PO2 Values Research Articles

A-349 Evaluation of i-STAT® Point of Care Blood Gas Cartridges and Competitor Blood Gas Devices Against Reference Standard for PCO2 and PO2

Abstract Background The i-STAT System provides laboratory quality results in minutes at the patient’s bedside. Accurate and rapid test results are critical for clinical decision making in the presence of blood gas disorders, including oxygenation and acid-base status, where the partial pressure oxygen (PO2) and partial pressure carbon dioxide (PCO2) are needed. The purpose of this study was to compare the analytical performance of the PO2 and PCO2 tests in the i-STAT G3+ and i-STAT CG8+ cartridges to the theoretical PO2 and PCO2 in prepared reference standards. Two other blood gas instruments, a benchtop device and a laboratory device were also compared to the reference PO2 and PCO2. Methods Venous whole blood samples were contrived using saturation tonometry with U.S. NIST (National Institute of Science and Technology) traceable gas tanks to prepare the reference standards, which were value assigned to theoretical PO2 or PCO2 levels based on the molar composition of the gas mixture used. Eleven levels spanning the reportable range of each PO2 (5 mmHg - 800 mmHg) and PCO2 (5 mmHg - 130 mmHg) were prepared and tested in duplicate on the i-STAT G3+ and i-STAT CG8+ cartridges, benchtop device, and the laboratory device. Passing-Bablok linear regression analysis was performed to evaluate the slope and correlation coefficient, comparing each blood gas device against the reference PO2 and PCO2 values. Study designs followed CLSI (Clinical and Laboratory Standards Institute) EP09C-ED3:2018, Measurement Procedure Comparison and Bias Estimation using Patient Samples, 3rd Edition. Passing-Bablok regression analysis was also performed for the i-STAT cartridges and benchtop device against the laboratory device. Results The regression analysis was performed against the reference standards. For PO2, slopes for the i-STAT cartridges ranged from 0.93 - 0.97, the slope for the benchtop device was 0.99, and the slope for the laboratory device was 0.97. Correlation coefficients for all devices were 1.00. For PCO2, slopes for the i-STAT cartridges ranged from 0.98 - 1.02, the slope for the benchtop device was 0.85, and the slope for the laboratory device was 1.01. Correlation coefficients were 1.00 for the i-STAT cartridges and laboratory device, and 0.99 for the benchtop device. The regression analysis was also performed against the laboratory device. For PO2, slopes for the i-STAT cartridges ranged from 0.96 - 1.00, and the slope for the benchtop device was 1.02. Correlation coefficients for all devices were 1.00. For PCO2, slopes for the i-STAT cartridges ranged from 0.97 - 1.01, and the slope for the benchtop device was 0.85. Correlation coefficients were 1.00 for the i-STAT cartridges and 0.99 for the benchtop device. Conclusions The study demonstrated that the i-STAT G3+ and i-STAT CG8+ cartridges used with the i-STAT System were shown to provide laboratory quality results within 2 minutes, showing good agreement to both reference standards and laboratory quality devices. For PCO2, the i-STAT System was shown to have better agreement to both theoretical reference standards and the laboratory device than the benchtop device. These studies were funded by Abbott Laboratories.

Characteristics of deep soil layer water deficit under different artificial vegetation types of the Loess Plateau, China

AbstractSoil water is a crucial factor for the growth of vegetation and sustainable development in water‐limited areas. After large‐scale vegetation restoration on the Chinese Loess Plateau, understanding the relationship between vegetation and deep soil moisture has become a crucial focus in current research. In this study, artificial forest (Pinus tabulaeformis [PT], Robinia pseudoacacia [RP] and Platycladus orientalis [PO]), apple orchard (AO), secondary forest (SF) and farmland (FL) were selected as the research objects, and grassland (GL) as the control, using soil‐drilling techniques. We systematically monitored the soil water content of 0–10 m soil layer over two hydrological years, and explored the effects of different vegetation types on soil water deficiency. The results showed that: (1) The deep soil water various significantly among different vegetation types. Compared with GL, the soil water content in all forest land was generally lower, and this difference became more pronounced in deeper soil layer (>7 m), which indicating the depth of the influence of vegetation on soil water has reached 10 m. (2) The mean soil water deficit size (SWDS) values of PT (0.14), RP (0.17), PO (0.07), AO (0.15), SF (0.10) and FL (0.27) in 0–1 m were all positive, indicating that surface soil water had accumulated during more than half of the sampling periods. In the 2–10 m soil layer, mean SWDS was negative in all vegetation types except in FL, leading to soil desiccation. SWDS was found to fluctuate with soil depth. (3) SWDS was affected by a combination of soil properties and vegetation growth. Our results indicate that the current afforestation model could lead to the deficiency of deep soil water. Therefore, it is imperative to make reasonable vegetation structure according to the available local soil and water resources in future vegetation allocation and management.

Changes in blood gas in supine and prone positions in percutaneous stone surgery: does position have any advantage for hemodynamics?

To evaluate whether different positions are advantageous for hemodynamics and respiratory balance in patients undergoing percutaneous nephrolithotomy (PCNL) procedures. Pre- and postoperative arterial blood gas data obtained during spontaneous breathing for 67 prone (Group 1) and 56 supine (Group 2) patients undergoing PCNL were analyzed. Additionally data on all patients' gender, age, body mass index, stone size, access and surgical duration, volume of irrigation fluid, length of hospital stay, requirement for blood transfusion, and residual stones were recorded: There were no differences between the groups in terms of age, stone size, operation time, access time, radiation exposure, transfusion requirements, stone-free rate, and length of hospitalization. A statistically significant pH decrease was observed in both groups in the postoperative period (p = 0.001 and p = 0.001, respectively). There was a statistically significant increase in pCO2 values in both groups in the postoperative period (p = 0.001 and p = 0.024, respectively), and that increase did not differ significantly between the groups (p = 0.624). A statistically significant decrease in pO2 and SpO2 values was observed in both groups in the postoperative period compared to the preoperative period. Again, no statistical difference was observed between the groups for these values. There was a statistically significant decrease in bicarbonate in both groups period (p < 0.001 and p = 0.001, respectively). Hemodynamics and the respiratory balance of the patient are impaired in both prone and supine positions. Neither position is superior to the other in this respect.

The use of venous blood gas in assessing arterial acid−base and oxygenation status – an analysis of aggregated data from multiple studies evaluating the venous to arterial conversion (v-TAC) method

ABSTRACT Background Several methods exist to reduce the number of arterial blood gases (ABGs). One method, Roche v-TAC, has been evaluated in different patient groups. This paper aggregates data from these studies, in different patient categories using common analysis criteria. Research design and methods We included studies evaluating v-TAC based on paired arterial and peripheral venous blood samples. Bland-Altman analysis compared measured and calculated arterial values of pH, PCO2, and PO2. Subgroup analyses were performed for normal, chronic hypercapnia and chronic base excess, acute hyper- and hypocapnia, and acute and chronic base deficits. Results 811 samples from 12 studies were included. Bias and limits of agreement for measured and calculated values: pH 0.001 (−0.029 to 0.031), PCO2 −0.08 (−0.65 to 0.49) kPa, and PO2 0.04 (−1.71 to 1.78) kPa, with similar values for all sub-group analyses. Conclusion These data suggest that v-TAC analysis may have a role in replacing ABGs, avoiding arterial puncture. Substantial data exist in patients with chronic hypercapnia and chronic base excess, acute hyper- and hypocapnia, and in patients with relatively normal acid−base status, with similar bias and precision across groups and across study data. Limited data exist for patients with acute and chronic base deficits.

Evaluation of agreement between a noninvasive method for real-time measurement of critical blood values with a standard point-of-care device.

The purpose of this work was to investigate the degree of agreement between two distinct approaches for measuring a set of blood values and to compare comfort levels reported by participants when utilizing these two disparate measurement methods. Radial arterial blood was collected for the comparator analysis using the Abbott i-STAT® POCT device. In contrast, the non-invasive proprietary DBC methodology is used to calculate sodium, potassium, chloride, ionized calcium, total carbon dioxide, pH, bicarbonate, and oxygen saturation using four input parameters (temperature, hemoglobin, pO2, and pCO2). Agreement between the measurement for a set of blood values obtained using i-STAT and DBC methodology was compared using intraclass correlation coefficients, Passing and Bablok regression analyses, and Bland Altman plots. A p-value of <0.05 was considered statistically significant. A total of 37 participants were included in this study. The mean age of the participants was 42.4 ± 13 years, most were male (65%), predominantly Caucasian/White (75%), and of Hispanic ethnicity (40%). The Intraclass Correlation Coefficients (ICC) analyses indicated agreement levels ranging from poor to moderate between i-STAT and the DBC's algorithm for Hb, pCO2, HCO3, TCO2, and Na, and weak agreement for pO2, HSO2, pH, K, Ca, and Cl. The Passing and Bablok regression analyses demonstrated that values for Hb, pO2, pCO2, TCO2, Cl, and Na obtained from the i-STAT did not differ significantly from that of the DBC's algorithm suggesting good agreement. The values for Hb, K, and Na measured by the DBC algorithm were slightly higher than those obtained by the i-STAT, indicating some systematic differences between these two methods on Bland Altman Plots. The non-invasive DBC methodology was found to be reliable and robust for most of the measured blood values compared to invasive POCT i-STAT device in healthy participants. These findings need further validation in larger samples and among individuals afflicted with various medical conditions.

Positronium lifetime measurement using a clinical PET system for tumor hypoxia identification

Positronium (Ps) imaging has been recently spotlighted for its potential applications in nuclear medicine. Among them, we expect that the Ps lifetime can be a sensor for tumor hypoxia; hence, we are aiming to achieve Ps lifetime imaging, Quantum PET (Q-PET), based on whole gamma imaging (WGI). A linear correlation was previously shown between the Ps lifetime and the oxygen partial pressure (pO2) in water by using a bench-top detector system. However, nobody has ever measured the Ps lifetimes for pO2 values of 10 mmHg and 40 mmHg, corresponding to hypoxic cancer cells and healthy tissue cells, respectively. Therefore, this study aimed at measuring the Ps lifetime of 22Na solutions each having such tiny differences in the pO2 value. For possible extension toward imaging, we used VRAIN, a clinical brain-dedicated time-of-flight (TOF) PET system. The pO2 values of the 22Na solutions were adjusted to 0, 10, 40, and 160 (air) mmHg by adjusting the inflow of nitrogen gas. Each 22Na solution was placed near the center of the detector geometry and measured. Three different energy windows (EWs) for 1275 keV gamma detection were compared (1100–1500 keV, 900–1500 keV and 700–1500 keV). Due to the increased number of events, the error values (σ: standard deviation) of the calculated Ps lifetimes decreased as the EW widened. The optimized EW was determined to be 700–1500 keV, which showed the lowest error value. The Ps lifetime values gradually became shorter as the pO2 values increased. The Ps lifetime values at 0 mmHg and 160 mmHg were 1.9389 ± 0.0025 ns and 1.9104 ± 0.0024 ns at the EW of 700–1500 keV. The difference between the lifetime values was more than three times the errors (±3σ), and we considered it was a statistically significant difference. The Ps lifetime values of 10 mmHg and 40 mmHg were 1.9360 ± 0.0026 ns and 1.9291 ± 0.0024 ns at the same condition, and the difference could be distinguished with an error value of more than ± 1σ.

Intracellular Oxygen Transient Quantification in Vivo During Ultra-High Dose Rate FLASH Radiation Therapy

Large, rapid extracellular oxygen transients (ΔpO2) have been measured in vivo during ultra-high dose rate radiation therapy; however, it has been unclear if they match intracellular oxygen levels. Here, the endogenously produced protoporphyrin IX (PpIX) delayed fluorescence signal was measured as an intracellular in-vivo oxygen sensor to quantify these transients, with direct comparison to extracellular pO2. Intracellular ΔpO2 is closer to the cellular DNA, the site of major radiobiological damage, and therefore should help elucidate radiochemical mechanisms of the FLASH effect and potentially be translated to human tissue measurement. PpIX was induced in mouse skin through intraperitoneal injection of 250 mg/kg of aminolevulinic acid. The animals were also administered a 50 µL intradermal injection of 10 µM oxyphor G4 (PdG4) for phosphorescence lifetime pO2 measurement. Paired oxygen transients were quantified in leg or flank tissues while delivering 10 MeV electrons in 3 µs pulses at 360 Hz for a total dose of 10 to 28 Gy. Transient reductions in pO2 were quantifiable in both PpIX delayed fluorescence and oxyphor phosphorescence, corresponding to intracellular and extracellular pO2 values, respectively. Reponses were quantified for 10, 22, and 28 Gy doses, with ΔpO2 found to be proportional to the dose on average. The ΔpO2 values were dependent on initial pO2 in a logistic function. The average and standard deviations in ΔpO2 per dose were 0.56 ± 0.18 mm Hg/Gy and 0.43 ± 0.06 mm Hg/Gy for PpIX and oxyphor, respectively, for initial pO2 > 20 mm Hg. Although there was large variability in the individual animal measurements of ΔpO2, the average values demonstrated a direct and proportional correlation between intracellular and extracellular pO2 changes, following a linear 1:1 relationship. A fundamentally new approach to measuring intracellular oxygen depletion in living tissue showed that ΔpO2 transients seen during ultra-high dose rate radiation therapy matched those quantified using extracellular oxygen measurement. This approach could be translated to humans to quantify intracellular ΔpO2. The measurement of these transients could potentially allow the estimation of intracellular reactive oxygen species production.

Characteristics of PB 260 clone rubber coagulated with natural coagulants: type of Averrhoa

The aim of this research was to determine the properties of the PB 260 clone rubber using the Averrhoa type coagulant. The natural coagulants used in this study were Averrhoa bilimbi and Averrhoa carambola. The latex used was 150 ml of PB 260 clone rubber with a concentration of 100% natural coagulant of 75 ml and 2% formic acid. The rubber properties that were tested were Po, PRI, DRC, ash content, dirt content, volatile matter content and Mooney viscosity. This research also uses a special treatment in the form of centrifugation speed. The higher the centrifugation speed, the higher the pH value of the natural coagulant and the lower the H+ ion value, which accelerates the coagulation time of the latex. In natural coagulant extract, the highest values of Po, PRI, DRC, ash content, dirt content and Mooney viscosity were obtained at 0 rpm for Averrhoa bilimbi extract with values of 40%, 94.17%, 32.83%, 0, 32%, 0.038% and 77 MU. Meanwhile, in the test for volatile matter content, the highest value was found in Averrhoa carambola at 5000 rpm with a value of 0.23%.

Increased Retinal Metabolism Induced by Flicker in the Isolated Mouse Retina.

Both the retina and brain exhibit neurovascular coupling, increased blood flow during increased neural activity. In the retina increased blood flow can be evoked by flickering light, but the magnitude of the metabolic change that underlies this is not known. Local changes in oxygen consumption (QO2) are difficult to measure in vivo when both supply and demand are changing. Here we isolated the C57BL/6J mouse retina and supplied it with oxygen from both sides of the tissue. Microelectrode recordings of PO2 were made in darkness and during 20 s of high scotopic flickering light at 1 Hz. Flicker led to a PO2 increase in the outer retina and a decrease in the inner retina, indicating that outer retinal QO2 (QOR) decreased and inner retinal QO2 (QIR) increased. A four-layer oxygen diffusion model was fitted to PO2 values obtained in darkness and at the end of flicker to determine the values of QOR and QIR. QOR in flicker was 76 ± 14% (mean and SD, n = 10) of QOR in darkness. The increase in QIR was smaller, 6.4 ± 5.0%. These metabolic changes are likely smaller than the maximum changes, because with no regeneration of pigment in the isolated retina, we limited the illumination. Further modeling indicated that at high illumination, QIR could increase by up to 45%, which is comparable to the magnitude of flow changes. This suggests that the blood flow increase is at least roughly matched to the increased metabolic demands of activity in the retina.

Physiologic Effects of Extracorporeal Membrane Oxygenation in Patients with Severe Acute Respiratory Distress Syndrome.

Rationale: Blood flow rate affects mixed venous oxygenation (SvO2) during venovenous extracorporeal membrane oxygenation (ECMO), with possible effects on the pulmonary circulation and the right heart function. Objectives: To describe the physiologic effects of different levels of SvO2 obtained by changing ECMO blood flow in patients with severe acute respiratory distress syndrome receiving ECMO and controlled mechanical ventilation. Methods: Low (SvO2 target, 70-75%), intermediate (SvO2 target, 75-80%), and high (SvO2 target, >80%) ECMO blood flows were applied for 30 minutes in random order in 20 patients. Mechanical ventilation settings were left unchanged. The hemodynamic and pulmonary effects were assessed with pulmonary artery catheter and electrical impedance tomography. Measurements and Main Results: Cardiac output decreased from low to intermediate and to high blood flow/SvO2 (9.2 [6.2-10.9] vs. 8.3 [5.9-9.8] vs. 7.9 [6.5-9.1] L/min; P = 0.014), as well as mean pulmonary artery pressure (34 ± 6 vs. 31 ± 6 vs. 30 ± 5 mm Hg; P < 0.001) and right ventricular stroke work index (14.2 ± 4.4 vs. 12.2 ± 3.6 vs. 11.4 ± 3.2 g × m/beat/m2; P = 0.002). Cardiac output was inversely correlated with mixed venous and arterial Po2 values (R2 = 0.257; P = 0.031; and R2 = 0.324; P = 0.05). Pulmonary artery pressure was correlated with decreasing mixed venous Po2 (R2 = 0.29; P < 0.001) and with increasing cardiac output (R2 = 0.378; P < 0.007). Measures of [Formula: see text]/[Formula: see text] mismatch did not differ between the three steps. Conclusions: In patients with severe acute respiratory distress syndrome, increased ECMO blood flow rate resulting in higher SvO2 decreases pulmonary artery pressure, cardiac output, and right heart workload.

Venous blood gases and electrolyte values of captive red foot tortoise (Chelonoidis carbonarius).

Blood gas analysis reflects the exchange of oxygen and carbon dioxide in the lungs. This test provides important information, since the relationship between these gases has a direct impact on the acid-basic balance in the body. Given the significance of blood gas analysis in Brazilian reptiles, this study set out to establish temperature-corrected and uncorrected reference intervals for venous blood gas measurements in Chelonoidis carbonarius, and to compare values between females and males. In this study, 19 animals were used, 8 males and 11 females. Blood samples were collected from the dorsal coccygeal vein, and the analyses were performed immediately after blood sample collection. The following parameters were measured: pH, PO2, HCO3-, TCO2, BEecf, Na, K, ICa, and Glu, and were compared between females and males. Additionally, pH, pCO2, and pO2 values were compared with and without temperature correction. Oxygen saturation and Na levels were significantly higher (p<0.05) in males. Furthermore, it was possible to infer that the lower the body temperature relative to the environmental temperature, the larger the difference in pH following temperature correction.

Cross-Validation of the Remarkably High Surface Oxygen Exchange Kinetics of PrBa0.5Sr0.5Co1.5Fe0.5O5+δ: A Combined Thin-Film Mass Relaxation and Bulk Electrical Conductivity Relaxation Study.

In this work, we measure the oxygen kinetic properties of double perovskite PrBa0.5Sr0.5Co1.5Fe0.5O5+δ (PBSCF), a material widely used as the air electrode in solid oxide electrochemical cells, by mass relaxation (MR) and electrical conductivity relaxation (ECR) experiments. MR studies are carried out using thin films deposited on a gallium phosphate piezocrystal microbalance, and ECR studies are performed using a bulk bar sample with 97% theoretical density. Measurements are performed at 600 °C over the temperature oxygen partial pressure range from 10-4 to 0.21 atm. Despite the differences in experimental formats and surface microstructural features, the ks values extracted from the two methods are found to be in good agreement with one another. The rate constant is found to increase with oxygen partial pressure with a power law dependence, rising from 1.0 × 10-6 cm/s at 3.2 × 10-4 atm to 1.2 × 10-4 cm/s at 0.24 atm, as averaged over the oxidation and reduction directions. The rates in the oxidation direction are observed to be slightly higher than those in the reduction direction for a given pair of pO2 values, suggesting that the final pO2 value controls the overall relaxation behavior. The power law exponent describing the dependence of ks on pO2 is found to be 0.74 ± 0.01. The ECR study of the bulk sample reveals that even with a diffusion length of 1.8 mm, the relaxation process is largely free of diffusion limitations, indicating that PBSCF has the high bulk transport properties required for a double-phase boundary oxidation/reduction pathway.

Assessment of blood-brain barrier leakage and brain oxygenation in Connexin-32 knockout mice with systemic neuroinflammation using pulse electron paramagnetic resonance imaging techniques.

The determination of blood-brain barrier (BBB) integrity and partial pressure of oxygen (pO2) in the brain is of substantial interest in several neurological applications. This study aimed to assess the feasibility of using trityl OX071-based pulse electron paramagnetic resonance imaging (pEPRI) to provide a quantitative estimate of BBB integrity and pO2 maps in mouse brains as a function of neuroinflammatory disease progression. Five Connexin-32 (Cx32)-knockout (KO) mice were injected with lipopolysaccharide to induce neuroinflammation for imaging. Three wild-type mice were also used to optimize the imaging procedure and as control animals. An additional seven Cx32-KO mice were used to establish the BBB leakage of trityl using the colorimetric assay. All pEPRI experiments were performed using a preclinical instrument, JIVA-25 (25 mT/720 MHz), at times t = 0, 4, and 6 h following lipopolysaccharide injection. Two pEPRI imaging techniques were used: (a) single-point imaging for obtaining spatial maps to outline the brain and calculate BBB leakage using the signal amplitude, and (b) inversion-recovery electron spin echo for obtaining pO2 maps. A statistically significant change in BBB leakage was found using pEPRI with the progression of inflammation in Cx32 KO animals. However, the change in pO2 values with the progression of inflammation for these animals was not statistically significant. For the first time, we show the ability of pEPRI to provide pO2 maps in mouse brains noninvasively, along with a quantitative assessment of BBB leakage. We expect this study to open new queries from the field to explore the pathology of many neurological diseases and provide a path to new treatments.

Enrofloxacin pharmacokinetics in yellow catfish (Pelteobagrus fulvidraco): A comparative analysis of oral, intramuscular, and bath administration.

Enrofloxacin (ENR) residues in yellow catfish (Pelteobagrus fulvidraco) often exceed the standard due to excessive use. This study explored the pharmacokinetics of ENR and its metabolite ciprofloxacin (CIP) in yellow catfish following a single dose of 10 mg/kg body weight via intramuscular injection (IM), oral gavage (PO), or a 5-h drug bath at 10 mg/L and 25°C. High-performance liquid chromatography-mass spectrometry was used to determine the ENR and CIP concentrations in various tissues. The highest ENR concentration occurred with IM administration, peaking at 4.124 mg/L in the plasma, 8.359 mg/kg in the kidney, 6.272 mg/kg in the liver, and 5.192 mg/kg in the muscle. However, PO administration resulted in the longest metabolic time, with elimination half-lives of 56.47 h in plasma, 86.43 h in the kidney, 76.25 h in the liver, and 64.75 h in muscle. Additionally, the area under the concentration-time curve values for IM, PO, and bath administration in yellow catfish plasma were 108.36, 88.96, and 22.08 mg·h/L, respectively. These results indicate the effectiveness of all three administration methods in treating bacterial diseases in yellow catfish. The selection of an appropriate administration method depends on the minimal inhibitory concentration of ENR against pathogenic bacteria. Yellow catfish subjected to PO and IM administration require longer resting periods before they can be marketed than those receiving drug bath administration.

Two rare variants that affect the same amino acid in CFTR have distinct responses to ivacaftor.

Some residues in the cystic fibrosis transmembrane conductance regulator (CFTR) channel are the site of more than one CFTR variant that cause cystic fibrosis. Here, we investigated the function of S1159F and S1159P, two variants associated with different clinical phenotypes, which affect the same pore-lining residue in transmembrane segment 12 that are both strongly potentiated by ivacaftor when expressed in CFBE41o- bronchial epithelial cells. To study the single-channel behaviour of CFTR, we applied the patch-clamp technique to Chinese hamster ovary cells heterologously expressing CFTR variants incubated at 27°C to enhance channel residence at the plasma membrane. S1159F- and S1159P-CFTR formed Cl- channels activated by cAMP-dependent phosphorylation and gated by ATP that exhibited thermostability at 37°C. Both variants modestly reduced the single-channel conductance of CFTR. By severely attenuating channel gating, S1159F- and S1159P-CFTR reduced the open probability (Po ) of wild-type CFTR by ≥75% at ATP (1mM); S1159F-CFTR caused the greater decrease in Po consistent with its more severe clinical phenotype. Ivacaftor (10-100nM) doubled the Po of both CFTR variants without restoring Po values to wild-type levels, but concomitantly, ivacaftor decreased current flow through open channels. For S1159F-CFTR, the reduction of current flow was marked at high (supersaturated) ivacaftor concentrations (0.5-1μM) and voltage-independent, identifying an additional detrimental action of elevated ivacaftor concentrations. In conclusion, S1159F and S1159P are gating variants, which also affect CFTR processing and conduction, but not stability, necessitating the use of combinations of CFTR modulators to optimally restore their channel activity. KEY POINTS: Dysfunction of the ion channel cystic fibrosis transmembrane conductance regulator (CFTR) causes the genetic disease cystic fibrosis (CF). This study investigated two rare pathogenic CFTR variants, S1159F and S1159P, which affect the same amino acid in CFTR, to understand the molecular basis of disease and response to the CFTR-targeted therapy ivacaftor. Both rare variants diminished CFTR function by modestly reducing current flow through the channel and severely inhibiting ATP-dependent channel gating with S1159F exerting the stronger adverse effect, which correlates with its association with more severe disease. Ivacaftor potentiated channel gating by both rare variants without restoring their activity to wild-type levels, but concurrently reduced current flow through open channels, particularly those of S1159F-CFTR. Our data demonstrate that S1159F and S1159P cause CFTR dysfunction by multiple mechanisms that require combinations of CFTR-targeted therapies to fully restore channel function.

Isoflurane lowers the cerebral metabolic rate of oxygen and prevents hypoxia during cortical spreading depolarization in vitro: An integrative experimental and modeling study

Cortical spreading depolarization (SD) imposes a massive increase in energy demand and therefore evolves as a target for treatment following acute brain injuries. Anesthetics are empirically used to reduce energy metabolism in critical brain conditions, yet their effect on metabolism during SD remains largely unknown. We investigated oxidative metabolism during SD in brain slices from Wistar rats. Extracellular potassium ([K+]o), local field potential and partial tissue oxygen pressure (ptiO2) were measured simultaneously. The cerebral metabolic rate of oxygen (CMRO2) was calculated using a reaction-diffusion model. By that, we tested the effect of clinically relevant concentrations of isoflurane on CMRO2 during SD and modeled tissue oxygenation for different capillary pO2 values. During SD, CMRO2 increased 2.7-fold, resulting in transient hypoxia in the slice core. Isoflurane decreased CMRO2, reduced peak [K+]o, and prolonged [K+]o clearance, which indicates reduced synaptic transmission and sodium-potassium ATPase inhibition. Modeling tissue oxygenation during SD illustrates the need for increased capillary pO2 levels to prevent hypoxia. In the absence thereof, isoflurane could improve tissue oxygenation by lowering CMRO2. Therefore, isoflurane is a promising candidate for pre-clinical studies on neuronal survival in conditions involving SD.

Superoxide, nitric oxide and peroxynitrite production by macrophages under different physiological oxygen tensions

Macrophages count on two O2-consuming enzymes to form reactive radical species: NAPDH oxidase 2 (Nox2) and nitric oxide synthase 2 (inducible isoform, iNOS) that produce superoxide radical (O2•−) and nitric oxide (•NO), respectively. If formed simultaneously, the diffusion-controlled reaction of O2•− and •NO yields peroxynitrite, a potent cytotoxic oxidant. In human tissues and cells, the oxygen partial pressure (pO2) normally ranges within 2–14 %, with a typical average pO2 value for most tissues ca. 5 %. Given that O2 is a substrate for both Nox2 and iNOS, its tissue and cellular concentration can affect O2•− and •NO production. Also, O2 is a modulator of the macrophage adaptative response and may influence iNOS expression in a hypoxia inducible factor 1-α (HIF1α-)-dependent manner. However, most of the reported experiments in cellula, analyzing the formation and effects of O2•− and •NO during macrophage activation and cytotoxicity towards pathogens, have been performed in cells exposed to atmospheric air supplemented with 5 % CO2; under these conditions, most cells are exposed to supraphysiologic oxygen tensions (ca. 20 % O2) which are far from the physiological pO2. Here, the role of O2 as substrate in the oxidative response of J774A.1 macrophages was explored upon exposure to different pO2 and O2•− and •NO formation rates were measured, obtaining a KM of 26 and 42 μM O2 for Nox2 and iNOS, respectively. Consequently, peroxynitrite formation was influenced by pO2, reaching a maximum at ≥ 10 % O2, but even at levels as low as 2 % O2, a substantial formation rate of this oxidant was detected. Indeed, the cytotoxic capacity of immunostimulated macrophages against the intracellular parasite T. cruzi was significant, even at low pO2 values, confirming the role of peroxynitrite as a potent oxidizing cytotoxin within a wide range of physiological oxygen tensions.

Spatial O2 Profile in Coix lacryma-jobi and Sorghum bicolor along the Gas Diffusion Pathway under Waterlogging Conditions.

While internal aeration in plants is critical for adaptation to waterlogging, there is a gap in understanding the differences in oxygen diffusion gradients from shoots to roots between hypoxia-tolerant and -sensitive species. This study aims to elucidate the differences in tissue oxygen concentration at various locations on the shoot and root between a hypoxia-tolerant species and a -sensitive species using a microneedle sensor that allows for spatial oxygen profiling. Job's tears, a hypoxia-tolerant species, and sorghum, a hypoxia-susceptible species, were tested. Plants aged 10 days were acclimated to a hypoxic agar solution for 12 days. Oxygen was profiled near the root tip, root base, root shoot junction, stem, and leaf. An anatomical analysis was also performed on the roots used for the O2 profile. The oxygen partial pressure (pO2) values at the root base and tip of sorghum were significantly lower than that of the root of Job's tears. At the base of the root of Job's tears, pO2 rapidly decreased from the root cortex to the surface, indicating a function to inhibit oxygen leakage. No significant differences in pO2 between the species were identified in the shoot part. The root cortex to stele ratio was significantly higher from the root tip to the base in Job's tears compared to sorghum. The pO2 gradient began to differ greatly at the root shoot junction and root base longitudinally, and between the cortex and stele radially, between Job's tears and sorghum. Differences in the root oxygen retention capacity and the cortex to stele ratio are considered to be related to differences in pO2.

A novel minimally invasive fixation method for flail chest management in a Canine model: an animal research

BackgroundMultiple rib fractures can lead to flail chest with up to 35% mortality rate due to severe pulmonary complications. Current treatments of flail chest remain controversial. Studies have shown that surgical treatments can improve outcomes and reduce mortality, comparing to non-operative treatments. Current surgical fixation methods focus on stabilization of ribs on the outward facing side, and they require division of intercostal muscles. Damages to surrounding nerves and vessels may lead to chronic pain. This study tests a novel interior fixation method that minimizes neurovascular injuries.MethodsTwelve healthy canines were divided in two surgical operation groups for exterior and interior fixation using titanium metal plates. Osteotomy with oblique fractures was prepared under general anesthesia. Exterior fixation was performed in open surgery. Interior fixation was minimally invasive using custom made tools including a flexible shaft extension screwdriver, solid plate stand, guiding wire loop and metal plates with threaded holes.ResultsRespiratory and cardiovascular functions (RR, PO2, PCO2, SpO2, and HR) together with body temperature were measured before anesthesia and within 48 h after surgery. The difference in measurements was not statistically significant between the two groups before surgery with P values greater than 0.05. However, the interior group canines had better RR and PO2 values starting from the 24th hour, and better PCO2, SpO2, and HR values starting from the 48th hour. It took longer operation time to complete the minimally invasive interior fixation surgery (P value less than 0.001), but the total blood loss was less than the exterior fixation group (P value less than 0.001). Results also showed that interior group canines suffered less pain, and they had quicker recovery in gastrointestinal and physical mobility.ConclusionsThe investigative interior fixation method was safe and effective in rib stabilization on a canine rib fracture model, comparing to the exterior fixation method. The interior fixation was minimally invasive, with less damages to tissues and nerves surrounding the ribs, leading to better postoperative outcomes.

Abstract 321: Manual vs Automated Ventilation During Automated Head-Up Cardiopulmonary Resuscitation in a Porcine Model

Background: The efficacy of mechanical ventilation during CPR with the combination of active compression-decompression, an impedance threshold device, and head-up positioning, collectively termed automated head-up (AHUP)-CPR, is unknown. Hypothesis: Hemodynamic and ventilatory parameters will be similar with manual bag ventilation (MBV) versus automated bag ventilation (ABV) during AHUP-CPR in a porcine model of cardiac arrest. Aim: Assess the proof-of-concept that ABV is safe and effective during AHUP-CPR. Methods: Nine male and female swine (~40 kg) were anesthetized and ventilated. VF was induced and left untreated for 8 min. AHUP-CPR was performed at 105 compressions/min for 7 min using MBV, followed by 6 min using an automated mechanical bag compressor to deliver 10ml/kg of tidal volume (TV) over 1 sec at 10 breaths/min. Pigs were randomized during ABV to a synchronized (Sync) breath delivered at the start of decompression or an asynchronous (Async) breath. Cerebral perfusion pressure, coronary perfusion pressure, end-tidal CO2, intracranial pressure, esophageal intrathoracic pressure, peak airway pressure (PAP), inspiratory and expiratory TVs as well as arterial blood gases were continuously measured. Values (mean ± SD) were compared by paired and unpaired student’s t-tests with a Bonferroni correction. Results: Parameters during the last minute of MBV and ABV are summarized in the table. No significant differences were observed in hemodynamic and ventilatory parameters, except for PAP and pO2 values which were significantly lower with MBV. No significant differences were also observed between the Sync and Async ABV modes. Conclusion: Manual and mechanical ventilation resulted in overall similar physiological effects. The clinical relevance of the observed significant differences in PAP and pO2 is unclear. Additional studies are warranted to further assess the safety and effectiveness of mechanical ventilation during AHUP-CPR.