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ANESTHETIC PHARMACOLOGY

The Inotropic and Lusitropic Effects of Ketamine in Isolated Human Atrial Myocardium: The Effect of Adrenoceptor Blockade

Laboratoire d’Anesthésiologie Expérimentale et de Physiologie Cellulaire, UPRES EA 3212, Département d’Anesthésie-Réanimation, Centre Hospitalier Universitaire (CHU) Côte de Nacre, Caen; France

Address correspondence and reprint requests to Jean-Luc Hanouz, MD, PhD, Département d’Anesthésie-Réanimation, CHU de Caen, Avenue Côte de Nacre, 14033 Caen Cedex, France. Address e-mail to hanouz-jl{at}chu-caen.fr

We studied the direct myocardial effects of racemic ketamine, in the presence of - and ß-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 -adrenoceptor blockade (phentolamine 10^–6 M) and ß-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 ß-adrenoceptor blockade it induced a direct negative inotropic effect.

IMPLICATIONS: In isolated human myocardium, racemic ketamine induced a moderate positive inotropic effect but a profound direct negative inotropic effect in the presence of ß-adrenoceptor blockade. Furthermore, ketamine hastened relaxation through stimulation of ß-adrenoceptor. This should be interpreted with the known various physiopathologic states and treatments interfering with - and ß-adrenoceptors.

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