However, mild therapeutic hypothermia did not affect S100B serum levels in survivors of cardiac arrest in several clinical studies [41,42]. In addition, Xiao and colleagues have previously shown that cardiac arrest significantly GSK2656157? increased brain myeloperoxidase activity, but again, mild hypothermia had no effect. Thus, the hypothermia-elicited neuroprotection seemed not to be neutrophil-dependent, at least in that rat model of asphyxial cardiac arrest [43].Effects of pharmacological post-conditioning on cerebral inflammatory responseVolatile anesthetic agents have emerged as pre-conditioning-like agents with significant neuroprotective effects and the ability to reduce excitotoxic induced cell death, to decrease cerebral metabolic rate, to activate inducible nitrous oxide synthase and p38 mitogen-activated protein kinases, and to improve neurological deficits in models of both focal and global cerebral ischemia [6,44,45].
Most experimental studies have documented improved functional performance when neuroprotective agents were given before the insult. In patients with cardiac arrest, however, pretreatment is virtually impossible because of the unpredictable onset of ischemia. Therefore, as in our study, potential protective interventions should be initiated during or after experimental ischemia to affect reperfusion injury. In this context, pharmacological postconditioning with volatile anesthetics in addition to mild hypothermia may offer an attractive opportunity to further ameliorate brain damage and inflammation in the post-resuscitation period.
The effects of volatile agents on the inflammatory response after cardiac arrest have not yet been elucidated. In endotoxemic rats, inhalation of sevoflurane significantly attenuated plasma levels of TNF�� and IL-1�� [46]. In addition, sevoflurane post-conditioning showed anti-inflammatory and anti-necrotic effects in cultured kidney proximal tubule cells [47], and sevoflurane attenuated the inflammatory response upon stimulation of alveolar macrophages with endotoxin in vitro [48]. In our study, however, sevoflurane administered instead of propofol during reperfusion after successful CPR did not further attenuate local cerebral inflammatory response. These observations are comparable to those obtained in a study by Fries et al.
where the volatile anesthetic isoflurane did not reduce neurological dysfunction and histopathological alterations Anacetrapib induced by cardiac arrest [49]. However, it is conceivable that hypothermia alone has such potent anti-inflammatory properties compared to normothermia, that an additional effect of sevoflurane could not be revealed in the present study. Moreover, potential protective effects of volatile anesthetics depend on energy-dependent signal transduction, for example, protein synthesis and phosphorylation [50], that may be affected by hypothermia-induced decrease of metabolic rate as well as suppression of protein synthesis.