Klockgether-Radke A P, Huneck S, Meyberg S, Neumann P, Hellige G
Georg-August-University of Goettingen, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Department of Anaesthesiological Research, Goettingen, Germany.
Eur J Anaesthesiol. 2005 Mar;22(3):215-21. doi: 10.1017/s0265021505000372.
It has been shown that racemic ketamine increases coronary blood flow and that this effect is at least in part due to a direct vasorelaxing effect of this substance. This study was designed to determine whether ketamine might stereoselectively relax isolated porcine coronary arteries.
Using the model of isolated vessels we studied the effects of S(+) ketamine, R(-) ketamine, and racemic ketamine (5-500 microg mL(-1)) on artery strips pre-contracted by either potassium chloride (KCl) or prostaglandin F2alpha (PGF2alpha). To elucidate possible mechanisms of action these experiments were repeated in the presence of one of the following compounds: N(omega)-nitro-L-arginine (L-NNA), indomethacin, glibenclamide, and tetraethylammonium (TEA) chloride, an inhibitor of the BK(Ca) K+ channel.
Both isoforms and racemic ketamine relaxed isolated coronary arteries in a concentration-dependent manner in concentrations beyond those used in clinical practice. S(+) ketamine exerted the strongest vasorelaxing effect, followed by racemic ketamine and R(-) ketamine. Pretreatment with L-NNA, indomethacin, or glibenclamide did not alter the vasodilating properties of ketamine, whereas TEA chloride significantly attenuated the vasorelaxing effects of all the three forms of ketamine.
Ketamine dilates coronary arteries in vitro when administered in high concentrations. There is a stereoselective difference with a stronger vasorelaxing effect of S(+) ketamine compared to racemic and R(-) ketamine. The impact of TEA chloride suggests that the activation of the BK(Ca) channel may contribute to the vasodilating effect of ketamine.
已有研究表明，消旋氯胺酮可增加冠状动脉血流量，且该作用至少部分归因于该物质的直接血管舒张效应。本研究旨在确定氯胺酮是否能对离体猪冠状动脉产生立体选择性舒张作用。
我们采用离体血管模型，研究了S(+)氯胺酮、R(-)氯胺酮和消旋氯胺酮（5 - 500μg/mL）对预先由氯化钾（KCl）或前列腺素F2α（PGF2α）收缩的动脉条的影响。为阐明可能的作用机制，在下列化合物之一存在的情况下重复这些实验：N(ω)-硝基-L-精氨酸（L-NNA）、吲哚美辛、格列本脲和BK(Ca)钾通道抑制剂氯化四乙铵（TEA）。
在临床实践中使用浓度以上，两种异构体和消旋氯胺酮均以浓度依赖性方式舒张离体冠状动脉。S(+)氯胺酮发挥最强的血管舒张作用，其次是消旋氯胺酮和R(-)氯胺酮。用L-NNA、吲哚美辛或格列本脲预处理并未改变氯胺酮的血管舒张特性，而氯化TEA显著减弱了所有三种形式氯胺酮的血管舒张作用。
高浓度给药时，氯胺酮在体外可扩张冠状动脉。存在立体选择性差异，与消旋氯胺酮和R(-)氯胺酮相比，S(+)氯胺酮具有更强的血管舒张作用。氯化TEA的影响表明，BK(Ca)通道的激活可能有助于氯胺酮的血管舒张作用。
