Comparably, Mishra and colleagues have recently reported increased apoptosis in a pig model of cerebral hypoxia for 60 minutes, indicated by an increased ratio of Bax/Bcl-2 protein concentration, activation of caspase-9, lipid peroxidation, and DNA fragmentation in mitochondria of the cerebral cortex [51].Besides the regulation of inflammatory molecules, mild therapeutic hypothermia significantly attenuated the mRNA expression of the apoptosis-regulating proteins Bax and Bcl-2 in our study. These results are partly comparable to the findings of Ebersp?cher et al. [52,53], where hypothermia prevented an ischemia-induced increase of the pro-apoptotic protein Bax, but did not change or even increase expression of the anti-apoptotic protein Bcl-2. Potential discrepancies between the work presented here and those in the literature could be due to the type of species and duration of ischemia. In our pig model seven minutes of cardiac arrest were followed by resuscitation compared with the latter studies investigating a rat model of common carotid artery occlusion plus hemorrhagic hypotension [52,53]. In a similar rat model of cerebral ischemia, Pape et al investigated the effects of sevoflurane on neuronal damage and expression of apoptic factors. Sevoflurane was administered before, during and after cerebral ischemia, and has been found to modulate the balance between pro- and anti-apoptotic key proteins towards a reduction of active programmed cell death by increasing the hippocampal concentration of the anti-apoptotic proteins Bcl-2, and by inhibiting the ischemia-induced upregulation of the pro-apoptotic protein Bax [54].In our pig model of cardiac arrest, however, sevoflurane post-conditioning combined with mild hypothermia did not confer additional effects in terms of apoptotic-related mRNA expression. Again, it is conceivable that hypothermia alone has such potent anti-apoptotic effects, that an additional effect of sevoflurane could not be revealed in the present study.LimitationsAlthough we used a porcine model of cardiac arrest following myocardial ischemia reflecting a common clinical scenario, there are several points that need to be addressed in future studies: (i) both long-term survival and neurological outcome were not evaluated because of limitations posed by governmental regulations; therefore, we did not assess the relationship between the upregulation of cytokines and post-resuscitation cerebral dysfunction. (ii) Blinding the investigator was not possible throughout the experiment due to the cooling technique, but tissue samples were analyzed by a person blinded to treatment assignment.