Ketamine depresses myocardial contractility as evaluated by the preload recruitable stroke work relationship in chronically instrumented dogs with autonomic nervous system blockade

Previous investigations examining the direct actions of ketamine on myocardial contractility in vivo suggest that ketamine may produce depression of contractile function under certain circumstances. Such studies have had significant limitations in that reliable, easily quantified, load-independent indices of contractility were not used, and ketamine produces dramatic sympathomimetic pressor effects mediated via an intact autonomic nervous system. In the present investigation, eight experiments were performed using dogs chronically instrumented for measurement of aortic and left ventricular pressure; rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, and cardiac output. Contractility was evaluated using the linear relationship between preload recruitable stroke work and end-diastolic segment length. The slope (Mw) and length intercept of this relationship, and two derived variables, preload recruitable work area (PRWA) and stroke work at constant end-diastolic length (SWEDL), were used as indices of contractility. Pharmacologic blockade of the autonomic nervous system was instituted in all experiments since a portion of the systemic hemodynamic actions of ketamine are secondary to stimulation of the autonomic nervous system. Systemic hemodynamics and indices of contractile function were recorded and evaluated in the conscious state and after a 20-min equilibration at 25-, 50-, and 100-mg.kg-1.h-1 infusions of ketamine. A significant (P less than 0.05) and dose-dependent decrease in Mw (68 +/- 7 during control to 41 +/- 2 mmHg at 100 mg.kg-1.h-1) was observed, demonstrating depression of myocardial contractility.