Increased extracellular collagen matrix in myocardial sleeves of pulmonary veins: An additional mechanism facilitating repetitive rapid activities in chronic pacing-induced sustained atrial fibrillation

Introduction: Cell uncoupling due to fibrosis or increased extracellular collagen matrix (ECM) affects the formation of ectopic focal activity. Whether or not the increase of ECM also exists in the pulmonary veins (PVs) with rapid atrial pacing is unknown. We sought to test the hypothesis that in chronic atrial pacing dogs with sustained atrial fibrillation (AF), the amount of ECM was increased in both atria and the PVs. Methods and Results: We induced sustained AF in dogs by rapid atrial pacing. Computerized mapping techniques were used to map both atria and the PVs. We also used histological assessment to quantify the amount of ECM. After 118 +/- 24 days of rapid atrial pacing, sustained AF was induced in 7 dogs. Repetitive rapid activities (RRAs) either continuously or intermittently arose from the PVs during sustained AF. Histological study shows that there was no fibrosis in both atrial free walls and the PVs. However, the amount of ECM was increased in these regions. The mean ECM surface area fraction at each region in the dogs with sustained AF was all significantly higher compared to the corresponding region in normal dogs. Similarly, the heterogeneity of the ECM surface area fraction at each region in the dogs with sustained AF was also all significantly higher compared to normal dogs. Conclusions: In chronic atrial pacing-induced sustained AF, structural remodeling (i.e., inhomogeneous increase of ECM) also involves the PVs. Reduced coupling of the myocytes in the PV due to histological changes may provide an additional mechanism facilitating RRAs.