Szabó Adrienn, Szentandrássy Norbert, Birinyi Péter, Horváth Balázs, Szabó Gergely, Bányász Tamás, Márton Ildikó, Magyar János, Nánási Péter P
Department of Dentistry, University of Debrecen, Debrecen, Hungary.
Anesthesiology. 2008 Apr;108(4):693-702. doi: 10.1097/ALN.0b013e3181684b91.
Despite the widespread clinical application of ropivacaine, there is little information on the cellular cardiac effects of the drug. In the current study, therefore, the concentration-dependent effects of ropivacaine on action potential morphology and the underlying ion currents were studied and compared with those of bupivacaine in isolated canine ventricular cardiomyocytes.
Action potentials were recorded from the enzymatically dispersed cells using sharp microelectrodes. Conventional patch clamp and action potential voltage clamp arrangements were used to study the effects of ropivacaine on transmembrane ion currents.
Ropivacaine induced concentration- and frequency-dependent changes in action potential configuration, including shortening of the action potentials, reduction of their amplitude and maximum velocity of depolarization, suppression of early repolarization, and depression of plateau. Reduction in maximum velocity of depolarization was characterized with an EC50 value of 81 +/- 7 microm at 1 Hz. Qualitatively similar results were obtained with bupivacaine (EC50 = 47 +/- 3 microm). Under voltage clamp conditions, a variety of ion currents were blocked by ropivacaine: L-type calcium current (EC50 = 263 +/- 67 microm), transient outward current (EC50 = 384 +/- 75 microm), inward rectifier potassium current (EC50 = 372 +/- 35 microm), rapid delayed rectifier potassium current (EC50 = 303 +/- 47 microm), and slow delayed rectifier potassium current (EC50 = 106 +/- 18 microm).
Ropivacaine, similarly to bupivacaine, can modify cardiac action potentials and the underlying ion currents at concentrations higher than the usual therapeutic range. However, in cases of overdose, cardiac complications may be anticipated both during and after anesthesia due to the blockade of various ion currents.
尽管罗哌卡因在临床上已广泛应用，但关于该药物对心脏细胞的作用却知之甚少。因此，在本研究中，我们研究了罗哌卡因对动作电位形态及相关离子电流的浓度依赖性作用，并与布比卡因在离体犬心室肌细胞中的作用进行了比较。
使用锋利微电极记录酶解分散细胞的动作电位。采用传统膜片钳和动作电位电压钳技术研究罗哌卡因对跨膜离子电流的影响。
罗哌卡因可引起动作电位形态呈浓度和频率依赖性变化，包括动作电位缩短、幅度降低、去极化最大速度减慢、早期复极化受抑制及平台期压低。在1Hz时，去极化最大速度降低的半数有效浓度（EC50）值为81±7μmol。布比卡因也得到了定性相似的结果（EC50 = 47±3μmol）。在电压钳条件下，罗哌卡因可阻断多种离子电流：L型钙电流（EC50 = 263±67μmol）、瞬时外向电流（EC50 = 384±75μmol）、内向整流钾电流（EC50 = 372±35μmol）、快速延迟整流钾电流（EC50 = 303±47μmol）和缓慢延迟整流钾电流（EC50 = 106±18μmol）。
与布比卡因相似，罗哌卡因在高于通常治疗范围的浓度下可改变心脏动作电位及相关离子电流。然而，在过量使用的情况下，由于多种离子电流被阻断，麻醉期间及麻醉后可能会出现心脏并发症。
