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 α- and β-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 (T1/2) were recorded before and after addition of 10-6, 10-5 and 10-4 M racemic ketamine alone and in the presence of α-adrenoceptor blockade (phentolamine 10-6 M) and β-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 T1/2 (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 β-adrenoceptor blockade it induced a direct negative inotropic effect.