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 34degrees]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 (alpha]-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).