PO2 Difference Research Articles

Effects of Plasma Therapy on Laboratory Factors and Clinical Improvement of COVID-19 Patients

Objectives: Over 50 million confirmed cases and 1.5 million fatalities worldwide have been linked to the COVID-19 pandemic. Researchers have used convalescent plasma (CP) from recovered patients, which includes neutralizing antibodies, to develop therapeutics for virus neutralization and prevention. This study assessed the effectiveness of CP using several clinical and laboratory variables. Methods: The intervention group received two doses of CP on the day of hospitalization, while the control group received standard care. Clinical and analytical data were documented and evaluated before plasma therapy and on the third and fifth days after therapy. The results were measured in the patient’s blood using the ELISA method. Results: The present study showed that the ICU hospitalization times for the control and CP groups were similar, with a slightly lower mortality rate in the CP group (6.2% vs. 8.2%, p > 0.05). There was no significant association between COVID-19 and clinical factors such as blood pressure, heart rate (HR), respiration rate (RR), and temperature. The blood serum urea, serum LDH, ALT, PTT, PLT, and IL-6 were significantly higher in the CP group than in the control group (p <0.05). Our results indicated that there was no difference in blood pH, PO2 , HCO3 , ESR, WBC counts, serum troponin, Na, AST, CRP, D-dimer, and PT between patients in the CP and control groups. Conclusion: Overall, in certain instances, CP therapy may help individuals with COVID-19 recover. In general, additional research is required to determine the efficacy of plasma treatment in COVID-19 patient care.

Evaluations of an Early Change in Tumor Pathophysiology in Response to Radiotherapy with Oxygen Enhanced Electron Paramagnetic Resonance Imaging (OE EPRI).

Electron Paramagnetic Resonance Imaging (EPRI) can image the partial pressure of oxygen (pO2) within in vivo tumor models. We sought to develop Oxygen Enhanced (OE) EPRI that measures tumor pO2 with breathing gases of 21% O2 (pO221%) and 100% O2 (pO2100%), and the differences in pO2 between breathing gases (ΔpO2). We applied OE EPRI to study the early change in tumor pathophysiology in response to radiotherapy in two tumor models of pancreatic cancer. We developed a protocol that intraperitoneally administered OX071, a trityl radical contrast agent, and then acquired anatomical MR images to localize the tumor. Subsequently, we acquired two pO221% and two pO2100% maps using the T1 relaxation time of OX071 measured with EPRI and a R1-pO2 calibration of OX071. We studied 4T1 flank tumor model to evaluate the repeatability of OE EPRI. We then applied OE EPRI to study COLO 357 and Su.86.86 flank tumor models treated with 10Gy radiotherapy. The repeatability of mean pO2 for individual tumors was ± 2.6Torr between successive scans when breathing 21% O2 or 100% O2, representing a precision of 9.6%. Tumor pO221% and pO2100% decreased after radiotherapy for both models, although the decreases were not significant or only moderately significant, and the effect sizes were modest. For comparison, ΔpO2 showed a large, highly significant decrease after radiotherapy, and the effect size was large. MANOVA and analyses of the HF10 hypoxia fraction provided similar results. EPRI can evaluate tumor pO2 with outstanding precision relative to other imaging modalities. The change in ΔpO2 before vs. after treatment was the best parameter for measuring the early change in tumor pathophysiology in response to radiotherapy. Our studies have established ΔpO2 from OE EPRI as a new parameter, and have established that OE EPRI is a valuable new methodology for molecular imaging.

The effect of decafluorobutane lipid nanoemulsion concentration on oxygen scavenging via acoustic droplet vaporization

Acoustic droplet vaporization (ADV) is the phase transition of liquid droplets into gas microbubbles via ultrasound. Oxygen diffuses from the surrounding fluid into the microbubbles. This study determined the efficiency of oxygen scavenging using a lipid decafluorobutane (DFB) nanoemulsion. DFB nanoemulsions were prepared using high-shear pressure homogenization. Nanoemulsion size distributions and concentrations were measured (n = 10) using a Beckman Coulter Multisizer 4. Oxygen scavenging in 95% oxygenated water was measured in a flow phantom prior to introducing DFB nanoemulsion at concentrations of 0.05 × 10−4, 0.25 × 10−4, 0.5 × 10−4, 2.5 × 10−4, and 5 × 10−4 mL/mL and with ADV nucleated by an EkoSonic catheter driven with 47 W electrical power. The DFB nanoemulsion had a modal diameter of 920 ± 60 nm, polydispersity index (PDI) of 0.11 ± 0.03, and concentration of 3.11 × 10–2 ± 0.01 × 10–2 mL/mL. No statistical significant differences was detected in droplet size distribution metrics for at least 5 h at room temperature and 23 days at 4C. The baseline oxygen partial pressure (pO2) of the water was 553 ± 8 mmHg for all experiments. Peri-ADV pO2 dropped to 505 ± 16, 398 ± 44, 348 ± 11, 231 ± 27, 241 ± 7 mmHg for increasing concentration. A significant difference in pO2 was seen between thelowest and highest concentration (p = 0.0097). The computed ADV transition efficiency was highest at 0.25 × 10−4 mL/mL.

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.

Prone Positioning in Patients With COVID-19 and Non-COVID-19 Acute Respiratory Distress Syndrome.

Patients critically ill with COVID-19 develop acute respiratory distress syndrome (ARDS) and may undergo prone positioning. To compare the effects of prone positioning on oxygenation, intensive care unit length of stay, and intubation days in patients with COVID-19 ARDS and patients with non-COVID-19 ARDS. A convenience sample of intubated patients with COVID-19 and moderate to severe ARDS (per Berlin criteria) was compared with historical data from a retrospective, descriptive medical record review of patients with non-COVID-19 ARDS. The historical comparison group was age and sex matched. Differences in Po2 to fraction of inspired oxygen ratios between the COVID-19 ARDS group (n = 41) and the non-COVID-19 ARDS group (n = 6) during the first 7 days of prone positioning were significant at the end of prone positioning on day 1 (P = .01), day 3 (P = .04), and day 4 (P = .04). Wilcoxon signed-rank tests showed that prone positioning had a positive impact on Po2 to fraction of inspired oxygen ratios from day 1 through day 6 in the COVID-19 ARDS group and on day 2 in the non-COVID-19 ARDS group. This retrospective review found greater improvement in oxygenation in the COVID-19 ARDS group than in the non-COVID-19 ARDS group. This finding may be attributed to the assertive prone positioning protocol during the pandemic and teams whose skills and training were likely enhanced by the pandemic demand. Prone positioning did not affect intensive care unit length of stay or intubation days in either group.

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.

Breathing and Oxygen Carrying Capacity in Ts65Dn and Down Syndrome.

Individuals with Down syndrome (Ds) are at increased risk of respiratory infection, aspiration pneumonia, and apnea. The Ts65Dn mouse is a commonly used model of Ds, but there have been no formal investigations of awake breathing and respiratory muscle function in these mice. We hypothesized that breathing would be impaired in Ts65Dn vs. wild-type (WT), and would be mediated by both neural and muscular inputs. Baseline minute ventilation was not different at 3, 6, or 12 mo of age. However, VT/Ti, a marker of the neural drive to breathe, was lower in Ts65Dn vs. WT and central apneas were more prevalent. The response to breathing hypoxia was not different, but the response to hypercapnia was attenuated, revealing a difference in carbon dioxide sensing, and/or motor output in Ts65Dn. Oxygen desaturations were present in room air, demonstrating that ventilation may not be sufficient to maintain adequate oxygen saturation in Ts65Dn. We observed no differences in arterial PO2 or PCO2, but Ts65Dn had lower hemoglobin and hematocrit. A retrospective medical record review of 52,346 Ds and 52,346 controls confirmed an elevated relative risk of anemia in Ds. We also performed eupneic in-vivo electromyography and in-vitro muscle function and histological fiber typing of the diaphragm, and found no difference between strains. Overall, conscious respiration is impaired in Ts65Dn, is mediated by neural mechanisms, and results in reduced hemoglobin saturation. Oxygen carrying capacity is reduced in Ts65Dn vs. WT, and we demonstrate that individuals with Ds are also at increased risk of anemia.

Reducing Pulmonary Capillary Wedge Pressure During Exercise Exacerbates Exertional Dyspnea in Patients With Heart Failure With Preserved Ejection Fraction: Implications for [formula omitted] Mismatch

The primary cause of dyspnea on exertion in heart failure with preserved ejection fraction (HFpEF) is presumed to be the marked rise in pulmonary capillary wedge pressure during exercise; however, this hypothesis has never been tested directly. Therefore, we evaluated invasive exercise hemodynamics and dyspnea on exertion in patients with HFpEF before and after acute nitroglycerin (NTG) treatment to lower pulmonary capillary wedge pressure. Does reducing pulmonary capillary wedge pressure during exercise with NTG improve dyspnea on exertion in HFpEF? Thirty patients with HFpEF performed two invasive 6-min constant-load cycling tests (20 W): one with placebo (PLC) and one with NTG. Ratings of perceived breathlessness (0-10 scale), pulmonary capillary wedge pressure (right side of heart catheter), and arterial blood gases (radial artery catheter) were measured. Measurements of V˙/Q˙ matching, including alveolar dead space (Vdalv; Enghoff modification of the Bohr equation) and the alveolar-arterial Po2 difference (A-aDO2; alveolar gas equation), were also derived. The ventilation (V˙e)/CO2 elimination (V˙co2) slope was also calculated as the slope of the V˙e and V˙co2 relationship, which reflects ventilatory efficiency. Ratings of perceived breathlessness increased (PLC: 3.43 ± 1.94 vsNTG: 4.03 ± 2.18; P= .009) despite a clear decrease in pulmonary capillary wedge pressure at 20W (PLC: 19.7 ± 8.2 vsNTG: 15.9 ± 7.4mmHg; P< .001). Moreover, Vdalv (PLC: 0.28 ± 0.07 vsNTG: 0.31 ± 0.08 L/breath; P= .01), A-aDO2 (PLC: 19.6 ± 6.7 vsNTG: 21.1 ± 6.7; P= .04), and V˙e/V˙co2 slope (PLC: 37.6 ± 5.7 vsNTG: 40.2 ± 6.5; P< .001) all increased at 20W after a decrease in pulmonary capillary wedge pressure. These findings have important clinical implications and indicate that lowering pulmonary capillary wedge pressure does not decrease dyspnea on exertion in patients with HFpEF; rather, lowering pulmonary capillary wedge pressure exacerbates dyspnea on exertion, increases V˙/Q˙ mismatch, and worsens ventilatory efficiency during exercise in these patients. This study provides compelling evidence that high pulmonary capillary wedge pressure is likely a secondary phenomenon rather than a primary cause of dyspnea on exertion in patients with HFpEF, and a new therapeutic paradigm is needed to improve symptoms of dyspnea on exertion in these patients.

Multifactor theoretical study on ionic transport numbers of mixed oxygen ionic-electronic conducting oxides determined by the electromotive force method

The electromotive force (EMF) method is widely applied to measure the ionic transport numbers (ti) of mixed oxygen-ionic and electronic conducting oxides. However, the results determined by the EMF method are the average/apparent ti (tiapp), subjected to a given gradient of oxygen partial pressure (PO2), rather than ti at a specific PO2, making it challenging to reveal the accurate properties of materials. In this study, to clarify the impact of this issue, a precise defect distribution model of Gd doped CeO2 (GDC), considering defect equilibrium and local charge neutrality, is built. A multifactor theoretical analysis is conducted to compare tiapp and ti of the membrane at different sides. The modeling results reveal that a thick membrane is recommended for avoiding the influence of membrane thickness on tiapp. When there is a large difference of PO2 between two sides of the GDC membrane (PO2highPO2PO2lowPO2>1025), tiapp is inclined to ti at the side of high PO2. Only when both sides of the GDC membrane are reducing atmosphere, tiapp of the modified EMF method is approximately the average of ti at both sides. The findings of this study are instructive for the rational application of EMF methods.

Near-infrared spectroscopy estimation of combined skeletal muscle oxidative capacity and O2 diffusion capacity in humans.

The final steps of the O2 cascade during exercise depend on the product of the microvascular‐to‐intramyocyte PO2 difference and muscle O2 diffusing capacity (DmO2). Non‐invasive methods to determine DmO2 in humans are currently unavailable. Muscle oxygen uptake (mV˙O2) recovery rate constant (k), measured by near‐infrared spectroscopy (NIRS) using intermittent arterial occlusions, is associated with muscle oxidative capacity in vivo. We reasoned that k would be limited by DmO2 when muscle oxygenation is low (k LOW), and hypothesized that: (i) k in well oxygenated muscle (k HIGH) is associated with maximal O2 flux in fibre bundles; and (ii) ∆k (k HIGH – k LOW) is associated with capillary density (CD). Vastus lateralis k was measured in 12 participants using NIRS after moderate exercise. The timing and duration of arterial occlusions were manipulated to maintain tissue saturation index within a 10% range either below (LOW) or above (HIGH) half‐maximal desaturation, assessed during sustained arterial occlusion. Maximal O2 flux in phosphorylating state was 37.7 ± 10.6 pmol s−1 mg−1 (∼5.8 ml min−1 100 g−1). CD ranged 348 to 586 mm–2. k HIGH was greater than k LOW (3.15 ± 0.45 vs. 1.56 ± 0.79 min–1, P < 0.001). Maximal O2 flux was correlated with k HIGH (r = 0.80, P = 0.002) but not k LOW (r = –0.10, P = 0.755). Δk ranged –0.26 to –2.55 min–1, and correlated with CD (r = –0.68, P = 0.015). mV˙O2 k reflects muscle oxidative capacity only in well oxygenated muscle. ∆k, the difference in k between well and poorly oxygenated muscle, was associated with CD, a mediator of DmO2. Assessment of muscle k and ∆k using NIRS provides a non‐invasive window on muscle oxidative and O2 diffusing capacity. Key points We determined post‐exercise recovery kinetics of quadriceps muscle oxygen uptake (mV˙O2) measured by near‐infrared spectroscopy (NIRS) in humans under conditions of both non‐limiting (HIGH) and limiting (LOW) O2 availability, for comparison with biopsy variables.The mV˙O2 recovery rate constant in HIGH O2 availability was hypothesized to reflect muscle oxidative capacity (k HIGH) and the difference in k between HIGH and LOW O2 availability (∆k) was hypothesized to reflect muscle O2 diffusing capacity. k HIGH was correlated with phosphorylating oxidative capacity of permeabilized muscle fibre bundles (r = 0.80). ∆k was negatively correlated with capillary density (r = −0.68) of biopsy samples.NIRS provides non‐invasive means of assessing both muscle oxidative and oxygen diffusing capacity in vivo.

Physicochemical Analysis of Mixed Venous and Arterial Blood Acid-Base State in Horses at Core Temperature during and after Moderate-Intensity Exercise.

Simple SummaryThe purposes of the present study were to determine the effect of core body temperature on acid-base variables and determine the origins of acid-base changes in the arterial and mixed venous blood of horses during exercise and recovery. Moderate intensity exercise resulted in an increase in body temperature that, in addition to exercise, affected acid-base status and gas partial pressures. Moderate intensity exercise resulted in a mild alkalosis that had markedly different origins in arterial blood than in mixed venous blood, and this was affected by the increase in core temperature during exercise and its resolution during recovery. In order to fully understand how acid-base status changes during exercise and recovery, it is importance to quantify the changes in both arterial and mixed venous blood, with adjustment to core temperature. Acid-base assessments using jugular vein blood samples are limited in comparison.The present study determined the independent contributions of temperature, strong ion difference ([SID]), total weak acid concentration ([Atot]) and PCO2 to changes in arterial and mixed venous [H+] and total carbon dioxide concentration ([TCO2]) during 37 min of moderate intensity exercise (~50% of heart rate max) and the first 60 min of recovery. Six horses were fitted with indwelling carotid and pulmonary artery (PA) catheters, had PA temperature measured, and had blood samples withdrawn for immediate analysis of plasma ion and gas concentrations. The increase in core temperature during exercise (+4.5 °C; p < 0.001) significantly (p < 0.05) increased PO2, PCO2, and [H+], but without a significant effect on [TCO2] (p > 0.01). The physicochemical acid-base approach was used to determine contributions of independent variables (except temperature) to the changes in [H+] and [TCO2]. In both arterial and venous blood, there was no acidosis during exercise and recovery despite significant (p < 0.05) increases in [lactate] and in venous PCO2. In arterial blood plasma, a mild alkalosis with exercise was due to primarily to a decrease in PCO2 (p < 0.05) and an increase in [SID] (p < 0.1). In venous blood plasma, a near absence of change in [H+] was due to the acidifying effects of increased PCO2 (p < 0.01) being offset by the alkalizing effects of increased [SID] (p < 0.05). The effect of temperature on PO2 (p < 0.001) resulted in an increased arterio-venous PO2 difference (p < 0.001) that would facilitate O2 transfer to contracting muscle. The simultaneous changes in the PCO2 and the concentrations of the other independent acid-base variables (contributions from individual strong and weak ions as manifest in [SID] and [Atot]) show complex, multilevel control of acid-base states in horses performing even moderate intensity exercise. Correction of acid-base variables to core body temperature presents a markedly different physiological response to exercise than that provided by variables measured and presented at an instrument temperature of 37 °C.

Continuous monitoring of postirradiation reoxygenation and cycling hypoxia using electron paramagnetic resonance imaging.

Reoxygenation has a significant impact on the tumor response to radiotherapy. With developments in radiotherapy technology, the relevance of the reoxygenation phenomenon in treatment efficacy has been a topic of interest. Evaluating the reoxygenation in the tumor microenvironment throughout the course of radiation therapy is important in developing effective treatment strategies. In the current study, we used electron paramagnetic resonance imaging (EPRI) to directly map and quantify the partial oxygen pressure (pO2) in tumor tissues. Human colorectal cancer cell lines, HT29 and HCT116, were used to induce tumor growth in female athymic nude mice. Tumors were irradiated with 3, 10, or 20 Gy using an x‐ray irradiator. Prior to each EPRI scan, magnetic resonance imaging (MRI) was performed to obtain T2‐weighted anatomical images for reference. The differences in the mean pO2 were determined through two‐tailed Student's t‐test and one‐way analysis of variance. The median pO2 60 min after irradiation was found to be lower in HCT116 than in HT29 (9.1 ± 1.5 vs. 14.0 ± 1.0 mmHg, p = 0.045). There was a tendency for delayed and incomplete recovery of pO2 in the HT29 tumor when a higher dose of irradiation (10 and 20 Gy) was applied. Moreover, there was a dose‐dependent increase in the hypoxic areas (pO2 < 10 mmHg) 2 and 24 h after irradiation in all groups. In addition, an area that showed pO2 fluctuation between hypoxia and normoxia (pO2 > 10 mmHg) was also identified surrounding the region with stable hypoxia, and it slightly enlarged after recovery from acute hypoxia. In conclusion, we demonstrated the reoxygenation phenomenon in an in vivo xenograft model study using EPRI. These findings may lead to new knowledge regarding the reoxygenation process and possibilities of a new radiation therapy concept, namely, reoxygenation‐based radiation therapy.

Soluble Guanylyl Cyclase Stimulator Improves Contracting Skeletal Muscle Oxygen Pressures in Heart Failure Rats

IntroductionImpaired convective and diffusive oxygen (O2) transport is a hallmark of heart failure with reduced ejection fraction (HFrEF), largely attributed to nitric oxide‐soluble guanylyl cyclase (sGC)‐cyclic guanosine monophosphate pathway dysfunction. sGC stimulators were synthesized to independently and synergistically (with endothelial derived‐NO) promote vasodilation, thereby demonstrating the potential to improve skeletal muscle oxygenation in HFrEF. We tested the hypotheses that 2 weeks of administration of sGC stimulator BAY 41‐2272 would increase the O2 delivery (Q̇O2)‐to‐O2uptake (V̇O2) ratio in the skeletal muscle interstitial space (PO2is) of HFrEF rats at rest and during twitch contractions.MethodsHFrEF was induced in adult male Sprague‐Dawley (3‐4 mo. old) rats via myocardial infarction (MI). Following 5 weeks of HFrEF progression, rats were treated with 1.0 mg/kg of BAY 41‐2272 via oral gavage twice per day (HFrEF + BAY; n=6) for 2 weeks prior to the contraction protocol. The control heart failure group (HFrEF; n=5) received vehicle only. Phosphorescence quenching protocols determined the partial pressure of O2 in the spinotrapezius muscle interstitial space at rest and during twitch contractions, reflecting the dynamic relationship between Q̇O2 and V̇O2.ResultsThe degree of HFrEF was not different between groups as evidenced by left ventricular end‐diastolic pressure (16 ± 1 mmHg, both groups) and MI size (27 ± 1 vs. 29 ± 1%) (all P&gt;0.05). There were no differences in blood gases following contractions (P&gt;0.05). Kinetic analyses revealed no difference in PO2is at rest, however immediately following the onset of contractions and throughout the contraction steady‐state, HFrEF+BAY rats maintained a ~5‐7 mmHg higher PO2is (32‐180s of contractions, P&lt;0.05). Furthermore, HFrEF+BAY rats had an attenuated undershoot, decreased tau (time constant), and increased end PO2is (all P&lt;0.05) in comparison to HFrEF rats.ConclusionsDuring the rest‐contraction transient and throughout the contractions steady‐state BAY 41‐2272 increases PO2isin rats with moderate HFrEF. By improving O2delivery and relieving the HF‐induced O2‐dependence of V̇O2 kinetics these findings support the therapeutic potential for sGC stimulators to reduce vasomotor dysfunction and improve exercise tolerance in HFrEF.

Time of ovulation in sows is not related to intravaginal dissolved oxygen levels or temperature

Timing is a crucial factor in the success of artificial insemination (AI). In sows, the appropriate time for AI amounts 12 hours before to 4 hours after ovulation based on the period in which viable spermatozoa should be available at the site of fertilization. However, in contrast to the general period of estrus, which is associated with behavioral and physical changes, the exact time of ovulation is not visible externally. It is, therefore, important to consider and evaluate additional methods that allow a more accurate determination or prediction of the actual time of ovulation than just the occurrence of the standing reflex in sows. With this goal in mind, 14 DanBred sows (parity: 5.2 ± 2.4) were subjected to ultrasound scans of the ovaries. The examinations started 80 hours after weaning and were repeated in 8 hours intervals for up to 72 hours to monitor ovarian function and time of ovulation. Additionally, intravaginal dissolved oxygen (pO2 in mmHg) levels and temperature (in°C) were measured using a fluorescence-based technique (OxyLiteTM) to uncover possible relations between the time of ovulation and the amount of oxygen available to cells and tissue. On average, sows ovulated 121 ± 10 hours after weaning and 16 ± 9 hours (mean ± SD) after the onset of heat. There were no significant differences in the intravaginal pO2 (P=0.988) or temperature (P=0.985) between the time points and in any of the direct, pair-wise comparisons between the five respective time points (P>0.05; before ovulation: 20 hours, 12 hours, and 4 hours; after ovulation: 4 hours and 12 hours). In conclusion, intravaginal pO2 and temperature have limited usefulness in predicting the occurrence of ovulation in sows using the presented technology.

Feasibility of critical care ergometry: Exercise data of patients on mechanical ventilation analyzed as nine-panel plots.

Nine‐panel plots are standard displays of cardiopulmonary exercise data, used in cardiac and pulmonary medicine to investigate the nature of exercise limitation. We explored whether this approach could be used to analyze the data of critically ill patients on mechanical ventilation, capable of exercising actively. Patients followed an incremental exercise protocol using a bedside cycle ergometer. Respiratory gases were analyzed using indirect calorimetry, and blood gases were sampled from arterial catheters. Data of seven patients were combined into nine‐panel plots. Systematic analysis clarified the nature of exercise limitation in six cases. Resting metabolic rate was increased in all patients, with a median oxygen uptake (V˙O2) of 5.52 (IQR 4.29–6.31) ml/kg/min. Unloaded cycling increased the V˙O2 by 19.8% to 6.61 (IQR 5.99–7.08) ml/kg/min. Adding load to the ergometer increased the V˙O2 by another 20.0% to reach V˙O2peak at a median of 7.14 (IQR 6.67–10.75) ml/kg/min, corresponding to a median extrinsic workload of 7 W. This was accompanied by increased CO2 production, respiratory minute volume, heart rate, and oxygen pulse. Three patients increased their V˙O2 to >40% of predicted V˙O2max, two patients passed the anaerobic threshold. Dead space ventilation was 44%, decreasing to 42% and accompanied by lower ventilatory equivalents during exercise. Exercise produced no net change in alveolo‐arterial PO2 difference. We concluded that diagnostic ergometry in mechanically ventilated patients was feasible. Analysis of the data as nine‐panel plots provided insight into individual limitations to exercise.

Non-invasive Measurement of Pulmonary Gas Exchange Efficiency: The Oxygen Deficit.

The efficiency of pulmonary gas exchange has long been assessed using the alveolar-arterial difference in PO2, the A-aDO2, a construct developed by Richard Riley ~70years ago. However, this measurement is invasive (requiring an arterial blood sample), time consuming, expensive, uncomfortable for the patients, and as such not ideal for serial measurements. Recent advances in the technology now provide for portable and rapidly responding measurement of the PO2 and PCO2 in expired gas, which combined with the well-established measurement of arterial oxygen saturation via pulse oximetry (SpO2) make practical a non-invasive surrogate measurement of the A-aDO2, the oxygen deficit. The oxygen deficit is the difference between the end-tidal PO2 and the calculated arterial PO2 derived from the SpO2 and taking into account the PCO2, also measured from end-tidal gas. The oxygen deficit shares the underlying basis of the measurement of gas exchange efficiency that the A-aDO2 uses, and thus the two measurements are well-correlated (r2~0.72). Studies have shown that the new approach is sensitive and can detect the age-related decline in gas exchange efficiency associated with healthy aging. In patients with lung disease the oxygen deficit is greatly elevated compared to normal subjects. The portable and non-invasive nature of the approach suggests potential uses in first responders, in military applications, and in underserved areas. Further, the completely non-invasive and rapid nature of the measurement makes it ideally suited to serial measurements of acutely ill patients including those with COVID-19, allowing patients to be closely monitored if required.

Inflammatory and blood gas markers of COVID-19 delirium compared to non-COVID-19 delirium: a cross-sectional study

Objectives We aimed to find the association of inflammation and respiratory failure with delirium in COVID-19 patients. We compare the inflammatory and arterial blood gas markers between patients with COVID-19 delirium and delirium in other medical disorders. Methods This cross-sectional study used the CHART-DEL, a validated research tool, to screen patients for delirium retrospectively from clinical notes. Inflammatory markers C-reactive protein (CRP) and white cell count (WBC), and the partial pressures of oxygen (PO2) and carbon dioxide (PCO2) were compared between patients with COVID-19 delirium and delirium in other medical disorders. Results In bivariate analysis, CRP (mg/L) was significantly higher in the COVID-19 group, (81.7 ± 80.0 vs. 58.8 ± 87.7, p = 0.04), and WBC (109/L) was significantly lower (7.44 ± 3.42 vs. 9.71 ± 5.45, p = 0.04). The geometric mean of CRP in the COVID-19 group was 140% higher in multiple linear regression (95% CI = 7–439%, p = 0.03) with age and sex as covariates. There were no significant differences in pO2 or pCO2 across groups. Conclusion The association between higher CRP and COVID-19 in patients with delirium may suggest an inflammatory basis for delirium in COVID-19. Our findings may assist clinicians in establishing whether delirium is due to COVID-19, which may improve management and outcomes of infected patients.

The protective effect of high heme oxygenase-1 expression induced by propofol on the alveolar II type epithelial cells of rats with acute lung injury induced by oleic acid.

This study aimed to investigate the mechanism of propofol (PR) pretreatment inducing high heme oxygenase-1 (HO-1) expression to protect alveolar type II epithelial cells (AEC-II) in rats with acute lung injury (ALI) induced by oleic acid (OA). In this study, 32 male Sprague-Dawley rats (250 - 300 g) were randomly divided into four groups (n = 8 in each group) as follows: group C (the normal control group), the OA group (the oleic acid injury control group), the OA + PR group (the PR pretreatment group), and the OA + IX group (the zinc porphyrin IX pretreatment group). Arterial blood gases, bronchoalveolar lavage fluid (BALF), and serum pulmonary surfactant-associated protein A (SP-A) were measured in each group. The changes in the AEC-II ultrastructure were observed under an electron microscope. The HO-1 protein expression was detected by immunohistochemistry, and HO-1 messenger ribonucleic acid (mRNA) was detected by polymerase chain reaction. The results of this study showed that there were significant differences in PO2, pCO2, and PaO2/FiO2 among the different groups (p < 0.05). The difference between BALF and SP-A in each group was statistically significant (p < 0.01). There were also significant differences in the integrated optical density of the HO-1 protein expression and HO-1 mRNA in the pulmonary tissue of the different groups (p < 0.05 or p < 0.01). The results of the electron microscopy showed that AEC-II were relatively irregular in the OA group. The cells degenerated and even disintegrated, the microvilli on the cell surface decreased, the lamellar bodies in the cytoplasm were evacuated, and some were discharged into the alveolar cavity. The above-mentioned changes in the OA + PR group were lower than in the OA group, while the changes were greater in the OA + IX group, compared with those in the OA group. We conclude that PR can significantly increase the expression of HO-1 in pulmonary tissues and reduce pulmonary injury, and, therefore, protect the AEC-II.

Phenotyping placental oxygenation in Lgals1 deficient mice using 19F MRI

Placental hypoperfusion and hypoxia are key drivers in complications during fetal development such as fetal growth restriction and preeclampsia. In order to study the mechanisms of disease in mouse models, the development of quantitative biomarkers of placental hypoxia is a prerequisite. The goal of this exploratory study was to establish a technique to noninvasively characterize placental partial pressure of oxygen (PO2) in vivo in the Lgals1 (lectin, galactoside-binding, soluble, 1) deficient mouse model of preeclampsia using fluorine magnetic resonance imaging. We hypothesized a decrease in placental oxygenation in knockout mice. Wildtype and knockout animals received fluorescently labeled perfluoro-5-crown-15-ether nanoemulsion i.v. on day E14-15 during pregnancy. Placental PO2 was assessed via calibrated 19F MRI saturation recovery T1 mapping. A gas challenge with varying levels of oxygen in breathing air (30%, 60% and 100% O2) was used to validate that changes in oxygenation can be detected in freely breathing, anesthetized animals. At the end of the experiment, fluorophore-coupled lectin was injected i.v. to label the vasculature for histology. Differences in PO2 between breathing conditions and genotype were statistically analyzed with linear mixed-effects modeling. As expected, a significant increase in PO2 with increasing oxygen in breathing air was found. PO2 in Lgals1 knockout animals was decreased but this effect was only present at 30% oxygen in breathing air, not at 60% and 100%. Histological examinations showed crossing of the perfluorocarbon nanoemulsion to the fetal blood pool but the dominating contribution of 19F MR signal is estimated at > 70% from maternal plasma based on volume fraction measurements of previous studies. These results show for the first time that 19F MRI can characterize oxygenation in mouse models of placental malfunction.

High-flow nasal cannula oxygen versus conventional oxygen for hypercapnic chronic obstructive pulmonary disease: A meta-analysis of randomized controlled trials.

Low-concentration oxygen is an established way for the treatment of chronic obstructive pulmonary disease (COPD) with Type II respiratory failure. Hypercapnia can complicate both COPD exacerbations and stable COPD. Treating with noninvasive ventilation (NIV) can reduce carbon dioxide tension in arterial (PaCO2 ) in hypercapnic COPD. As an open system, high-flow nasal cannula oxygen (HFNC) is easy to tolerate and use. More researches are needed to focus on how HFNC is used to treat COPD patients with hypercapnic respiratory failure. The Cochrane Library, Medline, EMBASE, and CINAHL database were retrieved from inception to October 2019. Eligible trials were clinical randomized controlled trials comparing the effects of HFNC and conventional oxygen on hypercapnic COPD patients. Two researchers assessed the quality of each study and extracted the data into RevMan 5.3 independently. The primary outcome was PaCO2 and the secondary outcome was PaO2 . Four RCTs with 329 patients were included. The research results indicated that PaCO2 in the HFNC group was similar to the conventional oxygen group. No significant difference were observed in PaCO2 (MD -0.98, CI: -2.67 to 0.71, Z=1.14, p=0.25) and PaO2 (MD -0.72, CI: -6.99 to 5.55, Z=0.23, p=0.82) between the HFNC group and conventional oxygen group. Our meta-analysis showed no difference in PO2 and PCO2 between the HFNC and conventional oxygen. But we should treat this conclusion with caution because the number of studies and participants is small and, there is heterogeneity in the PaO2 and PCO2 measurements between stable and AECOPD.