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 isolat ed heart model, using optical reflectance spectroscopy. Design: Controlled laboratory investigation. Setting: Research laboratory. Subjects: Twenty adult guinea pigs, Interventions: Isolated hearts were perfused alternately with a modified ox ygenated Krebs-Henseleit buffer and with buffer containing varied concentra tions of propofol, Ninety seconds of ischemia were produced during perfusio n with each solution studied. Measurements and Main Results: Myoglobin oxygen saturation, cytochrome c an d cytochrome a/a(3) redox state, and ventricular pressure were continuously measured from isolated guinea pig hearts during a 2-hr period. Myoglobin o xygen saturation increased and both cytochromes became more oxidized in the presence of propofol, During ischemia, myoglobin desaturation and cytochro me reduction were delayed and less complete in the presence of propofol, Th e mean ischemic time to 50% myoglobin desaturation was, on average, 14.3 se es with buffer perfusion, and increased to 24.5, 27.9, and 41.8 sees, with 50, 100, and 200 mu M propofol perfusion, respectively, Ventricular functio n decreased linearly with increasing propofol concentration. From baseline buffer perfusion, maximal dP/dt per cardiac cycle decreased on average by 3 0.4%, 40.9%, and 69.4%, with 50, 100, and 200 mu M propofol perfusion, resp ectively. Conclusions: Propofol impairs either oxygen utilization or inhibits electro n flow along the mitochondrial electron transport chain in the guinea pig c ardiomyocyte. Propofol also significantly decreases ventricular performance in the isolated perfused heart. These effects are linearly correlated with propofol concentration in the range studied.