Gantenbein M, Attolini L, Bruguerolle B
Medical and Clinical Pharmacology Laboratory, Faculty of Medicine of Marseilles, France.
Can J Anaesth. 1996 Aug;43(8):871-6. doi: 10.1007/BF03013042.
The mechanisms of action of local anaesthetics and potassium channel agonists (PCAs) may interfere by acting in a direct or indirect manner on the same ion channels. In a previously reported study, the bupivacaine-induced mortality was shown to be modified in different ways by four PCAs tested (diazoxide (D), levcromakalim (L), nicorandil (N) and pinacidil (P)) since bupivacaine-induced mortality was increased by high doses of P and L, decreased by N and stayed unchanged by D. The present study was designed to document the changes in bupivacaine (B) local anaesthetic activity in mice after a single injection of one of the four PCAs (D, L, N and P).
Each PCA was tested at three different dosages. Controls received saline. The local anaesthetic activity was evaluated using sciatic nerve blockade. After injection of bupivacaine in the region of the sciatic nerve, the local anaesthetic activity was estimated as the loss of motor control of the injected limb.
PCA treatment increased (P = 0.0001) the time needed for recovery from bupivacaine-induced local anaesthesia. The area under the effect vs time curve, assessing the total anaesthetic effect, was greater for N (P = 0.0016) and P (P = 0.038) but not for L (P = 0.11). Compared with controls, the maximal effect (Emax) was less for D (P = 0.009) and N (P = 0.038) but not for L (P = 0.185) or P (P = 0.45) treated groups. The injection of the PCA in the region of the sciatic nerve of the right hindlimb did not induce any alteration of the motor activity of the injected limb.
The four PCAs decreased the maximal local anaesthetic effect and increased the duration of action of bupivacaine.
局部麻醉药和钾通道激动剂（PCAs）的作用机制可能通过直接或间接作用于相同离子通道而相互干扰。在先前报道的一项研究中，四种受试PCAs（二氮嗪（D）、左卡尼汀（L）、尼可地尔（N）和匹那地尔（P））以不同方式改变了布比卡因诱导的死亡率，因为高剂量的P和L增加了布比卡因诱导的死亡率，N降低了该死亡率，而D使其保持不变。本研究旨在记录单次注射四种PCAs（D、L、N和P）之一后小鼠体内布比卡因（B）局部麻醉活性的变化。
每种PCAs均以三种不同剂量进行测试。对照组给予生理盐水。使用坐骨神经阻滞评估局部麻醉活性。在坐骨神经区域注射布比卡因后，局部麻醉活性通过注射肢体运动控制丧失来估计。
PCAs治疗增加了（P = 0.0001）从布比卡因诱导的局部麻醉中恢复所需的时间。评估总麻醉效果的效应-时间曲线下面积，N（P = 0.0016）和P（P = 0.038）更大，但L（P = 0.11）并非如此。与对照组相比，D（P = 0.009）和N（P = 0.038）治疗组的最大效应（Emax）较小，但L（P = 0.185）或P（P = 0.45）治疗组并非如此。在右后肢坐骨神经区域注射PCAs未引起注射肢体运动活性的任何改变。
四种PCAs降低了布比卡因的最大局部麻醉效果并延长了其作用持续时间。
