Cardiovasc Toxicol. 2026 May 18;26(6):51. doi: 10.1007/s12012-026-10122-x.
ABSTRACT
Local anesthetics are widely used in medical care. However, their sodium channel blocking properties not only explain their analgesic potency but also their possible cardiotoxic effects. Due to the different pharmacodynamics and pharmacokinetics of different local anesthetics as well as the divergent cellular electrophysiological effects, we aimed to investigate and compare the electrophysiological effects of different local anesthetics in an established Langendorff model of the isolated rabbit heart. 50 hearts of New Zealand White rabbits were retrogradely perfused employing a Langendorff-setup. Eight catheters were placed endo- and epicardially, thereby recording monophasic action potentials. Hearts were paced at seven different cycle lengths (300-900 ms), thus obtaining cycle-length dependent action potential duration at 90% of repolarization (APD), QT intervals and dispersion of repolarization. In addition, burst pacing was utilized to assess ventricular vulnerability. Thereafter, bradycardic AV-blocked hearts were perfused with a hypokalemic solution to enhance the occurrence of triggered activity. After generating baseline data, the hearts were assigned to four groups: In group 1, hearts were treated with 25 µM, and 50 µM lidocaine. Group 2 was perfused with 25 µM, and 50 µM mepivacaine. Group 3 was perfused with 0.5 µM, and 1 µM bupivacaine. Group 4 was perfused with 5 µM, and 10 µM ropivacaine. As expected, perfusion with all local anesthetics led to a significant prolongation of the effective refractory period as a result of sodium channel blockade. Perfusion with bupivacaine and ropivacaine resulted in pronounced cardiotoxic effects, characterized by electromechanical uncoupling or loss-of-capture phenomena, in the majority of hearts. Perfusion with mepivacaine and ropivacaine resulted in the comparatively most pronounced prolongation of the effective refractory period. Accompanied by a pronounced dispersion of repolarization, the highest incidence of ventricular tachycardia and ventricular fibrillation episodes was observed during perfusion with bupivacaine. Perfusion with the local anesthetics showed pronounced electrophysiological effects, which differed between the various local anesthetics. Bupivacaine showed the most pronounced cardiotoxic effects even at low doses.
PMID:42149351 | DOI:10.1007/s12012-026-10122-x