Mechanisms by which adenosine restores conduction in dormant canine pulmonary veins

Circulation. 2010 Mar 2;121(8):963-72. doi: 10.1161/CIRCULATIONAHA.109.893107. Epub 2010 Feb 16.

Abstract

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.

Methods and 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.

MeSH terms

  • Action Potentials / drug effects*
  • Action Potentials / physiology
  • Adenosine / pharmacology*
  • Animals
  • Catheter Ablation
  • Dogs
  • Heart Conduction System / drug effects*
  • Heart Conduction System / physiology
  • Microelectrodes
  • Models, Animal
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Patch-Clamp Techniques
  • Potassium Channels, Inwardly Rectifying / drug effects
  • Potassium Channels, Inwardly Rectifying / metabolism
  • Pulmonary Veins / drug effects*
  • Pulmonary Veins / metabolism
  • Pulmonary Veins / surgery
  • Receptors, Purinergic P1 / metabolism
  • Time Factors

Substances

  • Potassium Channels, Inwardly Rectifying
  • Receptors, Purinergic P1
  • Adenosine