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Combined blockade of early and late activated atrial potassium currents suppresses atrial fibrillation in a pig model of obstructive apnea.

Abstract：

BACKGROUND:Negative tracheal pressure (NTP) during tracheal obstruction in obstructive apnea increases vagal tone and causes pronounced shortening of the atrial effective refractory period (AERP), thereby perpetuating atrial fibrillation (AF). The role of different atrial potassium channels under those conditions has not been investigated. OBJECTIVE:The purpose of this study was to evaluate the atrial effects of blockade of the late activated potassium current (I(Kr)) by sotalol, of blockade of the early activated potassium currents (I(Kur)/I(to)) by AVE0118, and of the multichannel blocker amiodarone during tracheal occlusions with applied NTP. METHODS:Twenty-one pigs were anesthetized, and an endotracheal tube was placed to apply NTP (up to -100 mbar) comparable to clinically observed obstructive sleep apnea for 2 minutes. Right AERP and AF inducibility were measured transvenously by a monophasic action potential recording and stimulation catheter. RESULTS:Tracheal occlusion with applied NTP caused pronounced AERP shortening. AF was inducible during all NTP maneuvers. Blockade of I(Kr) by sotalol, blockade of I(Kur)/I(to) by AVE0118, and amiodarone did not affect NTP-induced AERP shortening, although they prolonged the AERP during normal breathing. Atropine given after amiodarone completely inhibited NTP-induced AERP shortening. The combined blockade of I(Kr) and I(Kur)/I(to) by sotalol plus AVE0118, however, attenuated NTP-induced AERP shortening and AF inducibility independent of the order of administration. CONCLUSION:The atrial proarrhythmic effect of NTP simulating obstructive apneas is difficult to inhibit by class III antiarrhythmic drugs. Neither amiodarone nor blockade of I(Kr) or I(Kur)/I(to) attenuated NTP-induced AERP shortening. However, the combined blockade of I(Kur)/I(to) and I(Kr) suppressed NTP-induced AERP shortening.

journal_name

Heart Rhythm

journal_title

Heart rhythm

authors

Linz D,Schotten U,Neuberger HR,Böhm M,Wirth K

doi

10.1016/j.hrthm.2011.07.018

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

1933-9

issue

12

eissn

1547-5271

issn

1556-3871

pii

S1547-5271(11)00830-7

journal_volume

8

pub_type

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