Pressure Of Oxygen In Arterial Blood Research Articles

Blood gas parameters of Brahman cattle

Blood gas test evaluates hydroelectrolyte, acid-base balance, and lung function. The physiological parameters can be influenced by age and management and environmental factors, as well as the blood sample used: venous or arterial. The objective of this study was to analyze arterial and venous blood gas parameters of healthy Brahman cattle in Brazil, to determine reference values for this breed, comparing age and sex, in addition to evaluating the correlation between arterial and venous results. For the purpose of this research, 80 healthy cattle (40 males and 40 females) were grouped according to different age groups (Group I: from 5 to 30 days; Group II: from 31 days to 6 months; Group III: from 7 to 18 months; Group IV: from 19 to 36 months) and sex. The animals were examined by physical examination prior to the collection of the venous and arterial blood samples. Blood gas analyses were performed immediately after blood collections, using the I-STAT® portable device with EG7+ cartridge. There was a difference among age groups for rectal temperature (RT), respiratory rate (RR) and heart rate (HR), and age × sex interaction for RT and RR. Younger animals (Group I) had higher RT, HR and RR, regardless of sex. Females had higher RT than males, regardless of age. As for blood gas parameters, only oxygen pressure (PO2) and arterial and venous concentrations of sodium ions (Na+) experienced the interaction between age × sex, while pH, carbon oxygen pressure (PCO2), oxygen saturation (SO2), potassium (K+), and calcium (iCa2+) concentrations of arterial and venous blood were influenced by the age of the animals. Calves in the Group I showed the main differences in blood gas parameters compared to adults (Groups III and IV). The neonates (Group I) had lower values of pH and SO2, and higher values of PCO2, K+ and iCa2+ of arterial and venous blood. High correlation could be observed in the values of pH, Na+, hematocrit and hemoglobin when measured in arterial and venous blood, therefore, one value can be obtained by the other. The other variables were very dispersed, confirming the differences pointed out in the literature between arterial and venous blood. Finally, the results of this study can be used as a reference for healthy animals of the Brahman breed.

Effect of Interposed Abdominal Compression on Cardiopulmonary Resuscitation Outcomes; a Randomized Clinical Trial.

Introduction:Standard cardiopulmonary resuscitation (STD-CPR) is successful in only 10-15% of cases in emergency department (ED). This study aimed to determine the effect of interposed abdominal compression (IAC) during resuscitation on outcomes of ED cardiac arrests.Methods:In this randomized clinical trial study, non-trauma patients aged 18-85 years, patients with in-hospital cardiac arrest hospitalized in the ED were randomly assigned into two either STD-CPR or IAC-CPR group on a 1:1 basis and using computer-generated random numbers. Participants in the intervention group, received abdominal compression during the diastole phase of STD-CPR. The rate of return of spontaneous circulation (ROSC), heart rate (HR), respiratory rate (RR), arterial blood gas (ABG) indicators, and survival rate were compared between the two groups. Results:Ninety patients were enrolled (45 in each group). There were no differences between the two groups regarding age (p = 0.76), sex (p = 0.39), employment status (p = 0.62) and Charlson comorbidity scale (p = 0.46). Abdominal compression had a positive effect on heart rate (p < 0.001), mean arterial pressure (p = 0.003), arterial blood oxygen pressure (p = 0.001), and arterial blood carbon dioxide pressure (p = 0.001) as well as a negative effect on arterial blood oxygen saturation (p = 0.029) 30 minutes after resuscitation. Out of the 90 CPR cases, 8 (17.7%) cases in intervention group and 8 (17.7%) cases in control group were successful, among which all of the 8 patients in the intervention group and 5 of the patients in the control group had been discharged from hospital without any complications. Conclusion: The results showed that abdominal compression during CPR can improve resuscitation outcomes in patients with cardiac arrest. Therefore, in order to use this technique, further research is recommended.

Machine learning-based model for prediction of clinical deterioration in hospitalized patients by COVID 19

Despite the publication of great number of tools to aid decisions in COVID-19 patients, there is a lack of good instruments to predict clinical deterioration. COVID19-Osakidetza is a prospective cohort study recruiting COVID-19 patients. We collected information from baseline to discharge on: sociodemographic characteristics, comorbidities and associated medications, vital signs, treatment received and lab test results. Outcome was need for intensive ventilatory support (with at least standard high-flow oxygen face mask with a reservoir bag for at least 6 h and need for more intensive therapy afterwards or Optiflow high-flow nasal cannula or noninvasive or invasive mechanical ventilation) and/or admission to a critical care unit and/or death during hospitalization. We developed a Catboost model summarizing the findings using Shapley Additive Explanations. Performance of the model was assessed using area under the receiver operating characteristic and prediction recall curves (AUROC and AUPRC respectively) and calibrated using the Hosmer–Lemeshow test. Overall, 1568 patients were included in the derivation cohort and 956 in the (external) validation cohort. The percentages of patients who reached the composite endpoint were 23.3% vs 20% respectively. The strongest predictors of clinical deterioration were arterial blood oxygen pressure, followed by age, levels of several markers of inflammation (procalcitonin, LDH, CRP) and alterations in blood count and coagulation. Some medications, namely, ATC AO2 (antiacids) and N05 (neuroleptics) were also among the group of main predictors, together with C03 (diuretics). In the validation set, the CatBoost AUROC was 0.79, AUPRC 0.21 and Hosmer–Lemeshow test statistic 0.36. We present a machine learning-based prediction model with excellent performance properties to implement in EHRs. Our main goal was to predict progression to a score of 5 or higher on the WHO Clinical Progression Scale before patients required mechanical ventilation. Future steps are to externally validate the model in other settings and in a cohort from a different period and to apply the algorithm in clinical practice.Registration: ClinicalTrials.gov Identifier: NCT04463706.

The clinical characteristics of patients with pulmonary hypertension combined with obstructive sleep apnoea

ObjectiveObstructive sleep apnoea (OSA) is one cause of pulmonary hypertension (PH) and can also emerge along with PH. The clinical diagnosis and treatment of OSA in patients with PH are still controversial. The purpose of this clinical observation study was to observe and summarize the incidence and clinical characteristics of OSA in patients with PH and to explore possible predictors of PH combined with OSA.MethodsPatients with PH diagnosed by right heart catheterization who underwent overnight cardiorespiratory monitoring from December 2018 to December 2020 were enrolled. OSA was defined as an apnoea–hypopnoea index of ≥ 5/h with ≥ 50% of apnoeic events being obstructive. Baseline clinical characteristics and parameters were collected to compare PH patients with and without OSA. Logistic regression analysis was run to determine the risk factors for OSA in PH patients.ResultsA total of 35 (25%) of 140 patients had OSA. OSA is relatively frequent in patients with PH, especially in patients with chronic thromboembolic pulmonary hypertension and patients with lung disease– or hypoxia-associated PH. The patients who had OSA were mostly male and had a higher age and a lower daytime arterial oxygen pressure. Logistic regression analysis found that older age, male sex, and lower daytime arterial blood oxygen pressure correlated with OSA in PH patients.ConclusionOSA is common in patients with PH. Lower daytime arterial oxygen pressure is a risk factor for OSA in older male patients with PH.

Assessment of biventricular function in patients with hepatopulmonary syndrome.

Cardiac function impairment in the setting of hepatopulmonary syndrome (HPS) in patients with end stage liver disease remains an issue of debate. The current study evaluated possible correlations between HPS and biventricular systolic function in patients with decompensated cirrhosis. Consecutive liver transplantation candidates with stable decompensated cirrhosis were prospectively evaluated. HPS was defined as the presence of an elevated alveolar-arterial oxygen gradient and intrapulmonary vasodilatation, detected by contrast enhanced echocardiography. HPS severity was determined based on arterial blood oxygen pressure values, while shunt size was assessed with a semi-quantitative method. Demographic, clinical and laboratory parameters were also prospectively collected. In total, 130 patients (mean age 56.5, M/F: 94/36, MELD score 14.6 ± 5.6) were enrolled, of whom 45 (34.6%) fulfilled the criteria for HPS diagnosis (mild: 57.7%, moderate: 33.3%, severe 4.4% and very severe 4.4%). Significantly lower absolute left ventricular (LV) global longitudinal strain (GLS) values (- 21.6 ± 2.3 vs. - 22.6 ± 2.5%, p = 0.041) were measured in patients with HPS compared to cirrhotic patients without HPS, while there was no statistically significant difference regarding right ventricular GLS (- 22.1 ± 3.3 vs. - 23.2 ± 3.5%, p = 0.061) between the two groups. Lower LV ejection fraction values were also recorded in the HPS group (53.9 ± 3.5 vs. 56.3 ± 4.5%, p < 0.01). No other echocardiographic parameter was correlated to HPS. Intrapulmonary shunt grading was correlated to HPS classification (χ2 = 19.8, p < 0.01), with lower arterial oxygen values being recorded in higher stages of intrapulmonary shunt. In patients with cirrhosis, the presence of HPS is associated with worse LV contractile performance.

Machine learning algorithms to predict seizure due to acute tramadol poisoning.

This study was designed to develop and evaluate machine learning algorithms for predicting seizure due to acute tramadol poisoning, identifying high-risk patients and facilitating appropriate clinical decision-making. Several characteristics of acute tramadol poisoning cases were collected in the Emergency Department (ED) (2013-2019). After selecting important variables in random forest method, prediction models were developed using the Support Vector Machine (SVM), Naïve Bayes (NB), Artificial Neural Network (ANN) and K-Nearest Neighbor (K-NN) algorithms. Area Under the Curve (AUC) and other diagnostic criteria were used to assess performance of models. In 909 patients, 544 (59.8%) experienced seizures. The important predictors of seizure were sex, pulse rate, arterial blood oxygen pressure, blood bicarbonate level and pH. SVM (AUC = 0.68), NB (AUC = 0.71) and ANN (AUC = 0.70) models outperformed k-NN model (AUC = 0.58). NB model had a higher sensitivity and negative predictive value and k-NN model had higher specificity and positive predictive values than other models. A perfect prediction model may help improve clinicians' decision-making and clinical care at EDs in hospitals and medical settings. SVM, ANN and NB models had no significant differences in the performance and accuracy; however, validated logistic regression (LR) was the superior model for predicting seizure due to acute tramadol poisoning.

Case report: new development of fibrosing interstitial lung disease triggered by HIV-related pneumocystis pneumonia

BackgroundFibrosing interstitial lung disease is the poor prognostic non-infectious lung disease by unknown etiology. Here, we present one case developing interstitial pneumonia with fibrosis after treatment of pneumocystis pneumonia (PCP) in newly diagnosed HIV-1 infected case.Case presentationA previously healthy 63-year old male was referred to our institute because of protracted dyspnea on effort in 2 weeks after pneumocystis pneumonia treatment. At referral, arterial blood oxygen pressure was within normal range (93.5 mmHg) at rest, but decreased rapidly 30 s after a slow walk (44.5 mmHg). Respiratory function tests showed severe restrictive ventilator impairment (vital capacity = 36.5%; forced expiratory volume in 1 s = 107.4%). Chest computed tomography showed severe fibrotic changes at bilateral basal parts and diffuse fibrotic changes in which PCP lesions were seen initially in previous images although β-D glucan was not elevated and P. jirovecii was not detected in saliva at referral. Other etiologies of fibrotic IP including infectious and/or autoimmune diseases were excluded by serology. Fibrotic lesion did not expand thereafter although it had not responded to the high-dose corticosteroid therapy.ConclusionWe report the first case of fibrosing interstitial lung disease triggered by HIV-related PCP.

Роль кисневого дисбалансу в механізмах порушень процесів ліпідної пероксидації, антиоксидантного захисту та ендотоксикозу за умов експериментального гострого респіраторного дистрес-синдрому та їх корекція

Мета. З’ясувати роль кисневого дисбалансу в механізмах порушень процесів ліпідної пероксидації, антиоксидантного захисту та ендотоксикозу за умов експериментального гострого респіраторного дистрес-синдрому (ГРДС) та встановити ефективність їх корекції корвітином і мексидолом.&#x0D; Матеріали і методи. В експериментах на 58 нелінійних середньостійких до гіпоксії статевозрілих щурах-самцях моделювали ГРДС та досліджували ефективність профілактичного застосування мексидолу, корвітину та їх поєднання.&#x0D; Результати. Через 2 год експерименту виникав виражений кисневий дисбаланс зі зниженням в артеріальній крові напруження кисню (рО2), насичення киснем (SAT) та його вмісту (O2CT). Загинуло 58,3% піддослідних тварин. Ефективність окремого застосування мексидолу була достовірно вища, ніж корвітину. У разі поєднаного застосування мексидолу та корвітину загинуло 8,3% піддослідних тварин.&#x0D; Висновки. Після застосування комбінації мексидолу та корвітину найменшими були порушення рО2 в артеріальній крові, прояви ендотоксикозу та кількість загиблих тварин.

Inhibition of alveolar Na transport and LPS causes hypoxemia and pulmonary arterial vasoconstriction in ventilated rats.

Oxygen diffusion across the alveolar wall is compromised by low alveolar oxygen but also by pulmonary edema, and leads to hypoxemia and hypoxic pulmonary vasoconstriction (HPV). To test, whether inhibition of alveolar fluid reabsorption results in an increased pulmonary arterial pressure and whether this effect enhances HPV, we established a model, where anesthetized rats were ventilated with normoxic (21% O2) and hypoxic (13.5% O2) gas received aerosolized amiloride and lipopolisaccharide (LPS) to inhibit alveolar fluid reabsorption. Right ventricular systolic pressure (RVsP) was measured as an indicator of pulmonary arterial pressure. Oxygen pressure (PaO2) and saturation (SaO2) in femoral arterial blood served as indicator of oxygen diffusion across the alveolar wall. Aerosolized amiloride and bacterial LPS decreased PaO2 and SaO2 and increased RVsP even when animals were ventilated with normoxic gas. Ventilation with hypoxic gas decreased PaO2 by 35 mmHg and increased RVsP by 10 mmHg. However, combining hypoxia with amiloride and LPS did not aggravate the decrease in PaO2 and SaO2 and had no effect on the increase in RVsP relative to hypoxia alone. There was a direct relation between SaO2 and PaO2 and the RVsP under all experimental conditions. Two hours but not 1 h exposure to aerosolized amiloride and LPS in normoxia as well as hypoxia increased the lung wet‐to‐dry‐weight ratio indicating edema formation. Together these findings indicate that inhibition of alveolar reabsorption causes pulmonary edema, impairs oxygen diffusion across the alveolar wall, and leads to an increased pulmonary arterial pressure.

Influence of Ventilation Parameters on Intraabdominal Pressure.

Intraabdominal pressure monitoring is not routinely performed because the procedure assumes some invasiveness and, like other invasive procedures, it needs to have a clear indication to be performed. The causes of IAH are various. Mechanically ventilated patients have numerous parameters set in order to be optimally ventilated and it is important to identify the ones with the biggest interference in abdominal pressure. Although it was stated that mechanical ventilation is a potential factor of high intraabdominal pressure the set parameters which may lead to this diagnostic are not clearly named. To evaluate the relation between intraabdominal pressure and ventilator parameters in patients with mechanical ventilation and to determine the correlation between intraabdominal pressure and body mass index. This is an observational study which enrolled 16 invasive ventilated patients from which we obtained 61 record sheets. The following parameters were recorded twice daily: ventilator parameters, intraabdominal pressure, SpO2, Partial Oxygen pressure of arterial blood. We calculated the Body Mass Index (BMI) for each patient and the volume tidal/body weight ratio for every recorded data point. We observed a significant correlation between intraabdominal pressure (IAP) and the value of PEEP (p=0.0006). A significant statistical correlation was noted regarding the tidal volumes used for patient ventilation. The mean tidal volume was 5.18 ml/kg. Another significant correlation was noted between IAP and tidal volume per kilogram (p=0.0022). A positive correlation was found between BMI and IAP (p=0.0049), and another one related to the age of the enrolled patients. (p=0.0045). The use of positive end-expiratory pressures and high tidal volumes during mechanical ventilation may lead to the elevation of intraabdominal pressure, a possible way of reducing this risk would be using low values of PEEP and also low volumes for the setting of ventilation parameters. There is a close positive correlation between the intraabdominal pressure levels and body mass index.

Nueva metodología para la evaluación de la presión de oxígeno en sangre arterial desarrollada en el contexto de la teoría de los sistemas dinámicos

BackgroundThe application of fractal geometry and the theory of dynamic systems have enabled the cardiac dynamics to be objectively and reproducibly characterised from the construction of chaotic attractors. ObjectiveTo develop a new methodology for evaluating the pressure of oxygen pressure based on dynamic systems in arterial blood of patients in intensive care units. MethodsArterial blood gases were analysed in 10 selected patients, and taking the values of the arterial oxygen pressure recorded in their medical charts during the days in post-surgical intensive care unit, chaotic attractors were constructed using the delay map. The minimum and maximum values of the attractor on the delay map were then determined. ResultsThe maximum and minimum values of the attractors of pressure of oxygen in arterial blood ranged between 24.30 and 191.30mmHg. ConclusionsThe geometry of the attractor of oxygen pressure in arterial blood demonstrates chaotic behaviour, which can be more easily be analysed from the theory of dynamical systems, making it useful for the assessment of intensive care unit patients.

Adrenaline aggravates lung injury caused by liver ischemia-reperfusion and high-tidal-volume ventilation in rats.

BackgroundWe often administer adrenaline to improve hypotension of patients undergoing systemic inflammation that is not treated with volume resuscitation. The effects of adrenaline on injured lungs during shock status have not been elucidated. We previously demonstrated that hepatic ischemia–reperfusion followed by high-tidal-volume ventilation-induced systemic inflammation, hypotension, and lung injury in rats. Using this animal model, we investigated the effects of adrenaline on lung injury and hemodynamics.MethodsAnesthetized rats were ventilated and underwent hepatic inflow interruption for 15 min twice. After the second liver ischemia–reperfusion, the tidal volume was increased to 24 ml · kg−1 body weight from 6 ml · kg−1, and 12 rats in each group were observed for 360 min after reperfusion with or without continuous intravenous adrenaline administration. Extra fluid was administered according to the decline in the arterial blood pressure.ResultsAdrenaline administration significantly reduced the volume of intravenous resuscitation fluid. The wet-to-dry weight ratio of the lungs was higher (7.53 ± 0.37 vs. 4.63 ± 0.35, P < 0.001), the partial oxygen pressure in arterial blood was lower (213 ± 48 vs. 411 ± 33, P = 0.004), and the tumor necrosis factor-α concentration in bronchoalveolar lavage (BAL) fluid was higher (102.64 ± 100.22 vs. 101.91 ± 100.27, P = 0.015), with adrenaline. Histopathological examinations revealed marked exudation in the alveolar spaces in rats receiving adrenaline.ConclusionsContinuous administration of adrenaline partially prevented a rapid decline in blood pressure but deteriorated lung injury in a rat model of liver ischemia–reperfusion with high-tidal-volume ventilation. A possibility that adrenaline administration aggravate ventilator-induced lung injury during systemic inflammation should be considered.

MDCT in ARDS: A single center experience

Acute respiratory distress syndrome (ARDS) is a clinical condition first described by Ashbaugh et al in 1967 using the term ?adult respiratory distress syndrome?1. In order to establish a diagnosis of ARDS, radiological findings are necessary and they serve as one of the postulates. According to the latest definition, which was created by a panel of experts in 2011 in Berlin, thus termed the Berlin definition of ARDS, ARDS2 is a condition starting within 1 week of clinical insult with bilateral infiltrates detectable by chest imaging (either conventional radiography or multidetector computed tomography (MDCT) scan of lungs) and severe hypoxemia in the absence of evidence for cardiogenic pulmonary edema or fluid overload. It is necessary to explain the origin of edema, and to do that we need objective assessment (e.g., echocardiography) in order to exclude cardiogenic factors. Severity of ARDS is based on ratio between partial oxygen pressure in arterial blood and fraction of oxygen in the inspired air (PaO2 /FIO2) on 5 cm of continuous positive airway pressure (CPAP). The 3 categories are mild (PaO2/FIO2 200-300), moderate (PaO2/FIO2 100-200) and severe (PaO2/FIO2 =100). The definition itself says that in order to make a diagnosis we must do radiology imaging, although it does not say which one should be performed, the conventional radiography or MDCT. ARDS represents a stereotypic response to many different inciting insults and goes through a number of different phases, from alveolar capillary damage to lung resolution or a fibro-proliferative and fibrotic phase. The pulmonary epithelial and endothelial cellular damage is characterized by inflammation, apoptosis, necrosis and increased alveolar capillary permeability, which lead to development of alveolar edema. Purpose and role of radiographic methods is to assist in the visualization of above mentioned pathomorphological substrate. Because of the fact that sensitivity of conventional radiography is significantly lower than that of MDCT imaging, MDCT could be the primary method of choice in the initial diagnosis, but for the patient with ARDS it is most important that he has the best conditions concerning mechanical ventilation, which is very complicated to provide during the transportation of the patient from intensive care unit to MDCT diagnostic unit. As the disease evolves inside the lung area, some of the complications can be visualized only with MDCT. That is one of the main reasons MDCT is used for that period of disease evolution. Because of everything that is mentioned above, it is hard to decide whether and when MDCT scan should be performed.

1,25-Dihydroxycholecalciferol with low-calcium diet reduces acute rejection in rat lung allotransplantation

The effect of 1,25-dihydroxycholecalciferol (calcitriol, vitamin D3) with a low-calcium diet on the acute lung allograft rejection in a rat unilateral left lung transplantation model was evaluated. Three transplantation groups were studied (n = 5, male Brown-Norway to Fischer F344, 235 ± 15 g body weight): calcitriol and low-calcium diet, low-calcium diet and normal diet. Calcitriol (4 μg/kg/day) was injected intraperitoneally for 5 days, starting from the day of transplantation. In addition, two non-transplantation groups were compared: (n = 3, Brown-Norway) to measure the level of cytokines, and Fischer F344 receiving calcitriol and a low-calcium diet to measure the serum calcium level. The recipients of transplantation were killed on Day 5 post-transplant. The contralateral right main bronchus and the pulmonary artery were occluded for 5 min and blood was drawn for the blood gas analysis, and the grafts were assessed for histology (International Society for Heart and Lung Transplantation 1996/rank scale). Lung levels of interleukin (IL)-2, IL-6, IL-12 and tumour necrosis factor-α (TNF-α) were assessed within the calcitriol and low-calcium diet, low-calcium diet and Brown-Norway groups. The serum calcium level was assessed in the Fischer F344 group. An analysis of variance with Tukey's post hoc test was used to compare the arterial blood oxygen pressure and the lung cytokine expression between groups. A non-parametric Kruskal-Wallis test followed by the Siegel and Castellan post hoc test was used to assess the differences between the groups according to the lung graft rejection grading. Student's paired t-test was used to compare the serum calcium level. The arterial PaO(2) was significantly higher in the calcitriol and the low-calcium diet groups when compared with low-calcium diet or normal diet groups (356 ± 72 mmHg; P < 0.05 vs other groups). The arterial and bronchial rejection observed in calcitriol and low-calcium diet group was significantly milder than in the low-calcium diet or normal diet groups (A1-2, B1-2; P < 0.05 vs other groups). IL-2 and IL-6 levels were significantly higher in low-calcium diet vs calcitriol and low-calcium diet and Brown-Norway groups. IL-12 and TNF-α did not differ among the groups. There was no significant difference in serum calcium level before and after the treatment in the Fischer F344 group. Calcitriol with a low-calcium diet treatment improves lung function, reduces lung allograft acute rejection, decreases IL-2 and IL-6 allograft expression and does not change the serum calcium level significantly.

Effects of mild hypothermia on low cardiac output after cardiac surgery

To evaluate the effectiveness of mild hypothermia on low cardiac output in patients after cardiac surgery. Twelve patients manifesting low cardiac output after cardiac surgery despite of the use of massive doses of catecholamine and intra-aortic balloon pump (IABP) underwent mild hypothermia during May 2009 to February 2011. Changes in hemodynamic parameters of the patients were measured, including cardiac index (CI),mixed venous oxygen saturation [SvO(2)] and urine volume. In the process of mild hypothermia treatment, bladder temperature of patients was lowered to 33-35 centigrade in order to reduce the body oxygen demand. The CI [ml·s(-1)·m(-2)]of patients after mild hypothermia treatment was increased obviously (38.34 ± 5.00 vs. 30.01 ± 5.00), the same as SvO(2) (0.64 ± 0.07 vs. 0.54 ± 0.08) and urine output [ml·kg(-1)·h(-1): 3.0 ± 2.1 vs. 1.5 ± 1.1, all P < 0.05]. However, there was no significant change in heart rate, mean arterial pressure and blood oxygen pressure. Mild hypothermia is an effective and simple procedure to improve the cardiac function in patients after cardiac surgery complicated with low cardiac output.

An oral fluoropyrimidine agent S-1 induced interstitial lung disease: A case report

A 66-year-old Japanese man with pancreatic cancer received eleven courses of gemcitabine monotherapy. The tumor responded to gemcitabine until metastatic liver tumors progressed. Subsequently, he was treated with S-1, an oral fluoropyrimidine anticancer agent, as salvage chemotherapy. Forty-two days after initiating S-1, he presented with dyspnea and fever. Chest computed tomography showed diffuse interstitial lesions with thickening of the alveolar septa and ground glass opacity. Serum KL-6 level was elevated to 1,230 U/mL and he did not use any other drugs except insulin. Thus, the development of interstitial lung disease (ILD) was considered to be due to S-1. Arterial blood oxygen pressure was 49.6 Torr in spite of oxygen administration (5 L/min). Steroid therapy improved his symptoms and the interstitial shadows on chest radiograph. Although S-1-induced ILD has mostly been reported to be mild, clinicians should be aware that S-1 has the potential to cause fatal ILD.

Variation analysis of early gene expression profiles of lung in rats with endotoxic shock

Objective To observe the difference of gene expression profiles of lung in rats before and after endotoxic shock （ES）. Methods A total of 20 male Wistar rats were randomly divided into control group and lipopolysaceharide （LPS） group （ 10 rats per group）. The LPS rat model was made by injecting LPS into tail vein. Six hours after ES, partial pressure of oxygen in the arterial blood （ PaO2 ）was measured. Gene expression profiles of the lung in each group were detected by rats oligo gene chip Affymetrix RAT 230A. The expression level of five genes was verified via semi-quantitative RT-PCR. The data were analyzed in combination with type of differential gene and character of ES. Results Compared with control group, PaO2 in LPS group was decreased more significantly （P 〈0.05）. Among 15 650 probes detected, 158 genes showed differential expression in ES group in comparison with control group. The expression level of 117 genes was up-regulated while that of 34 genes down-regulated significantly. According to their biological function, differentially expressed genes were classified as inflammation genes, material transporter genes, transcription regulator genes, signal transduction genes, stress response genes, metabolic genes, apoptosis genes and cell adhesion genes. The results of Semi-quantitative RT-PCR of five genes were consistent with those of the microarray examination. Conclusion The expression of many genes of the lung may change in ES rats, especially the inflammatory genes. Key words: Lung ; Endotoxin ; DNA chip ; Gene expression

Changes in arterial PO2, physiological blood parameters and intracellular antioxidants in free-swimming Atlantic cod (Gadus morhua) exposed to varying levels of hyperoxia

Free-swimming Atlantic cod (Gadus morhua) were exposed to water oxygen pressures (P(w)O₂) ranging from 18.1 to 41.5 kPa and sampled for blood using an indwelling caudal artery cannula. Arterial blood oxygen pressure (P(a)O₂) increased with increasing P(w)O₂, from 12.0 kPa in normoxia (18.1 kPa) to 34.2 kPa in the highest hyperoxic level tested (41.5 kPa). Blood CO₂ pressure and plasma bicarbonate concentration increased with P(w)O₂, indicating reduced ventilation with increased P(w)O₂. Plasma glucose, sodium and potassium were not affected by water oxygen level. Blood oxidative stress biomarkers, reduced glutathione, oxidized glutathione and the oxidative stress index (ratio between oxidized and total glutathione) differed intermittently between normoxia and hyperoxia. The oxidative stress index was higher in the blood of exposed compared to unexposed control cod. Together with elevated P(a)O₂, these findings suggest increased production of reactive oxygen species and increased oxidative stress in Atlantic cod exposed to hyperoxia.

Involvement of thromboxane A2 (TXA2) in the early stages of oleic acid-induced lung injury and the preventive effect of ozagrel, a TXA2 synthase inhibitor, in guinea-pigs.

An intravenous injection of oleic acid into animals can produce a lung injury with hypoxaemia and pulmonary vascular hyper-permeability. Although oleic acid lung injury is used as a model of acute respiratory distress syndrome (ARDS), the precise mechanisms of the lung injury are still unclear. We have investigated whether thromboxane A(2) (TXA(2)) participated in the lung injury and have evaluated the efficacy of ozagrel, a TXA(2) synthase inhibitor, on the lung injury in guinea-pigs. Oleic acid injection increased the plasma level of TXB(2), a stable metabolite of TXA(2), and the time-course of plasma TXB(2) was similar to that of the decreased partial oxygen pressure of arterial blood (Pao(2)) induced with oleic acid. Ozagrel administered intravenously 30 min before oleic acid injection prevented the decrease in Pao(2) and pulmonary vascular hyper-permeability. It also prevented increases in lactate dehydrogenase activity, a measure of lung cell injury, TXB(2 )and its weight ratio to 6-keto prostaglandin F(1alpha) in bronchoalveolar lavage fluid. Although ozagrel administered simultaneously with oleic acid ameliorated the decrease in Pao(2), post treatment showed little effect. We suggest that TXA(2) participated in the oleic acid lung injury, as an "early phase" mediator, and rapidly-acting TXA(2) synthase inhibitors were effective in the prevention of acute lung injury.

Protection afforded by a herbal medicine, Sho-seiryu-to (TJ-19), against oleic acid-induced acute lung injury in guinea-pigs

Abstract Objectives The effect of a herbal medicine, Sho-seiryu-to (TJ-19), on oleic acid-induced lung injury, an animal model of acute respiratory distress syndrome or acute lung injury (ARDS/ALI), was examined. Methods Acute lung injury was induced by an intravenous injection of 15 μl/kg oleic acid to guinea-pigs. TJ-19 was administered by a single oral dose (3 g/kg) or by multiple oral doses (0.75 g/kg). Key findings The decrease in partial oxygen pressure of arterial blood (Pao2) and the increase in airway vascular permeability induced by the oleic acid injection were attenuated by a single dose of TJ-19. When TJ-19 was administered orally twice a day for two weeks and then oleic acid was injected, a potent prophylactic effect of the drug was observed. TJ-19 also prevented airway vascular hyperpermeability, lung cell injury, oxidative stress and thromboxane A2 generation, associated with the oleic acid injection. Conclusions TJ-19 significantly attenuated the oleic acid-induced lung injury probably through the antioxidative effect and inhibitory effect of thromboxane A2 generation, although the precise inhibitory mechanisms were not fully elucidated due to the diversity in constituents of the herbal medicine. We suggest that TJ-19 is a promising drug candidate and a medicinal resource for preventing ARDS/ALI.