title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany. Dominik.Linz@uks.eu
authors.forename: Dominik
authors.initials: D
authors.lastname: Linz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schotten
authors.forename: Hans-Ruprecht
authors.initials: HR
authors.lastname: Neuberger
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.forename: Klaus
authors.initials: K
authors.lastname: Wirth
mesh_terms: D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000150:complications / Q000503:physiopathology*; D008297:Male; D023421:Models, Animal; D011188:Potassium / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects*; D020181:Sleep Apnea, Obstructive / Q000150:complications*; D013015:Sotalol / Q000494:pharmacology*; D013552:Swine
chemical_list: D000889:Anti-Arrhythmia Agents; D024642:Potassium Channels, Voltage-Gated; D013015:Sotalol; D000638:Amiodarone; D011188:Potassium