Mechanisms by which adenosine restores conduction in dormant canine pulmonary veins.
BACKGROUND
Adenosine acutely reconnects pulmonary veins (PVs) after radiofrequency application, revealing "dormant conduction" and identifying PVs at risk of reconnection, but the underlying mechanisms are unknown.


RESULTS
Canine PV and left-atrial (LA) action potentials were recorded with standard microelectrodes and ionic currents with whole-cell patch clamp before and after adenosine perfusion. PVs were isolated with radiofrequency current application in coronary-perfused LA-PV preparations. Adenosine abbreviated action potential duration similarly in PV and LA but significantly hyperpolarized resting potential (by 3.9+/-0.5%; P<0.05) and increased dV/dt(max) (by 34+/-10%) only in PV. Increased dV/dt(max) was not due to direct effects on I(Na), which was reduced similarly by adenosine in LA and PV but correlated with resting-potential hyperpolarization (r=0.80). Adenosine induced larger inward rectifier K(+)current (I(KAdo)) in PV (eg, -2.28+/-0.04 pA/pF; -100 mV) versus LA (-1.28+/-0.16 pA/pF). Radiofrequency ablation isolated PVs by depolarizing resting potential to voltages positive to -60 mV. Adenosine restored conduction in 5 dormant PVs, which had significantly more negative resting potentials (-57+/-6 mV) versus nondormant (-46+/-5 mV, n=6; P<0.001) before adenosine. Adenosine hyperpolarized both, but more negative resting-potential values after adenosine in dormant PVs (-66+/-6 mV versus -56+/-6 mV in nondormant; P<0.001) were sufficient to restore excitability. Adenosine effects on resting potential and conduction reversed on washout. Spontaneous recovery of conduction occurring in dormant PVs after 30 to 60 minutes was predicted by the adenosine response.


CONCLUSIONS
Adenosine selectively hyperpolarizes canine PVs by increasing I(KAdo). PVs with dormant conduction show less radiofrequency-induced depolarization than nondormant veins, allowing adenosine-induced hyperpolarization to restore excitability by removing voltage-dependent I(Na) inactivation and explaining the restoration of conduction in dormant PVs.
5000 Belanger St East, Montreal, Quebec H1T 1C8, Canada.
Tomás
T
Datino
Laurent
L
Macle
Xiao-Yan
XY
Qi
Ange
A
Maguy
Philippe
P
Comtois
Denis
D
Chartier
Peter G
PG
Guerra
Angel
A
Arenal
Francisco
F
Fernández-Avilés
Stanley
S
Nattel
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D017115:Catheter Ablation; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D008839:Microelectrodes; D023421:Models, Animal; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000378:metabolism; D011667:Pulmonary Veins / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013997:Time Factors
D024661:Potassium Channels, Inwardly Rectifying; D018047:Receptors, Purinergic P1; D000241:Adenosine