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.

The aim of the study was to characterize the presence and the distribution of ICCs in human pulmonary veins.

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.

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 mm², with the highest density reaching 14.6 ICCs/3 mm² in a pulmonary vein of a patient with a history of AF. A positive immunostaining of Cajal cells with HCN4 was also demonstrated.

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.