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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Action Potentials, Adrenergic Agonists, Animals, Atrial Fibrillation, Calcium, Calcium Signaling, Cardiac Pacing, Artificial, Dose-Response Relationship, Drug, Electrophysiologic Techniques, Cardiac, Indican, Microelectrodes, Microscopy, Confocal, Microscopy, Fluorescence, Oxidative Stress, Patch-Clamp Techniques, Pulmonary Veins, Rabbits, Sarcoplasmic Reticulum, Time Factors.
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Does the uremic toxin indoxyl sulfate increase pulmonary vein and atrial arrhythmogenesis? Context: Chronic kidney disease (CKD) is associated with a higher incidence of atrial fibrillation (AF) with unclear mechanisms. Indoxyl sulfate (IS) accumulates in CKD patients. IS increases oxidative stress, which contributes to the genesis of AF. The arrhythmogenic effect of IS is unclear. Conventional microelectrodes recorded the action potentials (AP) of isolated rabbit left atrium (LA), right atrium (RA), pulmonary vein (PV), and sinoatrial nodes (SANs) before and after treatment with IS with and without an antioxidant (ascorbic acid). Confocal microscopy with fluorescence and whole-cell patch clamp were used to evaluate intracellular calcium in isolated PV cardiomyocytes with and without IS. Compared to the control, IS induced more PV delayed afterdepolarizations at 0.1, 1, 10, and 100 μM, and induced more PV burst firings at 1, 10, and 100 μM. In contrast, IS (10 and 100 μM) reduced the SAN spontaneous beating rate. IS (100 μM) significantly shortened LA AP durations, but not RA. IS (100 μM)-treated PV cardiomyocytes had a similar calcium transient and sarcoplasmic reticulum calcium content, but a larger calcium leak than control PV cardiomyocytes. Burst pacing and isoproterenol induced a greater AF occurrence (50% vs. 100%; P = 0.009) and a longer AF duration (26 ± 9 vs. 5 ± 3 seconds; P < 0.05) in the LA (n = 8) with IS (100 μM) than without IS. Moreover, ascorbic acid (1 mM) attenuated the effects of IS on the LA, PV, and SANs.
assistant
IS increases PV and atrial arrhythmogenesis through oxidative stress. They may contribute to the occurrence of AF in CKD patients. Final Decision: yes