부산대학교 도서관

Arrhythmias and sudden cardiac death have a circadian pattern of occurrence in humans. We hypothesized that a circadian pattern of arrhythmias is also present in transgenic mice with cardiac-specific overexpression of tumor necrosis factor alpha, which develop a dilated cardiomyopathy, arrhythmias and heart failure. To test this hypothesis, telemetry monitors were implanted and 24hr, ambulatory ECG was recorded ≥ 5 days later. Animals were maintained on a 12hr light/dark cycle. The incidence of ventricular arrhythmias increased between 3pm and 12am, whereas atrial arrhythmias surged between 4am and 12pm. This circadian pattern of arrhythmias is in excellent agreement with human data (taking into account a 12-hour shift between activity periods in diurnal humans and nocturnal rodents). The molecular mechanisms underlying such circadian patterns of arrhythmias were examined using gene expression analysis and mathematical modeling.