Altered Atrial Cytosolic Calcium Handling Contributes to the Development of Postoperative Atrial Fibrillation
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Altered Atrial Cytosolic Calcium Handling Contributes to the Development of Postoperative Atrial Fibrillation. / Fakuade, Funsho E; Steckmeister, Vanessa; Seibertz, Fitzwilliam; Gronwald, Judith; Kestel, Stefanie; Menzel, Julia; Pronto, Julius Ryan D; Taha, Karim; Haghighi, Fereshteh; Kensah, George; Pearman, Charles M; Wiedmann, Felix; Teske, Arco J; Schmidt, Constanze; Dibb, Katharine M; El-Essawi, Aschraf; Danner, Bernhard C; Baraki, Hassina; Schwappach, Blanche; Kutschka, Ingo; Mason, Fleur E; Voigt, Niels.
In: CARDIOVASC RES, Vol. 117, No. 7, 16.06.2021, p. 1790-1801.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Altered Atrial Cytosolic Calcium Handling Contributes to the Development of Postoperative Atrial Fibrillation
AU - Fakuade, Funsho E
AU - Steckmeister, Vanessa
AU - Seibertz, Fitzwilliam
AU - Gronwald, Judith
AU - Kestel, Stefanie
AU - Menzel, Julia
AU - Pronto, Julius Ryan D
AU - Taha, Karim
AU - Haghighi, Fereshteh
AU - Kensah, George
AU - Pearman, Charles M
AU - Wiedmann, Felix
AU - Teske, Arco J
AU - Schmidt, Constanze
AU - Dibb, Katharine M
AU - El-Essawi, Aschraf
AU - Danner, Bernhard C
AU - Baraki, Hassina
AU - Schwappach, Blanche
AU - Kutschka, Ingo
AU - Mason, Fleur E
AU - Voigt, Niels
N1 - © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.
PY - 2021/6/16
Y1 - 2021/6/16
N2 - AIMS : Atrial fibrillation (AF) is a commonly occurring arrhythmia after cardiac surgery (postoperative AF, poAF) and is associated with poorer outcomes. Considering that reduced atrial contractile function is a predictor of poAF and that Ca2+ plays an important role in both excitation-contraction coupling and atrial arrhythmogenesis, this study aims to test whether alterations of intracellular Ca2+ handling contribute to impaired atrial contractility and to the arrhythmogenic substrate predisposing patients to poAF.METHODS AND RESULTS : Right atrial appendages were obtained from patients in sinus rhythm undergoing open-heart surgery. Cardiomyocytes were investigated by simultaneous measurement of [Ca2+]i and action potentials (APs, patch-clamp). Patients were followed-up for 6 days to identify those with and without poAF. Speckle-tracking analysis of preoperative echocardiography revealed reduced left atrial contraction strain in poAF patients. At the time of surgery, cellular Ca2+ transients (CaTs) and the sarcoplasmic reticulum (SR) Ca2+ content were smaller in the poAF group. CaT decay was slower in poAF, but the decay of caffeine-induced Ca2+ transients was unaltered, suggesting preserved sodium-calcium exchanger function. In agreement, western blots revealed reduced SERCA2a expression in poAF patients but unaltered phospholamban expression/phosphorylation. Computational modelling indicated that reduced SERCA activity promotes occurrence of CaT and AP alternans. Indeed, alternans of CaT and AP occurred more often and at lower stimulation frequencies in atrial myocytes from poAF patients. Resting membrane potential and AP duration were comparable between both groups at various pacing frequencies (0.25-8 Hz).CONCLUSIONS : Biochemical, functional, and modelling data implicate reduced SERCA-mediated Ca2+ reuptake into the SR as a major contributor to impaired preoperative atrial contractile function and to the pre-existing arrhythmogenic substrate in patients developing poAF.
AB - AIMS : Atrial fibrillation (AF) is a commonly occurring arrhythmia after cardiac surgery (postoperative AF, poAF) and is associated with poorer outcomes. Considering that reduced atrial contractile function is a predictor of poAF and that Ca2+ plays an important role in both excitation-contraction coupling and atrial arrhythmogenesis, this study aims to test whether alterations of intracellular Ca2+ handling contribute to impaired atrial contractility and to the arrhythmogenic substrate predisposing patients to poAF.METHODS AND RESULTS : Right atrial appendages were obtained from patients in sinus rhythm undergoing open-heart surgery. Cardiomyocytes were investigated by simultaneous measurement of [Ca2+]i and action potentials (APs, patch-clamp). Patients were followed-up for 6 days to identify those with and without poAF. Speckle-tracking analysis of preoperative echocardiography revealed reduced left atrial contraction strain in poAF patients. At the time of surgery, cellular Ca2+ transients (CaTs) and the sarcoplasmic reticulum (SR) Ca2+ content were smaller in the poAF group. CaT decay was slower in poAF, but the decay of caffeine-induced Ca2+ transients was unaltered, suggesting preserved sodium-calcium exchanger function. In agreement, western blots revealed reduced SERCA2a expression in poAF patients but unaltered phospholamban expression/phosphorylation. Computational modelling indicated that reduced SERCA activity promotes occurrence of CaT and AP alternans. Indeed, alternans of CaT and AP occurred more often and at lower stimulation frequencies in atrial myocytes from poAF patients. Resting membrane potential and AP duration were comparable between both groups at various pacing frequencies (0.25-8 Hz).CONCLUSIONS : Biochemical, functional, and modelling data implicate reduced SERCA-mediated Ca2+ reuptake into the SR as a major contributor to impaired preoperative atrial contractile function and to the pre-existing arrhythmogenic substrate in patients developing poAF.
U2 - 10.1093/cvr/cvaa162
DO - 10.1093/cvr/cvaa162
M3 - SCORING: Journal article
C2 - 32520995
VL - 117
SP - 1790
EP - 1801
JO - CARDIOVASC RES
JF - CARDIOVASC RES
SN - 0008-6363
IS - 7
ER -