European Journal of Anaesthesiology 1997, 14, 320–326 Propofol neuroprotection in a rat model of ischaemia reperfusion injury Y. Young*, D. K. Menon*‡, N. Tisavipat†, B. F. Matta* and J. G. Jones* *Departments of Anaesthesia, †Neurosurgery and ‡MRC Centre for Brain Repair, University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UK Y. Young et al. (1997) European Journal of Anaesthesiology , 14, 320–326 Propofol neuroprotection in a rat model of ischaemia reperfusion injury Summary which have been shown to reliably produce EEG burst suppression). After a further 30 min, reperfusion was This study was designed to test the hypothesis that induced by withdrawing the filament. Animals were propofol, which possesses antioxidant properties, killed following 240 min of reperfusion. Rats in the would produce greater protection than isoflurane in propofol group showed a 21% reduction in mean cerebral ischaemia reperfusion injury, at dose levels hemispheric infarct volume when compared with the that produced similar effects on brain electrical ac- isoflurane group (P<0.0001). These data suggest that tivity. Twenty Sprague-Dawley rats were anaesthetized propofol may act by mechanisms in addition to CMRO 2 using isoflurane 1.5% in air/oxygen, and mechanically depression, and provide a basis for further studies of ventilated to a PaCO 2 of 4.5 kPa. Following 90 min of propofol neuroprotection. middle cerebral artery occlusion using an intraluminal filament, rats were given, in random order, either Keywords: ,   -   ,  , . propofol 1 mg kg -1 min -1 or isoflurane 3% (both of relation to their protective effects in experimental isch- Introduction aemia, and suggest that we should be looking for Ischaemic cerebral lesions consist of a central area of other explanations of their protective effects. dense infarct, surrounded by a penumbra of po- Propofol (Diprivan∈) suppresses brain electrical ac- tentially viable tissue, which may be salvaged to vary- tivity and decreases cerebral oxygen consumption and ing degrees by prompt reperfusion or pharmacological cerebral blood flow [4,5], but also possesses anti- intervention [1]. The phenomenon of reperfusion may, oxidant properties [6]. In a feline model of incomplete by itself, increase the amount of tissue injury, in part cerebral ischaemia, propofol ameliorated post-isch- by mechanisms that involve oxidant damage [2]. Many aemic extracellular fluid acidosis, hyperkalaemia, groups have investigated the use of anaesthetic agents and hypoperfusion, but failed to improve neuro- to reduce cerebral metabolism in animal models of histopathological outcome [7]. In a rodent model of cerebral ischaemia, believing that a reduction in the incomplete forebrain ischaemia, Kochs et al. [8] cerebral metabolic rate for oxygen (CMRO 2 ) would showed a reduction in hemispheric infarct volume by alter favourably the balance between energy supply doses of propofol that produced EEG burst-sup- and demand, thus protecting against ischaemia. How- pression, when compared with animals anaesthetized ever, Todd and Warner[3] point out that the cerebral with a combination of nitrous oxide and fentanyl. In depressant effects of anaesthetic agents bear little contrast, Ridenour et al. found that propofol provided no neuroprotection when compared with halothane in a model of cerebral ischaemia reperfusion injury in Accepted October 1996 Correspondence: Dr D. K. Menon. spontaneously hypertensive rats [9]. Further studies 320  1997 European Academy of Anaesthesiology