Summary
To study the role of the adrenergic nervous system in the genesis of nonlethal reperfusion arrhythmias, the proximal left anterior descending coronary artery was occluded for either 1 or 3 hours in 48 open-chest dogs anesthetized with alpha-chloralose. Heart rate was controlled (90 to 110 beats/min) by bilateral vagotomy and continuous right vagal stimulation. Dogs were treated with either saline, timolol (0.1 mg/kg), or prazosin (0.5 mg/kg) 15 minutes prior to reperfusion. Reperfusion after 1 hour of occlusion in saline-treated dogs evoked sustained polymorphic ventricular tachycardia (204±9 beats/min) that reverted to sinus rhythm by 15 minutes of reperfusion. The maximum rate of ventricular tachycardia was significantly reduced by both prazosin and timolol. Both drugs also caused about a 50% reduction in the total number of ectopic beats in the first 10 minutes of reperfusion. With a 3-hour occlusion, reperfusion in saline-treated dogs caused sustained polymorphic ventricular tachycardia (135±15 beats/min) which persisted for several hours. Neither timolol nor prazosin significantly altered the ventricular ectopic rate in these dogs. Furthermore, bilateral stellate transection, left stellate stimulation, isoproterenol (0.5 mg/kg), or methoxamine (100 ug/kg) all failed to alter the ventricular ectopic rate in the saline-treated dogs. Ventricular ectopy induced by reperfusion after a 1- or 3-hour occlusion was overdriven in all dogs by rapid atrial pacing. The results suggest that the nature of reperfusion-induced ventricular ectopy is highly dependent upon the preceeding duration of coronary occlusion. Whereas both alpha-1- and beta-adrenergic receptors appear to play an important role in the genesis of reperfusion-induced ectopy after a 1-hour occlusion, these receptors have little influence on reperfusion-induced ectopy after a 3-hour occlusion.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Pogwizd SM, Corr PB. Electrophysiologic mechanisms underlying arrhythmias due to reperfusion of ischemic myocardium. Circulation 1987;76:404–426.
Kabell G, Scherlag BJ, Brachmann J, et al. Ventricular arrhythmias following one-stage and two-stage coronary reperfusion: Evidence for both reentry and enhanced automaticity. J Electrocardiol 1985;18:87–96.
Kaplinski E, Ogawa S, Michelson EL, Dreifus LS. Instantaneous and delayed ventricular arrhythmias after reperfusion of acutely ischemic myocardium: Evidence for multiple mechanisms. Circulation 1981;63:333–340.
Murdock DK, Loeb JM, Euler DE, Randall WC. Electrophysiology of coronary reperfusion: A mechanism for reperfusion arrhythmias. Circulation 1980;61:175–182.
Penkoske PA, Sobel BE, Corr PB. Disparate electrophysiological alterations accompanying dysrhythmia due to coronary occlusion and reperfusion in the cat. Circulation 1978;58:1023–1035.
Balke CW, Kaplinski E, Michelson EL, et al. Reperfusion ventricular tachyarrhythmias: Correlation with antecedent coronary artery occlusion tachyarrhythmias and duration of myocardial ischemia. Am Heart J 1981;101:449–455.
Sheridan DJ, Penkoske PA, Sobel BE, Corr PB. Alpha adrenergic contributions to dysrhythmia during myocardial ischemia and reperfusion in cats. J Clin Invest 1980;65:161–171.
Euler DE, Murdock D, Scanlon PJ. Sympathetic infuences on canine reperfusion arrhythmias. Circulation 1987;76:IV-108.
Misu Y, Kirpekar SM. Effects of vagal and sympathetic nerve stimulation on the isolated atria of the cat. J Pharmacol Exp Ther 1968;163:330–342.
Martin P, Levy MN, Matsuda Y. Fade of cardiac responses during tonic vagal stimulation. Am J Physiol 1982;243 (Heart Circ Physiol 12: H219–H225).
Constantine JW, Lebel W, Weeks R. The hypotensive effect of trimazosin is not caused solely by alpha-1-adrenoceptor blockade. J Cardiovasc Pharmacol 1984;6:142–150.
Karagueuzian HS, Fenoglio JJ Jr, Weiss MB, Wit AL. Protracted ventricular tachycardia induced by premature stimulation of the canine heart after coronary artery occlusion and reperfusion. Circ Res 1979;44:833–846.
Scherlag BJ, El-Sherif N, Hope R, Lazzara R. Characterization and localization of ventricular arrhythmias resulting from myocardial ischemia and infarction. Circ Res 1974;35: 372–383.
Shell WE, Sobel BE. Deleterious effects of increased heart rate on infarct size in the conscious dog. Am J Cardiol 1973;31:474–479.
Zuanetti G, De Ferrari GM, Priori SG, Schwartz PJ. Protective effect of vagal stimulation on reperfusion arryhthmias in cats. Circ Res 1987;61:429–435.
Thames MD, Klopfenstein HS, Abboud FM, et al. Preferential distribution of inhibitory cardiac receptors with vagal afferents to the inferiorposterior wall of the left ventricle activated during coronary occlusion in the dog. Circ Res 1978;43:512–519.
Inoue H, Zipes DP. Changes in atrial and ventricular refractoriness and in atrioventricular nodal conduction produced by combinations of vagal and sympathetic responses that result in a constant spontaneous sinus cycle length. Circ Res 1987;60:942–951.
Corr PB, Shayman JA, Kramer JB, Kipnis RJ. Increased alpha-adrenergic receptors in ischemic cat myocardium. A potential mediator of electrophysiological derangements. J Clin Invest 1981;67:1232–1236.
Stewart JR, Burmeister WE, Burmeister J, Lucchesi BR. Electrophysiologic and antiarrhythmic effects of phentolamine in experimental coronary artery occlusion and reperfusion in the dog. J Cardiovasc Pharmacol 1980;2:77–91.
Aubry ML, Davey MJ, Petch B. Cardioprotective and antidysrhythmic effects of alpha 1-adrenoceptor blockade during myocardial ischaemia and reperfusion in the dog. J Cardiovasc Pharmacol 1985;7:S93-S102.
Bolli R, Fisher D, Taylor AA, et al. Effect of alpha-adrenergic blockade on arrhythmias induced by acute myocardial ischemia and reperfusion in the dog. J Mol Cell Cardiol 1984;16:1101–1117.
Dukes ID, Vaughan Williams EM. Electrophysiological effects of α-adrenoceptor antagonists in rabbit sino-atrial node, cardiac Purkinje cells and papillary muscles. Br J Pharmacol 1984;83:419–426.
Wilber DJ, Lynch JJ, Montgomery DG, Lucchesi BR. Alpha-adrenergic influences in canine ischemic sudden death: Effects of alpha-1 adrenoceptor blockade with prazosin. J Cardiovasc Pharmacol 1987;10:96–107.
Ciuffo AA, Ouyang P, Becker LC, et al. Reduction of sympathetic inotropic response after ischemia in dogs. Contributor to stunned myocardium. j Clin Invest 1985;75:1504–1509.
Martins JB, Kerber RE, Marcus ML, et al. Inhibition of neurotransmission in ischemic regions of canine left ventricle. Cardiovasc Res 1980;14:116–124.
Kloner RA, Ganote CE, Jennings RB. The “no-reflow” phenomenon after temporary coronary occlusion in the dog. J Clin Invest 1974;54:1496–1508.
Danilo P Jr, Langan WB, Rosen MR, Hoffman BF. Effects of the phenothiazine analog, EN-313, on ventricular arrhythmias in the dog. Eur J Pharmacol 1977;45:127–139.
Le Marec H, Dangman KH, Danilo P Jr, Rosen MR. An evaluation of automaticity and triggered activity in the canine heart one to four days after myocardial infarction. Circulation 1985;71:1224–1236.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Euler, D.E., Scanlon, P.J. The duration of coronary occlusion influences adrenergic contributions to reperfusion ventricular arrhythmias. Cardiovasc Drug Ther 2, 513–521 (1988). https://doi.org/10.1007/BF00051190
Issue Date:
DOI: https://doi.org/10.1007/BF00051190