[Mechanisms of the cardiac toxicity of bupivacaine].

Of all the amide local anaesthetics, bupivacaine is said to be the most cardiotoxic. This toxicity is seen mostly when there is a sudden increase in the plasma concentration of bupivacaine. It involves both, or either, electrical and mechanical structures within the heart. The main site of action on cardiac conduction tissue is the Vmax of phase 0 of the action potential of fast-reacting structures (INa current). Bupivacaine, like lidocaine and the other class I antiarrhythmic drugs, blocks the sodium channels, this block being more slowly reversible. The disturbance of sodium channels throughout the heart leads to a decreased conduction speed throughout the conduction system, thus explaining possible acute conduction disturbances originating below the bundle of His. The ventricular dysrhythmias described are due to a re-entry circuit secondary to a slowing in conduction speed. However, the sinus bradycardias and junctional disturbances seen in toxic accidents are probably due to an inhibition of the slow current of the atrial and atrio-ventricular nodes (Isi current). The experimental observation of an increase in the atrial monophase potential and the corrected QT interval suggests that repolarization currents are also involved (IK current ?). It would therefore seem that modifications in membrane permeabilities are the cause of the seriousness of the clinical picture. Bupivacaine, at toxic levels, has a direct effect on contractility. The negative inotropic effects seem to be due to a fall in the intracytoplasmic calcium concentration on which depends the excitation-contraction couple, as well as disturbed cellular energetic events dependent on the contraction.(ABSTRACT TRUNCATED AT 250 WORDS)