Intracellular sodium increase and susceptibility to ischaemia in hearts from type 2 diabetic db/db mice.
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.
Anzawa
R
R
UMR CNRS 8078, Université Paris-Sud XI, Hôpital Marie Lannelongue, 133 avenue de la Résistance, 92350 Le Plessis Robinson, France.
Bernard
M
M
Tamareille
S
S
Baetz
D
D
Confort-Gouny
S
S
Gascard
J P
JP
Cozzone
P
P
Feuvray
D
D
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
D012964:Sodium