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.
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.
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DOI：
10.1186/s12871-015-0049-1
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发表时间：
2015-04-30
影响因子：
2.2
通讯作者：
Xu X
中科院分区：
文献类型：
--
作者：
Liu F;Wu B;Du Y;Wu Y;Chen H;Xia F;Jin Z;Xu X
肾上腺素是心肺复苏的一线药物，但其在治疗布比卡因引起的心脏毒性方面的疗效仍存在疑问。我们假设肾上腺素可以通过调节大鼠心室肌细胞膜通道的离子流动来逆转布比卡因对心脏的抑制作用。本研究的目的是观察和报道肾上腺素对高浓度布比卡因诱导的大鼠心室肌细胞钠（INa）、l型钙（ICa-L）和瞬时外向钾（Ito）电流的抑制作用。采用急性酶解法分离Sprague-Dawley大鼠（250 ~ 300 g）心室肌细胞。采用全细胞膜片钳技术记录给药前后单个心室肌细胞的离子通道电流。布比卡因100 μmol/L显著降低了INa （P < 0.05）。100 μmol/L布比卡因与0.15 μmol/ ml肾上腺素联合使用对INa恢复无明显影响。布比卡因给药100 μmol/L后，ICa-L和Ito明显下降（P < 0.05）。与INa相比，上述布比卡因与肾上腺素联合用药后，ICa-L和Ito明显改善（P < 0.05）。肾上腺素可以逆转高浓度布比卡因诱导的ICa-L和Ito抑制，但不能逆转INa。因此，肾上腺素在逆转布比卡因引起的继发于钠通道抑制的心脏毒性方面的有效性可能有限。
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. 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. 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). 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.
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影响因子：
10.8
作者：
Köster, OF;Szigeti, GP;Beuckelmann, DJ
通讯作者：
Beuckelmann, DJ
影响因子：
5.7
作者：
Harvey, Martyn;Cave, Grant;Lahner, Daniel
通讯作者：
Lahner, Daniel
影响因子：
3.1
作者：
SHIBUYA, N;MOMOSE, Y;ITO, Y
通讯作者：
ITO, Y
影响因子：
8.2
作者：
Wang, Hong-wei;Yang, Zhi-fang;Li, Ci-zhen
通讯作者：
Li, Ci-zhen
影响因子：
5.7
作者：
HEAVNER, JE;PITKANEN, MT;ROSENBERG, PH
通讯作者：
ROSENBERG, PH