The effects of nadolol on various cardiac tissues in normoxia, and on atrial muscle in simulated ischaemia

Abstract

Nadolol, a non-selective beta-blocker with a long duration of action, reportedly is devoid of membrane stabilizing action. Since such action is augmented by ischaemic conditions, it was of interest to investigate whether, in simulated ischaemia, a direct membrane effect of nadolol might be revealed. We have confirmed that in normoxia nadolol had no effects on intracellulary recorded potentials in isolated rabbit atrial or ventricular muscle at a concentration of 4.84 microM, but significantly reduced action potential amplitude and maximum rate of depolarisation at 14.5 microM. In Purkinje cells a small reduction of action potential amplitude was produced by 1.61 microM nadolol, but the effect was not increased by nadolol 4.84 microM. There were no drug-induced changes in action potential duration (APD), spontaneous frequency, conduction velocity, contractions, electrical threshold, effective refractory period or the maximum frequency at which a stimulus could be followed. Nadolol 14.5 microM did not reduce the positive inotropic effect of increasing extracellular calcium concentrations. Nadolol was 25 times less potent than procaine as a local anaesthetic on desheathed frog nerve. In a solution simulating ischaemia (8 mM KCl, 10 mM NaHCO3, gassed with 20% O2, pH 7.0) nadolol had a significant class 1 action on atrial muscle, however, even at 4.84 microM and reduced the shortening of APD caused by the solution. It is concluded that nadolol has no class 1, 3 or 4 antiarrhythmic activity in normoxia, but could have an additional protective effect in ischaemic myocardium against the arrhythmogenic factor of shortened APD.