Enhanced prevention on postoperative atrial fibrillation by using anti-inflammatory biodegradable drug patch

Postoperative atrial fibrillation (POAF) is the most prevalent form of secondary atrial fibrillation and increases the risk of adverse cardiovascular outcomes, such as stroke, heart failure and increased mortality. Herein, we designed an andrographolide (Andr)-loaded degradable polymer patch to deliver the drug directly to the atrial tissue for prevention of POAF. The sterile pericarditis (SP) rat model was adopted for highly relationship to clinical practice. The patch-released Andr effectively reduced the incidence of atrial fibrillation from 90 to 20%, and alleviated local atrial inflammation and oxidative stress <i>in vivo</i>, by using electrophysiological detection and histological analysis such as immunofluorescence, western blot and PCR. In HL-1 cells, we found the use of Andr-loaded patch could strongly inhibit the cell death, reactive oxygen species (ROS) generation and mitochondrial injury caused by LPS. Meanwhile, the use of Andr-loaded patch could effectively inhibited macrophages polarize towards M1. Mechanistically, we verified that the regulation of the cytoplasm and mitochondria Ca²⁺ and ROS dynamic balance was quite important both <i>in vivo</i> and <i>in vitro</i>. Our strategy proved by regulating the inflammatory microenvironment, ROS balance and Ca²⁺ homeostasis and the Andr-loaded atrial patch was effective for POAF in the SP rat model. The electrical signal of atrial stromal reentry in the case of this model was successfully mined, and the results of calcium channel were basically consistent with that of electrical signal channel. In addition, we have reported the infiltration and polarization of local inflammatory cells in the atrial of POAF at the tissue section level. Our study served as a new inspiration for the treatment of arrhythmic diseases and other ROS- and Ca²⁺- associated local illnesses.