Effects of lidocaine on catecholamine release in the ischemic rat heart.
The effects of lidocaine (5 or 10 mg/kg bolus + 2.5 mg/kg/h) on arrhythmias and changes in myocardial and plasma catecholamines (CAs) after left coronary artery occlusion were investigated in anesthetized rats. Myocardial intraneuronal CAs were assessed histofluorimetrically and CA concentrations were measured using high-pressure liquid chromatography (HPLC). Both doses of lidocaine caused reductions in heart rate and blood pressure. The higher dose significantly reduced the number of ischemia-induced ventricular extrasystoles from 425 +/- 123 to 25 +/- 12 in the first 60 min of ischemia and abolished ventricular tachycardia and fibrillation. In the myocardium of untreated animals, the area of fluorescing adrenergic neurons (as percentage of total field area) was 0.42 +/- 0.02% after 60 min of ischemia as compared with 1.38 +/- 0.17% in sham-operated animals. Lidocaine pretreatment resulted in a dose-dependent inhibition of this ischemia-induced CA release from adrenergic neurons (0.96 +/- 0.06 and 1.30 +/- 0.05% for the lower and higher dose, respectively). Tissue and plasma CA concentrations were not significantly affected by lidocaine pretreatment and by coronary occlusion. It is concluded that lidocaine inhibits CA release from sympathetic nerve endings in the ischemic myocardium by its endoanesthetic and membrane-stabilizing properties. The reduction in CA release may also contribute to its antiarrhythmic effects.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003327:Coronary Disease / Q000378:metabolism*; D004837:Epinephrine / Q000097:blood*; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains
D008012:Lidocaine; D009638:Norepinephrine; D004837:Epinephrine