The effect of glutamine on cerebral ischaemic injury after cardiac arrest.

OBJECTIVES: The aim of this study is to investigate whether glutamine (GLN) enhances heat shock protein-25 (Hsp-25) and heat shock protein-72 (Hsp-72) expressions and attenuates cerebral ischaemic injury in rat cardiac arrest model. METHODS: Rats survived from cardiac arrest model were randomly assigned to CPR+GLN group (0.75 g/kg of alanyl-glutamine, n=6) or CPR group (same volume of 0.9% saline, n=6). Additional 6 rats were used for SHAM group. For the outcome measures, neurologic deficit score (NDS, 0-80) was checked at 24h and 72 h after cardiac arrest. At 72 h after cardiac arrest, rats were euthanised and the brain was harvested. Then, right hemisphere was used for cresyl-violet and TUNEL staining. Left hemisphere was used for Western blot analysis of phosphorylated heat shock factor-1 (p-HSF-1), Hsp-25, Hsp-72, and cleaved caspase-3. Kruskal-Wallis test and Mann-Whitney U post hoc test with Bonferroni correction were used for the analysis. RESULTS: Resuscitation variables were not different between CPR and CPR+GLN. NDS in CPR+GLN was higher than that in CPR (p<0.017) and lower than that in SHAM (p<0.017) at both 24h and 72 h. p-HSF-1, Hsp-25 and Hsp-72 expressions in CPR+GLN were significantly enhanced (p<0.017) than those in other groups. Cleaved caspase-3 expression in CPR was significantly higher (p<0.017) than in SHAM and CPR+GLN. Ischaemic and TUNEL-positive neurons were more frequently observed in CPR than in CPR+GLN. CONCLUSIONS: Glutamine attenuates cerebral ischaemic injury in cardiac arrest model of rats and this is associated with the enhancement of Hsp-25 and Hsp-72 expressions.

Accuracy of the cardiopulmonary resuscitation registry in an emergency department.

BACKGROUND: The cardiopulmonary resuscitation (CPR) registry has been documented for medical records and investigational purposes. Although the accuracy of the CPR registry is generally adequate, it is difficult to precisely describe CPR in emergency situations. OBJECTIVES: To evaluate the accuracy of the CPR registry in an emergency department (ED) and to determine whether closed-circuit television (CCTV) is useful for recording CPR events. METHODS: To assess the accuracy of the CPR registry, CCTV clips of the room in which CPR was performed in the ED and the corresponding CPR registry were consecutively collected and reviewed. The contents of the registry, specifically the time interval between patient arrival and CPR procedures, were compared with those determined by the CCTV clips. Accuracy was defined as the frequency of accurately registered time intervals differing by <30 s. RESULTS: In a university-based ED between May and November 2009, 46 CPRs were performed and 150 CPR time intervals were documented in the CPR registry. The level of CPR registry accuracy was 54% (81/150). CONCLUSIONS: The accuracy of the CPR registry was improved by the use of CCTV. These results indicate that more detailed CPR investigations could be performed with the addition of CCTV-based information to the CPR registry.

A combination of metabolic strategies plus cardiopulmonary bypass improves short-term resuscitation from prolonged lethal cardiac arrest.

BACKGROUND: The metabolic or late phase of cardiac arrest is highly lethal. Emergency cardiopulmonary bypass (ECPB) can resuscitate many patients even after prolonged cardiac arrest and provides immediate vascular access for correction of metabolic derangement during the reperfusion process. We developed a rodent model of ECPB resuscitation which showed the superiority of ECPB over conventional CPR, especially when combined with hypothermia. For this study we examined a metabolic strategy against ischemia-reperfusion injury (MS-IR) that included: leukoreduction, low Ca(2+), Mg(2+), buffered pH, red blood cells and a colloid. We tested whether ECPB plus MS-IR and/or hypothermia improves short-term hemodynamic outcomes compared to a standard ECPB reperfusate. METHODS: Using a 2×2 factorial design we tested ECPB with (a) MS-IR versus a standard crystalloid solution; and (b) hypothermia versus normothermia in our rat model. The four reperfusion strategies included: (1) MS-IR plus hypothermia, (2) MS-IR with normothermia, (3) standard plasma-lyte (STD) reperfusate plus hypothermia, or (4) STD plus normothermia. Animals underwent 12 min of untreated asphyxial arrest and were resuscitated with ECPB and one of the four strategies for 30 min. Thereafter, ECPB was discontinued and ventilatory support was provided for 3 hours, while hemodynamic, perfusion and other metrics were serially measured. RESULTS: All rats achieved ROSC with ECPB. Significant differences between the groups emerged after 3 hrs: the best outcomes were in animals with MS-IR plus hypothermia (lactate: 1.1 ± 0.1 mmol/L; MAP: 83 ± 4 mm Hg, seizures: 0/10), while the worst outcomes were with STD and normothermia (lactate: 8.9 ± 1.4 mmol/L, MAP: 36 ± 4 mm Hg, seizures: 7/10, p < 0.001). The outcomes of the other two groups (MS-IR only; hypothermia only) were intermediate. MS-IR and hypothermia improved outcome in an additive fashion. CONCLUSIONS: While most human ECPB is applied with a normothermic crystalloid priming solution, we observed that in rodents the addition of MS-IR plus hypothermia resulted in considerable short-term benefit after prolonged arrest. Future long-term and translational survival studies are warranted to optimize ECPB resuscitation methods.

Glutamine attenuates acute lung injury by inhibition of high mobility group box protein-1 expression during sepsis.

Heat shock protein 70 (HSP70) is reported as the main factor responsible for the beneficial effects of glutamine (GLN) and as a negative regulator of high mobility group box protein-1 (HMGB-1) expression. Our aim was to determine whether GLN attenuates acute lung injury (ALI) by the inhibition of HMGB-1 expression during sepsis. Male Sprague-Dawley rats were subjected to caecal ligation and puncture (CLP) to induce sepsis. GLN or saline was administered through tail vein 1 h after CLP. Then, quercetin (Q), an inhibitor of HSP70, was utilised to assess the role of the enhanced HSP70. We observed the survival of the subjects. At 24 h post-CLP, we measured lung HSP70, phosphorylated heat shock factor-1 (HSF-1-p) and HMGB-1 expressions, NF-kappaB DNA-binding activity and ALI occurrence. We also measured serum HSP70, IL-6 and HMGB-1 concentrations. GLN improved survival during sepsis. In GLN-treated rats, lung HSP70 and HSF-1-p expressions were enhanced, lung HMGB-1 expression and NF-kappaB DNA-binding activity were suppressed, and ALI was attenuated. Furthermore, in GLN-administered rats, serum HSP70 concentration was higher, and serum IL-6 and HMGB-1 concentrations were lower than those in non-treated rats. Q inhibited the enhancement of HSP70 and HSF-1-p expressions and abrogated the GLN-mediated benefits. In conclusion, GLN attenuated ALI and improved survival by the inhibition of HMGB-1 expression during sepsis in rats. These benefits were associated with the enhancement of HSP70 expression by GLN.

Effect of an independent-capacity protocol on overcrowding in an urban emergency department.

OBJECTIVES: The authors hypothesized that a new strategy, termed the independent-capacity protocol (ICP), which was defined as primary stabilization at the emergency department (ED) and utilization of community resources via transfer to local hospitals, would reduce ED overcrowding without requiring additional hospital resources. METHODS: This is a before-and-after trial that included all patients who visited an urban, tertiary care ED in Korea from July 2006 to June 2008. To improve ED throughput, introduction of the ICP gave emergency physicians (EPs) more responsibility and authority over patient disposition, even when the patients belonged to another specific clinical department. The ICP utilizes the ED as a temporary, nonspecific place that cares for any patient for a limited time period. Within 48 hours, EPs, associated specialists, and transfer coordinators perform secondary assessment and determine patient disposition. If the hospital is full and cannot admit these patients after 48 hours, the EP and transfer coordinators move the patients to other appropriate community facilities. We collected clinical data such as sex, age, diagnosis, and treatment. The main outcomes included ED length of stay (LOS), the numbers of admissions to inpatient wards, and the mortality rate. RESULTS: A total of 87,309 patients were included. The median number of daily patients was 114 (interquartile range [IQR] = 104 to 124) in the control phase and 124 (IQR = 112 to 135) in the ICP phase. The mean ED LOS decreased from 15.1 hours (95% confidence interval [CI] = 14.8 to 15.3) to 13.4 hours (95% CI = 13.2 to 13.6; p < 0.001). The mean LOS in the emergency ward decreased from 4.5 days (95% CI = 4.4 to 4.6 days) to 3.1 days (95% CI = 3.0 to 3.2 days; p < 0.001). The percentage of transfers from the ED to other hospitals decreased from 3.5% to 2.5% (p < 0.001). However, transfers from the emergency ward to other hospitals increased from 2.9% to 8.2% (p < 0.001). Admissions to inpatient wards from the ED were significantly reduced, and admission from the emergency ward did not change. The ED mortality and hospital mortality rates did not change (p = 0.15 and p = 0.10, respectively). CONCLUSIONS: After introduction of the ICP, ED LOS decreased without an increase in hospital capacity.

Comparison of a pulsatile blood pump and a peristaltic roller pump during hemoperfusion treatment in a canine model of paraquat poisoning.

This study examined the treatment efficacy and the damage to the blood during hemoperfusion for treating paraquat poisoning using two blood pump mechanisms. Paraquat-poisoned animal models were prepared. A conventional hemodialysis machine, AK90, with a peristaltic roller pump and a cardiopulmonary support system, T-PLS, with a pulsatile blood pump were used during the animal experiments. A total of 12 dogs were treated with hemoperfusion using a charcoal column. Six dogs were treated with hemoperfusion and T-PLS, and the other six were treated with AK90. A paraquat dose of 30 mg/kg was administrated by an intravenous injection. Both pumps maintained blood flow rates of 125 mL/min measured by an ultrasonic flowmeter. For anticoagulation, heparin was administrated by an initial bolus (250 IU/kg) and a continuous injection (100 IU/kg/h). During the experiments, T-PLS and AK90 showed a similar toxin removal efficacy. Both devices decreased the plasma paraquat concentration to 10% of the initial dose within 4-h hemoperfusion. The two pumps showed similar hemolysis properties with acceptable levels. Although T-PLS was developed as a cardiopulmonary bypass system, it can also be used as a hemoperfusion treatment device.

Etomidate should be used carefully for emergent endotracheal intubation in patients with septic shock.

Etomidate and midazolam are the most popular drugs among the induction agents for emergent endotracheal intubation. The purpose of this study was to compare the incidence of adrenal insufficiency and mortality between the septic shock patients who received etomidate (ETM group) and those who received midazolam (MDZ group). Between November 2004 and September 2006, 65 patients were analyzed in this study. The hospital mortality rate was 36% in the ETM group (n=25) and 50% in the MDZ group (n=40), which was not statistically significant (p=0.269). The incidence of relative adrenal insufficiency was significantly higher in the ETM group than in the MDZ group (84% and 48%, respectively; p=0.003). On multivariate analysis, the use of etomidate was the only significant factor affecting the incidence of relative adrenal insufficiency (odds radio, 5.59; 95% confidence interval, 1.61-19.4). In conclusion, we think that physicians who treat patients with septic shock should be aware that etomidate can cause adrenal insufficiency, and should start corticosteroids if etomidate is administered.

Association between polymorphism in intron 1 of cocaine- and amphetamine-regulated transcript gene with alcoholism, but not with bipolar disorder and schizophrenia in Korean population.

Cocaine- and amphetamine-regulated transcript (CART) peptide is a novel neuropeptide involved in feeding, drug reward, and stress. We hypothesized that the polymorphism of CART gene might be related with susceptibility to neuropsychiatric diseases such as alcoholism, bipolar disorder, and schizophrenia. The polymorphism (rs2239670) in intron 1 was selected for study among other single nucleotide polymorphisms (SNPs) located at the area of CART gene, because it had not been tested until to date. The study included patients of alcoholism (100), bipolar disorder (76) and schizophrenia (169) from the Korean population. Healthy controls for bipolar disorder and schizophrenia consisted of 333 individuals. For alcoholism, both patient group and control subjects included only male. The restriction fragment length polymorphism (RFLP) using the AvaII restriction enzyme was designed to analyze the selected SNP. The distribution of GG, GA, and AA genotypes in the 333 controls was 50.2, 41.1, and 8.7%, respectively. The frequency of G and A alleles in the 333 controls was 70.7 and 29.3%, respectively. The distribution of genotype and allele frequencies of the AvaII polymorphism showed a significant difference between alcoholism and controls (P = 0.037 and P = 0.044). However, the AvaII polymorphism of the CART gene did not show association with bipolar disorder and schizophrenia. In conclusion, we report for the first time that the AvaII polymorphism (rs2239670) in intron 1 of the CART gene is associated with alcoholism in the Korean male population.