EFFECTS OF PROGESTERONE ON THE CARDIAC ELECTROPHYSIOLOGIC ACTION OF BUPIVACAINE AND LIDOCAINE

Pregnancy is accompanied by an increased cardiac and neural sensitivity to some local anesthetic agents such as bupivacaine. The current study was initiated to investigate the relationship between increased progesterone concentrations and the electrophysiologic effects of bupivacaine, and lidocaine in isolated Purkinje fiber (PF)-ventricular muscle (VM) preparations. Twenty-four oophorectomized female white rabbits were killed after receiving 30 mg.kg-1.day-1 of progesterone intramuscularly or peanut oil alone for 4 days. PF and VM action potentials were recorded using standard electrophysiologic procedures. Plasma progesterone concentrations were 5 +/- 2.9 ng/ml in control animals compared to 59.8 +/- 11.0 ng/ml in progesterone-treated animals (P < 0.05). Bupivacaine (3.5 - 17.4-mu-M) depressed the maximal rate of depolarization (V(max)) of PF to a significantly greater extent in tissues from progesterone-treated animals as compared to control animals. For example, at 3.5 mu-M bupivacaine decreased PF V(max) 52% in progesterone-treated tissues compared to 32% in controls (P < 0.05); the V(max) of V(M) was also depressed to a greater extent in tissues from progesterone-treated animals (P < 0.001). Lidocaine did not demonstrate an enhanced depressant effect in tissues from progesterone-treated animals. These results indicate that progesterone selectively increases the cardiac membrane depressant effects of bupivacaine but not lidocaine. This may contribute to the enhanced toxicity of bupivacaine in pregnant animals.