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 Ba2+, the diastolic slope was only slightly affected by Ni2+ (500 micromol/L), but was significantly suppressed by Cd2+ (200 micromol/L). Ryanodine (2 micromol/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 Ba2+-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.
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 Ba2+, the diastolic slope was only slightly affected by Ni2+ (500 micromol/L), but was significantly suppressed by Cd2+ (200 micromol/L). Ryanodine (2 micromol/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 Ba2+-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.
Authors: Reena Mehra; Katie L Stone; Paul D Varosy; Andrew R Hoffman; Gregory M Marcus; Terri Blackwell; Osama A Ibrahim; Rawan Salem; Susan Redline Journal: Arch Intern Med Date: 2009-06-22