Epinephrine reversed high-concentration bupivacaine- induced inhibition of calcium channels and transient outward potassium current channels, but not on sodium channel in ventricular myocytes of rats

BACKGROUND: Epinephrine is a first-line drug for cardiopulmonary resuscitation, but its efficacy in the treatment of bupivacaine-induced cardiac toxicity is still in question. We hypothesized that epinephrine can reverse cardiac inhibition of bupivacaine by modulating ion flows through the ventricular myocyte membrane channels of rats. The aim of this study was to observe and report the effects of epinephrine on high-concentration bupivacaine-induced inhibition of sodium (I(Na)), L-type calcium (I(Ca-L)), and transient outward potassium (I(to)) currents in the ventricular myocytes of rats. METHODS: The ventricular myocytes were isolated from Sprague-Dawley rats (250-300 g) by acute enzymatic dissociation. The whole-cell patch clamp technique was used to record the ion channel currents in single ventricular myocytes both before and after administration of medications. RESULT: Administration of bupivacaine 100 μmol/L significantly reduced I(Na), (P < 0.05). However, administration of bupivacaine 100 μmol/L in conjunction with epinephrine 0.15 μg/ml had no effect in restoring I(Na) to its previous state. Similarly, a sharp decline of I(Ca-L) and I(to) was observed after administration of bupivacaine 100 μmol/L (P < 0.05). In contrast to I(Na), I(Ca-L) and I(to) were significantly improved after the administration of the aforementioned combination of bupivacaine and epinephrine (P < 0.05). CONCLUSION: Epinephrine can reverse high-concentration bupivacaine induced inhibition of I(Ca-L) and I(to), but not I(Na). Thus, epinephrine’s effectiveness in reversal of bupivacaine-induced cardiac toxicity secondary to sodium channel inhibition may be limited.