An investigation into the characteristics of reperfusion‐induced arrhythmias in the anaesthetized rat and their susceptibility to antiarrhythmic agents

Abstract

Reperfusion‐induced arrhythmias were elicited in the pentobarbitone‐anaesthetized rat by occlusion of the left main coronary artery and subsequent release. These arrhythmias were rapid in onset, occurring within 20 s after release of the ligature, and were of short duration (1–2 min). Their severity was dependent upon the duration of the preceding occlusion. A 5 or 15 min occlusion period produced the most severe arrhythmias on release, the incidence of ventricular fibrillation being 56 and 50% respectively. Evidence that reperfusion had occurred was provided by fluorescein dye distribution and intramyocardial temperature studies. The severity of reperfusion arrhythmias and mortality was unaffected by bilateral vagotomy, β‐adrenoceptor blockade by atenolol (2 mg kg−1 i.v.) or a combination of the two. The incidence of reperfusion‐induced ventricular fibrillation was significantly reduced by Org 6001 (which blocks the fast inward sodium current), melperone (which acutely prolongs the cardiac action potential duration) and bepridil (which blocks both fast and slow inward currents). It was unaffected by nitroglycerine and the calcium antagonists verapamil, prenylamine and nifedipine. We have shown that reperfusion‐induced cardiac arrhythmias can be consistently elicited in the anaesthetized rat and that they are particularly susceptible to drugs that can block the fast inward sodium current. 1984 British Pharmacological Society