Prevention of ischemic ventricular tachycardia of Purkinje origin: role for alpha(2)-adrenoceptors in Purkinje?
Recent studies have shown the presence of postjunctional alpha(2)-adrenergic receptors on canine Purkinje fibers but not muscle cells. Stimulation of these receptors results in prolongation of the action potential duration and the Purkinje relative refractory period. We studied the effect of alpha(2)-adrenergic agonists on inducible ischemic ventricular tachycardia (VT) of both Purkinje fiber and myocardial origin. Open-chest dogs in whom VT was induced with extrastimuli after occlusion of the anterior descending coronary artery were studied. A mapping system, incorporating Purkinje signals, characterized the mechanisms of VT. The alpha(2)-adrenergic agonists clonidine (0.5-4.0 microg/kg) or UK 14,304 (4-5 microg/kg) versus saline were given intravenously after reproducibility of inducible sustained monomorphic VT had been demonstrated. Eighteen dogs were given clonidine, eleven of which had focal Purkinje VT. Of these 11 dogs, clonidine blocked VT induction in 9 (81.9%) and rendered VT nonsustained in 1 (9.1%), and VT remained inducible in 1 dog (9.1%), although this was focal midmyocardial VT only. In the seven dogs with VT of myocardial origin, six (85.6%) remained inducible with clonidine, whereas one dog (14.4%) had only nonsustained VT after clonidine. Of the six dogs, UK 14,304 blocked VT induction in four (66.6%) and rendered VT nonsustained in one (16.7%), and VT remained inducible in one dog (16.7%). In four dogs with VT of myocardial origin, VT remained inducible. In the eight control dogs that were given saline, focal Purkinje VT was repeatedly inducible. Pharmacological stimulation of postjunctional alpha(2)-adrenoceptors on Purkinje fibers may selectively prevent induction of VT of Purkinje fiber origin in the ischemic canine ventricle.
Arnar
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Division of Cardiovascular Diseases, Department of Internal Medicine, University of Iowa College of Medicine and Veterans Administration Medical Center, Iowa City, Iowa 52242, USA.
Xing
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Lee
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Martins
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D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D003000:Clonidine / Q000494:pharmacology; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D011690:Purkinje Fibers / Q000378:metabolism / Q000503:physiopathology*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D014682:Vena Cava, Inferior / Q000503:physiopathology
D000316:Adrenergic alpha-Agonists; D018341:Receptors, Adrenergic, alpha-2; D003000:Clonidine