Mild hypothermia is an effective therapeutic strategy to improve poor neurological outcomes in patients following cardiac arrest (CA). However, the underlying mechanism remains unclear. The aim of the study was to evaluate the effect of mild hypothermia on intracellular autophagy and mitophagy in hippocampal neurons in a rat model of CA. CA was induced in Sprague-Dawley (SD) rats by asphyxia for 5 min. After successful resuscitation, the surviving rats were randomly divided into two groups, the normothermia (NT) group and the hypothermia (HT) group. Mild hypothermia (32 °C) was induced following CA for 4 h, and animals were rewarmed at a rate of 0.5 °C/h. Neurologic deficit scores (NDS) were used to determine the status of neurological function. Cytoplasmic and mitochondrial protein from the hippocampus was extracted, and the expression of LC3B-II/I and Parkin were measured as markers of intracellular autophagy and mitophagy, respectively. Of the 60 rats that underwent CA, 44 were successfully resuscitated (73 %), and 33 survived until the end of the experiment (55 %). Mild hypothermia maintained eumorphism of nuclear and mitochondrial structures and significantly improved NDS (p < 0.05). Expression of LC3B-II/I and Parkin in hippocampal nerve cells were significantly increased (p < 0.05) in the NT group relative to the control. Meanwhile, mild hypothermia reduced the level of LC3B-II/I and Parkin (p < 0.05) relative to the NT group. Mild hypothermia protected mitochondria and improved neurological function following CA and resuscitation after ischemia/reperfusion (I/R) injury, likely by reducing excessive autophagy and mitophagy in neurons.

BACKGROUND: Cardiac arrest (CA) is a common and serious event in emergency medicine. Despite recent improvements in resuscitation techniques, the survival rate of patients with CA is unchanged. The present study was undertaken to observe the effect of mild hypothermia (MH) on the reactive oxygen species (ROS) and the effect of neurological function and related mechanisms. METHODS:Sixty-five healthy male Sprague Dawley (SD) adult rats were randomly (random number) divided into 2 groups: blank control group (n=5) and CPR group (n=60). CA was induced by asphyxia. The surviving rats were randomly (random number) divided into two groups: normothermia CPR group (NT) and hypothermia CPR group (HT). Normothermia of 37 °C was maintained in the NT group after return of spontaneous circulation (ROSC), hypothermal intervention of 32 °C was carried out in the HT group for 4 hours immediately after ROSC. Both the NT and HT groups were then randomly divided into 2 subgroups 12 hours and 24 hours after ROSC (NT-12, NT-24, HT-12, HT-24 subgroups). During observation, the neurological defi cit scores (NDSs) was recorded, then the bilateral hippocampi were obtained from rats' head, and monoplast suspension of fresh hippocampus tissue was made immediately to determine the level of intracellular ROS by flow cytometry. Transmission electron microscope was used to observe the ultramicro changes of cellular nucleus and mitochondria. Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression of caspase-3 mRNA, and western-blotting (WB) was used to determine the level of LC3 in frozen hippocampus tissue. Measured data were analyzed with paired sample t test and One-Way ANOVA.RESULTS: Of 60 rats with CA, 44 (73%) were successfully resuscitated and 33 (55%) survived until the end of the experiment. The NDSs of rats in the NT and HT groups were more signifi cantly reduced than those in the BC group (F=8.107, P<0.05), whereas the NDSs of rats in the HT-12 and HT-24 subgroups were significantly increased in comparison with those NDSs of rats in the NT-12 and NT-24 subgroups, respectively (t=9.692, P<0.001; t=14.374, P<0.001). The ROS in hippocampus nerve cells in the NT and HT groups signifi cantly increased compared to the BC group (F=16.824, P<0.05), whereas the ROS in the HT-12 and HT-24 subgroups significantly reduced compared with that ROS in the respectively (t=9.836, P<0.001; t=7.499, P<0.001). The expression of caspase-3 mRNA in hippocampus nerve cells in the NT and HT groups were signifi cantly increased compared to the BC group (F=24.527, P<0.05), whereas the expression of caspase-3 mRNA in rats of the HT-12 and HT-24 subgroups was signifi cantly reduced compared to the respectively (t=6.935, P<0.001; t=4.317, P<0.001). The expression of LC3B-II/I in hippocampus nerve cells of rats in the NT and HT groups signifi cantly www.wjem.org 299 World J Emerg Med, Vol 5, No 4, 2014 increased compared to the BC group (F=6.584, P<0.05), whereas the expression of LC3B-II/I in rats of the HT-12 and HT-24 ...

Sepsis‐induced cerebral injury is a systemic inflammatory response associated with high mortality rate and cognitive impairment. Rho/ROCK pathway activation is involved in initiating the inflammatory response and promoting cerebral dysfunction. The present study explored the beneficial effects of ROCK inhibitors in sepsis‐induced cerebral injury and cognitive impairment in rats. The model of sepsis was established by employing cecal ligation and puncture (CLP). CLP significantly augmented cerebral injury assessed in terms of intensified activity of caspases‐3 and decrease in BCL‐2 in the brain along with the release of S100β and NSE, and assessed on day 7. Significant increase in inflammatory biomarkers IL‐1β and TNF‐α as well as increase in the protein levels of ROCK1 and ROCK2 was observed in the brain. A significant decrease in learning and memory ability was observed because of increased escape latency time on day 4 and significant decrease in time spent in the target quadrant on day 7 in CLP‐subjected rats. Administration of nonselective ROCK inhibitor, fasudil (10 and 30 mg/kg), and selective ROCK1 inhibitor, Y27632 (10 and 30 mg/kg), attenuated the sepsis‐induced increase in the S100β and NSE, IL‐1β, TNF‐α, BCL‐2, caspase‐3, ROCK1 and ROCK2 in septic rats and significantly memory and learning.The beneficial effects of Y27632 and fasudil were comparable suggesting the key role of ROCK1 in sepsis‐induced deleterious effects. It may be concluded that sepsis may increase cerebral and cognitive injury through Rho‐kinase/ROCK pathway in septic rats, and ROCK inhibitors may be potentially employed to overcome sepsis‐induced deleterious effects in the brain.

Objective To investigate the characteristics of early catheter-related bloodstream infection (CRBSI) in severe burn injury patients induced by a massive aluminum dust explosion. Methods Sixty-eight severe burn injury patients experienced a massive dust explosion in Kunshan were included in this study. Patients received central venous catheter placement, arterial catheterization to monitor blood pressure and PiCCO cardiac monitoring, tracheostomy, mechanical ventilation, analgesics and sedation treatment, and fluid resuscitation. Clinical data including age, gender, burn surface area, fluid intake and output, urine temperature, and APACHE II score information were collected from each patient. Ultrasound screening was performed to exclude heart failure, which may lead to the change of NT-proBNP. When CRBSI was suspected, 10 ml central venous blood and peripheral arterial blood were sent for testing. For patients with suspected CRBSI, the level of PCT and NT-proBNP were monitored every day until the infection was controlled. Results Among the 68 patients, 29 showed CRBSI. The most common pathogenic bacteria of CRBSI were A. baumannii (39.8%), P. aeruginosa (26.4%), and K. pneumoniae (13.7%). Procalcitonin (PCT) (2.98 ng/ml) and NT-proBNP (355 pg/ml) were significantly associated with CRBSI results. The sensitivity of PCT, NT-proBNP, WBC, and CRP was 94.2%, 89.7%, 88.3%, and 90.5%, respectively (P < 0.05). The area under curve (AUC) of PCT combined with NT-proBNP for prediction of CRBSI was 0.981, and the sensitivity and specificity was 0.812 and 0.857, respectively. Conclusion PCT and NT-proBNP combination improves the diagnosis of CRBSI. PCT and NT-proBNP may be alternative candidates for potential prediction of CRBSI in patients with severe injury.

Aims Lactate and lactate clearance were supposed to be associated with cardiac arrest outcomes, but studies obtained different results. Thus, we conducted this meta-analysis to investigate the association between lactate or lactate clearance and neurological outcomes and their usefulness for prediction of neurological outcomes. Methods We conducted a systematic search in PubMed, Web of science, EMBASE, Medline, and Google Scholar until May 1, 2018, for relevant studies. Studies reporting lactate, lactate clearance on admission, or other time points after admission associated with neurological outcomes were included in our analysis. Pooled effect date was shown as weighed mean difference (WMD) and 95% confidence interval (CI). To measure the usefulness of lactate on admission to predict neurological outcomes, we also pooled the data of diagnostic test. Results 23 studies involving 6720 cardiac arrest (CA) patients were included. Results from our analysis indicated that patients with good neurological outcomes tended to have a lower lactate level on admission (WMD: -2.66 mmol/L, 95%CI: -3.39 to -1.93) and 12h, 24h, and 48h after admission (P<0.001). Furthermore, the pooled AUC for lactate level on admission to predict neurological outcomes was 0.77 (95%CI: 0.73-0.80). However, a significant association between lactate clearance and neurological outcomes was only found in 24h but not 12h lactate clearance rate. Conclusions Lactate levels on admission and all time points up to 48h were associated with neurological outcomes after CA, whereas the association between lactate clearance and neurological outcomes was not so stable. Lactate was a more robust surrogate marker than lactate clearance to predict neurological outcomes after CA.