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- W1998446737 abstract "Heart failure (HF) patients are known to have increased susceptibility to ventricular arrhythmias. Although abnormal intracellular calcium (Ca) cycling is recognized as an important contributor to the pathogenesis of ventricular arrhythmias, the specific cellular and molecular mechanisms of these arrhythmias remain to be defined. The objective of present study was to investigate the sub-cellular mechanisms of Ca-dependent arrhythmia using time-resolved Ca imaging in the cytosolic and sarcoplasmic reticulum (SR) luminal compartments and the patch-clamp technique in a canine model of tachypacing-induced HF. When rhythmically paced in the presence of the β-adrenergic agonist, isoproterenol, HF myocytes displayed a higher frequency of diastolic Ca waves than control myocytes. In both HF and control myocytes, diastolic Ca waves occurred when [Ca]SR rose above a certain threshold level, which was significantly lower in HF than in control myocytes. Ca signaling refractoriness determined as the time delay between systolic SR Ca depletion and Ca wave initiation was significantly reduced in HF myocytes. Electrical and Ca signaling activities exhibited several distinct potentially arrhythmogenic patterns, including: 1) delayed afterdepolarizations and extrasystolic action potentials (APs) linked to diastolic spontaneous Ca waves; 2) intermittent prolongations of AP duration associated with pre-systolic spontaneous Ca waves and post-systolic triggered Ca waves; and 3) disorganized release uncoupled from myocyte electrical activity. The level of [Ca]SR threshold for spontaneous Ca waves and the time to attain the threshold during the pacing cycle were critical in determining the type of arrhythmogenic abnormality. These experiments suggest a common mechanistic framework for apparently different arrhythmic phenotypes and provide new insights into the relationship between abnormal Ca release and arrhythmogenesis in HF." @default.
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- W1998446737 date "2010-01-01" @default.
- W1998446737 modified "2023-09-30" @default.
- W1998446737 title "Abnormal Intra-Store Calcium Handling and Arrhythmogenesis in Heart Failure" @default.
- W1998446737 doi "https://doi.org/10.1016/j.bpj.2009.12.591" @default.
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