title: Effects of selective alpha 1A-adrenoceptor antagonists on reperfusion arrhythmias in isolated rat hearts.
abstract: Stimulation of alpha 1-adrenoceptors (AR) during ischaemia in the rat heart by exogenous phenylephrine exacerbates reperfusion arrhythmias, an effect apparently mediated by the alpha 1A-AR subtype. We tested whether alpha 1A-AR stimulation by endogenous catecholamines, released during ischaemia, could modulate reperfusion arrhythmias, using as pharmacological tools the selective alpha 1A-AR antagonists abanoquil (UK52046) and WB4101. Isolated rat hearts (n = 12/group) were subjected to dual coronary perfusion. After 15 min of aerobic perfusion of both coronary beds, abanoquil or WB4101 was infused selectively into the left coronary bed (LCB) for 5 min. The LCB was then subjected to 10 min of zero-flow ischaemia and 5 min of reperfusion. Effects on PR interval, width of the ventricular complex (QRST90) and reperfusion arrhythmias were assessed. Abanoquil at concentrations of 0.03, 0.1 and 0.3 microM tended to reduce the incidence of reperfusion-induced ventricular fibrillation (VF) in a dose-dependent manner from 75% in controls to 58, 33 and 25%, but this effects did not achieve statistical significance. Similarly, WB4101 at 0.1, 0.3 and 1 microM also tended to reduce VF incidence from 67% in controls to 67, 42% and 33% (NS). The incidence of ventricular tachycardia (VT) was 100% in all groups and ECG parameters were not altered significantly by either drug. These results suggest that, in this denervated isolated heart preparation, alpha 1A-AR stimulation during ischaemia by endogenous catecholamines does not significantly modulate reperfusion arrhythmias.
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism* / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects; D004146:Dioxanes / Q000494:pharmacology; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D044005:Tetrahydroisoquinolines; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000317:Adrenergic alpha-Antagonists; D000634:Aminoquinolines; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D044005:Tetrahydroisoquinolines; D010656:Phenylephrine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; C058534:abanoquil