The mechanism of ropivacaine in GABA_A receptor-mediated cardiotoxicity

Objective: To investigate the mechanism of ropivacaine in GABA_A receptor-mediated cardiotoxicity. Methods: By intravenous injection of ropivacaine into New Zealand white rabbits, we examined the plasma concentration of the drug when cardiotoxicity occurred after intracerebroventricular pretreatment with muscimol (a drug that enhances GABA_A activity) and picrotoxin (a drug that decreases GABA_A activity). Results: Intracerebroventricular infusion of muscimol could significantly prolong the time of ropivacaine-induced cardiotoxicity and significantly increase the plasma concentration of ropivacaine. In contrast, intracerebroventricular infusion of picrotoxin significantly shortened the time of ropivacaine-induced cardiotoxicity and significantly decreased the plasma concentration of ropivacaine. Conclusion: Our results suggest that intravenous injection of ropivacaine produces some of its cardiotoxicity mediated by GABA_A receptor in the central nervous system apart from the drug's own direct cardiotoxicity.