Na(i)(+)) plays a causative role in the enhanced sensitivity to ischaemia observed in db/db diabetic hearts.
authors.affiliation: UMR CNRS 8078, Université Paris-Sud XI, Hôpital Marie Lannelongue, 133 avenue de la Résistance, 92350 Le Plessis Robinson, France.
authors.forename: R
authors.initials: R
authors.lastname: Anzawa
authors.forename: M
authors.initials: M
authors.lastname: Bernard
authors.forename: S
authors.initials: S
authors.lastname: Tamareille
authors.forename: D
authors.initials: D
authors.lastname: Baetz
authors.forename: S
authors.initials: S
authors.lastname: Confort-Gouny
authors.forename: J P
authors.initials: JP
authors.lastname: Gascard
authors.forename: P
authors.initials: P
authors.lastname: Cozzone
authors.forename: D
authors.initials: D
authors.lastname: Feuvray
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004198:Disease Susceptibility / Q000378:metabolism / Q000473:pathology; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012964:Sodium / Q000378:metabolism*; D017725:Ventricular Pressure
chemical_list: D012964:Sodium