右美托咪定可增强离体大鼠心脏对布比卡因心脏毒性的耐受
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Dexmedetomidine enhances tolerance to bupivacaine cardiotoxicity in the isolated rat hearts: alpha 2 adrenoceptors were not involved
背景与目的
研究表明右美托咪定可减轻布比卡因引起的心脏毒性，但其作用机制尚不清楚。本研究旨在探讨右美托咪定对布比卡因致离体大鼠心脏毒性的影响，并探讨α2肾上腺素受体在其中的作用。
方 法
大鼠离体心脏经Langendorff装置灌注，K-H液灌注10min后随机分为5组进行实验：（1）Con组，仅灌注KH液；(2) Dex组，KH液灌注5 min后，加入10 nmol/L的右美托咪定；（3）布比卡因组(Bupi)，KH液灌流25min，然后加入布比卡因（50μmol/L）；(4) Bupi + Dex组，KH液灌注5 min，加入10 nmol/L的右美托咪定20 min, KH液 +右美托咪定+布比卡因混合灌注；（5）Bupi+Dex+Yoh组：KH液+育亨宾（α2肾上腺素受体拮抗剂，1μmol/L）联合灌注5min，再加入右旋美托咪定（10nmol/L）20min，最后混合灌注KH液+育亨宾+右旋美托咪定+布比卡因。Con组和Dex组实验灌注持续35 min，其余三组灌注持续至停搏。
结 果
与Bupi组相比，右美托咪定显著延缓了Bupi + Dex组的首次心律失常（P<0.001）和停搏时间。此外，右旋美托咪定也显著增加了Bupi +Dex组心率和心率收缩压乘积（RPP）（P <0.001）。停搏时右美托咪定可增加心脏组织中布比卡因的消耗量（Bupi + Dex vs. Bupi，58.5 6.3 vs. 46.8 5.6 nmol / g，P = 0.003）。右美托咪定对布比卡因心脏毒性的作用未被育亨宾消除。
结 论
右美托咪定可延缓布比卡因诱发的大鼠心律失常和心脏停搏的发生，但α2肾上腺素受体并不参与该过程。
原始文献摘要
Fangfang Xia,Zhousheng Jin, Tingting Lin. Dexmedetomidine enhances tolerance to bupivacaine cardiotoxicity in the isolated rat hearts: alpha 2 adrenoceptors were not involved [J]. BMC Pharmacology and Toxicology. (2019) 20:70
Background: Dexmedetomidine was proved to mitigate bupivacaine-induced cardiotoxicity but mechanism of this ability is still unclear. This study was designed to investigate the direct effects of dexmedetomidine on cardiotoxicity induced by bupivacaine on Langendorff rat heart preparation and the role of alpha 2 adrenoceptors in this process was explored.
Methods: Hearts of rat were isolated, mounted on a Langendorff system. Five experimental groups were assessed after 10 min Krebs-Henseleit buffer (KHB) infusions as follow: (1) Group Con, only KHB was perfused; (2) Group Dex,
KHB was perfused for 5 min, then dexmedetomidine (10 nmol/L) was added; (3) Group Bupi, KHB was perfused for 25 min, then bupivacaine (50 μmol/L) was added; (4) Group Bupi + Dex, KHB was perfused for 5 min, then the dexmedetomidine (10 nmol/L) was added for 20 min, at last a mixture of KHB + dexmedetomidine + bupivacaine
were perfused; (5) Group Bupi + Dex + Yoh, a combination of KHB + yohimbine (alpha 2 adrenoceptor antagonists,1 μmol/L) was perfusion for 5 min, then dexmedetomidine (10 nmol/L) was added for 20 min, at last a mixture of KHB + yohimbine + dexmedetomidine + bupivacaine was perfused. The experimental perfusion was maintained for 35 min in group Con and group Dex, and the experimental perfusion was sustained until asystole in the other three groups.
Results: Compared with group Bupi, dexmedetomidine significantly increased the time to first arrhythmia(P < 0.001) and time to asystole (P < 0.001) in group Bupi + Dex. In addition, dexmedetomidine also significantly increased the time to 25, 50 and 75% reductions in heart rate (P < 0.001) and the time to 25, 50 and 75% reductions in rate-pressure product (P < 0.001) in group Bupi + Dex. Dexmedetomidine increased the cardiac tissue bupivacaine content when asystole (Bupi + Dex vs. Bupi, 58.5 ± 6.3 vs. 46.8 ± 5.6 nmol/g, P = 0.003). The benefit of dexmedetomidine on bupivacaine-induced cardiotoxicity were not eliminated by yohimbine.
Conclusions: Dexmedetomidine could delay the occurrence of bupivacaine-induced arrhythmia and asystole in the isolated rat hearts, but the alpha 2 adrenoceptors were not involved in this process.
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翻译：唐剑 编辑：何幼芹 审校：王贵龙