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Articles by A Maguy
Total Records ( 2 ) for A Maguy
  T Datino , L Macle , X. Y Qi , A Maguy , P Comtois , D Chartier , P. G Guerra , A Arenal , F Fernandez Aviles and S. Nattel

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/dtmax (by 34±10%) only in PV. Increased dV/dtmax was not due to direct effects on INa, 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 (IKAdo) 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 IKAdo. PVs with dormant conduction show less radiofrequency-induced depolarization than nondormant veins, allowing adenosine-induced hyperpolarization to restore excitability by removing voltage-dependent INa inactivation and explaining the restoration of conduction in dormant PVs.

  R Wakili , Y. H Yeh , X Yan Qi , M Greiser , D Chartier , K Nishida , A Maguy , L. R Villeneuve , P Boknik , N Voigt , J Krysiak , S Kaab , U Ravens , W. A Linke , G. J. M Stienen , Y Shi , J. C Tardif , U Schotten , D Dobrev and S. Nattel

Atrial fibrillation impairs atrial contractility, inducing atrial stunning that promotes thromboembolic stroke. Action potential (AP)-prolonging drugs are reported to normalize atrial hypocontractility caused by atrial tachycardia remodeling (ATR). Here, we addressed the role of AP duration (APD) changes in ATR-induced hypocontractility.

Methods and Results—

ATR (7-day tachypacing) decreased APD (perforated patch recording) by 50%, atrial contractility (echocardiography, cardiomyocyte video edge detection), and [Ca2+]i transients. ATR AP waveforms suppressed [Ca2+]i transients and cell shortening of control cardiomyocytes; whereas control AP waveforms improved [Ca2+]i transients and cell shortening in ATR cells. However, ATR cardiomyocytes clamped with the same control AP waveform had 60% smaller [Ca2+]i transients and cell shortening than control cells. We therefore sought additional mechanisms of contractile impairment. Whole-cell voltage clamp revealed reduced ICaL; ICaL inhibition superimposed on ATR APs further suppressed [Ca2+]i transients in control cells. Confocal microscopy indicated ATR-impaired propagation of the Ca2+ release signal to the cell center in association with loss of t-tubular structures. Myofilament function studies in skinned permeabilized cardiomyocytes showed altered Ca2+ sensitivity and force redevelopment in ATR, possibly due to hypophosphorylation of myosin-binding protein C and myosin light-chain protein 2a (immunoblot). Hypophosphorylation was related to multiple phosphorylation system abnormalities where protein kinase A regulatory subunits were downregulated, whereas autophosphorylation and expression of Ca2+-calmodulin-dependent protein kinase II and protein phosphatase 1 activity were enhanced. Recovery of [Ca2+]i transients and cell shortening occurred in parallel after ATR cessation.


Shortening of APD contributes to hypocontractility induced by 1-week ATR but accounts for it only partially. Additional contractility-suppressing mechanisms include ICaL current reduction, impaired subcellular Ca2+ signal transmission, and altered myofilament function associated with abnormal myosin and myosin-associated protein phosphorylation. The complex mechanistic basis of the atrial hypocontractility associated with AF argues for upstream therapeutic targeting rather than interventions directed toward specific downstream pathophysiological derangements.

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