[Show abstract][Hide abstract] ABSTRACT: The purpose of the current study was to investigate the protective effect of niacin on acute lung injury by the down-regulation of the nuclear factor κB (NF-κB) pathway in hemorrhagic shock (HS) rats.
HS was induced in male Sprague-Dawley rats by withdrawing blood to maintain a mean arterial pressure of 20 mm Hg to 25 mm Hg for 40 minutes. The rats were resuscitated by the reinfusion of the drawn blood, and a vehicle (HS), a low-dose of niacin (360 mg/kg, HS + LD-NA), or a high dose of niacin (1,080 mg/kg, HS + HD-NA) were administered orally. The survival of the subjects was observed for 72 hours, and a separate set of animals was killed at 6 hours after HS induction. We measured cytoplasmic phosphorylated inhibitor κB-α and inhibitor κB-α expressions, nuclear NF-κB p65 expression, NF-κB p65 DNA-binding activity, MEK partner 1 activity, tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-8, nicotinamide adenine dinucleotide (NAD+), reduced nicotinamide adenine dinucleotide phosphate, reduced glutathione, glutathione disulfide, malondialdehyde levels, and histologic damage in the lung tissue. We also measured TNF-α, IL-6, and IL-8 levels in the serum.
The survival rates of the sham, HS, HS + LD-NA, and HS + HD-NA groups were 6 of 6 (100%), 0 of 9 (0%), 1 of 9 (11.1%), and 3 of 9 (33.3%), respectively. A high dose of niacin increased lung NAD+, nicotinamide adenine dinucleotide phosphate levels, and glutathione-glutathione disulfide ratios; decreased lung malondialdehyde levels; down-regulated the NF-κB pathway; suppressed TNF-α, IL-6, and IL-8 levels in the lung tissue and serum; and attenuated histologic lung damage.
A high dose of niacin attenuated lung inflammation, suppressed proinflammatory cytokine release, reduced histologic lung damage, and improved survival after HS in rats. Its therapeutic benefits were associated with the down-regulation of the reactive oxygen species-dependent NF-κB pathway.
[Show abstract][Hide abstract] ABSTRACT: Background:
Mild therapeutic hypothermia (MTH) has been known to be associated with good neurological recovery after out-of-hospital cardiac arrest (OHCA). Prehospital return of spontaneous circulation (P-ROSC) is associated with better hospital outcomes than ROSC at emergency department (ED-ROSC). The study aims to examine the association between MTH by location of ROSC and good neurological recovery after OHCA.
Adult OHCA cases with presumed cardiac etiology who survived to hospital admission were collected from a nationwide cardiac registry between 2008 and 2013. MTH was defined as a case receiving hypothermia procedure regardless of procedure method. Primary outcome was good neurological recovery with cerebral performance category score of 1 and 2. Multivariable logistic regression analysis was performed adjusting for potential confounders with an interaction term between MTH and location of ROSC to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs).
Among 11,158 patients survived to admission, good neurological recovery was 23.6% (399/1691) in MTH vs. 15.0% (1400/9316) in non-MTH (p<0.001), and 58.2% (1074/1864) in P-ROSC vs. 7.9% (725/9161) in ED-ROSC (p<0.001). There was a significant association between MTH and good neurological recovery (AOR=1.32, 95% CI=1.11-1.57). In the interaction model, AOR of MTH and interaction effect with P-ROSC and ED-ROSC was 0.78 (0.58-2.70) and 1.68 (1.34-1.98), respectively.
MTH was significantly associated with good neurological recovery among OHCA survivors. In the interaction model, MTH showed significant benefits in patient group with ROSC at ED, not in P-ROSC group.
[Show abstract][Hide abstract] ABSTRACT: Background
The aim of this study were to investigate whether selenium treatment attenuates lipid peroxidation and downregulates the NF-κB pathway in small intestinal mucosa and to examine whether the effect of selenium is also observed in oral buccal mucosa, during small intestinal IR injury.
Materials and methods
Eighteen rats were assigned into three groups: sham, IR, and IR + selenium. Saline or selenium was administered through a tail vein. 24 hours later, the superior mesenteric artery was exposed and clamped in the IR and IR + selenium groups. After ischemic and reperfusion period, animals were sacrificed and oral buccal mucosa and small intestinal mucosa were harvested.
Glutathione peroxidase activity and cytoplasmic IκB-α expression was higher in the IR + selenium group than that in the IR group. A malondialdehyde level, cytoplasmic phosphorylated inhibitor κB-α, nuclear NF-κB p65 expressions, and NF-κB p65 DNA-binding activity were lower in the IR + selenium group than those in the IR group.
A selenium treatment may cause increased GPx activity, attenuated lipid peroxidation, and downregulated the NF-κB pathway during small intestinal IR injury. Furthermore, these therapeutic benefits of selenium can be observed in oral buccal mucosa as well as small intestinal mucosa.
Journal of Inflammation 12/2014; 11(1):36. DOI:10.1186/s12950-014-0036-1 · 2.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective Therapeutic hypothermia (TH) has become the standard strategy for reducing brain damage in the postresuscitation period. The aim of this study was to investigate current TH performance and outcomes in out-of-hospital cardiac arrest (OHCA) survivors using data from the Korean Hypothermia Network (KORHN) registry. Methods We used the KORHN registry, a web-based multicenter registry that includes 24 participating hospitals throughout the Republic of Korea. Adult comatose OHCA survivors treated with TH between 2007 and 2012 were included. The primary outcomes were neurological outcome at hospital discharge and in-hospital mortality. The secondary outcomes were TH performance and adverse events during TH. Results A total of 930 patients were included, of whom 556 (59.8%) survived to discharge and 249 (26.8%) were discharged with good neurologic outcomes. The median time from return of spontaneous circulation (ROSC) to the start of TH was 101 minutes (interquartile range [IQR], 46 to 200 minutes). The induction, maintenance, and rewarming durations were 150 minutes (IQR, 80 to 267 minutes), 1,440 minutes (IQR, 1,290 to 1,440 minutes), and 708 minutes (IQR, 420 to 900 minutes), respectively. The time from the ROSC to coronary angiography was 1,045 hours (IQR, 121 to 12,051 hours). Hyperglycemia (46.3%) was the most frequent adverse event. Conclusion More than one-quarter of the OHCA survivors (26.8%) were discharged with good neurologic outcomes. TH performance was appropriately managed in terms of the factors related to its timing, including cooling start time and rewarming duration.
[Show abstract][Hide abstract] ABSTRACT: Life-threatening rectal variceal bleeding is a rare complication of liver cirrhosis. Various therapeutic interventions including endoscopic variceal ligation and percutaneous transvenous obliteration have been proposed to control significant rectal variceal bleeding. However, these definite hemostasis modalities are not readily available and require an experienced endoscopist or interventional radiologist. Therefore, bridging therapy to control active bleeding is necessary especially in patients with massive bleeding. We report a case of massive rectal variceal bleeding in which a Sengstaken-Blakemore tube was effective at stopping the bleeding until percutaneous transvenous obliteration could be performed.
[Show abstract][Hide abstract] ABSTRACT: Introduction: Oxidative stress plays a key role in the pathophysiology of sepsis. The glutathione redox cycle is an important innate antioxidant system. The aim of this study was to investigate whether the changes in the components of the glutathione redox cycle, such as, reduced nicotinamide adenine dinucleotide phosphate (NADPH), reduced glutathione (GSH), and glutathione peroxidase (GPx) activity during the early period of therapy were associated with the 28-day mortality of patients with septic shock. Methods: This study was a prospective observational study conducted in a 12-bed intensive care unit (ICU) of a tertiary referral hospital. Consecutive patients admitted to the ICU with septic shock were enrolled from September, 2012 to February, 2013. According to the 28-day mortality, the enrolled patients were divided into the two groups: the survivors and the non-survivors. We obtained serum samples from the patients at admission (0 hr), 24 hrs (24 hrs), and 72 hrs after admission (72 hrs). We measured the serum levels of NADPH, GSH, and malondialdehyde (MDA) and GPx activity. Then we compared the data between the survivors and the non-survivors. Results: Fifty patients were enrolled in this study. Thirty-four patients were grouped into the survivors and sixteen into the non-survivors. Age and the severity scores including APACHE II score and SOFA score of the survivors were lower than those of the non-survivors (p = 0.013, p < 0.001, and p < 0.001, respectively). There were no significant differences in gender, co morbidity, pathogen, infection site, and the interval from visit to antibiotics treatment between the two groups. During the first 72 hrs of therapy, the serum levels of NADPH and GSH of the survivors were higher than those of the non-survivors (p = 0.006 and p = 0.001, respectively), and serum MDA level of the survivors were lower than that of the non-survivors (p = 0.008). There were no significant differences in serum GPx activity between the two groups. Conclusions: Low serum NADPH and GSH levels were associated with the increase of serum MDA level and the 28-day mortality of patients with septic shock.
[Show abstract][Hide abstract] ABSTRACT: Introduction: Oxidative stress plays a key role in pathophysiology of sepsis, and antioxidant is considered as one of therapeutic strategies for sepsis. The aim of this study was to examine whether combination therapy of a clinically relevant dose of niacin and selenium attenuates lung inflammation and improves survival during endotoxemia, and to determine if its beneficial effects are associated with synergistic activation of the glutathione redox cycle and down-regulation of the nuclear factor (NF)-[kappa]B pathway. Methods: This study was a prospective laboratory study conducted on male Sprague-Dawley rats and human lung alveolar epithelial (A549) cells. To induce endotoxemia in rats, lipopolysaccharide (LPS) at a dosage of 10 mg/kg was injected into a tail vein and 10 mins later, vehicle, niacin (360 mg/kg), selenium (60 [mu]g/kg), or niacin plus selenium were administered, respectively. Survival of the subjects was observed for 72 hrs, and a separated set of animals were euthanized at 6 hrs post-LPS. The A549 cells exposed to LPS (50 [mu]g/ml) were treated with niacin (0.3, 0.9, and 2.7 mM), selenium (0.05, 0.15, and 0.45 [mu]M), or niacin (0.9 mM) plus selenium (0.15 [mu]M), respectively. Cell viability was measured at 24 hrs post-LPS, and intracellular molecular changes were measured at 6 hrs post-LPS. Results: Combination therapy of a clinically relevant dose of niacin and selenium decreased malondialdehyde level, down-regulated the NF-[kappa]B pathway in lung tissues, attenuated lung inflammation, and improved survival in endotoxemic rats, but individual therapy of niacin or selenium failed to do so. In LPS-exposed A549 cells, niacin increased reduced nicotinamide adenine dinucleotide phosphate and reduced glutathione levels, but decreased hydrogen peroxide level and NF-[kappa]B p65 DNA-binding activity in a dose-related fashion. Selenium increased glutathione peroxidase activity and decreased hydrogen peroxide level and NF-[kappa]B p65 DNA-binding activity in a dose-related fashion. Furthermore, combination therapy of niacin and selenium enhanced these intracellular antioxidant effects. Conclusions: Combination therapy of a clinically relevant dose of niacin and selenium activated the glutathione redox cycle, decreased the hydrogen peroxide level, down-regulated the NF-[kappa]B pathway, attenuated lung inflammation, and improved survival during endotoxemia.
[Show abstract][Hide abstract] ABSTRACT: Extracorporeal cardiopulmonary resuscitation (ECPR) refers to the application of extracorporeal blood circulation with oxygenation as a resuscitation tool. The objective of this study is to observe the frequency component changes in the electrocardiogram (ECG) by ECPR during prolonged ventricular fibrillation (VF).
Six swine were prepared as a VF model. Extracorporeal blood circulation with a pulsatile blood pump and oxygenator was set up for the model. ECG signals were measured for 13 min during VF and analyzed using frequency analysis methods. The median frequency (MF), dominant frequency (DF), and amplitude spectrum area (AMSA) were calculated from a spectrogram obtained using short-time Fourier transform (STFT).
MF decreased from 11 Hz at the start to 9 Hz at 2 min after VF and then increased to 11 Hz at 4.5 min after VF. DF started at 7 Hz and increased to 11 Hz within the first min and decreased to 9 Hz at 2 min, then increased to 12 Hz at 4.5 min after VF. Both frequency components decreased gradually from 4.5 min until 10 min after VF. After the oxygenated blood perfusion was initiated, both MF and DF increased remarkably and exceeded 12 and 14 Hz, respectively. Similarly, AMSA decreased gradually for the first 10 min, but increased remarkably and varied beyond 13 mV[bullet operator]Hz after the oxygenated blood supply started. Remarkable frequency increases in ECG due to the oxygenated blood perfusion during ECPR were observed in the swine VF model.
The ECG frequency analysis during ECPR can give the resuscitation provider important information about the cardiac perfusion status and the appropriateness of the ECPR setup as well as the prediction of defibrillation success.
[Show abstract][Hide abstract] ABSTRACT: 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-δ, the cytosolic release of cytochrome c, and the cleavage of caspase 3 in a swine cardiac arrest model.
Prospective laboratory study.
Male domestic pigs (n = 24).
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.
We examined cellular apoptosis and neuronal damage in the brain hippocampal cornu ammonis 1 region. We also measured the cleavage of protein kinase C-δ, 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-δ, 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.
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-δ, the cytosolic release of cytochrome c, and the cleavage of caspase 3.
Critical care medicine 10/2013; 42(2). DOI:10.1097/CCM.0b013e3182a668e4 · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Critical care medicine 05/2013; 41(9). DOI:10.1097/CCM.0b013e31828a2394 · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Background:
The goal of this study is to better understand the trend in epidemiological features and the outcomes of emergency medical service (EMS)-assessed out-of-hospital cardiac arrest (OHCA) according to the community urbanization level: metropolitan, urban, and rural.
This study was performed within a nationwide EMS system with a single-tiered basic-to-intermediate service level and approximately 900 destination hospitals for eligible OHCA cases in South Korea (with 48 million people). A nationwide OHCA database, which included information regarding demographics, Utstein criteria, EMS, and hospital factors and outcomes, was constructed using the EMS run sheets of eligible cases who were transported by 119 EMS ambulances and followed by a medical record review from 2006 to 2010. Cases with an unknown outcome were excluded. The community urbanization level was categorized according to population size, with metropolitan areas (more than 500,000 residents), urban areas (100,000-500,000 residents), and rural areas (<100,000 residents). The primary end point was the survival to discharge rate. Age- and sex-adjusted survival rates (ASRs) and standardized survival ratios (SSRs) with 95% confidence intervals (CIs) were calculated compared to a standard population. The adjusted odds ratios (AORs) and 95% CIs for survival were calculated and adjusted for potential risk factors using stratified multivariable logistic regression analysis.
There were 97,291 EMS-assessed OHCAs with 73,826 (75.9%) EMS-treated cases analyzed, after excluding the patients with unknown outcome (N=4172). The standardized incidence rate increased from 37.5 in 2006 to 46.8 in 2010 per 100,000 person-years for EMS-assessed OHCAs, and the survival rate was 3.0% for EMS-assessed OHCAs (3.3% for cardiac etiology and 2.3% for non-cardiac etiology) and 3.6% for EMS-treated OHCAs. Significantly different trends were found by urbanization level for bystander CPR, EMS performance, and the level of the destination hospital. The ASRs for survival were significantly improved by year in the metropolitan areas (3.6% in 2006 to 5.3% in 2010) but remained low in the urban areas (1.4% in 2006 to 2.3% in 2010) and very low in the rural areas (0.5 in 2006 and 0.8 in 2010). The SSRs (95% CIs) in the metropolitan areas were 1.19 (1.06-1.34) in 2006 and 1.77 (1.64-1.92) in 2010, whereas the SSRs were observed to be less than 1.00 during the five-year period in both urban and rural areas. The AORs (95% CIs) for survival significantly increased to 1.42 (1.22-1.66) in the metropolitan areas and to 1.58 (1.18-2.11) in the urban areas while not increasing in the rural areas, compared to the level of each group of areas in 2006.
In this nationwide cohort study from 2006 to 2010, the standardized incidence rate and survival to discharge rate of EMS-assessed OHCAs increased annually in metropolitan and urban communities but did not increase in rural communities. Further investigations should be undertaken to improve the performance and outcomes in rural communities.