Reperfusion-induced ventricular fibrillation. Modification by pharmacological agents.

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.

• Authors: A S Manning, R Crome, K Isted, D J Coltart, D J Hearse
• Journal: Advances in myocardiology (Adv Myocardiol) Vol. 6 Pg. 515-28 ( 1985) ISSN: 0270-4056 [Print] United States
• PMID: 2581300 (Publication Type: Journal Article)

Chemical References

• Adrenergic beta-Antagonists
• Anti-Arrhythmia Agents
• Calcium Channel Blockers
• Ion Channels
• Sodium

Topics

• Adrenergic beta-Antagonists (therapeutic use)
• Animals
• Anti-Arrhythmia Agents (therapeutic use)
• Calcium Channel Blockers (therapeutic use)
• Cell Membrane (drug effects)
• Coronary Circulation (drug effects)
• Coronary Disease (drug therapy)
• Electrocardiography
• Energy Metabolism (drug effects)
• Heart Arrest, Induced
• Ion Channels (drug effects)
• Male
• Perfusion
• Rats
• Rats, Inbred Strains
• Sodium (metabolism)
• Ventricular Fibrillation (drug therapy)