Erschienen in:
01.03.2006 | Article
Intracellular sodium increase and susceptibility to ischaemia in hearts from type 2 diabetic db/db mice
verfasst von:
R. Anzawa, M. Bernard, S. Tamareille, D. Baetz, S. Confort-Gouny, J. P. Gascard, P. Cozzone, D. Feuvray
Erschienen in:
Diabetologia
|
Ausgabe 3/2006
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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.