A S Manning, R Crome, K Isted, D J Coltart, D J Hearse
{"title":"Reperfusion-induced ventricular fibrillation. Modification by pharmacological agents.","authors":"A S Manning, R Crome, K Isted, D J Coltart, D J Hearse","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>We have assessed the ability of several of the main groups of antiarrhythmic agents to modify the incidence of reperfusion-induced ventricular fibrillation in the isolated working rat heart preparation with transient coronary artery occlusion. Hearts were perfused with Krebs-Henseleit medium containing 5 microM epinephrine to provide some level of exogenous catecholamine support. Compounds selected were: the fast sodium channel inhibitors lignocaine (1 and 10 microM) and prenylamine (4 microM) (the latter also possessing slow calcium channel antagonistic actions); the beta-adrenergic blocking agents oxprenolol (1.2 microM), timolol (0.13 microM), metoprolol (1.0 microM), and acebutolol (5.6 microM); and the slow calcium channel antagonist nifedipine (0.05 and 0.5 microM). After 15 min of coronary artery occlusion, over 90% of control hearts fibrillated 30-60 sec after the onset of reperfusion. Drugs reduced this to the following: prenylamine, 0% (p less than 0.001); 1 microM lignocaine, 83%; 10 microM lignocaine, 33% (p less than 0.01); oxprenolol, 92% (NS); timolol, 92% (NS); metoprolol, 42% (p less than 0.01); acebutolol, 67% (p less than 0.05); 0.05 microM nifedipine, 83% (NS); and 0.5 microM nifedipine, 67% (NS). Thus, inhibition of the fast inward sodium channel with agents such as prenylamine and lignocaine, (when begun before coronary-artery occlusion) offers maximal protection against reperfusion-induced ventricular fibrillation, while beta-blockade with timolol and oxprenolol and slow calcium channel inhibition with nifedipine do not offer any significant protection. The beta-blocking agents metoprolol and acebutolol produce a partial reduction that may be due to a membrane-stabilizing action, rather than to beta-blockade.</p>","PeriodicalId":77831,"journal":{"name":"Advances in myocardiology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in myocardiology","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
We have assessed the ability of several of the main groups of antiarrhythmic agents to modify the incidence of reperfusion-induced ventricular fibrillation in the isolated working rat heart preparation with transient coronary artery occlusion. Hearts were perfused with Krebs-Henseleit medium containing 5 microM epinephrine to provide some level of exogenous catecholamine support. Compounds selected were: the fast sodium channel inhibitors lignocaine (1 and 10 microM) and prenylamine (4 microM) (the latter also possessing slow calcium channel antagonistic actions); the beta-adrenergic blocking agents oxprenolol (1.2 microM), timolol (0.13 microM), metoprolol (1.0 microM), and acebutolol (5.6 microM); and the slow calcium channel antagonist nifedipine (0.05 and 0.5 microM). After 15 min of coronary artery occlusion, over 90% of control hearts fibrillated 30-60 sec after the onset of reperfusion. Drugs reduced this to the following: prenylamine, 0% (p less than 0.001); 1 microM lignocaine, 83%; 10 microM lignocaine, 33% (p less than 0.01); oxprenolol, 92% (NS); timolol, 92% (NS); metoprolol, 42% (p less than 0.01); acebutolol, 67% (p less than 0.05); 0.05 microM nifedipine, 83% (NS); and 0.5 microM nifedipine, 67% (NS). Thus, inhibition of the fast inward sodium channel with agents such as prenylamine and lignocaine, (when begun before coronary-artery occlusion) offers maximal protection against reperfusion-induced ventricular fibrillation, while beta-blockade with timolol and oxprenolol and slow calcium channel inhibition with nifedipine do not offer any significant protection. The beta-blocking agents metoprolol and acebutolol produce a partial reduction that may be due to a membrane-stabilizing action, rather than to beta-blockade.