Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Shangcai village, Nanbaixiang town, Ouhai District, Wenzhou City, 325000, Zhejiang Province, China.
BMC Pharmacol Toxicol. 2019 Nov 21;20(1):70. doi: 10.1186/s40360-019-0371-1.
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.
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.
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.
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.
右美托咪定已被证明可减轻布比卡因的心脏毒性，但这种能力的机制仍不清楚。本研究旨在探讨右美托咪定对布比卡因诱导的 Langendorff 大鼠心脏毒性的直接作用，并探讨 α2 肾上腺素能受体在这一过程中的作用。
大鼠心脏分离后，置于 Langendorff 系统上。在 KHB 输注 10 min 后评估 5 个实验组：（1）Con 组，仅灌注 KHB；（2）Dex 组，灌注 5 min 后加入右美托咪定（10 nmol/L）；（3）Bupi 组，灌注 25 min 后加入布比卡因（50 μmol/L）；（4）Bupi + Dex 组，灌注 5 min 后加入右美托咪定（10 nmol/L）20 min，最后灌注 KHB + 右美托咪定 + 布比卡因混合液；（5）Bupi + Dex + Yoh 组，先灌注 KHB + 育亨宾（α2 肾上腺素能受体拮抗剂，1 μmol/L）5 min，再加入右美托咪定 20 min，最后灌注 KHB + 育亨宾 + 右美托咪定 + 布比卡因混合液。Con 组和 Dex 组的实验灌注持续 35 min，其他三组直到心搏停止。
与 Bupi 组相比，Dex 组中首次心律失常的时间（P < 0.001）和心搏停止的时间（P < 0.001）明显延长。此外，Dex 组还明显延长了心率降低 25%、50%和 75%的时间（P < 0.001）和速率-压力产物降低 25%、50%和 75%的时间（P < 0.001）。当发生心搏停止时，Dex 增加了心脏组织中的布比卡因含量（Bupi + Dex 与 Bupi 相比，58.5 ± 6.3 与 46.8 ± 5.6 nmol/g，P = 0.003）。育亨宾不能消除右美托咪定对布比卡因诱导的心脏毒性的作用。
右美托咪定可延迟布比卡因诱导的离体大鼠心律失常和心搏停止的发生，但 α2 肾上腺素能受体在此过程中不起作用。
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