Electrophysiological effects of alpha-adrenoceptor stimulation in normal and ischemic myocardium.
To investigate the mechanism by which alpha-adrenoceptor blocking drugs prevent ventricular arrhythmias associated with myocardial ischaemia and reperfusion, we studied the effects of alpha blockade, alpha-adrenoceptor agonists, and myocardial catecholamine depletion on arrhythmias and cellular electrophysiology during ischaemia and reperfusion in isolated perfused guinea pig hearts. Perfusion with phentolamine or indoramin significantly reduced ventricular tachycardia (VT) and ventricular fibrillation (VF) during ischaemia and reperfusion, and phentolamine was equally effective during reperfusion when added at the end of ischaemia. Both drugs prolonged action-potential duration (APD) and refractory period during ischaemia and reperfusion, and studies with phentolamine, in catecholamine-depleted hearts, indicated that its action was related to the presence of catecholamines. Myocardial catecholamine depletion also significantly reduced VT and VF during ischaemia and reperfusion. Perfusion with an alpha 1-adrenoceptor agonist, however, significantly reversed this antiarrhythmic effect, increasing the incidence of VT and VF during ischaemia and reperfusion. This arrhythmogenic effect was associated with a reduction in APD and refractory period, i.e., a reversal of the electrophysiological effects of catecholamine depletion. These results indicate that alpha-adrenoceptor stimulation is arrhythmogenic during myocardial ischaemia and reperfusion, and that the antiarrhythmic action of alpha-adrenoceptor antagonists is mediated via adrenergic rather than direct myocardial effects.
Sheridan
D J
DJ
Culling
W
W
D000200:Action Potentials / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D002395:Catecholamines / Q000502:physiology; D003327:Coronary Disease / Q000503:physiopathology*; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D007217:Indoramin / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D007217:Indoramin; D008729:Methoxamine; D010646:Phentolamine