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

• Published in: Anesthesiology (Philadelphia) Vol. 62; no. 2; pp. 155 - 160
• Main Authors: DAVIS, R. F, DEBOER, L. W. V, YASUDA, T, RUDE, R. E, RIBEIRO, L. G. T, MAROKO, P. R
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 01.02.1985
• Subjects: Animals; Antiarythmic agents; Arrhythmias, Cardiac - blood; Arrhythmias, Cardiac - etiology; Arrhythmias, Cardiac - prevention & control; Biological and medical sciences; Cardiovascular system; Coronary Circulation; Coronary Disease - blood; Coronary Disease - complications; Coronary Disease - metabolism; Dogs; Dose-Response Relationship, Drug; Female; Injections, Intravenous; Kinetics; Lidocaine - administration & dosage; Lidocaine - analysis; Lidocaine - metabolism; Male; Medical sciences; Myocardial Infarction - blood; Myocardial Infarction - metabolism; Myocardial Infarction - prevention & control; Myocardium - analysis; Myocardium - metabolism; Pharmacology. Drug treatments; Local anesthetic; Heart rate; Animal; Biological activity; Activity metabolism relation
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/00000542-198502000-00011

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.