Attenuation of the rise in extracellular potassium concentration during myocardial ischaemia by d.l-sotalol and d-sotalol.
OBJECTIVE
The aim was to study the effects of d.l-sotalol, d-sotalol or atenolol on the rate of rise of extracellular potassium concentration [( K+]o) and the electrophysiological changes that occur during myocardial ischaemia.


METHODS
The study was performed in isolated, arterially perfused interventricular septa from rabbit. Six septa were treated with d.l-sotalol 10(-4) mol.litre-1, six with d-sotalol 10(-4) mol.litre-1, six with atenolol 10(-5) mol.litre-1, and there were seven untreated controls. At these concentrations d.l and d-sotalol are equipotent in their class III effect, though d-sotalol has only 7% of the beta blocking activity of the racemic form, and atenolol is equipotent in its beta blocking activity to d.l-sotalol. [K+]o and electrophysiological variables were compared before and during a 30 min period of global zero flow ischaemia.


RESULTS
Prior to ischaemia [K+]o, measured using potassium sensitive valinomycin electrodes, was similar in all the groups. [K+]o rose during ischaemia in all the groups, and at 30 min was 13.0 (SEM 0.7) mmol.litre-1 in the control group which was not different from 12.7(0.5) mmol.litre-1 in the atenolol group. In the d.l and d-sotalol groups the increases were markedly attenuated, reaching 9.2(1.0) and 8.8(0.7) mmol.litre-1 respectively. During ischaemia the class III effect of d.l and d-sotalol was lost within 6 min though the fall in maximum upstroke velocity of the action potentials (dV/dtmax) and the extent of resting membrane potential (Em) depolarisation were less in comparison to the control and atenolol groups.


CONCLUSIONS
The results indicate an attenuation by sotalol of the ischaemic rise in [K+]o, with preservation of dV/dtmax and Em, despite the loss of an effect on action potential duration. This potentially antiarrhythmic effect of sotalol in ischaemic myocardium is attributable to a direct membrane effect rather than beta adrenoceptor antagonism.
Hicks
M N
MN
Department of Medical Cardiology, Royal Infirmary, Glasgow, United Kingdom.
Cobbe
S M
SM
D000200:Action Potentials; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D005110:Extracellular Space / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D011817:Rabbits; D012032:Refractory Period, Electrophysiological; D013015:Sotalol / Q000494:pharmacology*; D013237:Stereoisomerism
D013015:Sotalol; D011188:Potassium