Abstract
Background To study the cellular mechanisms governing cardiac atrial arrhythmias initiated by ectopic focus (or foci) from pulmonary veins (PVs). Methods In the present in vitro study, we applied the conventional microelectrode technique to record intracellular action potentials in PV sleeves from dogs. Results In 80 normal healthy dogs, all action potentials recorded in cardiomyocytes from PV sleeves were fast-response. The pharmacological responses to quinidine, nisoldipine, d-sotalol, 4-aminopyridine, isoproterenol, acetylcholine, and adenosine were characteristic of those in atrial cells. Diastolic depolarization and spontaneous activity could be induced by 1 mmol/L Ba 2+ in all the 22 PV specimens being tested, but only in 3 of 11 of left atrial specimens ( p<0.0001). In the presence of 1 mmol/L Ba 2+, the diastolic slope was only slightly affected by Ni 2+ (500 μmol/L), but was significantly suppressed by Cd 2+ (200 μmol/L). Ryanodine (2 μmol/L) caused a transient increase, followed by a marked decrease of Ba 2+-induced spontaneous activity. Isoproterenol shortened and acetylcholine prolonged the cycle length of the Ba 2+-induced automatic activity. In the presence of isoproterenol, washout of acetylcholine induced a rebound phenomenon, which triggered a short period of spontaneous activity. The results suggest an important role of intracellular cytoplasmic Ca 2+ loading. Under conditions that mimic ischemia/hypoxia, the resting membrane potential depolarized, upstroke of the action potential became depressed and the action potential duration shortened. In the presence of isoproterenol and elevated external K +, spontaneous activity was generated. Conclusions These findings indicate a lack of arrhythmogenic activity in normal healthy PV sleeves. Abnormal automaticity and triggered activity occurred exclusively under simulated pathologic conditions. Ba 2+-induced automaticity was more easily induced in PV than in the left atrium. The same conditions might also favor the genesis of reentry in the in vivo condition.
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