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Mechanisms by which adenosine restores conduction in dormant canine pulmonary veins.
Circulation. 2010 Mar 02; 121(8):963-72.Circ

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.

Authors+Show Affiliations

5000 Belanger St East, Montreal, Quebec H1T 1C8, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20159830

Citation

Datino, Tomás, et al. "Mechanisms By Which Adenosine Restores Conduction in Dormant Canine Pulmonary Veins." Circulation, vol. 121, no. 8, 2010, pp. 963-72.
Datino T, Macle L, Qi XY, et al. Mechanisms by which adenosine restores conduction in dormant canine pulmonary veins. Circulation. 2010;121(8):963-72.
Datino, T., Macle, L., Qi, X. Y., Maguy, A., Comtois, P., Chartier, D., Guerra, P. G., Arenal, A., Fernández-Avilés, F., & Nattel, S. (2010). Mechanisms by which adenosine restores conduction in dormant canine pulmonary veins. Circulation, 121(8), 963-72. https://doi.org/10.1161/CIRCULATIONAHA.109.893107
Datino T, et al. Mechanisms By Which Adenosine Restores Conduction in Dormant Canine Pulmonary Veins. Circulation. 2010 Mar 2;121(8):963-72. PubMed PMID: 20159830.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms by which adenosine restores conduction in dormant canine pulmonary veins. AU - Datino,Tomás, AU - Macle,Laurent, AU - Qi,Xiao-Yan, AU - Maguy,Ange, AU - Comtois,Philippe, AU - Chartier,Denis, AU - Guerra,Peter G, AU - Arenal,Angel, AU - Fernández-Avilés,Francisco, AU - Nattel,Stanley, Y1 - 2010/02/16/ PY - 2010/2/18/entrez PY - 2010/2/18/pubmed PY - 2010/4/1/medline SP - 963 EP - 72 JF - Circulation JO - Circulation VL - 121 IS - 8 N2 - 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. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/20159830/Mechanisms_by_which_adenosine_restores_conduction_in_dormant_canine_pulmonary_veins_ L2 - https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.109.893107?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -