Abstract 1164: The Causative Role of Na+/H+ Exchanger for Impaired Post-Ischemic Cardiac Function and Exacerbation of Cytoplasmic Ca2+ Overload During Ischemia-Reperfusion in Hearts From Diabetic db/db Mice
Background: We previously reported higher increase in intracellular Na+ (Na+i) via Na+/H+ exchanger (NHE) during ischemia in type 2 diabetic mouse hearts. The role of NHE for the changes in cytoplasmic Ca2+ concentration (Ca2+i) and in left ventricular contractility during ischemia-reperfusion in isolated beating type 2 diabetic mouse hearts was investigated.
Methods: Hearts from male diabetic db/db (12–15 weeks old) and age matched control db/+ mice were Langendorff perfused and were loaded with 4μM fura-2 (n=9, respectively). The hearts were exposed to no-flow ischemia for 15 min and then reperfused. Ca2+i was measured by monitoring the ratio of 500nm fluorescence excited at 340 and 380nm while left ventricular (LV) pressure was simultaneously measured.
Results: db/db hearts exhibited lower recovery in LV developed pressure compared with that in db/+ (42.5±3.8% vs 81.2±3.0%, p<0.01). When db/db hearts were pre-treated with NHE inhibitor cariporide (n=8, respectively), the recovery was similar to that of db/+ pre-treated with cariporide (80.5±5.2% vs 86.1±4.2%, p=NS). The diastolic Ca2+i in db/db increased clearly higher at end ischemia (56.0±7.2% vs 15.0±2.6%, p<0.01) and after reperfusion (40.0±8.5% vs 14.2±4.3%, p<0.05) compared with that in db/+. Cariporide attenuated those at end ischemia (20.8±4.1% vs 14.1±3.6%, p=NS) and after reperfusion (15.0±5.2% vs 11.0±4.5%, p=NS) in db/db and db/+ identically.
Conclusions: These results indicate that severely impaired post-ischemic cardiac function in diabetic db/db mouse hearts is correlated to the exacerbation of cytoplasmic Ca2+ overload following higher Na+i increase via NHE during ischemia-reperfusion.