Weigt H U, Kwok W M, Rehmert G C, Turner L A, Bosnjak Z J
Department of Anesthesiology, The Medical College of Wisconsin, Milwaukee 53226, USA.
Anesthesiology. 1997 Dec;87(6):1507-16. doi: 10.1097/00000542-199712000-00030.
Alpha1-adrenoceptor stimulation is known to produce electrophysiologic changes in cardiac tissues, which may involve modulations of the fast inward Na+ current (I(Na)). A direct prodysrhythmic alpha1-mediated interaction between catecholamines and halothane has been demonstrated, supporting the hypothesis that generation of halothane-epinephrine dysrhythmias may involve slowed conduction, leading to reentry. In this study, we examined the effects of a selective alpha1-adrenergic receptor agonist, methoxamine, on cardiac I(Na) in the absence and presence of equianesthetic concentrations of halothane and isoflurane in single ventricular myocytes from adult guinea pig hearts.
I(Na) was recorded using the standard whole-cell configuration of the patch-clamp technique. Voltage clamp protocols initiated from two different holding potentials (V(H)) were applied to examine state-dependent effects of methoxamine in the presence of anesthetics. Steady state activation and inactivation and recovery from inactivation were characterized using standard protocols.
Methoxamine decreased I(Na) in a concentration- and voltage-dependent manner, being more potent at the depolarized V(H). Halothane and isoflurane interacted synergistically with methoxamine to suppress I(Na) near the physiologic cardiac resting potential of -80 mV. The effect of methoxamine with anesthetics appeared to be additive when using a V(H) of -110 mV, a potential where no Na+ channels are in the inactivated state. Methoxamine in the absence and presence of anesthetics significantly shifted the half maximal inactivation voltage in the hyperpolarizing direction but had no effect on steady-state activation.
The present results show that methoxamine (alpha1-adrenergic stimulation) decreases cardiac Na+ current in a concentration- and voltage-dependent manner. Further, a form of synergistic interaction between methoxamine and inhalational anesthetics, halothane and isoflurane, was observed. This interaction appears to depend on the fraction of Na+ channels in the inactivated state. (Key words: Anesthetics, volatile: halothane; isoflurane; methoxamine. Patch clamp: whole-cell configuration; sodium current; ventricular guinea pig myocytes.)
已知α1 -肾上腺素能受体刺激可在心脏组织中产生电生理变化，这可能涉及快速内向钠电流（I(Na)）的调节。儿茶酚胺与氟烷之间直接的致心律失常性α1介导的相互作用已得到证实，支持了氟烷 -肾上腺素致心律失常的发生可能涉及传导减慢导致折返的假说。在本研究中，我们在成年豚鼠心脏单个心室肌细胞中，研究了选择性α1 -肾上腺素能受体激动剂甲氧明在不存在和存在等效麻醉浓度的氟烷和异氟烷的情况下对心脏I(Na)的影响。
使用膜片钳技术的标准全细胞模式记录I(Na)。应用从两个不同的钳制电位（V(H)）起始的电压钳制方案，以研究甲氧明在麻醉剂存在下的状态依赖性效应。使用标准方案对稳态激活、失活及失活后恢复进行表征。
甲氧明以浓度和电压依赖性方式降低I(Na)，在去极化的V(H)时作用更强。氟烷和异氟烷与甲氧明协同作用，在生理心脏静息电位 -80 mV附近抑制I(Na)。当使用 -110 mV的V(H)（此时没有钠通道处于失活状态）时，甲氧明与麻醉剂的作用似乎是相加的。在不存在和存在麻醉剂的情况下，甲氧明均使半数最大失活电压向超极化方向显著偏移，但对稳态激活无影响。
目前的结果表明，甲氧明（α1 -肾上腺素能刺激）以浓度和电压依赖性方式降低心脏钠电流。此外，观察到甲氧明与吸入麻醉剂氟烷和异氟烷之间存在一种协同相互作用形式。这种相互作用似乎取决于处于失活状态的钠通道比例。（关键词：挥发性麻醉剂：氟烷；异氟烷；甲氧明。膜片钳：全细胞模式；钠电流；豚鼠心室肌细胞。）
