Abstract
BackgroundAtrial fibrillation (AF) is often preceded by underlying cardiac diseases causing ventricular pressure overload.ObjectiveIt was our aim to investigate the progression of atrial remodeling in a small animal model of ventricular pressure overload and its association with induction of AF.MethodsMale mice were subjected to transverse aortic constriction (TAC) or sham operation. After four or eight weeks, echocardiographic measurements and hemodynamic measurements were made and AF induction was tested. The hearts were either fixed in formalin or ventricles and atria were separated, weighed and snap-frozen for RNA analysis.ResultsFour weeks of pressure overload induced ventricular hypertrophy and minor changes in the atria. After eight weeks a significant reduction in left ventricular function occurred, associated with significant atrial remodeling including increased atrial weight, a trend towards an increased left atrial cell diameter, atrial dilatation and increased expression of markers of hypertrophy and inflammation. Histologically, no fibrosis was found in the left atrium. But atrial gene expression related to fibrosis was increased. Minor changes related to electrical remodeling were observed. AF inducibility was not different between the groups. Left ventricular end diastolic pressures were increased and correlated with the severity of atrial remodeling but not with AF induction.ConclusionPermanent ventricular pressure overload by TAC induced atrial remodeling, including hypertrophy, dilatation and inflammation. The extent of atrial remodeling was directly related to LVEDP and not duration of TAC per se.
Highlights
Atrial fibrillation (AF) is the most common cardiac arrhythmia
AF is often preceded by conditions associated with ventricular pressure overload, atrial remodeling in this situation has not been investigated extensively, especially not in small animal models [10,11,12]
The transverse aortic constriction model (TAC) is a well established model in rodents, with left ventricular hypertrophy progressing to heart failure [17,18]
Summary
Male mice were subjected to transverse aortic constriction (TAC) or sham operation. After four or eight weeks, echocardiographic measurements and hemodynamic measurements were made and AF induction was tested. The hearts were either fixed in formalin or ventricles and atria were separated, weighed and snap-frozen for RNA analysis
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