Ketamine preconditions isolated human right atrial myocardium: roles of adenosine triphosphate-sensitive potassium channels and adrenoceptors.

BACKGROUND: The authors examined the effect of ketamine and its S(+) isomer on isolated human myocardium submitted to hypoxia-reoxygenation in vitro. METHODS: The authors studied isometric contraction of human right atrial trabeculae suspended in an oxygenated Tyrode's modified solution at 34 degrees C. Ten minutes before a 30-min hypoxic period followed by a 60-min reoxygenation, muscles were exposed for 15 min to racemic ketamine and its S(+) isomer at 10, 10, and 10 m alone or in the presence of 8.10 m 5-hydroxydecanoate, 10 m HMR 1098 (sarcolemmal adenosine triphosphate-sensitive potassium channel antagonist), 10 m phentolamine (alpha-adrenoceptor antagonist), and 10 m propranolol (beta-adrenoceptor antagonist). Force of contraction at the end of the 60-min reoxygenation period was compared between groups (mean +/- SD). RESULTS: Ketamine (10 m: 85 +/- 4%; 10 m: 95 +/- 10%; 10 m: 94 +/- 14% of baseline) and S(+)-ketamine (10-6 m: 85 +/- 4%; 10 m: 91 +/- 16%; 10 m: 93 +/- 14% of baseline) enhanced recovery of force of contraction at the end of the reoxygenation period as compared with the control group (47 +/- 10% of baseline; P < 0.001). Ketamine-induced preconditioning at 10 m was inhibited by 5-hydroxydecanoate (60 +/- 16%; P < 0.001), HMR 1098 (60 +/- 14%; P < 0.001), phentolamine (56 +/- 12%; P < 0.001), and propranolol (60 +/- 7%; P < 0.001). CONCLUSIONS: In vitro, ketamine preconditions isolated human myocardium, at least in part, via activation of adenosine triphosphate-sensitive potassium channels and stimulation of alpha- and beta-adrenergic receptors.

The inotropic and lusitropic effects of ketamine in isolated human atrial myocardium: the effect of adrenoceptor blockade.

We studied the direct myocardial effects of racemic ketamine, in the presence of alpha- and beta-adrenoceptor blockade, on isolated human right atrial myocardium. Isometric force of contraction (FoC), its first derivative with time (+dF/dt), the contraction relaxation coupling parameter R2 = (+dF/dt) / (-dF/dt), and time to half relaxation (T(1/2)) were recorded before and after addition of 10(-6), 10(-5) and 10(-4) M racemic ketamine alone and in the presence of alpha-adrenoceptor blockade (phentolamine 10(-6) M) and beta-adrenoceptor blockade (propranolol at 10(-6) M). Ketamine had a moderate positive inotropic effect at 10(-5) M (FoC, 104% +/- 5% of baseline value; P = 0.03) and 10(-4) M (FoC, 107% +/- 11% of baseline value; P = 0.09). Racemic ketamine had a negative inotropic effect in the presence of propranolol (FoC, ketamine 10(-6) M, 77% +/- 11%; ketamine 10(-5) M, 63% +/- 16%; ketamine 10(-4) M, 62% +/- 17% of baseline; P < 0.001) but not phentolamine (FoC, ketamine at 10(-6) M, 94% +/- 6%; ketamine 10(-5) M, 96% +/- 5%; and ketamine 10(-4) M, 98% +/- 15% of baseline). Ketamine decreased T(1/2) (ketamine 10(-5) M, 94% +/- 3% of baseline value; P < 0.001 and ketamine 10(-4) M, 90% +/- 9% of baseline value; P = 0.007) but did not modify R2. In human right atrial myocardium, racemic ketamine induced a moderate positive inotropic effect and hastened isometric relaxation. In the presence of beta-adrenoceptor blockade it induced a direct negative inotropic effect.