BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: IS increases PV and atrial arrhythmogenesis through oxidative stress. They may contribute to the occurrence of AF in CKD patients.
BACKGROUND:Chronic kidney disease (CKD) is associated with a higher incidence of atrial fibrillation (AF) with unclear mechanisms. Indoxyl sulfate (IS) accumulates in CKDpatients. IS increases oxidative stress, which contributes to the genesis of AF. The arrhythmogenic effect of ISis unclear. METHODS: 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. RESULTS: 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. CONCLUSION:IS increases PV and atrial arrhythmogenesis through oxidative stress. They may contribute to the occurrence of AF in CKDpatients.
Authors: Monika Gawałko; Thomas A Agbaedeng; Arnela Saljic; Dominik N Müller; Nicola Wilck; Renate Schnabel; John Penders; Michiel Rienstra; Isabelle van Gelder; Thomas Jespersen; Ulrich Schotten; Harry J G M Crijns; Jonathan M Kalman; Prashanthan Sanders; Stanley Nattel; Dobromir Dobrev; Dominik Linz Journal: Cardiovasc Res Date: 2022-08-24 Impact factor: 13.081
Authors: Yan Chen; Leila R Zelnick; Ke Wang; Andrew N Hoofnagle; Jessica O Becker; Chi-Yuan Hsu; Harold I Feldman; Rupal C Mehta; James P Lash; Sushrut S Waikar; Tariq Shafi; Stephen L Seliger; Michael G Shlipak; Mahboob Rahman; Bryan R Kestenbaum Journal: J Am Soc Nephrol Date: 2020-03-23 Impact factor: 10.121