Protection of cardiomyocyte function by propofol during simulated ischemia is associated with a direct action to reduce pro-oxidant activity

To demonstrate a direct protective effect of propofol on myocardial contractile performance during an ischemic episode and investigate underlying mechanisms, isolated adult rat ventricular cardiomyocytes were subjected for 2 h to (i) ischemic medium containing 2-deoxyglucose (20 mM), gassed with 100% N2 at pH 6.4, (ii) normal medium with 95% O2/5% CO2 at pH 7.4 or (iii) normal medium with addition of H2O2 (50 μM). Propofol under normal conditions decreased the peak amplitude of electrically stimulated contraction of cardiomyocytes from a basal value of 6.5 ± 0.37 μm to a maximum attenuation (not, vert, similar 37%) at 0.44 to 56 μM. Under ischemic conditions, the contraction amplitude at baseline was 2.8 ± 0.34 μm, but propofol, despite having a cardiodepressant effect per se, stimulated contraction, such that at ≥ 0.44 μM, normal and ischemic values in the presence of propofol were similar. Comparably, pro-oxidant (H2O2)-induced attenuation of cell shortening was reversed by propofol (0.5 μM) to the level of contractile activity produced by the anaesthetic alone. The protective effect against ischemia-induced injury was not reflected in an improved ATP/ADP ratio nor was it mediated through diltiazem-sensitive L-type Ca2+ channels. Propofol (0.5 μM) did, however, attenuate the ischemia- and H2O2-induced increases in the membrane lipid hydroperoxides, MDA (by 83% and 30%) and 4-HNE (by 47% and 69%). It is concluded that propofol, at clinically relevant concentrations, can counteract the effects of increased production of free radical compounds by cardiomyocytes subjected to oxidant stress and improve contractile performance.