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- W2770847029 abstract "Background: Post-operative atrial fibrillation (poAF) after cardiac surgery is a common condition. Although usually self-limiting, poAF increases length of hospital stay and can cause debilitating strokes. A multifactorial pathophysiology involving triggered activity has been hypothesized, but the underlying cellular and molecular mechanisms are unknown and were the subject of this study. Methods: Multicellular action potentials (APs) were recorded with sharp microelectrodes in right atrial trabeculae obtained from sinus-rhythm patients during open-heart surgery and correlated with subsequent non-poAF (Ctl) or poAF status. Membrane currents (whole-cell voltage clamp) and [Ca 2+ ] i (Fluo-3) were also measured in right atrial cardiomyocytes isolated from Ctl and poAF patient samples. Protein expression was quantified by immunoblot. Results: In poAF, AP duration at 90% repolarization (APD 90 ) was slightly prolonged (Fig A), whereas AP amplitude, upstroke velocity, APD 20 , APD 50, and resting membrane potential (RMP) were unchanged. I Ca,L -triggered [Ca 2+ ] i transient (CaT) amplitude was 37% lower in poAF despite greater Ca 2+ influx via L-type Ca 2+ current (integral I Ca,L ), pointing to sarcoplasmic reticulum (SR) dysfunction (Fig B). Na + -Ca 2+ exchange (NCX) activity was similar in both groups (Fig C). SR Ca 2+ content calculated by integrating NCX current (I NCX ) during caffeine-induced SR Ca 2+ release was decreased by 50% in poAF (Fig C), likely because of smaller expression of SR Ca 2+ -ATPase-2a (SERCA2a) and decreased Ser16-phosphorylation (stronger SERCA2a inhibition) of the SERCA2a regulator phospholamban (PLB, Fig D). Expression of cardiac SR ryanodine receptor (RyR2) was reduced by 56% (Fig D), consistent with the reduced CaT amplitude. Conclusions: PoAF is associated with prolonged APD and impaired SR function. These abnormalities likely result in the Ca 2+ mishandling that predisposes patients to triggered activity underlying poAF." @default.
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- W2770847029 date "2016-11-11" @default.
- W2770847029 modified "2023-09-26" @default.
- W2770847029 title "Abstract 12646: Cellular Mechanisms Underlying Post-operative Atrial Fibrillation in Patients" @default.
- W2770847029 hasPublicationYear "2016" @default.
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