title: Regional myocardial lidocaine concentration determines the antidysrhythmic effect in dogs after coronary artery occlusion.
abstract: 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.
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D003326:Coronary Circulation; D003327:Coronary Disease / Q000097:blood / Q000150:complications / Q000378:metabolism*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007275:Injections, Intravenous; D007700:Kinetics; D008012:Lidocaine / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000378:metabolism / Q000517:prevention & control; D009206:Myocardium / Q000032:analysis / Q000378:metabolism*
chemical_list: D008012:Lidocaine