Electrophysiological and antiarrhythmic effects of UK 52,046-27 during ischaemia and reperfusion in the guinea-pig heart.

1. We studied the antiarrhythmic and electrophysiological effects of UK 52,046-27 (10(-8) M and 5 x 10(-8) M), a highly selective alpha 1-adrenoceptor antagonist, during global ischaemia (flow reduced to 10% of control for 30 min) and reperfusion, in isolated, buffer-perfused hearts of guinea-pigs. 2. The compound had few electrophysiological effects during normal perfusion, although action potential amplitude and Vmax were reduced with 10(-8) M (by 9% and 22%) and refractory period was increased with 5 x 10(-8) M (by 13%) compared to control hearts. 3. Perfusion with 5 x 10(-8) M UK 52,046-27 reduced the incidence of ventricular tachycardia during ischaemia from 67% to 25%, and during reperfusion reduced the incidence of ventricular tachycardia (from 83% to 17%) and ventricular fibrillation (from 67% to 8%). 4. The compound prolonged significantly action potential duration and refractory period during ischaemia and reperfusion. Vmax was reduced to a greater extent during reperfusion in the treated hearts, while greater increases in QRS width and stimulation threshold occurred during ischaemia in the treated group. 5. These results confirm that blockade of the alpha 1-adrenoceptor subpopulation during myocardial ischaemia and reperfusion decreases the incidence of arrhythmias and alters cellular electrophysiology during ischaemia and reperfusion.