Alpha adrenergic contributions to dysrhythmia during myocardial ischemia and reperfusion in cats

D. J. Sheridan, P. A. Penkoske, B. E. Sobel, P. B. Corr

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309 Scopus citations

Abstract

Alpha compared to beta adrenergic contributions to dysrhythmias induced by left anterior descending coronary occlusion and by reperfusion were assessed in chloralose-anesthetized cats (n = 96). Alpha receptor blockade with either phentolamine or prazosin significantly reduced the number of premature ventricular complexes during coronary reperfusion (321±62-14±10 premature ventricular complexes, P < 0.001), abolished early ventricular fibrillation (from 25% in controls to 0%), and prevented the increase in idioventricular rate seen with coronary reperfusion. However, β-receptor blockade was without effect. Ventricular dysrhythmias induced by coronary occlusion alone (without reperfusion) were attenuated markedly by α-receptor blockade under conditions in which perfusion (measured with radiolabeled microspheres) within ischemic zones was not affected. Alternative sympatholytic interventions including pretreatment with 6-hydroxydopamine to deplete myocardial norepinephrine from 8.8±1.4 to 0.83±0.2 ng/mg protein and render the heart unresponsive to tyramine (120 μg/kg) attenuated dysrhythmias induced by both coronary occlusion and reperfusion in a fashion identical to that seen with α-receptor blockade. Although efferent sympathetic activation induced by left stellate nerve stimulation increased idioventricular rate from 66±6 to 144±7 beats/min (P < 0.01) before coronary occlusion, this response was blocked by propranolol but not by phentolamine. In contrast, during reperfusion the increase in idioventricular rate induced by left stellate nerve stimulation (to 203±14) was not inhibited by propranolol but was abolished by phentolamine (79±10). Intracoronary methoxamine (0.1 μM) in animals depleted of myocardial catecholamines by 6-hydroxydopamine pretreatment did not affect idioventricular rate before coronary occlusion. However, early after coronary reperfusion, methoxamine increased idioventricular rate from 33±7 to 123±21 beats/min (P < 0.01). Thus, enhanced α-adrenergic responsiveness occurs during myocardial ischemia and appears to be a primary mediator of the electrophysiological derangements and resulting malignant dysrhythmias induced by catecholamines during myocardial ischemia and reperfusion.

Original languageEnglish
Pages (from-to)161-171
Number of pages11
JournalJournal of Clinical Investigation
Volume65
Issue number1
DOIs
StatePublished - 1980

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