Inducibility of abnormal automaticity and triggered activity in myocardial sleeves of canine pulmonary veins

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 Ba²⁺ 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 Ni²⁺ (500 μmol/L), but was significantly suppressed by Cd²⁺ (200 μmol/L). Ryanodine (2 μmol/L) caused a transient increase, followed by a marked decrease of Ba²⁺-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 Ca²⁺ 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. Ba²⁺-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.