Ketamine enantiomers differentially relax isolated coronary artery rings.
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 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.


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 BK(Ca) channel may contribute to the vasodilating effect of ketamine.
Klockgether-Radke
A P
AP
Georg-August-University of Goettingen, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Department of Anaesthesiological Research, Goettingen, Germany. klockgether-radke@gmx.de
Huneck
S
S
Meyberg
S
S
Neumann
P
P
Hellige
G
G
D000778:Anesthetics, Dissociative / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D019335:Nitroarginine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D013237:Stereoisomerism; D013552:Swine; D019789:Tetraethylammonium / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D000778:Anesthetics, Dissociative; D000889:Anti-Arrhythmia Agents; D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019335:Nitroarginine; D019789:Tetraethylammonium; D011189:Potassium Chloride; D007649:Ketamine; D015237:Dinoprost; D005905:Glyburide; D007213:Indomethacin