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 X kg-1 X 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 X kg-1 X 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.