Effects of 5-hydroxy-propafenone in guinea-pig atrial fibres

The effects of 5-hydroxy-propafenone (5-OH-P), an active metabolite of propafenone, were studied on isolated atrial muscle fibres obtained from non-treated guinea-pigs and from animals pretreated with 5-OH-P, 3 mg kg-1, for 28 days. In untreated atria 5-OH-P, 10(-8) M-10(-4) M, produced a dose-dependent decrease in amplitude and df/dtmax and reduced the amplitude of the slow contractions induced by isoprenaline and histamine in high K+ media. 5-OH-P also produced a dose-dependent decrease in atrial rate, prolonged the sinus node recovery time and reduced the maximum chronotropic responses to isoprenaline. In untreated atrial muscle fibres 5-OH-P depressed action potential amplitude and Vmax, reduced the resting membrane potential and prolonged the action potential duration (ADP) and the effective refractory period, lengthening the effective refractory period relative to APD. Pretreatment with 5-OH-P reduced atrial rate and increased contractile force, but did not modify the action potential characteristics from the values obtained in untreated atria. Further addition of 5-OH-P produced similar but more marked changes than in untreated atria. It is concluded that in guinea-pig isolated atrial muscle fibres 5-OH-P, like propafenone, exhibits class I (membrane stabilizing), class II (antisympathetic) and class IV (Ca antagonistic) antiarrhythmic actions. Therefore, this metabolite could be responsible, at least in part, for some of the antiarrhythmic effects previously attributed to propafenone.