Hanouz Jean-Luc, Repesse Yohann, Zhu Lan, Lemoine Sandrine, Rouet René, Sallé Laurent, Plaud Benoît, Gérard Jean-Louis
Département d'Anesthésie réanimation, CHU de Caen, Ave. Côte de Nacre, 14033 Caen Cedex, France.
Anesth Analg. 2008 Feb;106(2):365-70, table of contents. doi: 10.1213/ane.0b013e31816052b6.
Etomidate and ketamine are used during induction of anesthesia in high-risk patients. However, their effects on action potential (AP) variables and ischemia/reperfusion-induced arrhythmias and conduction blocks are unknown.
Guinea pig right ventricular muscle strips were mounted in a 5-mL double chamber bath with the strips separated into two zones by an impermeable latex membrane. One-half (normal zone) was exposed to normal perfusate while the other half (altered zone) was exposed to hypoxia, hyperkalemia, acidosis, and lack of glucose. AP variables were recorded continuously in the normal and altered zones. Spontaneous arrhythmias and conduction blocks were noted. Etomidate (10(-7), 10(-6), and 10(-5) M) and ketamine (10(-6), 10(-5), and 10(-4) M) were superfused into the bath throughout the experiment and the electrophysiologic effects compared with the control group.
We found that under control conditions, etomidate and ketamine did not modify resting membrane potential, maximal upstroke velocity, AP amplitude, or AP duration at 90% of repolarization (APD90). Ketamine (10(-4) M), but not weaker concentrations and none of the concentration of etomidate, reversed the ischemia-induced shortening of APD90 and APD dispersion. Etomidate and ketamine did not modify the occurrence of conduction block during simulated ischemia. In contrast, ketamine (25% at 10(-6) M, 13% at 10(-5) M, and 13% at 10(-4) M vs 90% in the control group, P < 0.05) but not etomidate (38% at 10(-7) M, 63% at 10(-6) M, and 63% at 10(-5) M vs 90% in the control group, NS) decreased the incidence of reperfusion-induced spontaneous arrhythmias.
In guinea pig myocardium, our data suggest that ketamine, in clinically relevant concentrations, decreases ischemia-induced AP shortening and spontaneous reperfusion-induced ventricular arrhythmias. Further study is required to precisely determine the effect of etomidate on reperfusion-induced arrhythmias.
依托咪酯和氯胺酮用于高危患者的麻醉诱导。然而，它们对动作电位（AP）变量以及缺血/再灌注诱导的心律失常和传导阻滞的影响尚不清楚。
将豚鼠右心室肌条置于5毫升双腔浴槽中，肌条被不透水的乳胶膜分隔为两个区域。一半（正常区）暴露于正常灌注液，另一半（改变区）暴露于缺氧、高钾血症、酸中毒和无糖环境。连续记录正常区和改变区的AP变量。记录自发性心律失常和传导阻滞情况。在整个实验过程中，将依托咪酯（10⁻⁷、10⁻⁶和10⁻⁵ M）和氯胺酮（10⁻⁶、10⁻⁵和10⁻⁴ M）灌注到浴槽中，并将电生理效应与对照组进行比较。
我们发现，在对照条件下，依托咪酯和氯胺酮不改变静息膜电位、最大除极速度、AP幅度或复极化90%时的AP持续时间（APD90）。氯胺酮（10⁻⁴ M），而非较低浓度的氯胺酮以及任何浓度的依托咪酯，可逆转缺血诱导的APD90缩短和APD离散度。依托咪酯和氯胺酮不改变模拟缺血期间传导阻滞的发生情况。相比之下，氯胺酮（10⁻⁶ M时为25%，10⁻⁵ M时为13%，10⁻⁴ M时为13%，而对照组为90%，P < 0.05），但依托咪酯（10⁻⁷ M时为38%，10⁻⁶ M时为63%，10⁻⁵ M时为63%，而对照组为90%，无显著性差异）可降低再灌注诱导的自发性心律失常的发生率。
在豚鼠心肌中，我们的数据表明，临床相关浓度的氯胺酮可减少缺血诱导的AP缩短和自发性再灌注诱导的室性心律失常。需要进一步研究以精确确定依托咪酯对再灌注诱导的心律失常的影响。
