EFFECT OF PROGESTERONE ON THE CARDIAC ELECTROPHYSIOLOGIC ALTERATIONS PRODUCED BY ROPIVACAINE AND BUPIVACAINE

Bupivacaine-induced cardiotoxicity is enhanced in pregnant laboratory animals and in progesterone-pretreated isolated cardiac tissues. Ropivacaine is a new local anesthetic chemically related to bupivacaine. Although clinically equipotent with bupivacaine, ropivacaine is less cardiodepressant. Progesterone levels are elevated during pregnancy, and exogenously increasing progesterone levels in rabbits has increased bupivacaine's depressive effects on excitability. In neural tissues, bupivacaine's increased onset of block and depression of compound action potentials in tissues from progesterone-treated animals was similar to its effect in nerves from pregnant animals. This study determined whether exogenously increased progesterone levels can increase myocardial sensitivity to ropivacaine. Female ovariectomized rabbits were pretreated with progesterone for 4 days. After killing, the hearts were removed and Purkinje fibers (PFs) and ventricular muscle (VM) action potential parameters recorded. Tissues from animals receiving either progesterone or placebo were exposed to either ropivacaine or bupivacaine at concentrations ranging from 3.5 to 18.7 muM. Preparations were routinely paced at 2 Hz except where rate-dependent effects on the maximal rate of depolarization of phase zero (V(max)) were determined. Progesterone increased depression of myocardial V(max) only to bupivacaine (P < 0.05). Ropivacaine was generally 3-5 times less potent in depressing cardiac electrophysiologic parameters. Bupivacaine demonstrated rate-dependent depression of V(max) that at higher frequencies was greater than ropivacaine's effects (P < 0.05). Ropivacaine is less cardiodepressant than bupivacaine in this isolated PF-VM preparation. Exogenously increasing progesterone levels in vivo does not increase ropivacaine's depression of myocardial V(max) in isolated PF-VM tissues as it does to bupivacaine. The rate-dependent effects of ropivacaine are less than those of bupivacaine, especially at higher stimulating frequencies.