title: Enhanced alpha-adrenergic responsiveness in ischemic myocardium: role of alpha-adrenergic blockade.
abstract: alpha-Adrenergic blockade with phentolamine or prazosin but not beta-adrenergic blockade reduces premature ventricular complexes and abolished ventricular fibrillation induced by coronary artery ligation or reperfusion in cats. The protective influences were independent of regional coronary flow or systemic hemodynamics. Efferent sympathetic nerve stimulation increased the idioventricular rate (IVR) prior to myocardial ischemia, a response blocked by propranolol, whereas during reperfusion the increased IVR was abolished only by alpha-blockade. Enhanced alpha-adrenergic responsiveness during reperfusion was also apparent with the alpha-agonist methoxamine. More recently we have demonstrated that alpha-adrenergic receptors, assessed by ligand binding with 3H-prazosin, increased nearly twofold in ischemic myocardium by 30 minutes (Bmax = 14 + 2 to 27 + 3 fmol/mg prot) and remain elevated during early reperfusion (12 + 1 to 18 + 1) before returning to control values by 15 minutes after reperfusion. 3H-DHA binding or Na+- -K+ adenosine triphosphatase activity was not altered at any time, indicating the specificity of the alteration. Thus enhanced alpha-adrenergic receptors and suggests the potential use of alpha-adrenergic blockade as one intervention to alleviate these malignant dysrhythmias.
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000209:etiology; D003327:Coronary Disease / Q000150:complications / Q000503:physiopathology*; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects*; D006801:Humans; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha