Clinical observation and ex vivo studies have established a strong association between
inflammation and postoperative atrial fibrillation (POAF). However, it is unclear
whether the inflammatory phenotype is causally linked to this event or is an epiphenomenon,
and it is not known which inflammatory meditators may increase susceptibility to POAF.
The limitations of available animal models of spontaneous POAF (sPOAF) makes it difficult
to select an experimental system. Here, we provide experimental and clinical evidence
for mechanistic involvement of interleukin-6 (IL-6) in sPOAF. PHASE I: We established
a mouse model of cardiac surgery with nonpaced sPOAF. IL-6 knockout mice were protected from sPOAF compared with wild-type mice. PHASE II: At
48 hours after surgery, the heart was separated into 6 regions and cultured. IL-6
was expressed in all regions, with highest abundance in the left atrium (LA). In PHASE
III, we demonstrated that IL-6 in the LA elicited early profibrotic properties in
atria via the pSTAT3/STAT3 signaling pathway and contributed to sPOAF. PHASE IV: In
a translational prospective clinical study, we demonstrated that humans with POAF
had a higher IL-6 concentration in pericardial drainage (PD). This study provides
preliminary evidence of a causal relationship between IL-6 and POAF in a novel nonpaced
sPOAF mouse model. IL-6 is a crucial prerequisite for eliciting profibrotic properties
in cardiac myocytes via the pSTAT3 pathway during the early postoperative period,
leading to an increased susceptibility to POAF. Measuring IL-6 in PD could be a new
noninvasive biomarker for the clinical prediction of POAF.
Abbreviations:
AI (anti-inflammatory), Cx40 (connexin 40), Cx43 (connexin 43), IL-6 (interleukin-6), KO (knockout), LA (left atrium), LV (left ventricle), NAI (non–anti-inflammatory), OPCAB (off-pump coronary bypass grafting surgery), PC (pericardium), PCF (pericardial fluid), PD (pericardial drainage), POAF (postoperative atrial fibrillation), PV (pulmonary vein), RA (right atrium), RV (right ventricle), sPOAF (spontaneous postoperative atrial fibrillation), ssPOAF (sustained spontaneous postoperative atrial fibrillation), STAT3 (signal transducer and activator of transcription 3), WT (wild type)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: January 16, 2021
Accepted:
January 14,
2021
Received in revised form:
January 12,
2021
Received:
July 9,
2020
Identification
Copyright
© 2021 Published by Elsevier Inc.
