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- W1988286020 abstract "Dantrolene is known as a therapeutic agent for malignant hyperthermia. We previously reported that the agent corrects defective inter-domain interactions within RyR2 in failing hearts induced by rapid RV pacing canine model. Here, we investigated effect of the agent on arrhythmia, using pressure-overloaded heart failure model (transverse aortic constriction: TAC model). Pressure-overload to 12 weeks old mice was induced by TAC using a 27-gauge needle. All analysis was done at the after 8-10 weeks from TAC/sham operation. The survival ratio of our TAC mouse at 8 weeks after TAC operation was 32%. In baseline ECG analysis, ventricular premature concentration were observed in TAC. Lethal arrhythmias such as ventricular tachycardia, and Torsades de pointes were frequently induced by 2mg/kg epinephrine and 120mg/kg caffeine ip administration. In isolated cardiomyocyte, calcium spark frequency (SpF) from sarcoplasmic reticulum(SR) was higher and SR Ca2+ contents (CaCont) was lower in TAC than Sham. In spontaneous [Ca2+] i transient (SCaT) analysis as a measure for diastolic calcium leak from RyR2, TAC cells were much higher SCaT than sham cells (21% vs 7%). With 1uM DAN, SCaT was significantly reduced (14%). DAN might be a novel therapeutic agent for lethal arrhythmia in pressure-overloaded failing heart." @default.
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- W1988286020 date "2014-10-01" @default.
- W1988286020 modified "2023-10-16" @default.
- W1988286020 title "Dantrolene Inhibits Aberrant Ca2+ Release and Arrhythmogenesis in Pressure-overloaded Heart Failure" @default.
- W1988286020 doi "https://doi.org/10.1016/j.cardfail.2014.07.235" @default.
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