Effects of chronic atrial fibrillation on gap junction distribution in human and rat atria

OBJECTIVES To elucidate the structural basis for the electrophysiologic rem odeling induced by chronic atrial fibrillation (AF), we investigated connex in40 and connexin43 (Cx40 and Cx43) expression and distribution in atria of patients with and without chronic AF and in an animal model of AF with add itional electrophysiologic investigation of anisotropy (ratio of longitudin al and transverse velocities). BACKGROUND Atrial fibrillation is a common arrhythmia that has a tendency t o become persistent. Since gap junctions provide the syncytial properties o f the atrium, changes in expression and distribution of intercellular conne ctions may accompany the chronification of AF. METHODS Atrial tissues isolated from 12 patients in normal sinus rhythm at the time of cardiac surgery and from 12 patients with chronic AF were proce ssed for immunohistology and immunoblotting for the detection of the gap ju nction proteins. The functional study of the cardiac tissue anisotropy was performed in rat atria in which AF was induced by 24 h of rapid pacing (10 Hz). RESULTS Immunoblotting revealed that AF did not induce any significant chan ge in Cx43 content in human atria. In contrast, a 2.7-fold increase in expr ession of Cx40 was observed in AF. Immunohistologic analysis indicated that AF resulted in an increase in the immunostaining of both connexins at the lateral membrane of human atrial cells. A similar spatial redistribution of the Cx43 signal was seen in isolated rat atria with experimentally-induced AF. In addition, AF in rat atria resulted in decreased anisotropy with sli ghtly enhanced transverse conduction velocity. CONCLUSIONS This experimental study showed that AF is accompanied by spatia l remodeling of gap junctions that might induce changes in the biophysical properties of the tissue. (C) 2001 by the American College of Cardiology