NEGATIVE INOTROPIC EFFECTS OF PROPOFOL AS EVALUATED BY THE REGIONAL PRELOAD RECRUITABLE STROKE WORK RELATIONSHIP IN CHRONICALLY INSTRUMENTED DOGS

Background. Propofol anesthesia often is associated with marked decreases in arterial blood pressure. Previous investigations in vivo have provided conflicting reasons for this clinical finding, including propofol-induced decreases in preload or afterload and/or direct myocardial depressant effects. Interpretation of the results of these studies is complicated by use of indices of myocardial contractility that may only indirectly indicate changes in inotropic state or are significantly dependent on ventricular loading conditions. Methods: Eight experiments were performed using dogs chronically instrumented for measurement of aortic and left ventricular pressure, the peak rate of increase of left ventricular pressure (dP/dt(max)), subendocardial segment length, intrathoracic pressure, and cardiac output. Myocardial contractility was evaluated in conscious and anesthetized dogs using the preload recruitable stroke work (PRSW) relationship, a sensitive, easily quantified, and relatively load-independent index of contractile function in normal canine myocardium in vivo. The relationship was derived from ventricular pressure-segment length loops generated by abrupt vena caval constriction. Respiratory variation in ventricular pressure was reduced by calculation of transmural pressure via instantaneous subtraction of intrathoracic pressure from corresponding left ventricular pressure. Systemic hemodynamics and myocardial contractility were recorded and evaluated in the conscious state and after a bolus of 5 mg/kg and a propofol infusion for 15 min at 15, 30, 60, and 120 mg - kg -1 . h -1. Results. A significant (P < .05) and dose-dependent decrease in PRSW slope (106 +/- 7 during control to 54 +/- 3 mmHg at the 120 mg.kg -1.h-1 infusion) was observed, demonstrating a direct depression of contractility. Concomitant decreases in left ventricular dP/dt(max) and percent segment shortening also were observed. In addition, a significant decrease in systemic vascular resistance occurred at the two largest infusions. Conclusions: The results indicate that the significant decrease in systemic arterial blood pressure observed during continuous propofol anesthesia in dogs is a result of direct negative inotropic actions of propofol along with its direct effects upon arterial and venous vascular tone.