Eckle et al. [33] provided evidence for a critical role of HIF-1�� in cardioprotection by ischemic preconditioning. In addition, Zhao and colleagues [34] suggested recently that HIF-1�� is also involved in ischemic postconditioning, and pharmacological augmentation of HIF-1�� expression may even enhance the myocardial infarct-sparing effect. In the present inhibitor supplier study, expression of HIF-1�� was increased on mRNA and protein levels in the SEVO group compared to the CONTROL group. Thus our data confirm the results of several studies that found upregulation of HIF-1�� after preconditioning with volatile anesthetics in both in vitro [35,36] and in vivo [37] models of ischemia-reperfusion injury.After substantial myocardial ischemia, major tissue remodeling occurs to restore the structural architecture and cardiac function.

These remodeling events are parallel to increased expression and activity of MMPs in the postinfarct myocardium [38]. The interaction between global ischemia following CA, matrix remodeling and volatile anesthetics has been poorly studied to date.Regarding the effect of SEVO on myocardial tissue remodeling, we found that SEVO increased MMP-9 activity in myocardial tissue, whereas the effects on MMP-2 activity were indistinguishable. Since IL-1�� and other proinflammatory cytokines may also be actively involved in the regulation of matrix remodeling processes after myocardial ischemia [39], the issue of tissue remodeling and the regulatory effect of IL-1�� on MMP activity could be very important.

Interestingly, in vitro data from our group points toward positive regulatory effects of IL-1�� on MMP-2 and MMP-9 expression and activity [40]. These data suggest that the SEVO-induced attenuation of IL-1�� expression in the present study Entinostat might affect myocardial MMP-2 and MMP-9 activity in such a way as to facilitate tissue remodeling following global ischemia and CPR.Effects of sevoflurane on neurological function, cerebral apoptosis and inflammationVolatile anesthetics also possess a variety of neuroprotective mechanisms of action that include inhibition of spontaneous depolarization in the ischemic penumbra, antioxidant potential and N-methyl-D-aspartate receptor antagonism after cerebral ischemia [41,42]. For example, Blanck et al. [43] demonstrated functional reduction in neurological injury following 8 minutes of CA after SEVO-induced preconditioning. In the same way, isoflurane proved to be effective in rodent models of middle cerebral artery occlusion, causing increased tolerance of the brain to a subsequent ischemic insult [41].