Responses to ligation of a coronary artery in conscious rats and the actions of antiarrhythmics

Abstract

A method for ligating the left anterior descending coronary artery in conscious rats and measuring the resultant cardiovascular responses, arrhythmias, cardiac tissue loss, electrocardiogram (ECG), and mortality is described. Analyses of such responses identified statistically acceptable measures for which precision and interrelationships were defined. Responses to ligation were a variable function of the amount of ligated myocardial tissue. For example, arrhythmia score was a linear function of the square root of the occluded zone size. To test the ability of the model to detect beneficial drugs, verapamil, lidocaine, disopyramide, and quinidine were given. Low doses of verapamil (0.2 mg/kg i.v. + 0.3 mg∙kg−1∙h−1), and of disopyramide (10 mg/kg) had few antiarrhythmic, or other actions, whereas high doses of verapamil (20 mg/kg) and disopyramide (40 mg/kg i.v. repeated) were markedly antiarrhythmic as measured by all indices. Quinidine (20 mg/kg i.v. repeated) was also antiarrhythmic but less so than high dose disopyramide and verapamil. Lidocaine (10 mg/kg i.v. + 5 mg∙kg−1∙h−1) reduced the incidence of ventricular flutter and fibrillation. High-dose verapamil and quinidine, but not disopyramide, increased the number of nonarrhythmic deaths and the incidence of atrioventricular conduction defects.