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.
Hanouz
Jean-Luc
JL
Laboratoire d'Anesthésiologie Expérimentale et de Physiologie Cellulaire, UPRES EA 3212, Département d'Anesthésie-Réanimation, Centre Hospitalier Universitaire (CHU) Côte de Nacre, Caen; France.
Persehaye
Emmanuel
E
Zhu
Lan
L
Lammens
Stéphane
S
Lepage
Olivier
O
Massetti
Massimo
M
Babatasi
Gérard
G
Khayat
André
A
Bricard
Henri
H
Gérard
Jean-Louis
JL
D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D002316:Cardiotonic Agents; D006321:Heart / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology
D018674:Adrenergic Antagonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000778:Anesthetics, Dissociative; D002316:Cardiotonic Agents; D007649:Ketamine; D011433:Propranolol; D010646:Phentolamine