EFFECTS OF KETAMINE ON THE CONTRACTILITY OF FAILING AND NONFAILING HUMAN HEART MUSCLES IN-VITRO

Background: Induction of anesthesia with ketamine may decrease cardiac output in critically ill patients. The direct effects of ketamine on the failing human myocardium are unknown. This study examined the effe cts of ketamine on contractility of human failing and nonfailing myoca rdium in vitro. Methods: Trabecular muscles were obtained from the lef t ventricles and right atria of 10 patients with heart failure undergo ing transplantation and from the tight atria of 14 patients undergoing coronary artery bypass surgery. Muscles were dissected and mounted in a 37 degrees C bath and stimulated at 1 Hz. Isometric contraction var iables were recorded before and after addition of ketamine (concentrat ions between 0.44 and 440.0 mu M) to the bath. The effects of ketamine were compared with those of buffer. To test muscle contractility, at the end of each experiment, 1 mu M isoproterenol was added. Results: K etamine caused a significant dose-dependent decrease in developed tens ion in nonfailing atrial and failing atrial and ventricular muscles (P < 0.01 for all). In vehicle-treated muscles, developed tension remain ed stable, and isoproterenol increased developed tension 136% (nonfail ing atrial muscles) and 178% (failing atrial and ventricular muscles; P < 0.01). In nonfailing atrial muscle, isoproterenol restored the ket amine-induced decrease in developed tension toward the baseline value. In falling atrial and ventricular muscles exposed to ketamine, isopro terenol did not counteract the ketamine. Conclusions: Ketamine exerts a direct dose-dependent negative inotropic effect in human heart muscl es. The failing myocardium exposed to ketamine has reduced ability to increase contractility even in the presence of increased beta-adrenerg ic stimulation.