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 myorcardium 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(-6), 10(-5), and 10(-4) m alone or in the presence of 8.10(-4) m 5-hydroxydecanoate, 10(-5) m HMR 1098 (sarcolemmal adenosine triphosphate-sensitive potassium channel antagonist), 10(-6) m phentolamine (a-adrenoceptor antagonist), and 10(-6) 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(-6) m: 85 +/- 4%; 10(-5) m: 95 +/- 10%; 10(-4) m: 94 +/- 14% of baseline) and S(+)-ketamine (10(-6) m: 85 +/- 4%; 10(-5) m: 91 +/- 16%; 10(-4) 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(-4) 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.