BackgroundWith chronic ischemia after myocardial infarction, the resulting scar tissue result in electrical and structural remodeling vulnerable to an arrhythmogenic substrate. The cholinergic anti‐inflammatory pathway elicited by vagal nerve via α7 nicotinic acetylcholine receptors (α7‐nAChR) can modulate local and systemic inflammatory responses. Here, we aimed to clarify a novel mechanism for the antiarrhythmogenic properties of vagal nerve during the ischemic cardiomyopathy (ICM).Methods and ResultsLeft anterior descending artery of adult male Sprague‐Dawley rats was ligated for 4 weeks to develop ICM. Western blot revealed that eliciting the cholinergic anti‐inflammatory pathway by nicotine treatment showed a significant reduction in the amounts of collagens, cytokines, and other inflammatory mediators in the left ventricular infarcted border zone via inhibited NF‐κB activation, whereas it increased the phosphorylated connexin 43. Vagotomy inhibited the anti‐inflammatory, anti‐fibrosis, and anti‐arrhythmogenic effect of nicotine administration. And immunohistochemistry confirmed that the nicotine administration‐induced increase of connexin 43 was located in intercellular junctions. Furthermore nicotine treatment suppressed NF‐κB activation in lipopolysaccharide‐stimulated RAW264.7 cells, and α‐bungarotoxin (an α7‐nAChR selective antagonist) partly inhibited the nicotine‐treatment effect. In addition, 4‐week nicotine administration slightly improved the cardiac function, increased cardiac parasympathetic tone, decreased the prolonged QTc, and decreased the arrhythmia score of programmed electric stimulation‐induced ventricular arrhythmia.ConclusionsEliciting the cholinergic anti‐inflammatory pathway exerts anti‐arrhythmogenic effects against ICM‐induced ventricular arrhythmia accompanied by downregulation of cytokines, downgenerating of collagens, decrease in sympathetic/parasympathetic ratio, and prevention of the loss of phosphorylated connexin 43 during ICM. Our findings may suggest a promising therapy for the generation of ICM‐induced ventricular arrhythmia by eliciting the cholinergic anti‐inflammatory pathway.

Summary Aims To investigate whether there exists a cardio‐protective effect of Fasudil, a selective Rho kinase (ROCK) inhibitor, in an experimental murine model of acute viral myocarditis. Methods Male BALB/c mice were randomly assigned to three groups: control, myocarditis treated with placebo and myocarditis treated with Fasudil (n = 40 animals per group). Myocarditis was established by intraperitoneal injection with coxsackievirus B3 (CVB3). Twenty‐four hours after infection, Fasudil was intraperitoneally administered for 14 consecutive days. Twenty mice were randomly selected from each group to monitor a 14‐day survival rate. On day 7 and day 14, eight surviving mice from each group were sacrificed and their hearts and blood were obtained to perform serological and histological examinations. Expression of ROCKs, IL‐17, IL‐1b, TNFα, RORgt, and Foxp3 were quantified with RT‐PCR. Plasma levels of TNF alpha, IL‐1 beta, and IL‐17 were measured by ELISA. In addition, protein levels of IL‐17 and ROCK2 in cardiac tissues were analyzed with Western blot. Results Fasudil treatment significantly increased survival, attenuated myocardial necrotic lesions, reduced CVB3 replication and expression of ROCK2 and IL‐17 in the infected hearts. This treatment also imposed a T‐cell subpopulation shift, from Th17 to Treg, in cardiac tissues. Conclusions ROCK pathway inhibition was cardio‐protective in viral myocarditis with increased survival, decreased viral replication, and inflammatory response. These findings suggest that Fasudil might be a potential therapeutic agent for patients with viral myocarditis.

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This study was to explore the application and effect of three-dimensional (3D) images of the esophagus in the treatment of atrial septal defect (ASD) combined with tricuspid regurgitation (TR) surgery under the processing of marching cubes (MC) image reconstruction algorithm. The MC image reconstruction algorithm was improved as the optimized MC image reconstruction algorithm. 100 patients who had successfully undergone the ASD combined with TR surgery in the hospital from January 2017 to December 2019 were selected as the research objects and grouped based on size of the defect. The preoperative and postoperative conditions of the patients were analyzed with the MC image reconstruction algorithm. Compared with the traditional MC image algorithm, the optimized MC was advanced with less running time and fewer fixed points ( P < 0.05 ). There were significant differences in TR of all ASD patients after the surgery ( P < 0.05 ), and the TR of all patients showed obvious declines from the 1st day to 30th day after surgery and gradually stabilized from the 3rd month to the 6th month after surgery. Compared with patients with normal pulmonary artery pressure, the amount of TR in patients with elevated pulmonary artery pressure increased significantly, and the difference was statistically significant ( P < 0.05 ). In addition, the improvement of TR after occlusion was correlated with the preoperative ASD of the patient. The optimized MC algorithm had been improved greatly in the number of fixed points and running time. The analysis using the optimized MC algorithm showed that ASD patients generally suffered different degrees of TR, TR increased with the increase of the defect, and good effect could be achieved in surgery of all kinds of ASD patients.