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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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References

Domino EF, Chodoff P, Corssen G. Pharmacologic effects of CI-581, a new dissociative anesthetic, in man. Clin Pharmacol Ther 1965; 6: 279–291.Google Scholar
Wong DHW, Jenkins LC. An experimental study of the mechanism of action of ketamine on the central nervous system. Can Anaesth Soc J 1974; 21: 57–67.Google Scholar
Folts JD, Alfonso S, Rowe GG. Systemic and coronary haemodynamic effects of ketamine in intact anaesthetized and unanaesthetized dogs. Br J Anesth 1975; 47: 686–693.Google Scholar
Klockgether-Radke A, Hagemann I, Frerichs A, Majowski K, Hellige G. Influence of high-dose ketamine on the vascular reactivity of human and porcine isolated coronary artery segments. Acta Anaesthesiol Scand 1997; 41: 1200–1203.Google Scholar
Klockgether-Radke AP, Frerichs A, Hellige G. Ketamine attenuates the contractile response to vasoconstrictors in isolated coronary artery rings. Anaesthesiol Intensivmed Notfallmed Schmerzther 2003; 38: 767–771.Google Scholar
Domino EF, Zsigmond EK, Domino LE, Domino KE, Kothary SP, Domino SE. Plasma levels of ketamine and two of its metabolites in surgical patients using a gas chromatographic mass fragmentographic assay. Anesth Analg 1982; 61: 87–92.Google Scholar
Akata T, Izumi K, Nakashima M. Mechanisms of direct inhibitory action of ketamine on vascular smooth muscle in mesenteric resistance arteries. Anesthesiology 2001; 95: 452–462.Google Scholar
Coughlan MG, Flynn NM, Kenny D, Warltier DC, Kampine JP. Differential relaxant effect of high concentrations of intravenous anesthetics on endothelin-constricted proximal and distal canine coronary arteries. Anesth Analg 1992; 74: 378–383.Google Scholar
Fukuda S, Murakawa T, Takeshita H, Toda N. Direct effects of ketamine on isolated canine cerebral and mesenteric arteries. Anesth Analg 1983; 62: 553–558.Google Scholar
Taga K, Fukuda S, Nishimura N, Tsukui A, Morioka M, Shimoji K. Effects of thiopental, pentobarbital, and ketamine on endothelin-induced constriction of porcine cerebral arteries. Anesthesiology 1990; 72: 939–941.Google Scholar
Wendling WW, Daniels FB, Chen D, Harakal C, Carlsson C. Ketamine directly dilates bovine cerebral arteries by acting as a calcium entry blocker. J Neurosurg Anesthesiol 1994; 6: 186–192.Google Scholar
Lee TS, Hou X. Vasoactive effects of ketamine on isolated rabbit pulmonary arteries. Chest 1995; 107: 1152–1155.Google Scholar
Maruyama K, Maruyama J, Yokochi A, Muneyuki M, Miyasaka K. Vasodilatory effects of ketamine on pulmonary arteries in rats with chronic hypoxic pulmonary hypertension. Anesth Analg 1995; 80: 786–792.Google Scholar
Kaye AD, Banister RE, Anwar M, Feng CJ, Kadowitz PF, Nossaman BD. Pulmonary vasodilation by ketamine is mediated in part by L-type calcium channels. Anesth Analg 1998; 87: 956–562.Google Scholar
Kaye AD, Banister RE, Fox CJ, Ibrahim IN, Nossaman BD. Analysis of ketamine responses in the pulmonary vascular bed of the cat. Crit Care Med 2000; 28: 1077–1082.Google Scholar
Kanmura Y, Missiaen L, Casteels R. The effects of ketamine on Ca2+ movements in A7r5 vascular smooth muscle cells. Anesth Analg 1996; 83: 1105–1109.Google Scholar
Ogawa K, Tanaka S, Murray PA. Inhibitory effects of etomidate and ketamine on endothelium-dependent relaxation in canine pulmonary artery. Anesthesiology 2001; 94: 668–677.Google Scholar
Shakunaga K, Kojima S, Jomura K, Shimizu Y, Satone T, Ito Y. Ketamine suppresses the production and release of endothelin 1 from cultured bovine endothelial cells. Anesth Analg 1998; 86: 1098–1102.Google Scholar
Kanellopoulos A, Lenz G, Mühlbauer B. Stereoselective differences in the vasorelaxing effects of S(+) and R(−) ketamine on rat isolated aorta. Anesthesiology 1998; 88: 718–724.Google Scholar
Wendling WW, Chen D, Daniels FB, et al. The effects of N-methyl-d-aspartate agonists and antagonists on isolated bovine cerebral arteries. Anesth Analg 1996; 82: 264–268.Google Scholar
White PF, Ham J, Way WL, Trevor AJ. Pharmacology of ketamine isomers in surgical patients. Anesthesiology 1980; 52: 231–239.Google Scholar
Sohn JT, Murray PA. Inhibitory effects of etomidate and ketamine on adenosine triphosphate-sensitive potassium channel relaxation in canine pulmonary artery. Anesthesiology 2003; 98: 104–113.Google Scholar
Dojo M, Kinoshita H, Iranami H, Nakahata K, Kimoto Y, Hatano Y. Ketamine stereoselectively affects vasorelaxation mediated by ATP-sensitive K(+) channels in the rat aorta. Anesthesiology 2002; 97: 882–886.Google Scholar
Nagao T, Vanhoutte PM. Endothelium-derived hyperpolarizing factor and endothelium-dependent relaxation. Am J Respir Cell Mol Biol 1993; 8: 1–6.Google Scholar
Wallerstedt SM, Törnebrandt K, Bodelsson M. Relaxant effects of propofol on human omental arteries and veins. Br J Anaesth 1998; 80: 655–659.CrossRefGoogle Scholar