Ketamine attenuates the contractile response to vasoconstrictors in isolated coronary artery rings

Abstract

Objective: Ketamine was shown to increase coronary blood flow. It was the aim of this study to answer the question whether ketamine directly dilates coronary arteries. Methods: Using the model of isolated vessel rings we studied the effects of ketamine (2.5, 25, and 250 mug ml(-1)) on the contractile response to three vasoconstrictors, acetylcholine, histamine, and serotonin in porcine coronary artery segments. Other rings were contracted with KCl or PGF(2a) and then treated with ketamine (5 up to 500 mug ml(-1) added cumulatively). Results: Ketamine dose-dependently dilated coronary arteries in concentrations beyond those used in clinical practice. In intact rings ketamine racemate (250 mug ml(-1)) attenuated contractions mediated by acetylcholine by 38.8 +/- 2.8%, histamine by 33.0 +/- 4.4% and serotonin by 42.1 +/- 3.7% (p < 0.05). There were no differences between intact and denuded rings (acetylcholine 38.5 +/- 2.8%, histamine 26.6 +/- 4.7%, serotonin 30.0 +/- 3.2%). With low concentrations of ketamine (2.5 mug ml(-1)) a slight tendency towards a contraction was recorded (n.s.). In rings precontracted with either KCl or PGF(2a) ketamine caused a small enhancement of contraction (KCl: 101.4 +/- 0.4%, PGF(2a): 101.3 +/- 1.4%) when administered in low concentration (5 mug ml(-1)), but almost complete relaxation (KCl: 0.4 +/- 1.3%, PGF(2): 0.0 +/- 5.4%) in high concentration (500 mug ml(-1)). Conclusions: it is concluded that ketamine dose-dependently dilates porcine coronary arteries in concentrations beyond those used in clinical practice and that this effect is independent of endothelial function.