Cao Ying, Song Yingnan, Wang Zijun, Tang Jian, Yi Jing, Liu Yanqiu, An Li, Pan Zhijun, Gao Hong
School of Clinical Medicine, Guizhou Medical University, Guiyang, China.
Department of Anesthesiology, The Affiliated Jinyang Hospital of Guizhou Medical University, The Second People's Hospital of Guiyang, Guiyang, China.
Ann Transl Med. 2022 Jul;10(14):772. doi: 10.21037/atm-22-2614.
Esketamine is favored in clinical settings. Relative to other anesthetics it preserves protective airway reflexes, maintains spontaneous respiration, stabilizes hemodynamics, and alleviates neuropathic pain. This study sought to evaluate the cardiac safety of esketamine at 3 sub-anesthetic gradient concentrations.
We examined the cardiac electrophysiological effects of esketamine with infusion rates of 0.125, 0.25, and 0.5 mg·kg·h. Short-term studies were performed in ventricular myocytes using patch-clamp techniques and optically mapped Langendorff-perfused guinea-pig hearts. Long-term studies were performed using Langendorff-perfused guinea-pig hearts and electrically mapping the receipt of the infusion for 3 hours.
Esketamine changed the action potential (AP) morphology of cardiomyocytes. Notably, it increased the resting membrane potential (RMP), attenuated the amplitude of action potential (APA), reduced the maximum upstroke velocity (Vmax), and shortened the action potential duration (APD) at 30% to 70%, which led to relatively prolonged monophasic action potentials (MAP) triangulation in G and G. All the effects were partially eluted. Optical mapping demonstrated almost equal and heterogeneous conduction. G resulted in an increased heart rate (HR) accompanied by a shortened APD. No detectable arrhythmia was observed at the cycle lengths (CLs) used. Long-term electrical mapping demonstrated the dose-dependent deceleration of the Vmax and APA, but only prolonged the AP parameters in G. Left-ventricular isochronal conduction maps revealed the conduction heterogeneities at G, and conduction velocity (CV) was increased in G and G None of these effects were reversed on drug washout. Electrocardiogram (ECG) traces revealed an accelerated HR with the associated curtailment of QT intervals in G; HRs were decreased in G and G; the PR intervals and QRS duration differed between G and G, G, which elicited electrical alternans. Connexin43 (Cx43) expression were significantly decreased in G, G and G.
These data provide a basic electrophysiology for esketamine. Specifically, we found that (I) various methods of esketamine infusion had different effects on cardiac conduction at different dosages; (II) the heterogeneous expression of Cx43 is associated with spatially dispersed conduction; and (III) potential cardiac risks should be considered for high-risk patients receiving continuous esketamine infusions of high dosages.
艾氯胺酮在临床环境中受到青睐。相对于其他麻醉剂，它能保留保护性气道反射、维持自主呼吸、稳定血流动力学并减轻神经性疼痛。本研究旨在评估3个亚麻醉梯度浓度的艾氯胺酮的心脏安全性。
我们以0.125、0.25和0.5mg·kg·h的输注速率研究了艾氯胺酮的心脏电生理效应。短期研究在心室肌细胞中使用膜片钳技术和光学映射的Langendorff灌注豚鼠心脏进行。长期研究使用Langendorff灌注豚鼠心脏并对输注3小时的情况进行电映射。
艾氯胺酮改变了心肌细胞的动作电位（AP）形态。值得注意的是，它增加了静息膜电位（RMP），减弱了动作电位幅度（APA），降低了最大上升速度（Vmax），并使动作电位持续时间（APD）在30%至70%缩短，这导致G和G中单相动作电位（MAP）三角测量相对延长。所有这些效应均部分消退。光学映射显示传导几乎相等且不均匀。G导致心率（HR）增加，同时APD缩短。在所使用的心动周期长度（CL）下未观察到可检测到的心律失常。长期电映射显示Vmax和APA呈剂量依赖性减慢，但仅在G中延长了AP参数。左心室等时传导图显示G处存在传导不均匀性，G和G中的传导速度（CV）增加。这些效应在药物洗脱时均未逆转。心电图（ECG）记录显示G中HR加快，QT间期相应缩短；G和G中HR降低；G与G、G之间的PR间期和QRS持续时间不同，G引发了电交替现象。G、G和G中连接蛋白43（Cx43）表达显著降低。
这些数据为艾氯胺酮提供了基本的电生理学依据。具体而言，我们发现（I）不同剂量的艾氯胺酮输注方法对心脏传导有不同影响；（II）Cx43的不均匀表达与空间分散的传导有关；（III）对于接受高剂量艾氯胺酮持续输注的高危患者，应考虑潜在的心脏风险。
