Propofol impairment of mitochondrial respiration in isolated perfused guinea pig hearts determined by reflectance spectroscopy.
OBJECTIVE
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.


METHODS
Controlled laboratory investigation.


METHODS
Research laboratory.


METHODS
Twenty adult guinea pigs.


METHODS
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.


RESULTS
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 microM 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 microM propofol perfusion, respectively.


CONCLUSIONS
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.
Schenkman
K A
KA
Department of Pediatrics, University of Wisconsin, Madison, USA. kschen@chmc.org
Yan
S
S
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D017936:Cytochrome a Group / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000502:physiology; D009211:Myoglobin / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D015742:Propofol / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects
D018686:Anesthetics, Intravenous; D017936:Cytochrome a Group; D003574:Cytochrome c Group; D009211:Myoglobin; D010100:Oxygen; D015742:Propofol