Article

Diabetologia

, Volume 49, Issue 3, pp 598-606

First online:

Intracellular sodium increase and susceptibility to ischaemia in hearts from type 2 diabetic db/db mice

  • R. AnzawaAffiliated withUMR CNRS 8078, Université Paris-Sud XI, Hôpital Marie Lannelongue
  • , M. BernardAffiliated withCNRS UMR 6612-CRMBM, Faculté de Médecine
  • , S. TamareilleAffiliated withUMR CNRS 8078, Université Paris-Sud XI, Hôpital Marie Lannelongue
  • , D. BaetzAffiliated withUMR CNRS 8078, Université Paris-Sud XI, Hôpital Marie Lannelongue
  • , S. Confort-GounyAffiliated withCNRS UMR 6612-CRMBM, Faculté de Médecine
  • , J. P. GascardAffiliated withUMR CNRS 8078, Université Paris-Sud XI, Hôpital Marie Lannelongue
  • , P. CozzoneAffiliated withCNRS UMR 6612-CRMBM, Faculté de Médecine
  • , D. FeuvrayAffiliated withUMR CNRS 8078, Université Paris-Sud XI, Hôpital Marie Lannelongue Email author 

Abstract

Aims/hypothesis

An important determinant of sensitivity to ischaemia is altered ion homeostasis, especially disturbances in intracellular Na+ \({\left( {Na^{ + }_{i} } \right)}\) 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. 23Na nuclear magnetic resonance (NMR) spectroscopy was used to monitor\(Na^{ + }_{i} \) and 31P NMR spectroscopy to monitor intracellular pH (pHi).

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\( Na^{ + }_{i} \) induced by ischaemia was higher in db/db hearts than in control hearts, and the rate of pHi 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/interpretation

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.

Keywords

Cardiac ischaemia–reperfusion Db/db mice Intracellular sodium Type 2 diabetes Ventricular arrhythmias