| First Author | Anzawa R | Year | 2006 |
| Journal | Diabetologia | Volume | 49 |
| Issue | 3 | Pages | 598-606 |
| PubMed ID | 16425033 | Mgi Jnum | J:107891 |
| Mgi Id | MGI:3622491 | Doi | 10.1007/s00125-005-0091-5 |
| Citation | Anzawa R, et al. (2006) Intracellular sodium increase and susceptibility to ischaemia in hearts from type 2 diabetic db/db mice. Diabetologia 49(3):598-606 |
| abstractText | AIMS/HYPOTHESIS: An important determinant of sensitivity to ischaemia is altered ion homeostasis, especially disturbances in intracellular Na(+) [Formula: see text] 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[Formula: see text] 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 [Formula: see text] 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 [Formula: see text] plays a causative role in the enhanced sensitivity to ischaemia observed in db/db diabetic hearts. |
