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

• Published in: Journal of molecular and cellular cardiology 2007-03, Vol.42 (3), p.600-608
• Main Authors: McDermott, Barbara J, McWilliams, Stewart, Smyth, Karen, Kelso, Elizabeth J, Spiers, J. Paul, Zhao, YouYou, Bell, David, Mirakhur, Rajinder K
• Format: Article
• Language: English
• Subjects: Adenine nucleotides; Animals; Cardiomyocyte; Cardiovascular; Contraction; Hydrogen peroxide; Hydrogen Peroxide - pharmacology; Ischemia; Lipid hydroperoxides; Lipid Peroxidation - drug effects; Male; Myocardial Contraction - drug effects; Myocardial Ischemia - drug therapy; Myocardial Ischemia - metabolism; Myocardial Ischemia - pathology; Myocardial Ischemia - physiopathology; Oxidative stress; Phosphates - metabolism; Propofol; Propofol - therapeutic use; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Sarcolemma - metabolism
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1016/j.yjmcc.2006.12.002

Abstract 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 H2 O2 (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 (∼ 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 (H2 O2 )-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 H2 O2 -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.