Document Detail

Intracellular sodium increase and susceptibility to ischaemia in hearts from type 2 diabetic db/db mice.
MedLine Citation:
PMID:  16425033     Owner:  NLM     Status:  MEDLINE    
AIMS/HYPOTHESIS: 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/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.
R Anzawa; M Bernard; S Tamareille; D Baetz; S Confort-Gouny; J P Gascard; P Cozzone; D Feuvray
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-01-20
Journal Detail:
Title:  Diabetologia     Volume:  49     ISSN:  0012-186X     ISO Abbreviation:  Diabetologia     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-02-21     Completed Date:  2006-11-21     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  598-606     Citation Subset:  IM    
UMR CNRS 8078, Université Paris-Sud XI, Hôpital Marie Lannelongue, 133 avenue de la Résistance, 92350 Le Plessis Robinson, France.
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MeSH Terms
Arrhythmias, Cardiac / etiology,  metabolism
Diabetes Mellitus, Type 2 / metabolism*,  pathology,  physiopathology
Disease Susceptibility / metabolism,  pathology
Hydrogen-Ion Concentration
Mice, Inbred C57BL
Myocardial Ischemia / complications,  metabolism*,  pathology,  physiopathology
Sodium / metabolism*
Ventricular Pressure
Reg. No./Substance:

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