STEREOSPECIFIC EFFECT OF BUPIVACAINE ISOMERS ON ATRIOVENTRICULAR-CONDUCTION IN THE ISOLATED-PERFUSED GUINEA-PIG HEART

Background: The local anesthetic bupivacaine is an equal mixture of tw o optically active isomers known to exert different cardiotoxic profil es in vivo. Enantiomer-specific forms of bupivacaine may have differen tial effects on cardiovascular function, specifically can cardiac elec trophysiology. The authors' aim was to determine if there mere any dir ect functional differences in the cardiac effects of bupivacaine isome rs. The isolated heart was used to avoid possible indirect cardiac eff ects of bupivacaine, such as autonomic nervous and hormonal influences , as well as preload and afterload factors. Methods: The hearts of 12 ketamine-anesthetized guinea pigs mere perfused with Krebs-Ringer's so lution (97% oxygen, 3% carbon dioxide) at constant perfusion pressure using the Langendorff technique. Atrial and ventricular bipolar electr odes mere placed to measure heart rate (HR) and atrioventricular (AV) conduction time. Left ventricular pressure (LVP), coronary flow, and i nflow and outflow oxygen tensions were also measured. Oxygen delivery, oxygen consumption (MVO(2)), and percentage of oxygen extraction were calculated. Each heart was perfused with increasing randomized concen trations (0.5, 1, 5, 10 mu M) of both isomers and the racemate of bupi vacaine. Results: Racemic and isomeric bupivacaine equally and dose de pendently decreased cardiac function. At 10 mu M bupivacaine these cha nges mere HR, -17 +/- 2%; LVP, -50 +/- 3%; coronary flow, -20 +/- 4%; and MVO(2), -46 +/- 4%. The (+) isomer significantly prolonged AV cond uction compared with the racemate and the (-) isomer at all concentrat ions. At 10 mu M, AV time was 54 +/- 6% longer with the (+) isomer and 30 +/- 4% longer with the (+/-) racemate than with the (-) isomer. Th e greater delay in AV time with the (+) than the racemate or (-) isome r led to a second-degree AV dissociation In 10 of 12 of hearts treated with (+) bupivacaine. Conclusions: This study shows that bupivacaine has an enantiomer-specific effect to delay AV conduction and to produc e second-degree API dissociation in the isolated perfused heart. This suggests that bupivacaine Isomers probably have differential effects o n one or more ion-specific channels regulating AV conduction. Other me asured direct cardiac effects of bupivacaine appear to be independent of the isomeric form.