Association of Advanced Airway Management in Preference to Intravenous Adrenaline on Neurological Outcomes Following Out-of-Hospital Cardiac Arrest.

AIM: To examine the preference for advanced airway management (AAM) or intravenous adrenaline administration (IVAd) provided by emergency medical services (EMS) for out-of-hospital cardiac arrest (OHCA) with shockable or nonshockable rhythms. METHODS: We conducted a retrospective analysis of a nationwide cohort of OHCA patients in Japan. Adult patients with witnessed collapse who were provided AAM and/or IVAd by EMS between June 2014 and December 2019 were divided into the AAM preferred group and IVAd preferred group, according to the initial advanced EMS intervention. The rates of favorable neurological outcomes (cerebral performance category 1 or 2 after 30 days) were compared between groups of patients with initial shockable or nonshockable rhythms. RESULTS: We analyzed 1365 and 9733 patients with initial shockable and nonshockable rhythms, respectively. Of these patients, 1033 (75.7%) with shockable and 7844 (80.6%) with nonshockable rhythms, respectively, were assigned to the AAM preferred group. Favorable neurological outcomes were significantly more frequent in the AAM preferred group than in the IVAd preferred group in patients with a shockable rhythm (13.6% vs 9.3%, respectively; P = 0.039), but not in those with a nonshockable rhythm (1.0% vs 0.8%, respectively; P = 0.509). Preferred AAM was independently associated with a higher probability of favorable neurological outcomes in patients with a shockable rhythm (adjusted odds ratio 1.66, 95% confidence interval 1.08-2.53, P = 0.020), but not in patients with a nonshockable rhythm. CONCLUSIONS: AAM provided by EMS in preference to IVAd was associated with the favorable neurological outcomes of OHCA patients with shockable rhythms.

Rapid rewarming rate associated with favorable neurological outcomes in patients with post-cardiac arrest syndrome patients treated with targeted temperature management.

Aim: To determine whether the rewarming rate is associated with neurological outcomes in patients with post-cardiac arrest syndrome treated with targeted temperature management (TTM) at 34°C. Methods: We conducted a retrospective analysis of a nationwide cohort study of out-of-hospital cardiac arrest in Japan. Adult patients who experienced a return of spontaneous circulation and completed TTM at 34°C between June 2014 and December 2019 were divided equally into three groups (slow, moderate, and rapid) according to their rewarming rates from 34°C to 36°C. The rates of favorable neurological outcomes (Cerebral Performance Category of 1-2 after 30 days) were compared among the groups, and the adjusted odds ratios for a favorable neurological outcome were calculated for the groups. Results: We analyzed 348, 357, and 358 patients in the slow, moderate, and rapid groups, respectively. The periods of rewarming from 34°C to 36°C were 41.9 ± 10.5, 22.4 ± 1.8, and 12.2 ± 3.6 h, respectively. The number of favorable neurological outcomes after 30 days was 121 (34.8%), 125 (35.0%), and 147 (41.1%), respectively, with no significant differences among the three groups (p = 0.145). Rapid rewarming was independently associated with a favorable neurological outcome compared with slow rewarming (adjusted odds ratio 1.57 [95% confidence interval 1.04-2.37]; p = 0.031). Conclusions: Rapid rewarming after TTM at 34°C was associated with a more favorable neurological outcome than slow rewarming.

Effects of cardiopulmonary resuscitation instructions on the outcomes of out-of-hospital cardiac arrest: An analysis of the JAAM-OHCA registry.

Aim: To determine whether dispatcher-provided cardiopulmonary resuscitation (CPR) instructions improve the outcomes of out-of-hospital cardiac arrest (OHCA). Methods: Cases registered in the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest (JAAM-OHCA) Registry between June 2014 and December 2019 were included. Cases in which the dispatcher provided CPR instructions to the bystander were included in the "Instructions" group", and cases without CPR instructions were included in the "No Instructions" group. The primary outcome was the proportion of patients with a favorable neurological outcome, defined as a Glasgow-Pittsburgh cerebral performance category scale of 1 to 2 at 1 month after OHCA. Results: Overall, 51,199 patients with OHCA were registered in the JAAM-OHCA Registry during the study period. Of these, 33,745 were eligible for the study, with 16,509 in the Instructions group and 17,236 in the No Instructions group. The proportion of patients with a favorable neurological outcome at 1 month after OHCA was inferior in the Instructions group than in the No Instructions group (2.3% versus 3.0%, p < 0.001). After adjustment for patient background characteristics, no association was found between CPR instructions provided by a dispatcher and favorable neurological outcomes at 1 month after OHCA (adjusted odds ratio, 1.000; 95% confidence interval, 0.869-1.151, p = 0.996). Conclusion: The present study found no clear clinical benefit of dispatcher-provided CPR instructions on the neurological outcomes of cases with OHCA.

Use of hyperbaric oxygen therapy for preventing delayed neurological sequelae in patients with carbon monoxide poisoning: A multicenter, prospective, observational study in Japan.

BACKGROUND: The purpose of this study was to clarify the practical clinical treatment for acute carbon monoxide (CO) poisoning in Japan and to investigate the efficacy of hyperbaric oxygen (HBO2) therapy in preventing delayed neurological sequelae (DNS) in the acute phase of CO poisoning. METHODS: We conducted a multicenter, prospective, observational study of acute CO poisoning in Japan. Patients with acute CO poisoning were enrolled and their treatment details were recorded. The primary endpoint was the onset of DNS within 2 months of CO exposure. Factors associated with DNS were assessed with logistic regression analysis. RESULTS: A total of 311 patients from 57 institutions were registered and 255 were analyzed: 171 received HBO2 therapy (HBO2 group) and 84 did not (normobaric oxygen [NBO2] group). HBO2 therapy was performed zero, once, twice, or three times within the first 24 h in 1.8%, 55.9%, 30.9%, and 11.3% of the HBO2 group, respectively. The treatment pressure in the first HBO2 session was 2.8 ATA (47.9% of the HBO2 group), 2.0 ATA (41.8%), 2.5 ATA (7.9%), or another pressure (2.4%). The incidence of DNS was 13/171 (7.6%) in the HBO2 group and 3/84 (3.6%) in the NBO2 group (P = 0.212). The number of HBO2 sessions in the first 24 h was one of the factors associated with the incidence of DNS (odds ratio, 2.082; 95% confidence interval, 1.101-3.937; P = 0.024). CONCLUSIONS: The practical clinical treatment for acute CO poisoning, including HBO2 therapy, varied among the institutions participating in Japan. HBO2 therapy with inconsistent protocols showed no advantage over NBO2 therapy in preventing DNS. Multiple HBO2 sessions was associated with the incidence of DNS.

Impact of type of emergency department on the outcome of out-of-hospital cardiac arrest: a prospective cohort study.

AIM: To assess whether the outcomes of out-of-hospital cardiac arrest (OHCA) differ between patients treated at tertiary or secondary emergency medical facilities. METHODS: Data from the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest (JAAM-OHCA) registry between June 2014 and December 2015 were analyzed and compared between patients treated at tertiary (tertiary group) and secondary (secondary group) emergency medical facilities. The primary outcome of this study was a favorable neurological outcome at 1 and 3 months after OHCA, defined as a Glasgow-Pittsburgh cerebral performance category of 1 or 2. RESULTS: Between June 2014 and December 2015, a total of 13,491 patients with OHCA were registered in the JAAM-OHCA registry. Of these, 12,836 were eligible in the present analysis, with 11,583 in the tertiary group and 1,253 in the secondary group. The proportions of patients with favorable neurological outcomes in the tertiary group were significantly higher than those in the secondary group at 1 (4.7% versus 2.0%, P < 0.001) and 3 (3.5% versus 1.6%, P < 0.001) months after OHCA. Even after adjusting for baseline characteristics of patients, treatment at a tertiary emergency medical facility was independently associated with favorable neurological outcomes at 1 (odds ratio, 2.856, 95% confidence interval, 1.429-5.710; P = 0.003) and 3 (odds ratio, 2.462, 95% confidence interval, 1.203-5.042; P = 0.014) months after OHCA. CONCLUSION: The neurological outcomes of patients with OHCA treated at tertiary emergency medical facilities were better than those of patients treated at secondary emergency medical facilities.

Severe Fever with Thrombocytopenia Syndrome Complicated with Pseudomembranous Aspergillus Tracheobronchitis in a Patient without Apparent Risk Factors for Invasive Aspergillosis.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease. A 91-year-old woman was admitted to our intensive-care unit with SFTS, and she developed dyspnea with wheezes 5 days after admission. Bronchoscopy showed scattered white mold in her central airway. An airway tissue biopsy and culture of bronchial lavage fluid revealed fungal hyphae in the necrotic tissue, confirmed as Aspergillus fumigatus. She was thus diagnosed with pseudomembranous aspergillus tracheobronchitis. She had no common risk factors for invasive aspergillosis (IA). Patients with SFTS, even those without apparent risk factors for IA, may be at risk of developing IA.

Evaluation of a Novel Classification of Heat-Related Illnesses: A Multicentre Observational Study (Heat Stroke STUDY 2012).

The Japanese Association for Acute Medicine Committee recently proposed a novel classification system for the severity of heat-related illnesses. The illnesses are simply classified into three stages based on symptoms and management or treatment. Stages I, II, and III broadly correspond to heat cramp and syncope, heat exhaustion, and heat stroke, respectively. Our objective was to examine whether this novel severity classification is useful in the diagnosis by healthcare professionals of patients with severe heat-related illness and organ failure. A nationwide surveillance study of heat-related illnesses was conducted between 1 June and 30 September 2012, at emergency departments in Japan. Among the 2130 patients who attended 102 emergency departments, the severity of their heat-related illness was recorded for 1799 patients, who were included in this study. In the patients with heat cramp and syncope or heat exhaustion (but not heat stroke), the blood test data (alanine aminotransferase, creatinine, blood urea nitrogen, and platelet counts) for those classified as Stage III were significantly higher than those of patients classified as Stage I or II. There were no deaths among the patients classified as Stage I. This novel classification may avoid underestimating the severity of heat-related illness.

Early enteral nutrition is associated with reduced in-hospital mortality from sepsis in patients with sarcopenia.

PURPOSE: To determine whether the association of early enteral nutrition (EEN) with mortality from sepsis differs between patients with and without sarcopenia. MATERIALS AND METHODS: We retrospectively reviewed septic patients treated at our centre between January 2010 and August 2017. The skeletal muscle area (SMA) at the level of the third lumbar vertebra was measured with CT on admission, and sarcopenia was defined as SMA < 80% of the predicted value. Patients were divided into two subgroups (sarcopenic and non-sarcopenic patients), and in-hospital mortality was compared in patients treated with and without EEN within each subgroup. We used logistic regression to examine factors associated with in-hospital mortality in each subgroup. RESULTS: EEN was administered to 35/91 sarcopenic patients and 43/100 non-sarcopenic patients. In-hospital mortality did not differ between non-sarcopenic patients with EEN and those without EEN (16% vs 16%, P = 0.947), but was significantly lower in sarcopenic patients with EEN than in those without EEN (9% vs 34%, P = 0.005). Logistic regression showed that EEN was independently associated with reduced in-hospital mortality in sarcopenic patients (OR 0.18, 95% CI 0.05-0.71, P = 0.014), but not in non-sarcopenic patients. CONCLUSIONS: EEN may be more beneficial in sarcopenic patients.

Variability in Treatment for Carbon Monoxide Poisoning in Japan: A Multicenter Retrospective Survey.

BACKGROUND: The aim of this study was to identify practice differences in the treatment of carbon monoxide (CO) poisoning with or without hyperbaric oxygen (HBO2) therapy in Japan. MATERIALS AND METHODS: Using an online survey website (Google form), we created a questionnaire and invited interested institutions to join the COP-J Study, a prospective observational study of CO poisoning in Japan. RESULTS: Forty-eight (63%) of 76 institutions replied to the questionnaire. Thirty-three institutions (69%) administered HBO2 therapy to patients with CO poisoning, and 15 institutions (31%) did not. Consciousness disturbance on arrival, exposure to CO for a long time, and elevation of arterial carboxyhemoglobin (CO-Hb) were the major indications for HBO2 therapy. The maximum therapeutic pressures were 2.0, 2.5, and 2.8 atmospheres absolute (ATA) at 19 (58%), 6 (18%), and 8 (24%) institutions, respectively. The number of HBO2 sessions on the first day was 1-3, and 1-7 sessions were administered on days 2-7. Seventeen (35%) institutions treated patients with delayed neurological sequelae (DNS) and 15 of them used HBO2 therapy for DNS. CONCLUSIONS: This survey indicates that HBO2 therapy for CO poisoning was varied in both the indications and practice regimens used in Japan.

Risk factors for late defecation and its association with the outcomes of critically ill patients: a retrospective observational study.

BACKGROUND: Late defecation was recently reported to be associated with worse clinical outcomes in critically ill patients. However, more research is needed to examine the causes and clinical significance of late defecation. The objectives of this study were to investigate the risk factors for late defecation and its association with the outcomes of intensive care unit (ICU) patients. METHODS: Patients in an ICU for ≥7 days between January and December 2011 were retrospectively assessed. Based on the time between admission and the first defecation, they were assigned to early (<6 days; n = 186) or late (≥6 days; n = 96) defecation groups. Changes in clinical variables between admission and ICU day 7 were assessed to investigate the effects of late defecation. The clinical outcomes were ICU mortality, length of ICU stay, and length of mechanical ventilation. RESULTS: Late enteral nutrition (odds ratio (OR) 3.42; 95 % confidence interval (CI) 1.88-6.22; P < 0.001), sedatives (OR 3.07; 95 % CI 1.71-5.52; P < 0.001), and surgery (OR 1.86; 95 % CI 1.01-3.42; P = 0.047) were the independent risk factors for late defecation. The median (interquartile) changes in body temperature (0.3 [-0.4 to 1.0] vs 0.7 [0.1 to 1.5] °C; P = 0.004), serum C-reactive protein concentration (1.6 [-0.5 to 6.6] vs 3.5 [0.7 to 8.5] mg/dL; P = 0.035), and Sequential Organ Failure Assessment score (-1 [-2 to 1] vs 0 [-1 to 2]; P = 0.008) between admission and ICU day 7 were significantly greater in the late defecation group than in the early defecation group. ICU stay was significantly longer in the late defecation group (12 [9 to 19] vs 16 [10 to 23] days; P = 0.021), whereas ICU mortality and the length of mechanical ventilation were similar in both groups. CONCLUSIONS: Late enteral nutrition, sedatives, and surgery were independent the risk factors for late defecation in critically ill patients. Late defecation was associated with prolonged ICU stay.

Microglia processes associate with diffusely injured axons following mild traumatic brain injury in the micro pig.

BACKGROUND: Mild traumatic brain injury (mTBI) is an all too common occurrence that exacts significant personal and societal costs. The pathophysiology of mTBI is complex, with reports routinely correlating diffuse axonal injury (DAI) with prolonged morbidity. Progressive chronic neuroinflammation has also recently been correlated to morbidity, however, the potential association between neuroinflammatory microglia and DAI is not well understood. The majority of studies exploring neuroinflammatory responses to TBI have focused on more chronic phases of injury involving phagocytosis associated with Wallerian change. Little, however, is known regarding the neuroinflammatory response seen acutely following diffuse mTBI and its potential relationship to early DAI. Additionally, while inflammation is drastically different in rodents compared to humans, pigs and humans share very similar inflammatory profiles and responses. METHODS: In the current study, we employed a modified central fluid percussion model in micro pigs. Using this model of diffuse mTBI, paired with various immunohistological endpoints, we assessed the potential association between acute thalamic DAI and neuroinflammation 6 h following injury. RESULTS: Injured micro pigs displayed substantial axonal damage reflected in the presence of APP+ proximal axonal swellings, which were particularly prominent in the thalamus. In companion, the same thalamic sites displayed extensive neuroinflammation, which was observed using Iba-1 immunohistochemistry. The physical relationship between microglia and DAI, assessed via confocal 3D analysis, revealed a dramatic increase in the number of Iba-1+ microglial processes that contacted APP+ proximal axonal swellings compared to uninjured myelinated thalamic axons in sham animals. CONCLUSIONS: In aggregate, these studies reveal acute microglial process convergence on proximal axonal swellings undergoing DAI, an interaction not previously recognized in the literature. These findings transform our understanding of acute neuroinflammation following mTBI and may suggest its potential as a diagnostic and/or a therapeutic target.

Predictive Factors for Hospitalization of Patients with Heat Illness in Yamaguchi, Japan.

The objective of the study was to investigate the predictive factors for the hospitalization of patients who presented with mild to moderate heat illness at an emergency department. We conducted a retrospective survey of hospitals with an emergency department in Yamaguchi Prefecture, Japan. The survey questionnaire entries included patient age, sex, use of an ambulance, vital signs, blood examination conducted at the emergency department, the length of hospitalization, and outcome. We analyzed the predictive factors for hospitalization in patients with heat illness. A total of 127 patients were analyzed. Of these, 49 (37%) were admitted, with 59% discharged on the day following admission. In univariate analysis, the following inpatient characteristics were predictive for hospitalization: old age, low Glasgow Coma Scale score, elevated body temperature, increased serum C-reactive protein, and increased blood urea nitrogen. In logistic regression multivariate analysis, the following were predictive factors for hospitalization: age of ≥ 65 years (odds ratio (OR) 4.91; 95% confidence interval (CI) 1.42-17.00), body temperature (OR 1.97; 95% CI 1.14-3.41), Glasgow Coma Scale (OR 0.40; 95% CI 0.16-0.98), and creatinine (OR 2.92; 95% CI 1.23-6.94). The results suggest that the elderly with hyperthermia, disturbance of consciousness, and elevated serum creatinine have an increased risk for hospitalization with heat illness.

Effects of uninterrupted chest compressions on the rescuer's physical condition.

STUDY OBJECTIVE: Recent guidelines have emphasized the need for uninterrupted chest compressions. The purpose of this study was to evaluate the rescuer's tolerability of uninterrupted chest compressions. METHODS: Twenty-five healthy subjects performed uninterrupted chest compressions for 7 minutes at a rate of 100 compressions per minute using a training manikin. The quality of chest compressions was assessed in terms of the total number and percentage of chest compressions, compression depth, recoil distance, and duty cycle. Correct chest compression was defined as a depth of 38 to 51 mm. Physiological and laboratory parameters were measured before and after the procedure. Fatigue was measured using a numerical rating scale. Data were compared before and after the procedure. RESULTS: The participants were 10 emergency physicians and 15 medical students. The compression rate was nearly 100 compressions per minute. The number and percentage of correct compressions decreased gradually after 3 minutes. The compression depth decreased significantly after 2 minutes. The recoil distance and duty cycle were unchanged over 7 minutes. Systolic blood pressure, pulse rate, respiratory rate, numerical rating scale, serum lactate, adrenalin, and noradrenalin increased significantly after the procedure. Noradrenalin levels measured before the procedure were significantly and negatively correlated with the total number and percentage of correct compressions (r = -0.587, P = .004; r = -0.549, P = .008, respectively). CONCLUSIONS: Performing uninterrupted chest compressions for 7 minutes is an arduous procedure. Higher noradrenalin levels before the procedure might be associated with incorrect chest compressions.

[Predictive prognostic factors in severe patients].

International classification of heat illness including heat stroke, heat exhaustion, the others is well known. However, the new classification from the grade III(severe) to the grade I(mild) is more common in Japan. There is a good correlation between the two classifications. The Heatstroke Surveillance Committee of the Japanese Association for Acute Medicine has collected the data using the new classification. The outcome of patients who were mechanically ventilated due to heat illness was not affected by cooling procedures but independently associated with systolic blood pressure and SpO2 at the scene, and arterial base excess on admission.

Peak value of blood myoglobin predicts acute renal failure induced by rhabdomyolysis.

PURPOSE: Acute renal failure (ARF) is the most important complication of rhabdomyolysis. Serial measurements of blood myoglobin might be useful for predicting rhabdomyolysis-induced ARF. METHODS: Thirty patients with rhabdomyolysis were examined. The causes of rhabdomyolysis were trauma, burns, and ischemia, among others. Serial blood myoglobin levels were measured by immunochromatography, and the peak value was determined. The relationship between blood myoglobin levels and the incidence of ARF was evaluated. RESULTS: The median peak blood myoglobin level was 3335 ng/mL. Acute renal failure occurred in 12 patients (40%). Nine patients (30%) underwent renal replacement therapy. Peak creatine kinase and peak blood myoglobin levels in the ARF group were significantly higher than those in the non-ARF group. Three patients in the ARF group were treated with renal replacement therapy before occurrence of uremia because of extremely high levels of blood myoglobin (>10,000 ng/mL). Receiver operating characteristic analysis showed that the area under the curve for blood myoglobin that predicted ARF was 0.88, and the best cutoff value for blood myoglobin was 3865 ng/mL. CONCLUSIONS: The peak value for blood myoglobin might be a good predictor of rhabdomyolysis-induced ARF. Early renal protective therapies should be considered for patients with rhabdomyolysis at high risk of ARF.

Moderate hypothermia suppressed excessive generation of superoxide anion radical and inflammatory reactions in blood and liver in heatstroke: laboratory study in rats.

Abstract The study was performed to demonstrate superoxide radical (O(2).-) generation, systemic inflammation and liver injury caused by heatstroke and to reveal suppressive effects of moderate hypothermia. Heatstroke was defined as achieving pharyngeal temperature of 40 degrees C with arterial pressure reduction. Heatstroke rats were divided to four groups by the temperature after the onset; 40 degrees C, 37 degrees C, 32 degrees C and sham-treated with 37 degrees C. O(2).- current was measured continuously in the right atrium using an electrochemical O(2).- sensor. The O(2).- current increased in all groups except for the sham-treated group during the induction. After the onset of heatstroke, the O(2).- current was suppressed with temperature-dependency. Plasma and liver high-mobility group box 1, intercellular adhesion molecule-1, plasma aspartate aminotransferase and alanine aminotransferase were also suppressed with the suppression of O(2).- generation. Therefore, excessive O(2).- generation might be a key factor in heatstroke and the suppression with moderate hypothermia would be a therapeutic modality.

Serum glial fibrillary acidic protein is a highly specific biomarker for traumatic brain injury in humans compared with S-100B and neuron-specific enolase.

BACKGROUND: Serum glial fibrillary acidic protein (GFAP) is a specific predictor of brain damage and neurologic outcome in patients with traumatic brain injury (TBI). In this study, serum GFAP, S-100B, and neuron-specific enolase (NSE) were compared in the same samples from severe trauma patients to assess their ability to predict abnormalities detectable on head computed tomography (CT). METHODS: This study was a retrospective analysis at a single university emergency center. Thirty-four trauma patients were included. Serum samples were collected from the patients for 3 days. Serum GFAP, S-100B, and NSE concentrations were measured with enzyme-linked immunosorbent assays and compared in patients with and without TBI, as evaluated by head CT. RESULTS: Serum GFAP, S-100B, and NSE were significantly higher in the TBI patients than in the non-TBI patients (p < 0.05 for each protein). The receiver operating characteristic curves for TBI were compared for the three biomarkers for 3 days. Serum GFAP on day 1 had the largest area under the receiver operating characteristic curve (0.983), with 88.9% sensitivity and 100% specificity. CONCLUSIONS: Serum GFAP has remarkable diagnostic value for TBI, defined by abnormal head CT findings, in prehospital-triaged patients with severe trauma.

Cholinergic agonist physostigmine suppresses excessive superoxide anion radical generation in blood, oxidative stress, early inflammation, and endothelial injury in rats with forebrain ischemia/reperfusion.

The cholinergic anti-inflammatory pathway is reportedly important in modulating the inflammatory response in local and systemic diseases, including ischemia/reperfusion pathophysiology. In this study, we investigated the effects of the cholinergic agonist, physostigmine, on jugular venous superoxide radical (O(2)(-)) generation, oxidative stress, early inflammation, and endothelial activation during forebrain ischemia/reperfusion (FBI/R) in rats. Fourteen male Wistar rat were allocated to the control group (n=7) or physostigmine group (n=7). The physostigmine group received 80 ng/g physostigmine intraperitoneally 24 h and 1 h before forebrain ischemia was established. The jugular venous O(2)(-) current was measured for 10 min during forebrain ischemia and for 120 min after reperfusion. The O(2)(-) current increased gradually during forebrain ischemia in both groups. The current increased markedly immediately after reperfusion in the control group but was significantly attenuated in the physostigmine group after reperfusion. Brain and plasma malondialdehyde, high-mobility group box 1 (HMGB1) protein, and intercellular adhesion molecule 1 (ICAM1) were significantly attenuated in the physostigmine group compared with the control group, except for brain HMGB1. The amount of O(2)(-) generated during FBI/R correlated with malondialdehyde, HMGB1, and ICAM1 in both the brain and plasma. In conclusion, the cholinergic agonist physostigmine suppressed jugular venous O(2)(-) generation, oxidative stress, early inflammation, and endothelial activation in the brain and plasma in the acute phase of cerebral ischemia/reperfusion. Therefore, the suppression of O(2)(-) is a key mechanism of the cholinergic anti-inflammatory pathway in the pathophysiology of cerebral ischemia/reperfusion.

Moderate hypothermia suppresses jugular venous superoxide anion radical, oxidative stress, early inflammation, and endothelial injury in forebrain ischemia/reperfusion rats.

The aim of this study was to assess the effect of moderate hypothermia (MH) on generation of jugular venous superoxide radical (O2-.), oxidative stress, early inflammation, and endothelial injury in forebrain ischemia/reperfusion (FBI/R) rats. Twenty-one Wistar rats were allocated to a control group (n=7, 37 degrees C), a pre-MH group (n=7, 32 degrees C before ischemia), and a post-MH group (n=7, 32 degrees C after reperfusion). MH was induced before induction of ischemia in the pre-MH group and just after reperfusion in the post-MH group. Forebrain ischemia was induced by occlusion of bilateral common carotid arteries with hemorrhagic hypotension for 10 min, followed by reperfusion. O(2)(-)(.) in the jugular vein was measured from the produced current using a novel O2-. sensor. The O2-. current showed a gradual increase during forebrain ischemia in the control and post-MH groups but was attenuated in the pre-MH group. Following reperfusion, the current showed a marked increase in the control group but was strongly attenuated in the pre- and post-MH groups. Concentrations of malondialdehyde, high-mobility group box 1 (HMGB1) protein, and intercellular adhesion molecule-1 (ICAM-1) in the brain and plasma 120 min after reperfusion in the pre- and post-MH groups were significantly lower than those in the control group, except for plasma HMGB1 in the post-MH group. In conclusion, MH suppressed O2-. measured in the jugular vein, oxidative stress, early inflammation, and endothelial injury in FBI/R rats.