Dose dependent effects of intramyocardial injection of human extracellular vesicles (EVs) on cardiac electrophysiology and atrial fibrillation inducibility in a model of rat sterile pericarditis. (A) Increasing doses of EVs or vehicle control were injected into the atria of middle-age female Sprague-Dawley rats at the time of talc application. A sham control group was included to demonstrate background inducibility. Three days after surgery, all rats underwent invasive electrophysiological testing prior to sacrifice for histological and molecular characterization. (B) Effect of EV treatment on the probability of inducing AF after burst pacing. A two-sided Chi square test was performed with no penalty for multiple comparisons. *P<0.05 vs. talc + vehicle. #P<0.05 vs. sham. (C) Effect of pericarditis and EV treatment on the duration of the longest AF episode recorded. Data is displayed using a logarithmic abscissa and was analyzed using Kruskal-Wallis testing for multiple comparisons. #P<0.05 vs. sham. (D) Effect of pericarditis and EV treatment on electrocardiographic and electrophysiological function. One-way ANOVA with individual-mean comparisons by Šídák's multiple comparisons test. *P<0.05 vs. talc + vehicle. #P<0.05 vs. sham. AF, Atrial fibrillation; EPS, electrophysiological study; EV, extracellular vesicles; veh, vehicle.