title: Alpha 2-Adrenergic stimulation is protective against ischemia-reperfusion-induced ventricular arrhythmias in vivo.
abstract: We previously reported that alpha(2)-adrenergic receptor (alpha(2)-AR) stimulation in Purkinje fibers in vitro prolongs action potential duration and suppresses beta-adrenergic-induced delayed afterdepolarizations and sustained triggered activities. We examined the effects of alpha(2)-AR stimulation on reperfusion-induced ventricular arrhythmias [ventricular tachycardia/ventricular fibrillation (VT/VF)] in vivo. Arterial blood pressure, heart rate, surface electrocardiogram, and renal sympathetic nerve activities were recorded simultaneously in Sprague-Dawley rats. The incidence of VT/VF was 87.5% for controls, 50% for the beta-blocker group, 72% for the alpha(1)-blocker group, and 12.5% for the alpha(1) + beta-blockers group (unopposed alpha(2)-adrenergic activation). Direct alpha(2)-AR stimulation with UK-14304 also prevented VT/VF. These effects were reversed by the alpha(2)-adrenergic antagonist yohimbine. Increases in renal sympathetic nerve activity were associated with left anterior descending coronary artery ligation and reperfusion (33 +/- 1.5 and 62 +/- 1.7% over baseline, respectively) in controls. Similar patterns were observed among all experimental groups irrespective of the incidence of VT/VF on reperfusion. We conclude that alpha(2)-AR stimulation has a potent antiarrhythmic effect on ischemia-reperfusion-induced VT/VF in vivo and that this effect is not centrally mediated.
authors.affiliation: Department of Internal Medicine, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City 52242, USA. jcai@lumc.edu
authors.forename: John J
authors.initials: JJ
authors.lastname: Cai
authors.forename: Donald A
authors.initials: DA
authors.lastname: Morgan
authors.forename: William G
authors.initials: WG
authors.lastname: Haynes
authors.forename: James B
authors.initials: JB
authors.lastname: Martins
authors.forename: Hon-Chi
authors.initials: HC
authors.lastname: Lee
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D000068438:Brimonidine Tartrate; D004195:Disease Models, Animal; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000294:innervation; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology; D015425:Myocardial Reperfusion; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000502:physiology; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D014693:Ventricular Fibrillation / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011810:Quinoxalines; D000068438:Brimonidine Tartrate