Hui Jai Lee

Antioxidant effects of selenium on lung injury in paraquat intoxicated rats

Context. Paraquat (PQ) causes lethal intoxication by inducing oxidant injury to the lung. Selenium is a cofactor for glutathione peroxidase (GPx), which is one of the major endogenous antioxidant enzymes. Objective. To determine whether selenium post-treatment activates GPx, decreases lung injury, and improves survival in PQ intoxicated rats. Materials and methods. Male Spraque–Dawley rats were categorized into three groups: sham (n = 6), PQ (n = 12), and PQ + Se (n = 12). In the PQ and PQ + Se groups, 50 mg/kg of PQ was administered intraperitoneally. After 10 minutes, 60 μg/kg of Se (PQ + Se) or saline (PQ) was administered via the tail vein. Six rats per group were euthanized 6 hours or 24 hours later. Lung tissues were harvested for the measurement of GPx activity, reduced glutathione (GSH), glutathione disulfide (GSSG) and malondialdehyde (MDA) and for histological analysis. Using separated set of rats, survival of PQ (n = 10) and PQ + Se (n = 10) were observed for 72 hours. Results. GPx activity in the PQ group at the 6-hour and 24-hour time points was lower than in the sham group (p < 0.006). GPx activity in the PQ + Se group at the 6-hour and 24-hour time points was higher than in the PQ group at the same time (p < 0.006). GPx activity in the PQ + Se group at 24 hours was higher than at 6-hour time point and also higher than in the sham group (p < 0.006). The GSH/GSSG ratio in the PQ + Se group at 24 hours was lower than that in the sham group (p < 0.006). MDA levels in the PQ group at 6 hours and 24 hours were higher than in the sham group (p < 0.006). MDA levels at 24 hours in the PQ + Se group was lower than in the PQ group (p < 0.006). Acute lung injury (ALI) scores in the PQ group at 6 hours and 24 hours were higher than in the sham group (p < 0.006). ALI scores at 24 hours in the PQ + Se group were lower than in the PQ group. Survival rates did not differ between PQ and PQ + Se (p = 0.869). Conclusion. Single dose of selenium post-treatment activates GPx and attenuates lipid peroxidation and lung injury early after paraquat intoxication, but does not improve 72 hours of survival.

Prolonged therapeutic hypothermia is more effective in attenuating brain apoptosis in a Swine cardiac arrest model.

Objectives:To investigate whether 48 hours of therapeutic hypothermia is more effective to attenuate brain apoptosis than 24 hours and to determine whether the antiapoptotic effects of therapeutic hypothermia are associated with the suppressions of the cleavage of protein kinase C-&dgr;, the cytosolic release of cytochrome c, and the cleavage of caspase 3 in a swine cardiac arrest model. Design:Prospective laboratory study. Setting:University laboratory. Subjects:Male domestic pigs (n = 24). Interventions:After 6 minutes of no-flow time that was induced by ventricular fibrillation, cardiopulmonary resuscitation was provided, and the return of spontaneous circulation was achieved. The animals were randomly assigned to the following groups: sham, normothermia, 24 hours of therapeutic hypothermia, or 48 hours of therapeutic hypothermia. Therapeutic hypothermia (core temperature, 32–34°C) was maintained for 24 or 48 hours post return of spontaneous circulation, and the animals were rewarmed for 8 hours. At 60 hours post return of spontaneous circulation, the animals were killed, and brain tissues were harvested. Measurements and Main Results:We examined cellular apoptosis and neuronal damage in the brain hippocampal cornu ammonis 1 region. We also measured the cleavage of protein kinase C-&dgr;, the cytosolic release of cytochrome c, and the cleavage of caspase 3 in the hippocampus. The 48 hours of therapeutic hypothermia attenuated cellular apoptosis and neuronal damage when compared with normothermia. There was also a decrease in the cleavage of protein kinase C-&dgr;, the cytosolic release of cytochrome c, and the cleavage of caspase 3. However, 24 hours of therapeutic hypothermia did not significantly attenuate cellular apoptosis or neuronal damage. Conclusions:We found that 48 hours of therapeutic hypothermia was more effective in attenuating brain apoptosis than 24 hours of therapeutic hypothermia. We also found that the antiapoptotic effects of therapeutic hypothermia were associated with the suppressions of the cleavage of protein kinase C-&dgr;, the cytosolic release of cytochrome c, and the cleavage of caspase 3.

Niacin Suppresses the Mitogen-activated Protein Kinase Pathway and Attenuates Brain Injury After Cardiac Arrest in Rats*

Objectives:To determine whether niacin attenuates brain injury and improves neurological outcome after cardiac arrest in rats and if its therapeutic benefits are associated with suppression of the mitogen-activated protein kinase pathway. Design:Prospective laboratory study. Setting:University laboratory. Subjects:Male Sprague-Dawley rats (n = 77). Interventions:After 6 minutes of no flow time induced by ventricular fibrillation, cardiopulmonary resuscitation was provided and return of spontaneous circulation was achieved. Animals were then administered vehicle, single low dose (360 mg/kg; at 1 hr postreturn of spontaneous circulation), single high dose (1080 mg/kg; at 1 hr), or repeated low dose of niacin (360 mg/kg/d for 3 d; at 1, 24, and 48 hr) through an orogastric tube. Measurements and Main Results:Neurologic deficit scales were scored at 24 hours, 72 hours, and 7 days postreturn of spontaneous circulation. Single high dose of niacin improved neurologic deficit scales at 48 hours and 7 days, and repeated low dose of niacin improved neurologic deficit scales at 7 days. Then, a separate set of animals were killed at 72 hours postreturn of spontaneous circulation, and brain tissues were harvested. Single high dose and repeated low dose of niacin attenuated cellular apoptosis and neuronal damage in hippocampal cornu ammonis 1 and decreased axonal injury and microglial activation in corpus callosum. They increased nicotinamide adenine dinucleotide, reduced nicotinamide adenine dinucleotide phosphate and reduced glutathione levels, and decreased malondialdehyde level in brain tissues. Furthermore, they suppressed the phosphorylations of p38 and c-Jun N-terminal kinase/stress-activated protein kinase and the cleavage of caspase 3. However, they failed to enhance extracellular signal-regulated kinases 1/2 phosphorylation. Conclusions:Single high dose and repeated low dose of niacin attenuated brain injury and improved neurological outcome after cardiac arrest in rats. Their therapeutic benefits were associated with suppressions of the phosphorylations of p38 and c-Jun N-terminal kinase/stress-activated protein kinase and the cleavage of caspase 3.

Comparison of CPR quality and rescuer fatigue between standard 30:2 CPR and chest compression-only CPR: a randomized crossover manikin trial

ObjectiveWe aimed to compare rescuer fatigue and cardiopulmonary resuscitation (CPR) quality between standard 30:2 CPR (ST-CPR) and chest compression only CPR (CO-CPR) performed for 8 minutes on a realistic manikin by following the 2010 CPR guidelines.MethodsAll 36 volunteers (laypersons; 18 men and 18 women) were randomized to ST-CPR or CO-CPR at first, and then each CPR technique was performed for 8 minutes with a 3-hour rest interval. We measured the mean blood pressure (MBP) of the volunteers before and after performing each CPR technique, and continuously monitored the heart rate (HR) of the volunteers during each CPR technique using the MRx monitor. CPR quality measures included the depth of chest compression (CC) and the number of adequate CCs per minute.ResultsThe adequate CC rate significantly differed between the 2 groups after 2 minutes, with it being higher in the ST-CPR group than in the CO-CPR group. Additionally, the adequate CC rate significantly differed between the 2 groups during 8 minutes for male volunteers (p =0.012). The number of adequate CCs was higher in the ST-CPR group than in the CO-CPR group after 3 minutes (p =0.001). The change in MBP before and after performing CPR did not differ between the 2 groups. However, the change in HR during 8 minutes of CPR was higher in the CO-CPR group than in the ST-CPR group (p =0.007).ConclusionsThe rate and number of adequate CCs were significantly lower with the CO-CPR than with the ST-CPR after 2 and 6 minutes, respectively, and performer fatigue was higher with the CO-CPR than with the ST-CPR during 8 minutes of CPR.

Heart-type Fatty Acid Binding Protein as an Adjunct to Cardiac Troponin-I for the Diagnosis of Myocardial Infarction

We hypothesized that when used in combination with cardiac troponins, heart-type fatty acid binding protein (H-FABP) would have greater diagnostic value than conventional markers for the early diagnosis of myocardial infarction (MI). Patients with typical chest pain at a single emergency department were consecutively enrolled. Initial blood samples were drawn for H-FABP, myoglobin, creatine kinase isoenzyme MB (CK-MB), and cardiac troponin-I (cTnI) measurements. MI was defined by serial cTnI measurements. To evaluate the adjunctive role of biochemical markers, we derived and compared logistic regression models predicting MI in terms of their discrimination (area under the receiver operating characteristics curve, AUC) and overall fit (Bayesian information criterion, BIC). Seventy-six of 170 patients were diagnosed as having MI. The AUC of cTnI, H-FABP, myoglobin, and CK-MB were 0.863, 0.827, 0.784, and 0.772, respectively. A logistic regression model using cTnI (P = 0.001) and H-FABP (P < 0.001) had the biggest AUC (0.900) and the best fit determined by BIC. Sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of this model at 30% probability were 81.6%, 80.9%, 4.26, and 0.23, respectively. H-FABP has a better diagnostic value than both myoglobin and CK-MB as an adjunct to cTnI for the early diagnosis of MI.

A Randomized Controlled Trial of Compression Rates during Cardiopulmonary Resuscitation.

The objective of this study was to compare the efficacy of cardiopulmonary resuscitation (CPR) with 120 compressions per minute (CPM) to CPR with 100 CPM in patients with non-traumatic out-of-hospital cardiac arrest. We randomly assigned patients with non-traumatic out-of-hospital cardiac arrest into two groups upon arrival to the emergency department (ED). The patients received manual CPR either with 100 CPM (CPR-100 group) or 120 CPM (CPR-120 group). The primary outcome measure was sustained restoration of spontaneous circulation (ROSC). The secondary outcome measures were survival discharge from the hospital, one-month survival, and one-month survival with good functional status. Of 470 patients with cardiac arrest, 136 patients in the CPR-100 group and 156 patients in the CPR-120 group were included in the final analysis. A total of 69 patients (50.7%) in the CPR-100 group and 67 patients (42.9%) in the CPR-120 group had ROSC (absolute difference, 7.8% points; 95% confidence interval [CI], -3.7 to 19.2%; P = 0.183). The rates of survival discharge from the hospital, one-month survival, and one-month survival with good functional status were not different between the two groups (16.9% vs. 12.8%, P = 0.325; 12.5% vs. 6.4%, P = 0.073; 5.9% vs. 2.6%, P = 0.154, respectively). We did not find differences in the resuscitation outcomes between those who received CPR with 100 CPM and those with 120 CPM. However, a large trial is warranted, with adequate power to confirm a statistically non-significant trend toward superiority of CPR with 100 CPM. (Clinical Trial Registration Information: www.cris.nih.go.kr, cris.nih.go.kr number, KCT0000231)

Incidence and clinical features of intracranial hemorrhage causing out-of-hospital cardiac arrest: a multicenter retrospective study

OBJECTIVE The general incidence of intracranial hemorrhage (ICH) as a cause of out-of-hospital cardiac arrest (OHCA) remains unclear, although the incidence of subarachnoid hemorrhage has been determined to be 4% to 18%. The main objectives of our study were to describe the incidence of ICH in OHCA and the different laboratory findings between ICH and non-ICH groups. METHODS A retrospective cohort study using the prospective OHCA registry was conducted at three university hospitals in Korea. All cases of OHCA that occurred over a period of 6 years, from January 2009 to December 2014, were examined. Pre-hospital and in-hospital variables and laboratory data taken during CPR were examined in order to compare the ICH and non-ICH groups. RESULTS A total of 2716 patients with OHCA were registered in the database. Among the 804 patients included in the final analysis, ICH was the cause of cardiac arrest in 92 patients (11.4%). Of those with ICH, 79 (86%) patients also had subarachnoid hemorrhage. No patient had a good neurological outcome in the ICH group. There were statistically significant differences in gender, age, pre-hospital return of spontaneous circulation, survival to hospital discharge, good neurologic outcomes, serum sodium, potassium, glucose, Pco2, and Po2 during CPR between the ICH and non-ICH groups. In multivariate analysis, gender, age, potassium, glucose and Po2 levels differed significantly between the two groups. CONCLUSIONS OHCA patients with confirmed ICH were identified in about 11% of cases after return of spontaneous circulation. Gender, age, higher glucose, and lower potassium and Po2 levels during CPR were associated with ICH.

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.

Clinical Effects of Activated Charcoal Unavailability on Treatment Outcomes for Oral Drug Poisoned Patients

Background Activated charcoal is the most frequently and widely used oral decontaminating agent in emergency departments (EDs). However, there is some debate about its clinical benefits and risks. In Korea, activated charcoal with sorbitol was unavailable as of the mid-2015, and our hospital had been unable to use it from September 2015. This study examined the differences of clinical features and outcomes of patients during the periods charcoal was and was not available. Methods We retrospectively reviewed the electronic medical records of patients who had visited an urban tertiary academic ED for oral drug poisoning between January 2013 and January 2017. Results For the charcoal-available period, 413 patients were identified and for the charcoal-unavailable period, 221. Activated charcoal was used in the treatment of 141 patients (34%) during the available period. The mortality rates during the available and unavailable periods were 1.9 and 0.9%, respectively (p = 0.507). There was also no interperiod difference in the development of aspiration pneumonia (9.9 versus 9.5%, p = 0.864), the endotracheal intubation rate (8.4 versus 7.2%, p = 0.586), and vasopressor use (5.3 versus 5.0%, p = 0.85). Intensive care unit (ICU) admission was higher in the unavailable period (5.8 versus 13.6%, p = 0.001). ICU days were lower in the unavailable period (10 [4.5-19] versus 4 [3-9], p = 0.01). Hospital admission (43.3 versus 29.9%, p = 0.001) was lower in the unavailable period. Conclusions In this single center study, there appeared to be no difference in mortality, intubation rates, or vasopressor use between the charcoal-available and charcoal-unavailable periods.