Proarrhythmic and Antiarrhythmic Effects of Bupivacaine in an In Vitro Model of Myocardial Ischemia and Reperfusion

Background: Bupivacaine may have toxic cardiovascular effects when accidentally administered by intravascular injection. However, its electrophysiologic effects in the presence of myocardial ischemia remain unknown. The authors evaluated the electrophysiologic and anti- and proarrhythmic effects of bupivacaine in an in vitro model of the ischemic and reperfused myocardium.

Methods: In a double-chamber bath, a guinea pig right ventricular muscle strip was subjected partly to normal conditions and partly to simulated ischemia followed by reperfusion. The electrophysiologic effects of bupivacaine were studied at 1, 5, and 10 micro Meter concentrations.

Results: Bupivacaine (5 and 10 micro Meter) decreased the maximal upstroke velocity of the action potential (Vmax) in normoxic conditions and further decreased (10 micro Meter) the Vmax decrease induced by ischemic conditions. Bupivacaine reduced the mean occurrence time to the onset of myocardial conduction blocks (9 +/- 3 min; mean +/- SD; P < 0.005 with 5 and 10 micro Meter, compared with 17 +/- 6 min during simulated ischemia with no drug or control), and it increased the number of preparations that became inexcitable to pacing (55% of preparations, with 1 micro Meter and 100% with 5 and 10 micro Meter, compared with 17% for the control group). The incidence of spontaneous arrhythmias was reduced by 5 and 10 micro Meter bupivacaine during ischemia and reperfusion and was enhanced by 1 micro Meter bupivacaine during the ischemic phase.