P117 Predominant left atrial antiarrhythmic actions of Ikur-, Ikr-, Iks-, IkAch-, betablockers, and class Ic-drugs in pigs.
1K.Knobloch, 2J.Brendel, 2A.E.Busch, 2M.Bleich, 2K.J.Wirth
1Thorax-, Herz- & Gefäßchirurgie, Medizinische Hochschule, Hannover; 2Aventis Pharma Germany, DG Cardiovascular Diseases, Frankfurt am Main.

Left (LA) and right atrial (RA) side differences of refractoriness as well as distinct pulmonary veins are reported in different species. The effects of novel atrial selective Ikur-blockers were investigated in this study in contrast to IKr-blockers dofetilide (DO), azimilide (AZ), ibutilide (IB), amiodarone (AM), IKs-blocker HMR 1556, IKAch-blocker atropine (ATR), class Ic drugs flecainide (FL) and propafenone (PR), and βblockers d,l-sotalol (SO), atenolol (ATE), and esmolol (ES) on LA and RA and ventricular refractoriness, and left atrial vulnerability (LAV)in vivo in pigs.

Methods: In pentobarbital-anesthetized pigs (n=81) LA and RA effective refractory periods (ERP) were measured with the S1-S2-extrastimulus-method. LAV was assessed after a S2-extrastimulus applied on the LA.

Results: All IKur-blockers, AVE 0118 (1mg/kg), S9947 (3mg/kg) and S20951 (3mg/kg) prolonged left stronger than right atrial refractoriness and did not change QTc-time. All IKr-blockers prolonged predominantly right vs. left atrial ERP as did IKs-blocker HMR 1556. AM was equally effective on both atria. IKAch-blocker atropine prolonged only left atrial ERP, as did pure βblockers with predominant left atrial ERP prolongation and class Ic drugs, FL and PR, while d,l-sotalol acted predominantly right atrial. IKur-blockers, S9947 and S20951, ibutilide, and d,l-sotalol significantly decreased left atrial vulnerability (-100%, -82%, -53%, -53%, p<0.05).

Conclusions: IKur-blockers, AVE 0118, S9947 and S20951, exhibit stronger left atrial effects with no effect on ventricular repolarization. By contrast, IKr-blockers, IKs-blockers, and d,l-sotalol exert predominant right atrial and known ventricular effects. These data demonstrate atrial side differences of antiarrhythmic drugs. IKur-blockers inhibit atrial tachyarrhythmias stronger than all available drugs, therefore IKur-blockers seem to be promising new atrial selective antiarrhythmic drugs.