Background: The major determinant of atrial fibrillation (AF) initiation is focal firing within the muscular portion of the pulmonary veins. We hypothesized that interstitial Cajal cells (ICCs), a known type of pacemaker cells, could underlie the pacemaking activity of isolated pulmonary veins.
Objective: The aim of the study was to characterize the presence and the distribution of ICCs in human pulmonary veins.
Methods: Immunohistochemistry was performed on a transversal section of each pulmonary vein of eight adult human hearts obtained at autopsy from January 2005 to December 2005. A history of AF was documented in two of these eight patients. Two immunostainings were performed on successive sections to differentiate ICCs from mast cells (antibody c-kit and antibody AA1). Morphological and distribution analyses were performed manually and automatically. Electron microscopy and immunostaining with HCN4 and smooth muscle alpha-actin antibodies were also used to further characterize Cajal cells.
Results: ICCs were found in the pulmonary vein sections of three of the eight patients and were mainly identified in sections with a thick muscular sleeve. Two of these three patients had a history of AF. The mean distribution density of these cells was 0.6 ICCs/3 mm(2), with the highest density reaching 14.6 ICCs/3 mm(2) in a pulmonary vein of a patient with a history of AF. A positive immunostaining of Cajal cells with HCN4 was also demonstrated.
Conclusions: ICCs may be detected in human pulmonary veins, particularly in patients with AF. Given the electrophysiological attributes of these cells, their role as AF triggers deserve to be more documented.