Differential effects of dofetilide, amiodarone, and class Ic drugs on leftand right atrial refractoriness and left atrial vulnerability in pigs

Objectives: Antiarrhythmic drugs have been shown to prolong right atrial re fractoriness while data on the left atrium are not available. In pigs we ha ve observed shorter effective refractory periods (ERP) of the left compared with the right atrium associated with a much higher left atrial vulnerabil ity for tachyarrhythmias. Since this could suggest a different distribution of repolarizing ion channels in left and right atrium, we investigated whe ther antiarrhythmic drugs blocking different ion channels have a differenti al effect on left and right atrial ERP and left atrial vulnerability. Metho ds: In pentobarbital-anesthetized pigs (n=40) we measured and compared ERPs in both atria before and after different drugs with the S1-S2 extrastimulu s method at three basic cycle lengths (BCL) and assessed the inducibility o f atrial fibrillation/flutter (AF/AFL) by the premature S2 stimulus. Result s: At the three BCL tested (240/300/400 ms) baseline ERPs were shorter in l eft vs. right atrium (112+/-2/124+/-2/129+/-2 ms vs. 147+/-2/163+/-2/167+/- 2 ms, P<0.001). Mostly non-sustained AF/AFL induced by the S2 extrastimulus was very frequent in the left (68%) and nearly absent in the right atrium (3%). Only amiodarone, 5 mg/kg i.v., which showed a balanced increase of le ft and right atrial ERP (29+/-5/33+/-4/35+/-3% vs. 30+/-5/35+/-5/42+/-7%), decreased the inducibility of AF/AFL significantly (-72%, P<0.01). Dofetili de, 10 mug/kg i.v., had a stronger effect on right than left atrial ERP (36 +/-4/39+/46+/-10% vs. 23+/-2/22+/- 7/22+/-5%, P<0.05), while flecainide, 1 mg/kg i.v., prolonged left more than right atrial ERP (58+/-15/36+/- 7/40+/ -7% vs. 26+/-5/24+/-5/21+/-4%, P<0.05) similar to 1 mg/ kg of propafenone ( 46+/-5/45+/-7/32+/-10% vs. 17+/-4/21+/-5/ 25+/-8%, P<0.05). Conclusion: The shorter refractoriness of the left compared with the right atrium observed in pigs was associated with a high left atrial vulnerability for tachyarrh ythmias, which was reduced only by amiodarone showing a balanced increase o f left and right atrial ERP. Dofetilide was stronger on right atrial ERP, f lecainide and propafenone on left atrial ERP. These differences suggest a d ifferential distribution of repolarizing ion channels between left and righ t atrium with possible relevance for the antiarrhythmic efficacy of drugs.