To simultaneously determine the effect of propofol on myocardial oxygenation, mitochondrial function, and whole organ function in an isolated heart model, using optical reflectance spectroscopy.
Controlled laboratory investigation.
Twenty adult guinea pigs.
Isolated hearts were perfused alternately with a modified oxygenated Krebs-Henseleit buffer and with buffer containing varied concentrations of propofol. Ninety seconds of ischemia were produced during perfusion with each solution studied.
Myoglobin oxygen saturation, cytochrome c and cytochrome a/a3 redox state, and ventricular pressure were continuously measured from isolated guinea pig hearts during a 2-hr period. Myoglobin oxygen saturation increased and both cytochromes became more oxidized in the presence of propofol. During ischemia, myoglobin desaturation and cytochrome reduction were delayed and less complete in the presence of propofol. The mean ischemic time to 50% myoglobin desaturation was, on average, 14.3 secs with buffer perfusion, and increased to 24.5, 27.9, and 41.8 secs, with 50, 100, and 200 μM propofol perfusion, respectively. Ventricular function decreased linearly with increasing propofol concentration. From baseline buffer perfusion, maximal dP/dt per cardiac cycle decreased on average by 30.4%, 40.9%, and 69.4%, with 50, 100, and 200 μM propofol perfusion, respectively.
Propofol impairs either oxygen utilization or inhibits electron flow along the mitochondrial electron transport chain in the guinea pig cardiomyocyte. Propofol also significantly decreases ventricular performance in the isolated perfused heart. These effects are linearly correlated with propofol concentration in the range studied.
From the Department of Pediatrics, Division of Critical Care Medicine, University of Wisconsin, Madison, WI.
Supported, in part, by grants from the University of Wisconsin Medical School, the University of Wisconsin Graduate School, and the University of Wisconsin Department of Pediatrics Research and Development Fund.
Address requests for reprints to: Kenneth A. Schenkman, MD, PhD, Department of Anesthesia and Critical Care, CH-05, Children's Hospital and Regional Medical Center, 4800 Sand Point Way NE, Seattle, WA 98105-0371. E-mail: firstname.lastname@example.org