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.

Background and objective: Isoflurane is a chiral, volatile anaesthetic with low metabolic rate (0.17%) that is routinely administered in its racemic form. Knowledge about the distribution of the enantiomers in human beings may give some important information about the understanding of the mechanisms of volatile anaesthetics.

Methods: Blood samples were drawn immediately after tracheal extubation and daily up to 8 days postoperatively from patients undergoing general anaesthesia with isoflurane racemate. The enantiomer enrichment of isoflurane was determined by headspace gas chromatography-mass spectrometry.

Results: At all time points, there was a statistically significant accumulation of the S(+) enantiomer in blood, especially at days 2 (52.01%) and 7 (52.1%). Separate analysis of obese patients or in a small group of patients with co-existing lung disease did not show any difference to the total population. In addition, duration of anaesthesia did not influence the enantiomer concentrations.

Conclusions: We suggest that a slower association and dissociation rate is responsible for the S(+) enrichment.