Pharmacological characterisation of a re-entry model for atrial tachycardia in conscious dogs

Abstract

We studied the effects of intravenously administered autonomic agents, the calcium channel blocker diltiazem, and Class I and III anti-arrhythmic agents on a re-entry model for atrial tachycardia in seven conscious dogs. The model was created by a Y-shaped incision in the intercaval region and front free wall of the right atrium. Acetylcholine (30 micrograms.kg-1) transiently but significantly shortened the cycle length of atrial tachycardia (CL) by 9 (SD 5)% while atropine (0.2 mg.kg-1) alone did not change or terminate the rhythm. Isoprenaline (4 micrograms.kg-1) briefly reduced CL, by 13(6)% whereas propranolol (1 mg.kg-1) alone significantly prolonged the CL and terminated the arrhythmia in 50% of the trials. Diltiazem (200 micrograms.kg-1) did not significantly change the CL. Class Ia agents procainamide (30 mg.kg-1) and quinidine (3.5 approximately 20 mg.kg-1, effective doses) increased CL by 60(30) and 43(28)% respectively and terminated the arrhythmias. Class Ib agents, phenytoin (5 and 10 mg.kg-1, cumulative doses), lignocaine (3.2 approximately 7 mg.kg-1), and mexiletine (6 approximately 20 mg.kg-1), prolonged CL by 31(14), 40(15), and 72(13)%; however, consistent conversion of the rhythm occurred only with mexiletine. Ic agents flecainide (0.5 approximately 3 mg.kg-1) and encainide (0.6 approximately 6.4 mg.kg-1) lengthened the CL by 58(17) and 75(43)% and converted the rhythm in all cases. Class III agents clofilium (0.5 mg.kg-1), d-sotolol (3.2 approximately 20 mg.kg-1), and N-acetylprocainamide (15 approximately 120 mg.kg-1) prolonged the CL by 14(4), 16(5), and 19(7)% and terminated the arrhythmia in all trials. The magnitudes of CL prolongation by the Class III agents were significantly smaller than those by the Class Ia, Ib, or Ic agents. These results show that in this re-entrant model for atrial tachycardia endogenous adrenergic but not cholinergic systems play a major role in maintaining impulse propagation and that calcium channel mediated slow inward currents do not participate in the impulse generation processes. Further, using CL as an index, the model serves as a useful tool for differentiating Class III from Class I anti-arrhythmic activities.