Experimental evidence in favor of role of intracellular actions of bupivacaine in myocardial depression

Bupivacaine is more cardiodepressant than lidocaine. Nevertheless, the marked depression of contractility induced by bupivacaine cannot be completely explained by its electrophysiologic properties alone. Biophysical differences such as the greater lipid solubility of bupivacaine versus lidocaine must be taken into consideration. Perhaps more bupivacaine enters the cardiac cells and interacts with contractile processes. To test this hypothesis, the entry of lidocaine into the cells was facilitated by a membrane-permeant lipophilic anion, tetraphenylboron. We compared the spontaneous atrial rate and the contractile force of rabbit right atria bathing in solutions containing either 0.5 μg/mL lidocaine or bupivacaine. Group 1 (n = 8) served to test the stability of the preparation. In group 2 (n = 6), tetraphenylboron (17 μg/mL) was added to Tyrode's solution; atrial rate was decreased by 8% and contractile force by 1.7%. In group 3 (n = 6), bupivacaine (0.5 μg/mL) was added; bupivacaine decreased atrial rate by 11.3% and markedly de-pressed contractile force by 68.3%. In group 4 (n = 6), lidocaine (0.5, μg/mL) was added; lidocaine did not change atrial rate but decreased contractile force by 6.0%. In group 5 (n = 6), both lidocaine and tetraphenylboron were added; atrial rate was decreased by 15.5% and contractile force was markedly de-pressed by 81.1%. In group 6 (n = 6), 0.2 mM adenosine triphosphate, tetraphenylboron, and then lidocaine were added; the addition of adenosine triphosphate partially counteracted the cardiodepressant effects of the combination of lidocaine and tetraphenylboron. Atrial rate was decreased by 10.4% and contractile force was depressed by 13.6%. The authors conclude that the mechanism of myocardial depression induced by bupivacaine can be explained at least in part by the easier access of bupivacaine into the myocardial cell.