Effects of lidocaine on isolated, blood-perfused ventricular contractility in the dog.
Direct inotropic effects of lidocaine on ventricular muscle were investigated in isolated canine left ventricular preparations which were perfused with a donor dog's arterial blood. Intravenous administration of lidocaine in doses of less than 1 mg/kg did not cause any significant hemodynamic or cardiac changes in the donor dog and in the isolated ventricular preparation. A large dose of 10mg/kg of lidocaine produced a marked depressor response in the donor and a negative inotropic effect in the isolated ventricle. Direct injection of lidocaine (1-30 micromol) to the isolated preparation induced a dose-related decrease in the ventricular contractile force. Infusion of lidocaine (3 micromol/ml per min) did not influence norepinephrine- or calcium chloride-induced positive inotropic effects. In the frequency-force relationship, lidocaine generally depressed the contractility, exhibiting the positive staircase phenomenon. On the other hand, a calcium entry inhibitor, diltiazem, readily caused the negative staircase. From these results, it is concluded that (1) a large amount of lidocaine has a cardiac depressant property, (2) lidocaine has no antiadrenergic properties, and (3) the action of lidocaine may probably be due to the effect of intracellular calcium movement but not to a modification of Ca inward currents.
Tsuboi
M
M
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Chiba
S
S
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D008012:Lidocaine; D004110:Diltiazem; D002122:Calcium Chloride; D002118:Calcium; D009638:Norepinephrine