In vivo and in vitro bradycardia induced by local anesthetics is potentiated by calcium channel blockers.

The present study examined the interactions of local anesthetics (LA) and calcium channel blockers (CCBs) on rhythmicity of heart using in vivo and in vitro experiments. ECG recordings were made from the anesthetized rats for in vivo preparations and spontaneously beating isolated rat right atrial potential for the in vitro experiments. The in vivo experiments with LA showed dose-dependent bradycardia with lignocaine (LIG, 100-500 microg/kg) and bupivacaine (BUP, 10-100 microg/kg). BUP was 4-5 times more potent than LIG. Verapamil (VML) and diltiazem (DTZ), CCBs also produced dose (10-100 microg/kg) -dependent bradycardia. However, none of them affected the PR/QT interval or QRS complex. Further, LA-induced bradycardia was potentiated by CCBs. In addition, flattening of P-wave in ECG was observed with doses (10-25 microg/kg) of LA in the presence of CCBs. Similarly, the in vitro experiments demonstrated a concentration-dependent decrease in atrial rate by BUP or VML. The BUP-induced decrease was potentiated in the presence of VML. Thus, the results suggest that CCBs potentiate the LA-induced bradycardia by involving pacemaker activity. Further, the flattening of P-wave in ECG serves as an early indicator of the cardiotoxicity produced by these drugs.