Sevoflurane preconditioning protects against acute MI/R injury via enhancing AdipoR1-Cav3 interaction and alleviating endoplasmic reticulum stress.

Whether and how sevoflurane preconditioning (SevoPre) exerts protection against acute myocardial ischemia/reperfusion (MI/R) injury remains elusive. We observed significant myocardial injury, as evidenced by infarct size, cardiomyocyte apoptosis, and circulating troponin-I, at 3 h of MI/R in both wildtype and adiponectin knockout mice. The injury was significantly ameliorated by SevoPre in wildtype mice, but not in adiponectin knockout mice. In wildtype mice, we found that MI/R could increase endoplasmic reticulum stress of cardiomyocytes, and impair association of adiponectin receptor 1 and ceveolin-3, both of which processes were largely restored by SevoPre. In summary, we demonstrated that significant injury had already took place at 3 h of MI/R, which could be ameliorated by SevoPre via promoting affinity of adiponectin receptor 1 and ceveolin-3, and then attenuating endoplasmic reticulum stress of cardiomyocytes.

Propofol Affects Different Human Brain Regions Depending on Depth of Sedation(△).

OBJECTIVE: To investigate the effect of propofol on brain regions at different sedation levels and the association between changes in brain region activity and loss of consciousness using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) and bispectral index (BIS) monitoring. METHODS: Forty-eight participants were enrolled at Peking Union Medical College Hospital from October 2011 to March 2012 and randomly assigned to a mild or a deep sedation group using computer- generated random numbers. Preliminary tests were performed a week prior to scanning to determine target effect site concentrations based on BIS and concomitant Observer's Assessment of Alertness/Sedation scores while under propofol. Within one week of the preliminary tests where propofol dose-response was established, BOLD-fMRI was conducted to examine brain activation with the subject awake, and with propofol infusion at the sedation level. RESULTS: Mild propofol sedation inhibited left inferior parietal lobe activation. Deep sedation inhibited activation of the left insula, left superior temporal gyrus, and right middle temporal gyrus. Compared with mild sedation, deep propofol sedation inhibited activation of the left thalamus, precentral gyrus, anterior cingulate, and right basal nuclei. CONCLUSION: Mild and deep propofol sedation are associated with inhibition of different brain regions, possibly explaining differences in the respective loss of consciousness processes.

Sevoflurane preconditioning improving cerebral focal ischemia-reperfusion damage in a rat model via PI3K/Akt signaling pathway.

In this study, we aimed to assess the neuroprotective effect of sevoflurane preconditioning in a cerebral focal ischemia-reperfusion rat model. Sixty Sprague Dawley rats were divided into six groups: sham operated group, cerebral focal ischemia-reperfusion (CIR) group, CIR+sevoflurane preconditioning (SP) (2%) group, CIR+sevoflurane preconditioning (2.5%) group, CIR+sevoflurane preconditioning (3%) group, and CIR+sevoflurane preconditioning (3.5%) group. All subjects were euthanized 2days post-surgery and their hippocampus tissues were removed. Tissue malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) levels were measured and hippocampus tissue samples were examined histopathologically. Results showed that significant difference in antioxidant, immunity indexes, and apoptosis-related protein expression was detected in hippocampus tissue between sham-operated control and CIR groups. Sevoflurane preconditioning significantly dose-dependently reduced MDA, IL-1ß, IL-6, IL-10 and TNF-α levels and enhanced antioxidant enzyme activities in hippocampus tissue of CIR+SP groups compared to CIR group. In addition, sevoflurane preconditioning significantly dose-dependently upregulated PI3K, p-Akt and Bcl-2 levels and downregulated caspase-3 and Bax levels in hippocampus tissue of CIR+SP groups compared to CIR group. It can be concluded that sevoflurane preconditioning demonstrates a strong and ameliorative effect on cerebral I/R damage in rats. The neuroprotective mechanisms of sevoflurane preconditioning are associated with its properties of anti-apoptosis and anti-oxidation as well as regulation of PI3K and p-Akt signal activation.

Effect of Sevoflurane postconditioning on gene expression in brain tissue of the middle cerebral artery occlusion rat model.

Ischemic postconditioning has been described in both heart and brain. The first aim of this study was to evaluate the effects of Sevoflurane postconditioning (SP) on brain biochemical parameters, Bcl-2, Bax, c-Fos and Caspase-3 protein levels and Bcl-2, Bax, TNF-α and Caspase-3 mRNA expression in the middle cerebral artery occlusion model. Results showed that SP markedly decreased cerebral oxidative injury and improved immunity activity. In addition, SP significantly enhanced cerebral Bcl-2, c-Fos and decreased Bax, Caspase-3 proteins positive expression. Reverse transcription polymerase chain reaction analysis showed that SP markedly enhanced Bcl-2, and decreased Bax, TNF-α and Caspase-3 mRNA expression. Our results confirm that SP can play the protective action against cerebral ischemia reperfusion-induced brain injury by regulating cerebral antioxidant enzymes activities, Bcl-2, Bax, c-Fos and Caspase-3 protein positive expression levels and Bcl-2, Bax, TNF-α and Caspase-3 mRNA expression.

[An audit of perioperative fluid management and electrolyte monitoring in children undergoing surgery for scoliosis].

OBJECTIVE: To audite and compare the perioperative practices of intravenous fluids and electrolyte & glucose monitoring in children undergoing operations for scoliosis in 2008, 2010, prior to and after the publication of guideline in 2009. METHODS: Retrospective audit was conducted at Peking Union Medical College Hospital, a tertiary referral teaching hospital in Beijing, China. Children under 14 years old with scoliosis treated surgically in 2008 and 2010 were recruited. The following data were collected from medical files: age, gender, weight, duration of hospitalization, concurrent illness, operation, anesthesia, fluid prescribed during perioperative fasting period, electrolyte monitoring and postoperative pain control, etc. RESULTS: Among 235 American Society of Anesthesiologists (ASA) I-II cases, 75 children received dextrose 5% or saline 0.9% during the preoperative fasting period. Intraoperatively, the anesthesiologists preferred dextrose 5% or saline 0.9% in children under 6 years old (n = 15, 2008; n = 15, 2010) and Ringer's solution in those aged 6 - 14 years (n = 84, 2008; n = 94, 2010) and hypotonic fluid was not used. And 82.3% and 94.3% of them received electrolyte examinations preoperatively. The electrolyte results were unavailable postoperatively in 27/122 (in 2008) and 13/113 (in 2010) and serum electrolytes were not assessed before fluid treatment postoperatively. Electrolytes were monitored only once in 82.3% (in 2008) and 70.5% (in 2010) patients. Compared with the preoperative concentration of sodium ion, the mean decrease was approximately 2.0 mmol/L at Day 1 postoperation. Hyponatremia at Day 1 postoperation in 2010 was more common than that in 2008 (26.2% vs 23.6%; P = 0.044). But no significant difference existed between the incidence of hyperglycemia of the same day in 2008 and that in 2010 (P = 0.306). CONCLUSION: Compared with that in 2008, our recent practice of intravenous fluid prescription and electrolyte monitoring is ill-consistent with the recommendations in 2009. Implementation of optimal perioperative fluid management is warranted.

Inhibition of sevoflurane postconditioning against cerebral ischemia reperfusion-induced oxidative injury in rats.

The volatile anesthetic sevoflurane is capable of inducing preconditioning and postconditioning effects in the brain. In this study, we investigated the effects of sevoflurane postconditioning on antioxidant and immunity indexes in cerebral ischemia reperfusion (CIR) rats. Rats were randomly assigned to five separate experimental groups I-V. In the sham group (I), rats were subjected to the same surgery procedures except for occlusion of the middle cerebral artery and exposed to 1.0 MAC sevoflurane 90 min after surgery for 30 min. IR control rats (group II) were subjected to middle cerebral artery occlusion (MCAO) for 90 min and exposed to O2 for 30 min at the beginning of reperfusion. Sevoflurane 0.5, 1.0 and 1.5 groups (III, IV, V) were all subjected to MCAO for 90 min, but at the beginning of reperfusion exposed to 0.5 MAC, 1.0 MAC or 1.5 MAC sevoflurane for 30 min, respectively. Results showed that sevoflurane postconditioning can decrease serum tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), nitric oxide (NO), nitric oxide synthase (NOS) and increase serum interleukin-10 (IL-10) levels in cerebral ischemia reperfusion rats. In addition, sevoflurane postconditioning can still decrease blood lipid, malondialdehyde (MDA) levels, infarct volume and increase antioxidant enzymes activities, normal pyramidal neurons density in cerebral ischemia reperfusion rats. It can be concluded that sevoflurane postconditioning may decrease blood and brain oxidative injury and enhance immunity indexes in cerebral ischemia reperfusion rats.

[Psychedelic effects of subanesthetic doses of ketamine].

OBJECTIVE: To study the psychedelic effects in healthy volunteers when given subanesthetic dose of ketamine. METHODS: Thirteen male healthy volunteers aged 24-39 years were enrolled. All subjects received subanesthetic doses of ketamine using target control infusion. A stepwise series of target plasma concentrations (0, 100, 200, and 300 ng/ml) were maintained for 20 minutes each. Visual analogue scale (VAS) of mechanical pain by von Frey hair was evaluated, and then the volunteers completed a VAS rating of 13 symptom scales. Pictures were shown to them at the same time. Heart rate, mean blood pressure, and SpO2 were monitored throughout the infusion. RESULTS: During the process of analgesia, ketamine produced dose-related analgesic effects. With the increase of ketamine dose, some psychedelic effects became more obvious and the memory impairment became worse stepwisely. CONCLUSION: Target control infusion of subanesthetic doses of ketamine produce obvious psychedelic effects in healthy volunteers.

[Comparison of cerebral state index and bispectral index accuracies in sedation monitoring during target control infusion of midazolam].

OBJECTIVE: To compare the accuracies of cerebral state index (CSI) and bispectral index (BIS) in sedation monitoring during target control infusion of midazolam. METHODS: Twenty informed adult male volunteers were intravenously administered with midazolam through plasma target control infusion from 30ng/ml (in increments of 10ng/ml every time) until they became unresponsive to tactile stimulation (i. e., mild prodding or shaking). The BIS and CSI were continuously recorded simultaneously. Sedation was assessed using the Observers' Assessment of Alertness/Sedation (OAA/S) scale at each time when Ct equaled to Ce. The electroencephalogram (EEG) parameters were correlated with the OAA/S scores using nonparametric Spearman's correlation analysis. The prediction probabilities were calculated at the points of lost of verbal contact (LVC) and lost of responses to stimulus (LOR). BIS05, BIS50, BIS95, and CSI05, CSI50, CSI95 were also calculated for LVC and LOR. RESULTS: BIS and CSI were well correlation with OAA/S scales during both the onset and recovery phases. When the sedation level increased, BIS and CSI progressively decreased. The prediction probabilities of BIS and CSI were 84%, 74% for LVC and 79%, 68% for LOR, while the BIS05, BIS50, and BIS95 as well as CSI05, CSI50, and CSI95 were 85.5, 60.6, and 35.7 (for BISs) and 82.2, 65.2, and 30.3 (for CSIs) at the point of LVC and 79.7, 47.6, and 15.6 (for BISs) and 75.9, 43.4, and 11 (for CSIs) at the point of LOR. CONCLUSIONS: Both CSI and BIS seem to be useful parameters for assessing midazolam-induced sedation. BIS is superior in the prediction of LVC and LOR.