Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF can lead to severe complications, including stroke, myocardial infarction, and sudden death. AF risk factors include pathological aging and conditions such as obesity, diabetes, and hypertension. Clinical data revealed that cardiothoracic and non-cardiothoracic surgeries are also important risk factors for AF. Post-operative AF (POAF) is associated with important public health costs caused by increased hospitalization, frequent emergency room visits, and enhanced healthcare utilization, which altogether lead to a low quality of life for the patients. Hence, POAF is a major clinical challenge, and there is an urgent need for the development of novel therapeutic strategies. Interestingly, evidence from clinical and fundamental research converges to identify cardiac oxidative stress and atrial inflammation as the common denominators of all AF risk factors. Unresolved inflammation is suspected to provoke cardiac fibrosis, which is an important contributor to cardiac arrhythmias and AF. Antioxidant, anti-inflammatory, and pro-resolution strategies may help to combat post-operative cardiac remodeling and POAF. This article aims to review the current scientific evidence supporting the role of inflammation in the pathogenesis of POAF and explore potential novel therapeutic strategies to prevent and mitigate inflammation in the management of AF.

Noreremophilanes are a rare class of cis-hydrindanes produced by genus Ligularia herbaceous plants which are known to exhibit interesting biological activities. We synthesized cis-hydrindanes based on a naturally occurring noreremophilane scaffold using a Diels–Alder/aldol sequence and screened them for multiple biological activities using high-content zebrafish embryonic development assays. We discovered a noreremophilane that has strong anti-angiogenic effects on the developing zebrafish embryos as well as on tumor-induced angiogenesis in a zebrafish xenograft model. We synthesized several derivatives of this class of noreremophilanes and performed structure–activity relationship studies in zebrafish to identify more potent and less toxic analogs of the original structure.

Background: Human in vitro models for atrial fibrillation (AF) are limited. Human-induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCMs) provide a valuable tool to study AF pathophysiology by facilitating in vitro modeling. Objectives: To investigate the effects of an intermittent tachypacing protocol (ITPP) in matured hiPSC-aCMs co-cultured with human atrial cardiac fibroblast (haCF) to mimic AF-associated electroanatomical phenotypes. Methods and Results: hiPSC-aCMs were cultured alone or co-cultured with haCFs at 90/10 and 70/30 ratios. ITPP was applied through field stimulation, and optical mapping assessed action potentials (APs) and calcium transients (CaTs). Immunostaining was performed to quantify pro-fibrotic biomarkers (Collagen III and TGFβ1). ITPP led to increased spontaneous AP frequency (Δ=+31±7%, P<0.0001) and reduced AP duration at 80% repolarization (APD _80% ; Δ=-15±4%, P=0.001). Additionally, the upstroke slope (Δ=-41±11%, P=0.001) and amplitude (dF/F ₀ ; Δ=-51±13%, P100-fold increase in Collagen III expression (P<0.0001), diminished excitability (ΔHz=-61±6%, P<0.0001), prolonged ΔAPD _80% (Δ=+130±10%, P<0.0001), prolonged AP triangulation (ΔAPD _Tri =+143±13%, P<0.0001), reduced upstroke slope (Δ=-66±6%, P<0.0001), conduction block (Δ=-52±18%, P=0.0260), and diminished intracellular calcium handling (upstroke slope Δ=-50±8%, P<0.0001; ΔdF/F0=-34±9%, P=0.0003). Finally, the application of ITPP to the 70/30 co-culture model recapitulated an AF-mediated phenotype (ΔHz=+25±8%, P=0.02; ΔAPD _80% =-16±6%, P=0.01) while introducing conduction block (ΔCV _{100/0 vs 70/30} = −27±15%; P=0.0005). Conclusions: Co-cultures of matured hiPSC-aCMs and haCFs exhibited structural and electrophysiological remodeling, including conduction abnormalities, mirroring key AF mechanisms. This model holds potential for patient-specific therapies and drug discovery. Abstract Figure: Graphical Abstract Human iPSC-Model for Atrial Fibrillation: