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 effects of ketamine on contractility of human failing and nonfailing myocardium in vitro.


METHODS
Trabecular muscles were obtained from the left ventricles and right atria of 10 patients with heart failure undergoing transplantation and from the right 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 variables were recorded before and after addition of ketamine (concentrations between 0.44 and 440.0 microM) to the bath. The effects of ketamine were compared with those of buffer. To test muscle contractility, at the end of each experiment, 1 microM isoproterenol was added.


RESULTS
Ketamine caused a significant dose-dependent decrease in developed tension in nonfailing atrial and failing atrial and ventricular muscles (P < 0.01 for all). In vehicle-treated muscles, developed tension remained stable, and isoproterenol increased developed tension 136% (nonfailing atrial muscles) and 178% (failing atrial and ventricular muscles; P < 0.01). In nonfailing atrial muscle, isoproterenol restored the ketamine-induced decrease in developed tension toward the baseline value. In failing atrial and ventricular muscles exposed to ketamine, isoproterenol did not counteract the ketamine.


CONCLUSIONS
Ketamine exerts a direct dose-dependent negative inotropic effect in human heart muscles. The failing myocardium exposed to ketamine has reduced ability to increase contractility even in the presence of increased beta-adrenergic stimulation.
Sprung
J
J
Department of General Anesthesiology, The Cleveland Clinic Foundation, Ohio 44195, USA. sprungj@cesmtp.ccf.org
Schuetz
S M
SM
Stewart
R W
RW
Moravec
C S
CS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006333:Heart Failure / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*
D000778:Anesthetics, Dissociative; D002316:Cardiotonic Agents; D007649:Ketamine; D007545:Isoproterenol