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Ketamine enantiomers differentially relax isolated coronary artery rings

Published online by Cambridge University Press:  19 April 2005

A. P. Klockgether-Radke ,
S. Huneck ,
S. Meyberg ,
P. Neumann  and
G. Hellige
A. P. Klockgether-Radke
Affiliation:
Georg-August-University of Goettingen, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Departments of Anaesthesiological Research, Goettingen, Germany
S. Huneck
Affiliation:
Georg-August-University of Goettingen, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Departments of Anaesthesiological Research, Goettingen, Germany
S. Meyberg
Affiliation:
Georg-August-University of Goettingen, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Departments of Anaesthesiological Research, Goettingen, Germany
P. Neumann
Affiliation:
Georg-August-University of Goettingen, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Departments of Anaesthesiological Research, Goettingen, Germany
G. Hellige
Affiliation:
Georg-August-University of Goettingen, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Departments of Anaesthesiological Research, Goettingen, Germany
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Abstract

Summary

Background and objective: 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.

Methods: Using the model of isolated vessels we studied the effects of S(+) ketamine, R(−) ketamine, and racemic ketamine (5–500 μg mL−1) on artery strips pre-contracted by either potassium chloride (KCl) or prostaglandin F2α (PGF2α). To elucidate possible mechanisms of action these experiments were repeated in the presence of one of the following compounds: Nω-nitro-l-arginine (l-NNA), indomethacin, glibenclamide, and tetraethylammonium (TEA) chloride, an inhibitor of the BKCa K+ channel.

Results: 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.

Conclusions: 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 BKCa channel may contribute to the vasodilating effect of ketamine.

Keywords

ANAESTHETICS, INTRAVENOUS, ketamineSTEREOISOMERISMCORONARY VESSELS, coronary arteriesSWINE, in-vitro
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 22 , Issue 3 , March 2005 , pp. 215 - 221
Copyright
2005 European Society of Anaesthesiology

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