https://doi.org/10.1007/s00392-025-02625-4
1Universitätsklinikum Münster Klinik für Kardiologie II - Rhythmologie Münster, Deutschland
Background:
Local anaesthetics 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 anaesthetics as well as the divergent cellular electrophysiological effects, our aim was to investigate different local anaesthetics in an established Langendorff model of the isolated rabbit heart.
Methods and results:
62 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 (300-900ms), thus obtaining cycle-length dependent action potential duration at 90% of repolarization (APD90), 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 25µM, 50µM, and 100µM Lidocaine. Group 2 was perfused with 0.5µM, 1µM, 5µM Bupivacaine. Group 3 was perfused with 5µM, 10µM, and 25µM Ropivacaine. Group 4 was perfused with 25µM, 50µM, and 100µM Mecaine.
As expected, perfusion with all local anaesthetics led to a significant prolongation of the effective refractory period as a result of sodium channel blockade. Perfusion with Bupivacaine and Ropivacaine led to pronounced cardiotoxic effects with electromechanical uncoupling or loss-of-capture phenomena in the majority of experiments. Perfusion with Mecaine resulted in the comparatively most pronounced prolongation of the effective refractory period. Accompanied by a pronounced dispersion of repolarisation, the highest incidence of ventricular tachycardia and ventricular fibrillation episodes was observed during perfusion with Mecaine.
Conclusion:
Perfusion with the local anaesthetics showed pronounced electrophysiological effects, which differed between the various local anaesthetics. Bupivacaine showed the most pronounced cardiotoxic effects even at low doses, while the most pronounced proarrhythmia was observed with Mecaine.