OBJECTIVES: To investigate the regulatory role of astrocytes in the dorsomedial hypothalamus (DMH) during sevoflurane anesthesia emergence. METHODS: Forty-two male C57BL/6 mice were randomized into 6 groups (n=7) for assessing astrocyte activation in the dorsomedial hypothalamus (DMH) under sevoflurane anesthesia. Two groups of mice received microinjection of agfaABC1D promoter-driven AAV2 vector into the DMH for GCaMP6 overexpression, and the changes in astrocyte activity during sevoflurane or air inhalation were recorded using calcium imaging. For assessing optogenetic activation of astrocytes, another two groups of mice received microinjection of an optogenetic virus or a control vector into the DMH with optic fiber implantation, and sevoflurane anesthesia emergence was compared using behavioral experiments. In the remaining two groups, electroencephalogram (EEG) recording during sevoflurane anesthesia emergence was conducted after injection of the hChR2-expressing and control vectors. Anesthesia induction and recovery were assessed by observing the righting reflex. EEG data were recorded under 2.0% sevoflurane to calculate the burst suppression ratio (BSR) and under 1.5% sevoflurane for power spectrum analysis. Immunofluorescence staining was performed to visualize the colocalization of GFAP-positive astrocytes with viral protein signals. RESULTS: Astrocyte activity in the DMH decreased progressively as sevoflurane concentration increased. During 2.0% sevoflurane anesthesia, the mice injected with the ChR2-expressing virus exhibited a significantly shortened wake-up time (P<0.05), and optogenetic activation of the DMH astrocytes led to a marked reduction in BSR (P<0.001). Under 1.5% sevoflurane anesthesia, optogenetic activation resulted in a significant increase in EEG gamma power and a significant decrease in delta power in ChR2 group (P<0.01). CONCLUSIONS Optogenetic activation of DMH astrocytes facilitates sevoflurane anesthesia emergence but does not significantly influence anesthesia induction. These findings offer new insights into the mechanisms underlying anesthesia emergence and may provide a potential target for accelerating postoperative recovery and managing anesthesia-related complications.
Animals ; Astrocytes/physiology* ; Sevoflurane ; Mice, Inbred C57BL ; Mice ; Male ; Electroencephalography ; Anesthetics, Inhalation/pharmacology* ; Hypothalamus/cytology* ; Anesthesia Recovery Period ; Methyl Ethers/pharmacology*

OBJECTIVE: To examine the mechanistic of organochlorine-associated changes in lung function. METHODS: This study investigated 76 healthy older adults in Jinan, Shandong Province, over a five-month period. Personal exposure to organochlorines was quantified using wearable passive samplers, while inflammatory factors and thyroid hormones were analyzed from blood samples. Participants' lung function was evaluated. After stratifying participants according to their thyroid hormone levels, we analyzed the differential effects of organochlorine exposure on lung function and inflammatory factors across the low and high thyroid hormone groups. Mediation analysis was further conducted to elucidate the relationships among organochlorine exposures, inflammatory factors, and lung function. RESULTS: Bis (2-chloro-1-methylethyl) ether (BCIE), was negatively associated with forced vital capacity (FVC, -2.05%, 95% CI: -3.11% to -0.97%), and associated with changes in inflammatory factors such as interleukin (IL)-2, IL-7, IL-8, and IL-13 in the low thyroid hormone group. The mediation analysis indicated a mediating effect of IL-2 (15.63%, 95% CI: 0.91% to 44.64%) and IL-13 (13.94%, 95% CI: 0.52% to 41.07%) in the association between BCIE exposure and FVC. CONCLUSION Lung function and inflammatory factors exhibited an increased sensitivity to organochlorine exposure at lower thyroid hormone levels, with inflammatory factors potentially mediating the adverse effects of organochlorines on lung function.
Environmental Exposure ; Hydrocarbons, Chlorinated/metabolism* ; China ; Ethyl Ethers/metabolism* ; Environmental Monitoring ; Thyroid Hormones/blood* ; Lung/physiology* ; Inhalation Exposure/statistics & numerical data* ; Air Pollution/statistics & numerical data* ; Air Pollutants/metabolism* ; Humans ; Male ; Female ; Middle Aged ; Aged

PURPOSE: The aim of this study was epidemiologic research on morbidity rate changes and causes of sepsis in severe burn patients, as they are highly vulnerable to sepsis which is closely related to mortality rate. METHODS: A retrospective review was conducted on 1,026 patients admitted to Burn Intensive Care Unit (BICU) of Hangang Sacred Heart Hospital from September 2011 to December 2015. Age, sex, burn size, whether the patient has inhalation injury, LOS (length of stay), LOSICU (Length of Stay in the Intensive Care Unit), and route of infection were taken into account. RESULTS: The average age, total body surface area (TBSA), the degree of inhalation injury, abbreviated burn severity index (ABSI), acute physiology and chronic health valuation score (APACHE) II, and LOS were higher in the dead than the survivors, and the differences were statistically significant. Incidence rate of sepsis was also meaningfully higher in the dead group, 64.8%. Patients with sepsis had higher average age, degree of inhalation injury, TBSA, and LOS, showing statistically significant differences as well compared to patients without sepsis. For five years from 2011 to 2015, rates of severe burn patients diagnosed with sepsis were 43.3%, 54.3%, 46.4%, 51.9%, and 43.9% respectively. CONCLUSION: Severe burn patients with higher age, larger burn size, and inhalation injury require more careful monitor as they are likely to be infected with sepsis. In addition, more laboratory parameters for early detection of sepsis need to be developed, so that follow-up studies can be conducted on prognostic factors correlated to sepsis.
Body Surface Area ; Burns* ; Critical Care ; Follow-Up Studies ; Heart ; Humans ; Incidence ; Inhalation ; Intensive Care Units ; Mortality ; Physiology ; Retrospective Studies ; Sepsis* ; Survivors

BACKGROUNDThe optimal ventilated status under total intravenous or inhalation anesthesia in neurosurgical patients with a supratentorial tumor has not been ascertained. The purpose of this study was to intraoperatively compare the effects of moderate hyperventilation on the jugular bulb oxygen saturation (SjO 2 ), cerebral oxygen extraction ratio (O 2 ER), mean arterial blood pressure (MAP), and heart rate (HR) in patients with a supratentorial tumor under different anesthetic regimens.

METHODSTwenty adult patients suffered from supratentorial tumors were randomly assigned to receive a propofol infusion followed by isoflurane anesthesia after a 30-min stabilization period or isoflurane followed by propofol. The patients were randomized to one of the following two treatment sequences: hyperventilation followed by normoventilation or normoventilation followed by hyperventilation during isoflurane or propofol anesthesia, respectively. The ventilation and end-tidal CO 2 tension were maintained at a constant level for 20 min. Radial arterial and jugular bulb catheters were inserted for the blood gas sampling. At the end of each study period, we measured the change in the arterial and jugular bulb blood gases.

RESULTSThe mean value of the jugular bulb oxygen saturation (SjO 2 ) significantly decreased, and the oxygen extraction ratio (O 2 ER) significantly increased under isoflurane or propofol anesthesia during hyperventilation compared with those during normoventilation (SjO 2 : t = -2.728, P = 0.011 or t = -3.504, P = 0.001; O 2 ER: t = 2.484, P = 0.020 or t = 2.892, P = 0.009). The SjO 2 significantly decreased, and the O 2 ER significantly increased under propofol anesthesia compared with those values under isoflurane anesthesia during moderate hyperventilation (SjO 2 : t = -2.769, P = 0.012; O 2 ER: t = 2.719, P = 0.013). In the study, no significant changes in the SjO 2 and the O 2 ER were observed under propofol compared with those values under isoflurane during normoventilation.

CONCLUSIONSOur results suggest that the optimal ventilated status under propofol or isoflurane anesthesia in neurosurgical patients varies. Hyperventilation under propofol anesthesia should be cautiously performed in neurosurgery to maintain an improved balance between the cerebral oxygen supply and demand.

Adolescent ; Adult ; Aged ; Anesthetics, Inhalation ; Anesthetics, Intravenous ; Arterial Pressure ; physiology ; Blood Gas Analysis ; Craniotomy ; methods ; Female ; Heart Rate ; physiology ; Humans ; Hyperventilation ; chemically induced ; physiopathology ; Isoflurane ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Propofol ; administration & dosage ; therapeutic use ; Young Adult

Alterations of the autophagy-lysosomal pathway (ALP) and autophagy have been involved in lung ischemia-reperfusion (I/R) injury. However, dynamic imaging of ALP function under lung I/R injury particularly is not fully understood. Here we depicted the live-cell fluorescence imaging of autophagosome to monitor ALP activation and autophagy function. The pAsRed2-N1-LC3 vectors were transfected into CRL-2192 NR8383 (an alveolar macrophage cell line) and CCL149 (an alveolar epithelial cell line) successfully. 0-h, 2-h, 4-h, and 6-h hypoxia/0-h, 2-h, 4-h, and 6-h reoxygenation were then induced with an ALP inhibitor (3-MA) or activator (rapamycin) in the culture of transfected cells separately. ALP activation was conformed by up-regulating AMPK and beclin1 expression. Apoptosis was not obvious in 2-h hypoxia/2-h reoxygenation. pAsRed2-N1-LC3 CCL149 and pAsRed2-N1-LC3 NR8383 cells revealed gradually enhanced AsRed2 from 2-h to 6-h hypoxia/reoxygenation. AsRed2 varied sensitively to 3-MA and rapamycin interventions during 2-h hypoxia/reoxygenation. Our data provides a simple method of autophagosome imaging to monitor ALP activation and autophagy function in lung I/R injury.
Animals ; Autophagy ; Base Sequence ; DNA Primers ; Hypoxia ; physiopathology ; In Vitro Techniques ; Lung ; physiopathology ; Lysosomes ; physiology ; Oxygen Inhalation Therapy ; Rats ; Real-Time Polymerase Chain Reaction

OBJECTIVETo compare the effects of high frequency oscillatory ventilation (HFOV) combined with incremental positive end-expiratory pressure (IP) and those of pure HFOV on myocardial ischemia and hypoxia and apoptosis of cardiomyocytes in dogs with smoke inhalation injury.

METHODSTwelve healthy male dogs were divided into group HFOV and group HFOV+IP according to the random number table, with 6 dogs in each group. After being treated with conventional mechanical ventilation, dogs in both groups were inflicted with severe smoke inhalation injury, and then they received corresponding ventilation for 8 hours respectively. After treatment, the blood samples were collected from heart to determine the activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase 1 (LDH1) in plasma. The dogs were sacrificed later. Myocardium was obtained for determination of content of TNF-α per gram myocardium by ELISA, apoptotic rate of cardiomyocytes by flow cytometer, degree of hypoxia with HE staining, and qualitative and quantitative expression of actin (denoted as integral absorbance value) with streptavidin-biotin-peroxidase staining. Data were processed with t test. The relationship between the content of TNF-α per gram myocardium and the apoptotic rate of cardiomyocytes was assessed by Spearman linear correlation analysis.

RESULTS(1) After treatment for 8 h, the values of activity of CK-MB and LDH1 in plasma of dogs in group HFOV+IP were respectively (734 ± 70) and (182 ± 15) U/L, which were both lower than those in group HFOV [(831 ± 79) and (203 ± 16) U/L, with t values respectively 2.25 and 2.35, P values below 0.05]. (2) Compared with that in group HFOV [(0.060 ± 0.018) µg], the content of TNF-α per gram myocardium of dogs in group HFOV+IP after treatment for 8 h was decreased significantly [(0.040 ± 0.011) µg, t=2.32, P<0.05]. (3) Compared with that in group HFOV [(33.4 ± 2.2)%], the apoptotic rate of cardiomyocytes of dogs in group HFOV+IP after treatment for 8 h was significantly decreased [(28.2 ± 3.4)%, t=3.15, P<0.05]. There was a positive correlation between the content of TNF-α per gram myocardium and the apoptotic rate of cardiomyocytes (r=0.677, P<0.05). (4) HE staining showed that myocardial fibers of dogs in both groups were arranged in wave shape in different degrees, indicating there was myocardial hypoxia in different degrees. Compared with that of group HFOV, the degree of hypoxia in group HFOV+IP was slighter. (5) The results of immunohistochemical staining showed that there was less loss of actin in myocardial fibers of dogs in group HFOV+IP than in group HFOV. The expression level of actin in myocardium of dogs in group HFOV+IP after treatment for 8 h (194.7 ± 3.1) was obviously higher than that in group HFOV (172.9 ± 2.6, t=13.20, P<0.01).

CONCLUSIONSCompared with pure HFOV, HFOV combined with IP can alleviate the inflammatory reaction in myocardium of dogs, reduce the apoptosis of cardiomyocytes, and ameliorate the myocardial damage due to ischemia and hypoxia.

Animals ; Apoptosis ; physiology ; Burns, Inhalation ; physiopathology ; therapy ; Dogs ; High-Frequency Ventilation ; Hypoxia ; Male ; Myocardial Ischemia ; physiopathology ; Myocytes, Cardiac ; Positive-Pressure Respiration ; Respiration, Artificial ; Smoke ; adverse effects ; Smoke Inhalation Injury ; therapy ; Treatment Outcome ; Tumor Necrosis Factor-alpha

Risk assessment considers the situations and characteristics of the exposure environment and host. Various physiological variables of the human body reflects the characteristics of the population that can directly influence risk exposure. Therefore, identification of exposure factors based on the Korean population is required for appropriate risk assessment. It is expected that a handbook about general exposure factors will be used by professionals in many fields as well as the risk assessors of the health department. The process of developing the exposure factors handbook for the Korean population will be introduced in this article, with a specific focus on the general exposure factors including life expectancy, body weight, surface area, inhalation rates, amount of water intake, and soil ingestion targeting the Korean population. The researchers used national databases including the Life Table and the 2005 Time Use Survey from the National Statistical Office. The anthropometric study of size in Korea used the resources provided by the Korean Agency for Technology and Standards. In addition, direct measurement and questionnaire surveys of representative samples were performed to calculate the inhalation rate, drinking water intake, and soil ingestion.
Asian Continental Ancestry Group ; Body Surface Area ; Body Weight/physiology ; Drinking Water/standards ; *Environmental Exposure ; Humans ; Inhalation/*physiology ; Life Expectancy ; Republic of Korea ; Risk Assessment ; Soil Pollutants/chemistry

The small airways have been neglected for many years, but interest in the topic has been rekindled with recent advances in measurement techniques to assess this region and also the ability to deliver therapeutics to the distal airways. Current levels of disease control in asthmatic patients remain poor and there are several contributory factors including; poor treatment compliance, heterogeneity of asthma phenotypes and associated comorbidities. However, the proposition that we may not be targeting all the inflammation that is present throughout the whole respiratory tree may also be an important factor. Indeed decades ago, pathologists and physiologists clearly identified the importance of small airways dysfunction in asthmatic patients. With improved inhaler technology to deliver drug to target the whole respiratory tree and more sensitive measures to assess the distal airways, we should certainly give greater consideration to treating the small airway region when seeing our asthmatic patients in clinic. The aim of this review is to address the relevance of small airways dysfunction in the daily clinical management of patients with asthma. In particular the role of small particle aerosols in the management of patients with asthma will be explored.
Adrenal Cortex Hormones ; Aerosols ; Asthma* ; Comorbidity ; Compliance ; Humans ; Inflammation ; Inhalation ; Nebulizers and Vaporizers ; Pharmacology ; Phenotype ; Physiology ; Population Characteristics

Pressure-support ventilation (PSV) is a form of important ventilation mode. Patient-ventilator synchrony of pressure support ventilation can be divided into inspiration-triggered and expiration-triggered ones. Whether the ventilator can track the patient's inspiration and expiration very well or not is an important evaluating item of the performance of the ventilator. The ventilator should response to the patient's inspiration effort on time and deliver the air flow to the patient under various conditions, such as different patient's lung types and inspiration effort, etc. Similarly, the ventilator should be able to response to the patient's expiration action, and to decrease the patient lung's internal pressure rapidly. Using the Active Servo Lung (ASL5000) respiratory simulation system, we evaluated the spontaneous breathing of PSV mode on E5, Servo i and Evital XL. The following parameters, the delay time before flow to the patient starts once the trigger variable signaling the start of inspiration, the lowest inspiratory airway pressure generated prior to the initiation of PSV, etc. were measured.
Exhalation ; Humans ; Inhalation ; Interactive Ventilatory Support ; Lung ; physiology ; Pressure ; Ventilators, Mechanical

OBJECTIVETo observe and compare the effects of two kinds of lung recruitment maneuvers, namely sustained inflation (SI) and incremental positive end-expiratory pressure (PEEP) (IP) on oxygenation, respiratory mechanics, and hemodynamics of dogs with severe smoke inhalation injury.

METHODSAfter being treated with conventional mechanical ventilation, 12 dogs were inflicted with severe smoke inhalation injury. They were divided into group SI and group IP according to the random number table, with 6 dogs in each group. Dogs in group SI were subjected to continuous positive airway pressure ventilation, with inspiratory pressure of 25 cmH2O (1 cmH2o = 0. 098 kPa), and it was sustained for 20 s. PEEP level in group IP was gradually increased by 5 cmH2O every 5 min up to 25 cmH2O, and then it was decreased by 5 cmH2O every 5 min until reaching 2-3 cmH2O. Then the previous ventilation mode was resumed in both groups for 8 hours. Blood gas analysis (pH value, PaO2, and PaCO2), oxygenation index (OI), respiratory mechanics parameters [peak inspiratory pressure (PIP), mean airway pressure, and dynamic lung compliance], and hemodynamic parameters [heart rate, mean arterial pressure (MAP), pulmonary arterial pressure (PAP), and cardiac output (CO)] were recorded or calculated before injury, immediately after injury, and at post ventilation hour (PVH) 2, 4, 6, 8. Data were processed with analysis of variance of repeated measurement and LSD-t test.

RESULTS(1) At PVH 6 and 8, pH values of dogs in group SI were significantly lower than those in group IP (with t values respectively 2. 431 and 2. 261, P values below 0.05); PaO2 levels in group SI [(87 ± 24), (78 ± 14) mmHg, 1 mmHg =0. 133 kPa] were lower than those in group IP [ (114 ± 18) , (111 ± 17) mmHg, with t values respectively 2. 249 and 3.671, P <0.05 or P <0.01]; OI values in group SI were significantly higher than those in group IP (with t values respectively 2.363 and 5.010, P <0.05 or P <0.01). No significant differences were observed in PaCO2 level within each group or between the two groups (with t values from 0. 119 to 1. 042, P values above 0.05). Compared with those observed immediately after injury, the pH values were significantly lowered (except for dogs in group IP at PVH 6 and 8, with t values from 2.292 to 3.222, P <0.05 or P <0.01), PaO2 levels were significantly elevated (with t values from 4. 443 to 6.315, P <0.05 or P <0.01), and OI values were significantly lowered (with t values from 2.773 to 9.789, P <0.05 orP <0.01) in both groups at all the treatment time points. (2) The PIP level at each time point showed no significant differences between two groups (with t values from 0. 399 to 1. 167, P values above 0. 05). At PVH 4 and 8, the mean airway .pressure values of dogs in group SI were significantly higher than those in group IP (with t values respectively 1.926 and 1. 190, P values below 0.05). At PVH 4, 6, and 8, the dynamic lung compliance levels of dogs in group SI [(9.5 ± 1.9), (12.8 ± 2. 1), (13. 1 ± 1.8) mL/cmH2O] were significantly lower than those in group IP [(11.6 ± 1.2), (15.4 ± 1.8), (14.9 ± 0.8) mL/cmH2O], with t values respectively 2. 289, 2. 303, 2. 238, P values below 0.05. Compared with those observed immediately after injury, PIP and the mean airway pressure values of dogs in two groups were significantly lowered at each treatment time point (with t values from 2. 271 to 7. 436, P <0. 05 or P < 0.01); the dynamic lung compliance levels were significantly elevated in both groups at PVH 6 and 8 (with t values from 2. 207 to 4. 195, P < 0.05 or P <0.01). (3) Heart rate, MAP, and PAP levels at each time point between two groups showed no significant differences (with t values from 0. 001 to 1. 170, P values above 0. 05). At PVH 4, 6, and 8, CO levels in group IP [(0. 6 + 0. 3), (0. 6 + 0. 4), (0. 5 + 0. 7) L/min] were significantly lower than those in group SI [(1.5 0.7), (1.8 + 1.1), (1.6 +0.9) L/min], with t values respectively 3. 028, 2.511, 2.363, P values below 0.05. Compared with that observed immediately after injury, CO level in group IP was significantly lowered at PVH 4, 6, or 8 (with t values respectively 2. 363, 2. 302, 2. 254, P values below 0. 05).

CONCLUSIONSBoth lung recruitment maneuvers can effectively improve oxygenation and lung compliance of dogs with severe smoke inhalation injury. IP is more effective in improving lung compliance, while SI shows less impact on the hemodynamic parameters.

Animals ; Blood Gas Analysis ; veterinary ; Dogs ; Hemodynamics ; Lung Compliance ; physiology ; Oxygen ; blood ; Oxygen Consumption ; physiology ; Positive-Pressure Respiration ; methods ; Respiration, Artificial ; Respiratory Mechanics ; Severity of Illness Index ; Smoke ; adverse effects ; Smoke Inhalation Injury ; physiopathology ; therapy