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 (INa), L-type calcium (ICa-L), and transient outward potassium (Ito) 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.


RESULTS
Administration of bupivacaine 100 μmol/L significantly reduced INa, (P < 0.05). However, administration of bupivacaine 100 μmol/L in conjunction with epinephrine 0.15 μg/ml had no effect in restoring INa to its previous state. Similarly, a sharp decline of ICa-L and Ito was observed after administration of bupivacaine 100 μmol/L (P < 0.05). In contrast to INa, ICa-L and Ito were significantly improved after the administration of the aforementioned combination of bupivacaine and epinephrine (P < 0.05).


CONCLUSIONS
Epinephrine can reverse high-concentration bupivacaine induced inhibition of ICa-L and Ito, but not INa. Thus, epinephrine's effectiveness in reversal of bupivacaine-induced cardiac toxicity secondary to sodium channel inhibition may be limited.
Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Road, 325000, Zhejiang, China. 903321930@qq.com.
Fuli
F
Liu
Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Road, 325000, Zhejiang, China. doudou198251@sina.com.
Bingjing
B
Wu
Environment and health institute, Wenzhou Medical University, Zhejiang, China. 75140942@qq.com.
Yongjun
Y
Du
Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Road, 325000, Zhejiang, China. wuyiquanspring@126.com.
Yiquan
Y
Wu
Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Road, 325000, Zhejiang, China. chhfei@126.com.
Hongfei
H
Chen
Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Road, 325000, Zhejiang, China. helenxia4271@yahoo.com.cn.
Fangfang
F
Xia
Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Road, 325000, Zhejiang, China. jzs185190370@163.com.
Zhousheng
Z
Jin
Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Road, 325000, Zhejiang, China. xuzhong@263.net.
Xuzhong
X
Xu
D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004837:Epinephrine / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects*
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D002045:Bupivacaine; D004837:Epinephrine