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ABSTRACT: AIM OF THE STUDY: Valproic acid (VPA) has been known to reduce neuronal injury, have anti-inflammatory and anti-apoptotic effects as a histone deacetylase (HDAC) inhibitor. Thus, this study was performed to investigate the effects of VPA on survival and neurological outcomes in an asphyxial cardiac arrest model of rats. METHODS: Male Sprague-Dawley rats were subjected to asphyxial cardiac arrest. For survival study, rats were subjected to 450seconds of asphyxial cardiac arrest. Cardiopulmonary resuscitation (CPR) was performed and then rats were blindly allocated to one of two groups (control group, n=10; VPA group, n=10). Valproic acid (300mg/Kg) or vehicle (normal saline) was administered via tail vein immediately after return of spontaneous circulation (ROSC) and observed for 72hours. For neurological outcome study, rats (n=7 for each group) were subjected to same experimental procedures except duration of cardiac arrest of 360seconds. Neurological deficit scale (NDS) score was measured every 24hours after ROSC for 72hours and was ranged from 0 (brain dead) to 80 (normal). Brain tissues were harvested at 72hours for evaluation of apoptotic injury and acetylation status of histone H3. RESULTS: In survival study, 2 rats in VPA group were excluded because cardiac arrest was not achieved in predetermined time. Thus, 10 rats were allocated to control group and 8 rats were allocated to VPA group. The survival rates at 72hours after cardiac arrest were significantly higher in VPA group than in control group (6/8 in VPA group, 3/10 rats in control group; log rank test, p<0.05). In neurological outcome study, all rats survived for 72hours and NDS at 72hour were significantly higher in VPA group than in control group (p<0.05). In brain tissues, expressions of acetylated histone H3 were not significantly different. However, expressions of cleaved caspase-3 were significantly lower in VPA group than in control group (p <0.05). CONCLUSION: VPA increased survival rates and improved neurologic outcome in asphyxial cardiac arrest model of rats while decreasing expressions of cleaved caspase-3.
Resuscitation 05/2013; · 3.60 Impact Factor
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ABSTRACT: OBJECTIVES: There are no guidelines regarding the hospitalization of female patients with acute pyelonephritis (APN); therefore, we performed a retrospective analysis to construct a clinical prediction model for hospital admission. METHODS: We conducted a retrospective analysis of a prospective database of women diagnosed as having APN in the emergency department between January 2006 and June 2012. Independent risk factors for admission were determined by multivariable logistic regression analysis in half of the patients in this database. The risk of admission was categorized into 5 groups. The internal and external validations were conducted using the remaining half of the patients and 192 independent patients, respectively. RESULTS: Independent risk factors for admission were age of 65 years or greater (odds ratio [OR], 2.62; 1 point), chill (OR, 2.40; 1 point), and the levels of segmented neutrophils greater than 90% (OR, 2.00; 1 point), serum creatinine greater than 1.5 mg/dL (OR, 2.41; 1 point), C-reactive protein greater than 10 mg/dL (OR, 2.37; 1 point), and serum albumin less than 3.3 g/dL (OR, 7.36; 2 points). The admission risk scores consisted of 5 categories, which were very low (0 points; 5.9%), low (1 point; 10.7%), intermediate (2 points; 20.7%), high (3-4 points; 51.9%), and very high (5-7 points; 82.8%) risk, showing an area under the curve of 0.770. The areas under the curve of the internal and external validation cohorts were 0.743 and 0.725, respectively. CONCLUSION: This model can provide a guideline to determine the admission of women with APN in the emergency department.
The American journal of emergency medicine 04/2013; · 1.54 Impact Factor
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ABSTRACT: OBJECTIVE: This study was performed to investigate the association of red cell distribution width (RDW) with 28-day mortality in patients with severe sepsis and septic shock. METHODS: We performed a retrospective analysis of patients with severe sepsis and septic shock. Patients' demographic data, comorbidities, the blood test results including RDW at admission to the emergency department, and Acute Physiologic and Chronic Health Evaluation II score were compared between 28-day survivors and nonsurvivors. Red cell distribution width was categorized into tertiles as 14% or less, 14.1% to 15.7%, and 15.8% or greater. Multivariate Cox proportional hazards regression analysis was performed to determine the risk factors for mortality. RESULTS: A total of 566 patients were included, and overall mortality was 29%. Red cell distribution width was significantly higher in nonsurvivors than in survivors, and the corresponding mortality of patients with an RDW of 14% or less, 14.1% to 15.7%, and 15.8% or greater was 13.1%, 30.1%, and 44.9%, respectively (P < .001). In Cox proportional hazards analysis, groups with higher RDW are independently associated with 28-day mortality compared with groups with an RDW of 14.0% or less: RDW 14.1% to 15.7% (hazard ratio, 1.66; 95% confidence interval [CI], 1.00-2.76) and RDW of 15.8% or greater (hazard ratio, 2.57; 95% CI, 1.53-4.34). The area under the receiver operating curve of RDW was 0.68 (95% CI, 0.63-0.72). CONCLUSION: Red cell distribution width is associated with 28-day mortality in patients with severe sepsis and septic shock.
The American journal of emergency medicine 02/2013; · 1.54 Impact Factor
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ABSTRACT: AIM OF STUDY: The effects of therapeutic hypothermia (HT) during experimental sepsis may be influenced by disease severity. We experimentally investigated the effect of therapeutic HT on varying disease severity in a septic rat model. MATERIALS AND METHODS: An adult male Sprague-Dawley rat model of intra-abdominal sepsis was used. To modify the disease severity, we used two different models; a moderate severe sepsis model (MSSM) and a severe septic shock model (SSSM). All rats were randomized to a hypothermia group (HT, 30-32°C) or a normothermia group (NT, 36-38°C) 1h after sepsis induction in each model. HT was maintained for 4h and rewarming was conducted for 2h. Survival time was recorded for up to 12h in the SSSM group and 24h in the MSSM group. Acute lung and liver injury, cytokine, and malondialdehyde (MDA) levels were investigated 7h after sepsis induction. Hemodynamic profiles were also evaluated. RESULTS: In the SSSM, there were survival benefits and reduced acute lung and liver injury with therapeutic HT. Therapeutic HT was also associated with significantly reduced levels of plasma interleukin-6 and tissue malondialdehyde (MDA) levels in the liver and lung compared with the NT group in the SSSM. There was a tendency for the mean arterial pressure to be higher in the HT group compared to the NT group in the SSSM. In MSSM, however, there was no such beneficial effect. CONCLUSION: In this rat model of severe septic shock, therapeutic HT showed beneficial effects. In contrast, therapeutic HT did not show protective effect in the moderate sepsis model.
Cytokine 09/2012; · 3.02 Impact Factor
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ABSTRACT: AIM OF THE STUDY: N-acetylcysteine (NAC) has been investigated to attenuate organ injury in various experimental and clinical studies. However, results in hemorrhagic shock (HS) were controversial. We determined the effects of continuous administration of NAC on acute lung injury (ALI) and acute kidney injury (AKI) in HS model. METHODS: Twenty male Sprague-Dawley rats were used. Pressure controlled HS model defined by mean arterial pressure (MAP) 40±2mmHg for 90min followed by resuscitation and observation was used. Rats (n=10 per group) were randomized into 2 groups with NAC or dextrose. Intravenous NAC was given continuously from 15min after induction of HS to the end of observation period (2h). We measured serum IL-6, nitrite/nitrate concentration. NF-κB p65 DNA binding activity, expressions of cytoplasmic phosphorylated IκB-α (p-IκB-α) and IκB-α, malondialdehyde (MDA) and histopathological injury scores in lung and kidney were also evaluated. RESULTS: MAP did not show any difference during the study period. NAC decreased histopathologic scores in both lung and kidney. Lung and kidney MDA levels were significantly lower in the NAC group compared to control group. Serum nitrite/nitrate and IL-6 were also significantly lower in the NAC group. The levels of lung cytoplasmic p-IκB-α expression was mitigated by NAC, and NF-κB p65 DNA binding activity was also significantly decreased in the NAC group. CONCLUSIONS: Continuous infusion of NAC attenuated inflammatory response and acute lung and kidney injury after hemorrhagic shock in rats.
Resuscitation 06/2012; · 3.60 Impact Factor
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Jae Hyuk Lee,
Kyuseok Kim,
You Hwan Jo,
Min A Kim,
Kwang Pil Rim,
Kyeong Won Kang,
Joong Eui Rhee,
Min Ji Lee,
Hyun Sook Lee,
Woon Yong Kwon,
Gil Joon Suh
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ABSTRACT: BACKGROUND: Therapeutic hypothermia has been proposed to protect organs in some diseases. However, the effect of therapeutic hypothermia on liver injury in sepsis is unknown. The aim of this study was to evaluate the effects of therapeutic hypothermia on liver injury in sepsis. METHODS: Male Sprague-Dawley rats underwent cecal ligation and incision (CLI). We randomly allocated rats into one of two groups 1 h after CLI: hypothermia (HT) and normothermia (NT). In the HT group, body temperature decreased to 32°C ± 0.5°C and was maintained 4 h, followed by rewarming to 37°C for 2 h. In the NT group, body temperature was maintained at 37°C ± 0.5°C throughout the experimental periods. At 7 h after CLI, we harvested blood and liver tissues and measured serum alanine aminotransferase and the histological liver injury score. We performed immunohistochemistry for cleaved caspase-3 and evaluated phosphorylation of Akt, GSK-3β and Bad with the Western blot assay. RESULTS: Serum alanine aminotransferase was significantly lower in the HT group than in the NT group (57.0 ± 6.0 IU/L versus 192.5 ± 92.5 IU/L; P = 0.028). The histological liver injury score was also significantly lower in the HT group than in the NT group (2.9 ± 0.5 versus 5.4 ± 0.6; P = 0.016). Phosphorylation of Akt, GSK-3β, and Bad was significantly increased in the HT group compared with the NT group (P < 0.001, P = 0.007, and P = 0.001, respectively). Hypothermia significantly mitigated expression of cleaved caspase-3 compared with the NT group (P = 0.032). CONCLUSIONS: Therapeutic hypothermia attenuated liver injury in a polymicrobial sepsis model of rats by enhancing the Akt signaling pathway and decreasing apoptosis.
Journal of Surgical Research 06/2012; · 2.25 Impact Factor
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ABSTRACT: OBJECTIVE: This study was performed to evaluate whether heart-type fatty acid-binding protein (H-FABP) could predict 28-day mortality in patients with severe sepsis and septic shock. METHODS: We performed a prospective observational study and included consecutive patients with severe sepsis and septic shock. Patients' demographic data, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and the blood test results including H-FABP concentrations were compared between the 28-day survivors and nonsurvivors. The association between the concentration of H-FABP and survival was analyzed with multivariate logistic regression and Cox proportional hazards regression analyses. The prognostic performance of H-FABP was compared with those of the APACHE II score and albumin using the area under the receiver operating characteristic curve. RESULTS: Of the 99 patients, 38 (38%) died. The mortality rate increased with increasing H-FABP concentration. In multivariate logistic regression analyses, H-FABP greater than 40 ng/mL was an independent predictor of mortality compared with H-FABP less than 7 ng/mL (odds ratios, 9.23; 95% confidence interval, 1.29-65.86). By Cox proportional hazards analysis, H-FABP greater than 40 ng/mL was associated with a 5.57-fold increased risk for death during the 28-day follow-up period (hazard ratio, 5.57; 95% confidence interval, 1.20-25.80). The area under the receiver operating characteristic curve of H-FABP was 0.739 (95% confidence interval, 0.640-0.839), which was comparable with those of the APACHE II score and albumin. CONCLUSION: The H-FABP was an independent prognostic factor and could be a useful biomarker for 28-day mortality in patients with severe sepsis and septic shock.
The American journal of emergency medicine 03/2012; · 1.54 Impact Factor
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ABSTRACT: Post-resuscitation therapeutic hypothermia has been recommended because of its neuroprotective effects. However, a few studies have reported the effects of therapeutic hypothermia on the heart, especially in ventricular fibrillation cardiac arrest. The aim of this study was to determine whether therapeutic hypothermia attenuates post-resuscitation myocardial injury in a swine cardiac arrest model.
A prospective animal study was performed in the university hospital animal research laboratory. Ventricular fibrillation cardiac arrest was induced in domestic pigs weighing 35-40 kg. After 6 min of no flow time, cardiopulmonary resuscitation was provided to pigs, and the restoration of spontaneous circulation (ROSC) was achieved. The subjects were randomly allocated to a normothermic (NT group, n=5) or hypothermic (HT group, n=5) group. In the HT group, therapeutic hypothermia (core temperature 32-34 °C) was maintained for 24h, and rewarming was performed over a period of 8 h. In the NT group, core temperature was maintained at 37 °C throughout the experiments. Sixty hours after ROSC, blood and myocardial tissues were harvested.
Serum troponin I was not significantly different between the groups. However, myocardial histological damage was attenuated in the HT group. Myocardial ATP contents were higher in the HT group than in the NT group. Immunohistochemistry for apoptosis-related protein showed that survivin expression was higher in the HT group, and XAF1 and cleaved caspase-3 expressions were lower in the HT group than in the NT group.
Therapeutic hypothermia attenuated histological myocardial injury in ventricular fibrillation cardiac arrest model of pigs while preserving more ATP and decreased apoptosis.
Resuscitation 11/2011; 83(5):633-9. · 3.60 Impact Factor
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Jae Hyuk Lee,
Kyuseok Kim,
You Hwan Jo,
Joong Eui Rhee,
Jung Chan Lee,
Kyung Su Kim,
Woon Yong Kwon,
Gil Joon Suh,
Hee Chan Kim,
Ho Il Yoon,
Sang Heon Park
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ABSTRACT: Glucose control is important in the management of critically ill patients. However, strict glucose control requires a large amount of nursing resources, especially in overcrowded emergency departments (EDs).
A continuous glucose monitoring system (CGMS) may be beneficial for glucose control in the ED. The objective of this study was to determine the test characteristics of CGMS in critically ill ED patients.
A prospective observational study of critically ill ED patients was conducted. During a patient's visit to the ED, a CGMS sensor measured their interstitial fluid glucose levels continuously. Capillary glucose was measured every hour and used for glucose control and as a reference value. CGMS values were recorded in real time and compared with capillary glucose values.
A total of 122 pairs of capillary and CGMS glucose values in 12 patients were analyzed. The correlation coefficient was 0.87, and Bland-Altman analysis showed that 117 pairs (95.9%) were within a 95% confidence interval. A Clarke Error Grid Analysis indicated an overall accuracy of 96.8% (Zones A and B). However, the mean absolute relative difference (MARD) was significantly higher in the hypoglycemic range than in a normo- or hyperglycemic range (p = 0.001). The sensitivity and positive predictive value of CGMS for detecting hypoglycemia were 33.3% and 16.7%, respectively. The CGMS specificity and negative predictive value were 95.8% and 98.3%, respectively. There was no linear correlation between MARD and body mass index, axillary temperature, inotrope score, and base deficit (all p-value >0.05).
CGMS demonstrated good clinical accuracy by Clarke Error Grid Analysis. There also was high agreement between CGMS and capillary glucose levels. However, CGMS demonstrated only limited real-time hypoglycemia detection ability in critically ill ED patients.
Journal of Emergency Medicine 10/2011; 43(2):251-7. · 1.31 Impact Factor
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ABSTRACT: This study aims to determine the association of commonly used biochemical markers, such as albumin and C-reactive protein (CRP), with mortality and the prognostic performance of these markers combined with the pneumonia severity index (PSI) for mortality and adverse outcomes in patients with community-acquired pneumonia (CAP).
The data were gathered prospectively for patients hospitalized with CAP via the emergency department. Laboratory values, including CRP and albumin, clinical variables, and the PSI were measured. Primary outcomes were 28-day mortality and survival times. Secondary outcome was admission to the intensive care unit, vasopressor use, or the need for mechanical ventilation during the hospital stay.
A total of 424 patients were included. The 28-day mortality was 13.7%. C-reactive protein and albumin were significantly different between survivors and nonsurvivors. In logistic regression analysis, CRP and albumin were independently associated with 28-day mortality (P < .05). Receiver operating characteristic curves showed improved mortality prediction by adding CRP or albumin to the PSI scale. The Cox proportional hazards analysis showed that high serum albumin (≥3.3 mg/dL) had a hazard ratio of 0.5 (95% confidence interval, 0.3-0.9), and high CRP (≥14.3 mg/dL) had a hazard ratio of 2.0 (95% confidence interval, 1.1-3.4). For predicting secondary outcome, adding albumin to PSI increased areas under the curve significantly, but CRP did not.
Albumin and CRP were associated with 28-day mortality in hospitalized patients with CAP, and these markers increased prognostic performance when combined with the PSI scale.
Journal of critical care 12/2010; 26(3):287-94. · 2.13 Impact Factor
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Jae Hyuk Lee,
Dong Hoon Kim,
Kyuseok Kim,
Joong Eui Rhee,
Tae Youn Kim,
You Hwan Jo,
Jin Hee Lee,
Gil Joon Suh,
Seung Sik Hwang,
Christopher C Lee,
Adam J Singer
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ABSTRACT: To investigate factors associated with change of post-transfusion hemoglobin level, and to derive an equation that predicts post-transfusion changes in hemoglobin levels in hemodynamically stable anemic patients who visited emergency department.
A retrospective medical record review of patients who were hemodynamically stable and transfused with packed red blood cells was undertaken. Patients were randomly divided into two groups. One group (derivation group, 70% of total patients) was analyzed for factors associated with changes in post-transfusion hemoglobin levels, and linear regression analysis was performed to derive a prediction equation. The derived prediction equation was then externally validated with the other group (validation group, 30% of total patients).
A total of 196 patients were enrolled. The 137 patients (70% of total patients) in the derivation group were analyzed for factors associated with changes in post-transfusion hemoglobin. Of those, body surface area and initial hemoglobin level were significantly correlated with changes in post-transfusion hemoglobin levels (p < 0.05). From these variables, linear regression analysis resulted in a prediction equation. The derived equation was validated externally with the 59 patients (30% of total patients) in the validation group and found to have an excellent correlation (r = 0.73, intraclass correlation = 0.84, p < 0.05).
Post-transfusion hemoglobin level in hemodynamically stable adult patients was associated with initial hemoglobin levels and body surface area. These factors must be considered when transfusing hemodynamically stable adult patients with anemia.
The Journal of trauma 02/2010; 68(2):337-41. · 2.48 Impact Factor
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ABSTRACT: Acute lung injury (ALI) develops in various clinical situations and is associated with high morbidity and mortality and therapeutic hypothermia (HT) has been studied to attenuate the ALI. However, the optimal method of rewarming has not been determined. We determined the effect of speed of rewarming and the administration of anti-inflammatory or anti-oxidant agents on ALI in an intestinal ischemia and reperfusion (I/R) model treated with HT.
A Sprague-Dawley rat model of intestine ischemia and reperfusion was used. Two parallel animal experiments were conducted. In the survival study, rats (n=5 per group) underwent normothermic intestinal ischemia (60min, 36-38 degrees C) and then randomized into 7 groups with reperfusion: normothermia (NT), HT without rewarming (30-32 degrees C, HT), 2h HT+rewarming for 1h (RW1), 2h HT+rewarming for 2h (RW2), RW1+N-acetyl cysteine (RW-NAC), RW1+ethylpyruvate (RW-EP), and RW1+dexamethasone (RW+Dexa). In the second experiment, we investigated the histological and biochemical effects on the lung 4h after reperfusion (n=8 per group).
The survival rate was lowest after NT. The HT, RW2, and RW-Dexa groups survived longer than the RW1, RW-NAC, and RW-EP groups. ALI scores were lower in the HT, RW2, and RW-Dexa groups than RW1. Lung malondialdehyde content was also lower in these groups. Interleukin (IL)-6 was significantly higher in the RW1 group. Inducible NO synthase gene expression in lung was lower in the HT, RW2, and RW-Dexa than RW1, and serum NO was lower in the RW2 and RW-Dexa than RW1.
Gradual rewarming and administration of dexamethasone improved survival and attenuated ALI after intestinal I/R injury treated with HT in rats.
Resuscitation 11/2009; 81(1):100-5. · 3.60 Impact Factor
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ABSTRACT: 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.
The British journal of nutrition 10/2009; 103(6):890-8. · 3.45 Impact Factor
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ABSTRACT: Severe hemorrhagic shock often results in cardiac arrest due to vital organ hypoperfusion, especially of the heart. Although fluid resuscitation is the mainstay of management in hemorrhagic shock, treatment of cardiac arrest in association with severe hemorrhagic shock is unclear.
This study was designed to determine the effect of early infusion of norepinephrine on hemodynamics and survival in hemorrhagic shock.
Twelve Sprague-Dawley rats were bled to about 35% of estimated blood volume for 30 min and randomized to one of two groups: the study group received norepinephrine (10 microg/kg/min) in 5% dextrose solution (n = 6); the control group received the same volume of 5% dextrose (n = 6) concurrently with Lactated Ringer's solution. After 30 min of resuscitation, half of the shed blood was transfused in both groups. Time to cardiac arrest and mean arterial pressure (MAP) were compared between the two groups.
MAP during the resuscitation period was higher in the norepinephrine group than in the control group. Five of 6 rats in the norepinephrine group but none of the control group survived until the transfusion period (83.3% vs. 0.0%, respectively; p = 0.003). Median time to cardiac arrest was significantly longer in the norepinephrine group (67.0 min, interquartile range [IQR] 60.0-77.0) than in controls (41.0 min, IQR 40.0-47.0; p = 0.002).
Early use of norepinephrine in a rat model of hemorrhagic shock increased mean arterial pressure during the resuscitation period and delayed the onset of cardiac arrest.
Journal of Emergency Medicine 01/2009; 37(4):376-82. · 1.31 Impact Factor
