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Monophasic action potentials during reentrant atrial flutter in the dog: effects of clofilium and acetylcholine.

Monophasic action potentials (MAP) were recorded from canine atrium during reentrant flutter resulting from circus movement in atrial tissue above the tricuspid ring. A catheter and plaque contact electrodes were developed to record MAP from the epicardium or endocardium during sinus rhythm, paced rhythms, and flutter. The transmembrane action potential duration of tricuspid ring tissue also was studied in vitro. During flutter at cycle lengths of 140-160 ms, MAP showed incomplete repolarization. Pacing at comparable cycle lengths had a similar effect. Acetylcholine (10 micrograms/kg, i.v.) shortened MAP duration during pacing and, during flutter, decreased cycle length and increased MAP amplitude. Clofilium (500 micrograms/kg, i.v.) prolonged flutter cycle length by 18% and terminated the flutter within 30-120 s. During pacing at a cycle length of 300 ms, clofilium increased MAP duration and effective refractory period (ERP) by 30%. Transmembrane action potentials showed that clofilium (0.2 mg/L) modified only action potential duration. Conduction velocity was significantly decreased by clofilium during flutter but not during pacing at a cycle length of 300 ms. These data support the conclusion that in this model of flutter, the circus movement occurs in partially repolarized tissue. The circus movement can be accelerated by agents (acetylcholine) that reduce ADP, and slowed and terminated by agents (clofilium) that increase it.

Acetylcholine↗

Therapy of refractory symptomatic atrial fibrillation and atrial flutter: a staged care approach with new antiarrhythmic drugs.

One hundred nine patients with recurrent episodes of symptomatic atrial fibrillation or flutter, or both, who had failed one to five previous antiarrhythmic drug trials were treated with propafenone and, subsequently, sotalol if atrial fibrillation recurred. The clinical profile of the study group was as follows: age 63 +/- 13 years, left atrial anteroposterior dimension 4.4 +/- 0.9 cm and left ventricular ejection fraction 57 +/- 14%. Paroxysmal atrial fibrillation occurred in 56 patients (51%) and chronic atrial fibrillation occurred in 53 patients (49%). After loading and dose titration phases were completed, the maintenance doses of drugs were 450 to 900 mg/day for propafenone and 160 to 960 mg/day for sotalol. Life table estimates of the duration of freedom from atrial fibrillation were constructed for each drug trial. The percent of patients free of recurrent symptomatic arrhythmia at 6 months was 39% for propafenone and 50% for sotalol. The cumulative proportion of patients successfully treated with propafenone or sotalol, or both, by 6 months was 55% and remained relatively constant beyond that point. The incidence of intolerable side effects necessitating discontinuation of therapy ranged from 7% to 8%. Thus, despite previous unsuccessful drug trials, a substantial proportion of patients with recurrent symptomatic atrial fibrillation refractory to conventional therapy can be treated successfully and safely with newer antiarrhythmic drugs. Treatment failures tend to occur early in the course of follow-up, permitting easy identification of candidates for alternative therapeutic approaches.

Adult↗