Abstract
Left atrial (LA) fibrosis is a major arrhythmogenic substrate for atrial fibrillation (AF). The purpose of this study was to assess whether isoproterenol (ISO) induces LA fibrosis and increases susceptibility to AF, exploring the underlying mechanisms. Male Sprague-Dawley rats were subcutaneously injected ISO once per day for 2 days. Five weeks after injection, the ISO group had higher susceptibility AF and prolonged AF duration compared with the control group. ISO decreased LA conduction velocity (CV) and increased LA conduction heterogeneity. ISO increased fibrosise areas and the protein levels of collagen types I and III in the left atrium. Antifibrosis drug pirfenidone decreased AF occurrence and reduced LA fibrosis in ISO treated rats. ISO injection induced atrial ischemia infarction by increasing heart rate and decreasing diastolic and systolic blood pressures. These findings demonstrated that ISO increases susceptibility to AF by increasing LA fibrosis and LA conduction abnormalities 5 weeks after injection. ISO injection induces atrial ischemic injury is the main cause of fibrosis. Rats with ISO-induced LA fibrosis may be used in further AF research.
Highlights
Atrial fibrillation (AF) is the most common tachyarrhythmia; its incidence increases due to widespread population aging
ISO administration resulted in increased deposition of type I (P< 0.05, Figure 1D) and III (P < 0.05, Figure 1E) collagen in the left atrium
This study showed that: (1) ISO increased atrial fibrillation (AF) inducibility and extended its duration in rats 5 weeks after injection; (2) ISO increased Left atrial (LA) fibrosis and LA conduction heterogeneity in rats 5 weeks after injection; (3) ISO injection induced atrial ischemic infarction by increasing the heart rate and decreasing coronary flow due to a significant drop in blood pressure; (4) Antifibrosis drug PFD decreased AF occurrence in rats 5 weeks after ISO injection by reducing LA fibrosis
Summary
Atrial fibrillation (AF) is the most common tachyarrhythmia; its incidence increases due to widespread population aging. AF is the final common endpoint of atrial remodeling caused by a variety of cardiac diseases and conditions, and promotes important remodeling that contributes to the progressive nature of arrhythmia (Tan and Zimetbaum, 2011). Left atrial (LA) fibrosis is considered the key element of atrial remodeling in patients with structural heart disease and persistent AF (Velagapudi et al, 2013). Experimental studies have provided convincing evidence that fibrotic transformation of the left atrium results in the deterioration of atrial conduction, increasing impulse propagation anisotropy and building boundaries that promote re-entry in the atrial wall, which may be directly relevant for the mechanisms responsible for AF maintenance (Heijman et al, 2014; Krul et al, 2015). Single or repeated doses of ISO administered to experimental animals induce fibrosis (Ma et al, 2017), cardiac hypertrophy, and myocardial damage in the left ventricle. The aim of this study was to assess whether ISO could induce LA fibrosis and increase susceptibility to AF and exploring the underlying mechanisms
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