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.
Hanouz
Jean-Luc
JL
Department of Anesthesiology, Centre Hospitalier Universitaire Caen, Avenue Côte de Nacre, 14033 Caen Cedex, France. hanouz-jl@chu-caen.fr
Zhu
Lan
L
Persehaye
Emmanuel
E
Massetti
Massimo
M
Babatasi
Gerard
G
Khayat
André
A
Ducouret
Pierre
P
Plaud
Benoit
B
Gérard
Jean-Louis
JL
D000255:Adenosine Triphosphate / Q000502:physiology*; D000368:Aged; D000369:Aged, 80 and over; D006325:Heart Atria / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D007649:Ketamine / Q000494:pharmacology*; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology*
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011941:Receptors, Adrenergic; D007649:Ketamine; D000255:Adenosine Triphosphate; D011433:Propranolol