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 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.
Wang
Tsui-Min
TM
Graduate Institute of Medical Science, Taipei Medical University, Taipei, Taiwan.
Luk
Hsiang-Ning
HN
Sheu
Joen-Rong
JR
Wu
Hsiao-Ping
HP
Chiang
Chern-En
CE
D000200:Action Potentials / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D016275:Atrial Function / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D022062:Electrophysiologic Techniques, Cardiac; D006325:Heart Atria / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000139:chemically induced / Q000503:physiopathology; D008839:Microelectrodes; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects; D011667:Pulmonary Veins / Q000378:metabolism* / Q000503:physiopathology; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D013268:Stimulation, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D018377:Neurotransmitter Agents; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents