The NHE inhibitor cariporide significantly improved the recovery of left ventricular developed pressure after ischemia in hearts from type 2 diabetic db/db mice (80.5% vs 42.5%) and reduced cytoplasmic Ca2+ overload.
Does NHE inhibition with cariporide reduce cytoplasmic Ca2+ overload and improve post-ischemic cardiac function in type 2 diabetic db/db mouse hearts?
Inhibition of the Na+/H+ exchanger with cariporide attenuates ischemia-induced cytoplasmic Ca2+ overload and improves post-ischemic functional recovery in type 2 diabetic mouse hearts.
Tasa de eventos absoluta: 80.5% vs 42.5%
valor p: p=<0.01
BACKGROUND: A higher increase in intracellular Na(+) via Na(+)/H(+) exchanger (NHE) during ischemia has been reported in type 2 diabetic mouse hearts. We investigated the role of NHE in inducing changes in cytoplasmic Ca(2+) concentration (Ca(2+)(i)) and alterations in ventricular function during ischemia-reperfusion in type 2 diabetic mouse hearts. METHODS: Hearts from male type 2 diabetic db/db (12-15 weeks old) and age-matched control db/+ mice were subjected to Langendorff perfusion and loaded with 4 μM of the Ca(2+) indicator fura-2. The hearts were exposed to no-flow ischemia for 15 minutes and then reperfused. Ca(2+)(i) was measured by monitoring fura-2 fluorescence at 500 nm (excitation wavelengths of 340 and 380 nm), while left ventricular (LV) pressure was simultaneously measured. RESULTS: db/db hearts exhibited a lower recovery of LV developed pressure than db/+ hearts during reperfusion following ischemia. Diastolic Ca(2+)(i) was increased to a greater level in diabetic hearts than in the control hearts during ischemia and reperfusion. Such an increase in cytoplasmic Ca(2+) overload during ischemia-reperfusion in diabetic hearts was markedly reduced in the presence of the NHE inhibitor cariporide. This was accompanied by a significantly improved recovery of ventricular function on reperfusion, as shown by a lower increase in diastolic pressure and increased recovery of developed pressure. CONCLUSION: NHE plays a key role in enhancing cytoplasmic Ca(2+) overload during ischemia-reperfusion and severely impairing post-ischemic cardiac function in hearts from type 2 diabetic db/db mice.
Anzawa et al. (Sun,) conducted a other in Type 2 diabetes and myocardial ischemia-reperfusion injury (n=34). Cariporide vs. No cariporide was evaluated on Recovery of left ventricular developed pressure (LVDP) at 15 minutes of reperfusion (p=<0.01). The NHE inhibitor cariporide significantly improved the recovery of left ventricular developed pressure after ischemia in hearts from type 2 diabetic db/db mice (80.5% vs 42.5%) and reduced cytoplasmic Ca2+ overload.
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