Napolitano C A, Raatikainen M J, Martens J R, Dennis D M
Department of Anesthesiology, University of Florida College of Medicine, Gainesville 32610-0254, USA.
Anesthesiology. 1996 Aug;85(2):393-402. doi: 10.1097/00000542-199608000-00022.
Supraventricular tachydysrhythmias such as atrial fibrillation frequently complicate the perioperative period. Two electrophysiologic factors critical to the pathogenesis of supraventricular tachydysrhythmias are: 1) atrial wavelength, the product of atrial conduction velocity (CV) and effective refractory period (ERP), and 2) atrioventricular nodal conduction. Modulation of these factors by drugs has important clinical ramifications. The authors studied the effects of propofol, thiopental, and ketamine on atrial wavelength and atrioventricular nodal function in guinea pig isolated atrial trabeculae and hearts, respectively.
Electrocardiogram recordings in superfused atrial tissue were obtained using hanging microelectrodes. A stimulating and two recording electrodes were placed on a single atrial trabecula, and the interelectrode distance was measured. Atrial ERP determinations were made using a premature stimulus protocol. The time (t) required for a propagated impulse to traverse the interelectrode distance (d) was measured. Conduction velocity was calculated as d/t. Langendorff-perfused guinea pig hearts were instrumented for low atrial pacing (cycle length = 300 ms) and for measurements of stimulusto-His bundle interval, an index of atrioventricular nodal conduction. To investigate the frequency-dependent behavior of the atrioventricular node, computer-based measurements were made of Wenckebach cycle length (WCL) and atrioventricular nodal ERP.
Thiopental significantly prolonged atrial ERP in a concentration-dependent manner, whereas propofol and ketamine had no significant effect on atrial refractoriness. In contrast, ketamine caused a dose-dependent decrease in atrial CV, but propofol and thiopental had no significant effect on CV. Therefore, thiopental, ketamine, and propofol caused an increase, a decrease, and no change, respectively, in atrial wavelength. All anesthetics caused a concentration-dependent prolongation of the stimulus-to-His bundle interval, atrioventricular nodal ERP, and WCL. However, on an equimolar basis, significant differences in potencies were found. The concentrations of drug that caused a 20% increase in ERP (ERP20) and WCL (WCL20) for propofol, thiopental, and ketamine were 14 +/- 2 microM, 26 +/- 3 microM, and 62 +/- 11 microM, and 17 +/- 2 microM, 50 +/- 1 microM, and 123 +/- 19 microM (mean +/- SEM), respectively. Therefore, the rank order of potency for frequency-dependent atrioventricular nodal effects is propofol > thiopental > ketamine.
The authors' results indicate that propofol would be most effective at filtering atrial impulses during supraventricular tachydysrhythmias, whereas thiopental would be most effective at preventing atrial reentrant dysrhythmias. In contrast, ketamine may be most likely to promote atrial reentry while having minimal effect on atrioventricular nodal conduction.
室上性快速心律失常，如心房颤动，在围手术期经常出现并发症。对于室上性快速心律失常的发病机制至关重要的两个电生理因素是：1）心房波长，即心房传导速度（CV）与有效不应期（ERP）的乘积；2）房室结传导。药物对这些因素的调节具有重要的临床意义。作者分别研究了丙泊酚、硫喷妥钠和氯胺酮对豚鼠离体心房小梁和心脏的心房波长及房室结功能的影响。
使用悬挂微电极在灌流的心房组织中记录心电图。将一个刺激电极和两个记录电极置于单个心房小梁上，并测量电极间距离。使用早搏刺激方案测定心房ERP。测量传播冲动穿过电极间距离（d）所需的时间（t）。传导速度计算为d/t。对Langendorff灌流的豚鼠心脏进行仪器化处理，用于低位心房起搏（周期长度 = 300 ms）以及测量刺激至希氏束间期，这是房室结传导的一个指标。为了研究房室结的频率依赖性行为，采用计算机测量文氏周期长度（WCL）和房室结ERP。
硫喷妥钠以浓度依赖性方式显著延长心房ERP，而丙泊酚和氯胺酮对心房不应期无显著影响。相比之下，氯胺酮导致心房CV呈剂量依赖性降低，但丙泊酚和硫喷妥钠对CV无显著影响。因此，硫喷妥钠、氯胺酮和丙泊酚分别使心房波长增加、降低和无变化。所有麻醉药均导致刺激至希氏束间期、房室结ERP和WCL呈浓度依赖性延长。然而，在等摩尔基础上，发现效价存在显著差异。使丙泊酚、硫喷妥钠和氯胺酮的ERP（ERP20）和WCL（WCL20）增加20%的药物浓度分别为14±2 microM、26±3 microM和62±11 microM，以及17±2 microM、50±1 microM和123±19 microM（平均值±标准误）。因此，频率依赖性房室结效应的效价顺序为丙泊酚 > 硫喷妥钠 > 氯胺酮。
作者的结果表明，在室上性快速心律失常期间，丙泊酚对于滤过心房冲动最为有效，而硫喷妥钠对于预防心房折返性心律失常最为有效。相比之下，氯胺酮可能最容易促进心房折返，而对房室结传导的影响最小。
