Regional myocardial lidocaine concentration determines the antidysrhythmic effect in dogs after coronary artery...

Ischemic ventricular dysrhythmias were produced in 40 of 47 anesthetized mongrel dogs by high ligation of the left anterior descending coronary artery. Dysrhythmias were treated with a single iv bolus of 20, 40, 80, or 120 mg of lidocaine (L) in order to determine the dose at which approximately 50% of animals had an antidysrhythmic response. Cardiac output and regional myocardial blood flow (RMBF) were measured by using radionuclide labeled microspheres. Lidocaine concentration [( L]) was measured from samples of arterial and venous blood and normal and ischemic myocardium. All dogs treated with 40, 80, or 120 mg of L had an antidysrhythmic effect. However, with 20 mg of L the dysrhythmia persisted in 12 and resolved in 14. With 20 mg of L, ischemic myocardial [L] was greater in dogs with an antidysrhythmic effect than in those with persistent dysrhythmias (1.14 +/- 0.12 vs. 0.76 +/- 0.04 micrograms X g-1), but no difference was seen for arterial, venous, and normal myocardial [L]. Ischemic RMBF was higher in the dogs that had an antidysrhythmic effect than in those that did not, 9.8 +/- 1.5 versus 6.9 +/- 1.3% of normal. With 20 mg of L, [L] in ischemic myocardium correlated well with ischemic RMBF. The antidysrhythmic response to L had a threshold at a tissue concentration of greater than or equal to 1.0 microgram X g-1 (chi-square = 8.55, P less than 0.005). For this model, the [L] in ischemic myocardium during acute ischemia correlates with the antidysrhythmic response to L, while the concentration in normal myocardium or blood does not.