Effect of -adrenoceptor Blocking Agents on Poststimulatory Atrial Flutter in the Dog, with Observations on the Participation of Adrenergic Mechanisms in This Experimental Arrhythmia

1. Four beta-adrenoceptor antagonists, viz. (+/-) propranolol (0.5 mg/kg), (-) alprenolol (0.25 mg/kg), practolol (5 mg/kg) and USVC 6524 (20 mug/kg), were tested for their effects on atrial flutter produced by electrical stimulation of the right atrium around the crushed inter-venae-caval bridge in anaesthetized dogs.2. All the drugs reduced atrial and ventricular rates; this was followed by the abrupt termination of flutter and restoration to normal sinus rhythm.3. Since all the drugs (including practolol, which is devoid of local anaesthetic activity) were given in doses just sufficient to block beta-adrenoceptors, it indicated that beta-adrenoceptor blockade was responsible for their antiarrhythmic property in this test procedure.4. Further evidences in support of participation of the sympathetic nervous system in poststimulatory flutter were: (i) flutter could not be produced in nine out of ten dogs whose catecholamine stores were depleted by pretreatment with reserpine; (ii) infusion of adrenaline in these animals resulted in the production of flutter; (iii) duration of flutter after termination of exposure to adrenaline was a few minutes, which is similar to the brief time previously reported to be taken for the disappearance of catecholamines from the hearts of reserpinized animals.5. The clinical significance of the above findings is discussed.