Effect of procainamide and N-acetylprocainamide on atrial flutter: studies in vivo and in vitro.

Abstract

We studied the effects of procainamide and N-acetylprocainamide (NAPA) in a conscious dog preparation of atrial flutter resulting from circus movement around the tricuspid orifice. We also recorded transmembrane potentials of atrial tissues from the circus path in vitro. In 12 instrumented dogs, average flutter cycle length was 157 msec, the duration of the excitable gap was 73 msec, and conduction velocity was 0.75 m/sec. At 4 and 8 mg/kg, procainamide moderately prolonged cycle length, but did not terminate the flutter. At a cycle length of 300 msec procainamide increased effective refractory period (ERP) December 1987 lamina.4 The reentrant excitation causing a flutter can be induced, reset, and terminated by premature stimulation. Furthermore, there is a partially excitable gap in the circus path and thus the rhythm can be entrained by programmed stimulation.3In this preparation of atrial flutter the path for circus movement is provided by electrophysiologically normal tissue4' 5; the reentrant impulse propagates in an anatomically discrete circuit and the arrhythmia can be studied over the long term in conscious animals. The preparation is thus suitable for study of the mechanism of action of antiarrhythmic agents. We do not argue here that flutter in our preparation results from the same mechanisms as flutter in the diseased human heart; indeed, in the latter different mechanisms probably operate in different cases. Nevertheless, our findings will be applicable to arrhythmias that result from the mechanism operative in our preparation. At

In Vivo Antiarrhythmic and Cardiac Electrophysiologic Effects of a Novel Diphenylphosphine Oxide IKur Blocker (2-Isopropyl-5-methylcyclohexyl) Diphenylphosphine Oxide

“…Early class III potassium channel blocking agents, including N-acetylprocainamide, clofilium, and d-sotalol, the latter predominantly a blocker of the rapidly activating component of delayed rectifier potassium current, I Kr (Sanguinetti and Jurkiewicz, 1990), terminated atrial arrhythmia in this model while producing greater increases in atrial refractoriness compared with slowing of conduction (Wu and Hoffman, 1987;Spinelli and Hoffman, 1989;Wu et al, 1989b). The modest slowing of flutter observed with class III agents has been attributed to increased refractoriness in the partially repolarized excitable gap, resulting in advancement of the reentrant wave front into less fully repolarized cells, thereby propagating at a reduced velocity (Wu et al, 1989b).…”

“…Class IA and IC sodium channel blocking agents tested previously in the canine Y-shaped atrial lesion model, including procainamide, quinidine, flecainide, and propafenone, terminated atrial flutter and produced a greater slowing of conduction and increases in flutter cycle length compared with changes in refractoriness (Wu and Hoffman, 1987;Spinelli and Hoffman, 1989;Wu et al, 1989a). It has been postulated that these agents terminate reentry by depressing conduction to a point where propagation fails (Spinelli and Hoffman, 1989).…”

Mechanisms of Antiarrhythmic Drug Action on Termination of Atrial Flutter

“…Experimental Study. In an animal model with a Y-shaped atrial lesion, Wu and Hoffman 39 have reported that procainamide could terminate sustained atrial flutter around the tricuspid ring. Termination was preceded by a marked increase in cycle length and correlated with depression of conduction rather than prolongation of refractoriness.…”

A dual model for cardiac arrhythmias: coexistence of re‐entry and abnormal automaticity and effects of antiarrhythmic agents

“…Recently, a conscious model for re-entry arrhythmia in the dog has 1 Author for correspondence. been developed (Frame et al, 1986;Wu & Hoffman, 1987). The arrhythmia is a result of re-entrant excitation propagated in a partially repolarized atrial tissue around the tricuspid ring (Frame et al, 1986;Wu et al, 1989a).…”

“…The circus movement is easy to induce, stable in cycle length, and persistent. Various antiarrhythmic agents have been studied in this model of arrhythmia (Wu & Hoffman, 1986;Frame & Colatsky, 1987;Spinelli & Hoffman, 1987;Wu & Hoffman, 1987).…”