Mild hypothermia alleviates excessive autophagy and mitophagy in a rat model of asphyxial cardiac arrest.

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.

Optimal indicator for changing the filter during the continuous renal replacement therapy in intensive care unit patients with acute kidney injury: A crossover randomized trial.

BACKGROUND: The study aims to investigate an optimal indicator for changing the filter during the continuous renal replacement therapy (CRRT) in intensive care unit (ICU) patients with acute kidney injury (AKI). METHODS: Patients with AKI requiring CRRT in an ICU were randomly divided into two groups for crossover trial, i.e., groups A and B. Patients in the group A were firstly treated with continuous veno-venous hemofiltration (CVVH), followed by continuous veno-venous hemodiafiltration (CVVHDF). Patients in the group B were firstly treated with CVVHDF followed by CVVH. Delivered doses of solutes with different molecular weights at the indicated time points between groups were compared. A correlation analysis between the delivered dose and pre-filter pressure (PPRE) and transmembrane pressure (PTM) was performed. Receiver operating characteristic (ROC) curves were constructed to evaluate the accuracy of PTM as an indicator for filter replacement. RESULTS: A total of 50 cases were analyzed, 27 in the group A and 23 in the group B. Delivered doses of different molecular-weight solutes significantly decreased before changing the filter in both modalities, compared with those at the initiation of treatment (all P<0.05). In the late stage of CRRT, the possible rebound of serum medium-molecular-weight solute concentration was observed. PTM was negatively correlated with the delivered dose of medium-molecular-weight solute in both modalities. The threshold for predicting the rebound of serum concentration of medium-molecular-weight solute by PTM was 146.5 mmHg (1 mmHg=0.133 kPa). CONCLUSIONS: The filter can be used as long as possible within the manufacturer's safe use time limits to remove small-molecular-weight solutes. PTM of 146.5 mmHg may be an optimal indicator for changing the filter in CRRT therapies to remove medium-molecular-weight solutes.

Blood Lactate or Lactate Clearance: Which Is Robust to Predict the Neurological Outcomes after Cardiac Arrest? A Systematic Review and Meta-Analysis.

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.

Neuroprotection of hyperbaric oxygen therapy in sub-acute traumatic brain injury: not by immediately improving cerebral oxygen saturation and oxygen partial pressure.

Although hyperbaric oxygen (HBO) therapy can promote the recovery of neural function in patients who have suffered traumatic brain injury (TBI), the underlying mechanism is unclear. We hypothesized that hyperbaric oxygen treatment plays a neuroprotective role in TBI by increasing regional transcranial oxygen saturation (rSO2) and oxygen partial pressure (PaO2). To test this idea, we compared two groups: a control group with 20 healthy people and a treatment group with 40 TBI patients. The 40 patients were given 100% oxygen of HBO for 90 minutes. Changes in rSO2 were measured. The controls were also examined for rSO2 and PaO2, but received no treatment. rSO2 levels in the patients did not differ significantly after treatment, but levels before and after treatment were significantly lower than those in the control group. PaO2 levels were significantly decreased after the 30-minute HBO treatment. Our findings suggest that there is a disorder of oxygen metabolism in patients with sub-acute TBI. HBO does not immediately affect cerebral oxygen metabolism, and the underlying mechanism still needs to be studied in depth.

Effects of mild hypothermia on the ROS and expression of caspase-3 mRNA and LC3 of hippocampus nerve cells in rats after cardiopulmonary resuscitation.

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 deficit 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 significantly 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 significantly 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 NT-12 and NT-24 subgroups, 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 significantly 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 significantly reduced compared to the NT-12 and NT-24 subgroups, 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 significantly 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 subgroups significantly reduced compared to the NT-12 and NT-24 subgroups, respectively (t=10.836, P<0.001; t=2.653, P=0.02). Ultrastructure damage of nucleus and mitochondria in the NT group was more evident than in the BC group, and eumorphism of nucleus and mitochondria were maintained in rats of the HT group compared with the NT group. CONCLUSION: Mild hypothermia lessened the injury of nerve cells and improved the neurological function of rats that survived from cardiac arrest by reducing the ROS production of nerve cells and inhibiting the expression of caspase-3 mRNA and LC3, leading to cellular apoptosis and massive autophagy in rats that survived from cardiac arrest after CPR.