The effects of mechanical stretch on the automaticity of the guinea pig isolated pulmonary vein preparations were studied in microelectrode experiments. The application of cumulative mechanical stretch to the preparations resulted in increases in the firing rate of spontaneous electrical activity in the myocardial layer. This effect was significantly inhibited by stretch-activated channel blockers such as gadolinium or streptomycin. These results suggest that acute mechanical stretch enhances the automaticity of the guinea pig pulmonary vein myocardium through the opening of the stretch-activated channels.Key words pulmonary vein; spontaneous activity; mechanical stretchThe pulmonary vein contains a myocardial layer which is connected to the left atrial myocardium and is capable of generating spontaneous or triggered action potentials.1) The finding that paroxysmal atrial fibrillation is initiated by trains of rapid discharges from the pulmonary veins, 2) has attracted great attention to the electrical activity of the pulmonary vein myocardium as a key player in the generation and maintenance of atrial fibrillation.3,4) Microelectrode recordings from the myocardial layer have been performed in isolated pulmonary vein preparations from several experimental species, and difference in the firing pattern and frequency was observed.5) Studies including those from our laboratory have clarified that factors such as reduced repolarizing power and elevated intracellular calcium ion are involved in the manifestation of automaticity in the pulmonary vein myocardium.
6)The electrical activity of the pulmonary vein myocardium was also shown to be affected by various neuronal and hormonal factors. However, less information is available concerning the relation between pathological condition and pulmonary vein automaticity.The major risk factors of atrial fibrillation include highblood pressure, heart failure and valvular dysfunction; conditions which are accompanied by mechanical stretch of the heart. Chronic mechanical stretch of the heart induces histological remodeling of the heart such as eccentric hypertrophy and atrial enlargement. 7) Based on the understanding that the pulmonary vein automaticity serves as a trigger for the initiation of atrial fibrillation, it is probable that chronic mechanical stretch of the atrial region including the pulmonary vein increases the tendency to generate atrial fibrillation through long-term enhancement of the automaticity of the pulmonary vein myocardium. On the other hand, mechanical stretch may acutely affect cardiomyocytes through the opening of stretch-activated channels (SACs) and lead to the generation the trigger for atrial fibrillation. It was indeed reported in the isolated sheep heart that acute application of intra-atrial pressure increases the rate and organization of excitation waves emanating from the pulmonary veins.8) It was also reported that the stretch-induced atrial fibrillation in perfused rabbit hearts was successfully inhibited by venom of the tarantula Grammosto...