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 itt 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 mu M concentrations. Results: Bupivacaine (5 and 10 mu M) decreased the maximal upstroke velocity of the action potential (V-max) in normoxic conditions and further decreased (10 mu M) the V-max 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 mu M, 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 mu M and 100% with 5 and 10 mu M, compared with 17% for the control group). The incidence of spontaneous arrhythmias was reduced by 5 and 10 mu M bupivacaine during ischemia and reperfusion and was enhanced by 1 mu M bupivacaine during the ischemic phase. Conclusions: In guinea pig myocardium under ischemic conditions, bupivacaine induced a loss of excitability at concentrations of 5 and 10 mu M. Proarrhythmic effects observed at 1 mu M were considered as lower than the cardiotoxic range in normoxic conditions. The incidence of reperfusion arrhythmias was decreased at all concentrations.