Document Detail

Electrophysiological effects of alpha-adrenoceptor stimulation in normal and ischemic myocardium.
MedLine Citation:
PMID:  2410737     Owner:  NLM     Status:  MEDLINE    
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.
D J Sheridan; W Culling
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  7 Suppl 5     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1985  
Date Detail:
Created Date:  1985-09-06     Completed Date:  1985-09-06     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  S55-60     Citation Subset:  IM    
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MeSH Terms
Action Potentials / drug effects
Adrenergic alpha-Antagonists / pharmacology
Arrhythmias, Cardiac / physiopathology
Catecholamines / physiology
Coronary Disease / physiopathology*
Guinea Pigs
Heart / physiology*
Indoramin / pharmacology
Methoxamine / pharmacology
Phentolamine / pharmacology
Receptors, Adrenergic, alpha / physiology*
Reg. No./Substance:
0/Adrenergic alpha-Antagonists; 0/Catecholamines; 0/Receptors, Adrenergic, alpha; 26844-12-2/Indoramin; 390-28-3/Methoxamine; 50-60-2/Phentolamine

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