Szabó A, Szentandrássy N, Birinyi P, Horváth B, Szabó G, Bányász T, Márton I, Nánási P P, Magyar J
Department of Dentistry, Medical and Health Science Center, University of Debrecen, PO Box 22, 4012 Debrecen, Hungary.
Br J Anaesth. 2007 Nov;99(5):726-33. doi: 10.1093/bja/aem263. Epub 2007 Sep 24.
In spite of its widespread clinical application, there is little information on the cellular cardiac effects of articaine. In the present study, the concentration-dependent effects of articaine on action potential morphology and the underlying ion currents were studied in isolated canine ventricular cardiomyocytes.
Action potentials were recorded from the enzymatically dispersed myocytes using sharp microelectrodes (16 cells from 3 dogs). Conventional patch clamp and action potential voltage clamp arrangements were used to study the effects of articaine on transmembrane ion currents (37 cells from 14 dogs).
Articaine-induced concentration-dependent changes in action potential configuration including shortening of the action potentials, reduction of their amplitude and maximum velocity of depolarization (V(max)), suppression of early repolarization and depression of plateau. The EC50 value obtained for the V(max) block was 162 (sd 30) microM. Both the reduction of V(max) and action potential shortening were frequency dependent: the former was more prominent at shorter, while the latter at longer pacing cycle lengths. A rate dependent V(max) block, having rapid offset kinetics [tau = 91 (20) ms], was observed in addition to tonic block. Under voltage clamp conditions, a variety of ion currents were blocked by articaine: I(Ca) [EC50 = 471 (75) microM], I(to) [EC50 = 365 (62) microM], I(K1) [EC50 = 372 (46) microM], I(Kr) [EC50 = 278 (79) microM], and I(Ks) [EC50 = 326 (65) microM]. Hill coefficients were close to unity indicating a single binding site for articaine, except for I(K1).
Articaine can modify cardiac action potentials and ion currents at concentrations higher than the therapeutic range which can be achieved only by accidental venous injection. Since its suppressive effects on the inward and outward currents are relatively well balanced, the articaine-induced changes in action potential morphology may be moderate even in the case of overdose.
尽管阿替卡因在临床上广泛应用，但关于其对心脏细胞作用的信息却很少。在本研究中，我们在离体犬心室心肌细胞中研究了阿替卡因对动作电位形态及相关离子电流的浓度依赖性影响。
使用锋利微电极从酶解分散的心肌细胞记录动作电位（来自3只犬的16个细胞）。采用传统膜片钳和动作电位电压钳记录模式研究阿替卡因对跨膜离子电流的影响（来自14只犬的37个细胞）。
阿替卡因引起动作电位形态呈浓度依赖性改变，包括动作电位缩短、幅度降低、最大去极化速度（V(max)）减慢、早期复极化抑制和平台期压低。V(max)阻断的半数有效浓度（EC50）值为162（标准差30）μM。V(max)降低和动作电位缩短均呈频率依赖性：前者在较短起搏周期长度时更显著，后者在较长起搏周期长度时更显著。除了持续性阻断外，还观察到一种具有快速消除动力学[时间常数（tau）= 91（20）ms]的频率依赖性V(max)阻断。在电压钳条件下，阿替卡因可阻断多种离子电流：L型钙电流[I(Ca)，EC50 = 471（75）μM]、瞬时外向钾电流[I(to)，EC50 = 365（62）μM]、内向整流钾电流[I(K1)，EC50 = 372（46）μM]、快速延迟整流钾电流[I(Kr)，EC50 = 278（79）μM]和缓慢延迟整流钾电流[I(Ks)，EC50 = 326（65）μM]。希尔系数接近1，表明阿替卡因存在单一结合位点，但I(K1)除外。
阿替卡因在高于治疗范围的浓度时可改变心脏动作电位和离子电流，而这一浓度仅在意外静脉注射时才能达到。由于其对内向和外向电流的抑制作用相对平衡，即使在过量情况下，阿替卡因引起的动作电位形态改变可能也较轻微。
