Dose‐dependent protective effect of propofol against mitochondrial dysfunction in ischaemic/reperfused rat heart: role of cardiolipin

Abstract

Background and purpose: Ischaemia damages to the cardiac mitochondria by increasing generation of reactive oxygen species (ROS) and peroxidation of cardiolipin. The inhibited mitochondrial function leads to the cardiac injury during reperfusion. Propofol (2, 6-diisopropylphenol), an intravenous anaesthetic, has been shown to decrease cardiac ischaemia and reperfusion injury. In the present study, we propose that propofol protects mitochondrial function and decreases cardiac injury by prevention of cardiolipin peroxidation during ischaemia and reperfusion. Experimental approach: After isolation of mitochondria from isolated rat heart perfused on a Langendorff model, various mitochondrial bioenergetic parameters were evaluated such as rates of mitochondrial oxygen consumption, H 2 O 2 production, complex I and III activity as well as the degree of lipid peroxidation and cardiolipin content. The action of propofol was also explored in isolated mitochondria. And the effect of cardiolipin was evaluated by fusing cardiolipin liposome with mitochondria. Key results: Propofol treatment had strong dose-dependent protection attenuating these parameters alterations in reperfused rat heart and isolated mitochondria. Additionally, cardiolipin treatment had the same protective effect, compared with propofol treatment at high concentration. Conclusions and implications:The protective effect of propofol appears to be due, at least in part, as a chemical uncoupler, to the interruption of the vicious circle of ROS-cardiolipin-complexes of the respiratory chain-ROS through preserving the content and integrity of cardiolipin molecules by ROS attack. These findings may provide an explanation for some of the factors responsible for cardioprotection and one approach exploring an available antioxidant.

Effects of propofol on myocardial ischemia-reperfusion injury in rats with type-2 diabetes mellitus

“…Evidence indicates that the intravenous anesthesic propofol may inhibit lipid peroxidation, improve mitochondrial function (14), protect the myocardium and reduce MIRI in rats (15). Furthermore, it improves the function of vascular endothelial cells and promotes the expression of anti-apoptotic proteins, thus reducing MIRI in T2DM.…”

Propofol alleviates acute lung injury following orthotopic autologous liver transplantation in rats via inhibition of the NADPH oxidase pathway

“…Takao et al (34) suggested that a high dose of propofol mitigates the physiological, biochemical and histological deterioration of ALI during endotoxemia. Propofol has also been reported to exert significant protective activity against ischemia-reperfusion-induced cardiac injury, partly through the reduction in ROS and H 2 O 2 generation (35,36). In the current study, propofol was demonstrated to produce a similar effect to that of NAC and AP on lung tissue; reducing expression of NADPH oxidase (Fig.…”

Concentration cible de propofol atteinte pendant une chirurgie cardiaque avec circulation extra-corporelle: une étude pilote de détermination de dose

“…The highest level we measured was approximately 7.5 lg Á mL -1 (45 mM), as seen in 17% of cases. This concentration is clinically and experimentally relevant, given these levels have been previously associated with the range expected to inhibit both lipid peroxidation 38 and mitochondrial permeability transition. 16 The absence of high drug levels among patients in Study 2 suggests that a large dose of propofol applied during CPB had no detrimental effect on early post-bypass functional recovery relative to lower infusion rates.…”