Measurement Of Oxygen Tension Research Articles

PO2 reporter composite hydrogel macroencapsulation devices for magnetic resonance imaging oxygen quantification.

Hydrogel cell encapsulation devices are a common approach to reduce the need for chronic systemic immunosuppression in allogeneic cell product transplantation. Macroencapsulation approaches are an appealing strategy, as they maximize graft retrievability and cell dosage within a single device; however, macroencapsulation devices face oxygen transport challenges as geometries increase from preclinical to clinical scales. Device design guided by computational approaches can facilitate graft oxygen availability to encapsulated cells in vivo but is limited without accurate measurement of oxygen levels within the transplant site and graft. In this study, we engineer pO2 reporter composite hydrogels (PORCH) to enable spatiotemporal measurement of oxygen tension within macroencapsulation devices using the proton Imaging of siloxanes to map tissue oxygenation levels (PISTOL) magnetic resonance imaging approach. We engineer two methods of incorporating siloxane oximetry reporters within hydrogel devices, an emulsion and microbead-based approach, and evaluate PORCH cytotoxicity on co-encapsulated cells and accuracy in quantifying oxygen tension in vitro. We find that both emulsion and microbead PORCH approaches enable accurate in situ oxygen quantification using PISTOL magnetic resonance oximetry, and that the emulsion-based PORCH approach results in higher spatial resolution.

Acute Hypoxia Does Not Alter Tumor Sensitivity to FLASH Radiation Therapy

Tumor hypoxia is a major cause of treatment resistance, especially to radiation therapy at conventional dose rate (CONV), and we wanted to assess whether hypoxia does alter tumor sensitivity to FLASH. We engrafted several tumor types (glioblastoma [GBM], head and neck cancer, and lung adenocarcinoma) subcutaneously in mice to provide a reliable and rigorous way to modulate oxygen supply via vascular clamping or carbogen breathing. We irradiated tumors using a single 20-Gy fraction at either CONV or FLASH, measured oxygen tension, monitored tumor growth, and sampled tumors for bulk RNAseq and pimonidazole analysis. Next, we inhibited glycolysis with trametinib in GBM tumors to enhance FLASH efficacy. Using various subcutaneous tumor models, and in contrast to CONV, FLASH retained antitumor efficacy under acute hypoxia. These findings show that in addition to normal tissue sparing, FLASH could overcome hypoxia-mediated tumor resistance. Follow-up molecular analysis using RNAseq profiling uncovered a FLASH-specific profile in human GBM that involved cell-cycle arrest, decreased ribosomal biogenesis, and a switch from oxidative phosphorylation to glycolysis. Glycolysis inhibition by trametinib enhanced FLASH efficacy in both normal and clamped conditions. These data provide new and specific insights showing the efficacy of FLASH in a radiation-resistant context, proving an additional benefit of FLASH over CONV.

Optimization of Transcutaneous Oxygenation Wearable Sensors for Clinical Applications

AbstractIn this manuscript, the development of an experimental and mathematical toolset is reported that allows for improved in vivo measurements of optical transcutaneous oxygen tension measurements (TCOM) wearable technology in humans. In addition to optimizing O2‐sensing films for higher sensitivity oxygen detection, calibration algorithms are additionally developed to account for excitation source leakage, as well as algorithms to combine readings of partial pressure of oxygen (pO2), derived from phosphorescence intensity and lifetime, into a single metric. This new iteration of the TCOM wearable device is then tested in a pilot human study. By implementing characterization and calibration algorithms, the data from the pilot study demonstrates the ability to obtain reliable transcutaneous pO2 readings with a TCOM sensor regardless of size and without the need for strict conditions of constant temperature, humidity, or motion that have limited the range of applications of this technology in the past.

Construction of Bone Hypoxic Microenvironment Based on Bone-on-a-Chip Platforms.

The normal physiological activities and functions of bone cells cannot be separated from the balance of the oxygenation level, and the physiological activities of bone cells are different under different oxygenation levels. At present, in vitro cell cultures are generally performed in a normoxic environment, and the partial pressure of oxygen of a conventional incubator is generally set at 141 mmHg (18.6%, close to the 20.1% oxygen in ambient air). This value is higher than the mean value of the oxygen partial pressure in human bone tissue. Additionally, the further away from the endosteal sinusoids, the lower the oxygen content. It follows that the construction of a hypoxic microenvironment is the key point of in vitro experimental investigation. However, current methods of cellular research cannot realize precise control of oxygenation levels at the microscale, and the development of microfluidic platforms can overcome the inherent limitations of these methods. In addition to discussing the characteristics of the hypoxic microenvironment in bone tissue, this review will discuss various methods of constructing oxygen gradients in vitro and measuring oxygen tension from the microscale based on microfluidic technology. This integration of advantages and disadvantages to perfect the experimental study will help us to study the physiological responses of cells under more physiological-relevant conditions and provide a new strategy for future research on various in vitro cell biomedicines.

High-Frequency versus Low-Frequency Spinal Cord Stimulation in Treatment of Chronic Limb-Threatening Ischemia: Short-Term Results of a Randomized Trial

Introduction: The objective of the study is to determine if high-frequency (1 kHz) spinal cord stimulation (SCS) is better than low-frequency SCS for pain relief in chronic limb-threatening ischemia (CLTI). Methods: HEAL-SCS trial was designed as an open-label, parallel-group, single-center randomized study with a 1:1 allocation ratio. The trial was conducted in Meshalkin National Medical Research Center between August 2018 and February 2020. Total 56 patients underwent screening, 50 were enrolled, 6 were rejected. The participants were randomized into 2 cohorts of 25 patients each by an external coordinator using an online tool. A neurosurgeon and a vascular surgeon both examined all patients and estimated the pain intensity using visual analog scale (VAS), quality of life with short-form-36 health survey (SF-36), and functional status by walking impairment questionnaire (WIQ) at 3 and 12 months. Tissue perfusion was evaluated for 34 patients using transcutaneous oxygen tension measurement (TcPO₂) at baseline and in 12 months. Results: All 50 patients (84% men, median age 66.5 y.o) were available for primary outcome assessment 3 and 12 months after implantation. Intention-to-treat analysis demonstrated comparative advantage of HF-SCS over LF-SCS at 3 months with mean VAS score 2.8 (95% CI, 2.4; 3.2) and 3.3 (95% CI, 3.0; 3.6), respectively (p = 0.031). Clinical superiority of HF-SCS persisted at 12-month follow-up (p < 0.001). HF-SCS produced significantly greater pain relief by WIQ at 3 (p < 0.001) and 12 months (p = 0.009). Despite stair-climbing ability was better in HF-SCS group (p = 0.02), no significant difference between groups was found at 1-year post-op in terms of speed (p = 0.92) and distance scores (p = 0.68). Accordingly, the general and mental health domains of SF-36 were significantly better in HF-SCS at 12 months. Despite a tendency toward better resting oxygen pressure in HF-SCS group, there was no intergroup difference by TcPO₂ (p = 0.076). Only 1 patient (2%) required above-the-knee amputation at 10 months after LF-SCS implantation. Conclusion: High-frequency SCS provides better pain relief, life quality, and functional performance in patients with CLTI during short-term follow-up. The lack of perfusion difference between high-frequency and conventional SCS requires further examination to the possible long-term advantages of the method.

Effects of changes in inspired oxygen fraction on urinary oxygen tension measurements

BackgroundContinuous measurement of urinary PO2 (PuO2) is being applied to indirectly monitor renal medullary PO2. However, when applied to critically ill patients with shock, its measurement may be affected by changes in FiO2 and PaO2 and potential associated O2 diffusion between urine and ureteric or bladder tissue. We aimed to investigate PuO2 measurements in septic shock patients with a fiberoptic luminescence optode inserted into the urinary catheter lumen in relation to episodes of FiO2 change. We also evaluated medullary and urinary oxygen tension values in Merino ewes at two different FiO2 levels.ResultsIn 10 human patients, there were 32 FiO2 decreases and 31 increases in FiO2. Median pre-decrease FiO2 was 0.36 [0.30, 0.39] and median post-decrease FiO2 was 0.30 [0.23, 0.30], p = 0.006. PaO2 levels decreased from 83 mmHg [77, 94] to 72 [62, 80] mmHg, p = 0.009. However, PuO2 was 23.2 mmHg [20.5, 29.0] before and 24.2 mmHg [20.6, 26.3] after the intervention (p = 0.56). The median pre-increase FiO2 was 0.30 [0.21, 0.30] and median post-increase FiO2 was 0.35 [0.30, 0.40], p = 0.008. PaO2 levels increased from 64 mmHg [58, 72 mmHg] to 71 mmHg [70, 100], p = 0.04. However, PuO2 was 25.0 mmHg [IQR: 20.7, 26.8] before and 24.3 mmHg [IQR: 20.7, 26.3] after the intervention (p = 0.65). A mixed linear regression model showed a weak correlation between the variation in PaO2 and the variation in PuO2 values. In 9 Merino ewes, when comparing oxygen tension levels between FiO2 of 0.21 and 0.40, medullary values did not differ (25.1 ± 13.4 mmHg vs. 27.9 ± 15.4 mmHg, respectively, p = 0.6766) and this was similar to urinary oxygen values (27.1 ± 6.17 mmHg vs. 29.7 ± 4.41 mmHg, respectively, p = 0.3192).ConclusionsChanges in FiO2 and PaO2 within the context of usual care did not affect PuO2. Our findings were supported by experimental data and suggest that PuO2 can be used as biomarker of medullary oxygenation irrespective of FiO2.

Therapeutic evaluation of calciphylaxis by transcutaneous oxygen tension measurement in a case treated with a combined regimen including sodium thiosulphate

Therapeutic evaluation of calciphylaxis by transcutaneous oxygen tension measurement in a case treated with a combined regimen including sodium thiosulphate

High-frequency spinal cord stimulation in treatment of chronic limb-threatening ischemia (HEAL-SCS): short-term results of a randomized trial

Background. Critical limb ischemia is defined as persistent ischemic pain attributed to a variety of severely compromised blood flow to affected extremities. The treatment of non-reconstructable critical limb ischemia is still challenging; the amputation rate was 9.3%, and mortality rate was 23.2% within 24 months. Spinal cord stimulation (SCS) has become an alternative clinical practice for the treatment of intractable pain of the extremities.Aim. To determine whether high-frequency spinal cord stimulation (SCS) is better than low-frequency SCS for pain relief in chronic limb-threatening ischemia treatment.Methods. Throughout enrollment 56 patients were examined, of whom 6 rejected to participate in the study. The participants were randomly allocated to high-frequency (HF) or low frequency (LF)-SCS groups of 25 patients each by an external statistician, using an online tool. The patients were examined by a neurosurgeon and a vascular surgeon to assess pain intensity by visual analog scale, quality of life by short-form-36 health survey (SF-36), and functional status by walking impairment questionnaire in 3 and 12 months. Tissue perfusion by transcutaneous oxygen tension measurement was also measured in 12 months.Results. Intention-to-treat analysis demonstrated comparative advantage of HF-SCS over LF-SCS in 3 months with mean visual analog scale score 2.8 [95% CI, 2.4; 3.2] and 3.3 [95% CI, 3.0; 3.6] respectively (p = 0.031). Clinical superiority of HF-SCS persisted at 12 months follow up (p&lt;0.001). HF-SCS produces significantly greater pain relief by walking impairment questionnaire in 3 (p&lt;0.001) and 12 months (p = 0.009). Accordingly, general and mental health domains of SF-36 were significantly better in HF-SCS in 12 months. Despite a tendency toward better resting oxygen pressure in HF-SCS group, there was no intergroup difference by transcutaneous oxygen tension (p = 0.076).Conclusion. High-frequency spinal cord stimulation imposes better pain relief, life quality and functional activity in patients with chronic limb-threatening ischemia in short-term follow up.

Bilateral Nephrectomy Impairs Cerebral Oxygen Delivery After Acute Hemodilution Anemia in Rats

HypothesisWe hypothesize that renal sensing of hypoxia is essential for activation of cardiovascular responses needed to maintain cerebral oxygen delivery during acute anemia and that bilateral nephrectomy will negatively affect brain oxygen delivery during acute hemodilutional anemia.MethodsAll experiments were approved by the Animal Care and Use Committee at St. Michael’s Hospital and conducted in accordance with ARRIVE‐2 guidelines. Sham or bilateral nephrectomy (n=5) were performed on isoflurane anesthetized Sprague‐Dawley rats prior to performing acute hemodilution (50% estimated blood volume) 1:1 with 6% hydroxyethyl starch. Heart rate (HR), mean arterial pressure (MAP) and rectal temperature were monitored continuously. Arterial blood gases and cooximetry samples were measured before and after hemodilution. Continuous measurements of brain microvascular oxygen tension (PbrO2) were measured via a phosphorescence quenching method using an intravascular oxygen probe, Oxyphor PdG4, and an OxyLED phosphorometer. Data were tested for normality and analysis performed by two‐way ANOVA with p&lt;0.05 taken to be significant.ResultsBilateral nephrectomy resulted in a reduction in baseline HR (p&lt;0.004). Hemodilution resulted in a comparable reduction in hemoglobin concentration in both groups (Sham: 5.1±0.3 g/dL; Nephrectomy: 4.2±0.4 g/dL) with no differences in arterial PaO2 or PaCO2. After hemodilution, HR increased significantly in both groups (p&lt;0.05). MAP tended to be lower in the bilateral nephrectomy group and decreased transiently in both groups following hemodilution (p&lt;0.01). Brain microvascular pO2 (PbrO2)was not significantly different between nephrectomy and sham at baseline. Post‐hemodilution the PbrO2 was significantly lower in nephrectomised rats (11.5±5.1 mmHg) compared to sham operated rats (25.4±11.3 mmHg) (p=0.031).ConclusionsWe observed that bilateral nephrectomy resulted in changes in baseline physiology, including a lower HR. Hemodilution resulted in a comparable reduction in hemoglobin concentration, without difference in PaO2 or PaCO2. MAP decreased more profoundly immediately after hemodilution in nephrectomised animals, and recovered with time. Nephrectomy resulted in a significant drop in brain microvascular pO2 (PbrO2) immediately after hemodilution. This was not observed in sham controls. These data suggest that the kidney serves an important sensing role during acute anemia which supports cardiovascular responses and preserves the adequacy of brain tissue oxygen delivery. Hypoxia sensing by the kidney, and other integrative systemic mechanisms, may be central to these findings.

Recovery of organ-specific tissue oxygen delivery at restrictive transfusion thresholds after fluid treatment in ovine haemorrhagic shock

BackgroundFluid resuscitation is the standard treatment to restore circulating blood volume and pressure after massive haemorrhage and shock. Packed red blood cells (PRBC) are transfused to restore haemoglobin levels. Restoration of microcirculatory flow and tissue oxygen delivery is critical for organ and patient survival, but these parameters are infrequently measured. Patient Blood Management is a multidisciplinary approach to manage and conserve a patient’s own blood, directing treatment options based on broad clinical assessment beyond haemoglobin alone, for which tissue perfusion and oxygenation could be useful. Our aim was to assess utility of non-invasive tissue-specific measures to compare PRBC transfusion with novel crystalloid treatments for haemorrhagic shock.MethodsA model of severe haemorrhagic shock was developed in an intensive care setting, with controlled haemorrhage in sheep according to pressure (mean arterial pressure 30–40 mmHg) and oxygen debt (lactate > 4 mM) targets. We compared PRBC transfusion to fluid resuscitation with either PlasmaLyte or a novel crystalloid. Efficacy was assessed according to recovery of haemodynamic parameters and non-invasive measures of sublingual microcirculatory flow, regional tissue oxygen saturation, repayment of oxygen debt (arterial lactate), and a panel of inflammatory and organ function markers. Invasive measurements of tissue perfusion, oxygen tension and lactate levels were performed in brain, kidney, liver, and skeletal muscle. Outcomes were assessed during 4 h treatment and post-mortem, and analysed by one- and two-way ANOVA.ResultsEach treatment restored haemodynamic and tissue oxygen delivery parameters equivalently (p > 0.05), despite haemodilution after crystalloid infusion to haemoglobin concentrations below 70 g/L (p < 0.001). Recovery of vital organ-specific perfusion and oxygen tension commenced shortly before non-invasive measures improved. Lactate declined in all tissues and correlated with arterial lactate levels (p < 0.0001). The novel crystalloid supported rapid peripheral vasodilation (p = 0.014) and tended to achieve tissue oxygen delivery targets earlier. PRBC supported earlier renal oxygen delivery (p = 0.012) but delayed peripheral perfusion (p = 0.034).ConclusionsCrystalloids supported vital organ oxygen delivery after massive haemorrhage, despite haemodilution to < 70 g/L, confirming that restrictive transfusion thresholds are appropriate to support oxygen delivery. Non-invasive tissue perfusion and oximetry technologies merit further clinical appraisal to guide treatment for massive haemorrhage in the context of Patient Blood Management.

Paired 18F-Fluorodeoxyglucose (18F-FDG), and 64Cu-Copper(II)-diacetyl-bis(N(4)-methylthiosemicarbazone) (64Cu-ATSM) PET Scans in Dogs with Spontaneous Tumors and Evaluation for Hypoxia-Directed Therapy.

Hypoxia is associated with neoplastic tissue, protecting cancer cells from death by irradiation and chemotherapy. Identification of hypoxic volume of tumors could optimize patient selection for hypoxia-directed medical, immunological, and radiation therapies. Clostridium novyi-NT (CNV-NT) is an oncolytic bacterium derived from attenuated wild-type Clostridium novyi spores, which germinates exclusively in the anaerobic core of tumors with low-oxygen content. The hypothesis was that 64Cu-ATSM would localize to regions of hypoxia, and that greater hypoxic volume would result in greater germination of Clostridium novyi-NT (CNV-NT). Tumor-bearing companion dogs were recruited to a veterinary clinical trial. Dogs received a CT scan, 18F-FDG PET scan (74 MBq) and 64Cu-ATSM PET scan (74 MBq). Scan regions of interest were defined as the highest 20% of counts/voxel for each PET scan, and regions with voxels overlapping between the two scans. Maximum standardized uptake value (MaxSUV) and threshold volume were calculated. Direct oximetry was performed in select tumors. Tumor types evaluated included nerve sheath tumor (10), apocrine carcinoma (1), melanoma (3) and oral sarcoma (6). MaxSUVATSM ranged from 0.3-6.6. Measured oxygen tension ranged from 0.05-89.9 mmHg. Inverse of MaxSUVATSM had a linear relationship with oxygen tension (R2 = 0.53, P = 0.0048). Hypoxia <8 mmHg was associated with an SUVATSM > 1.0. Hypoxic volume ranged from 0 to 100% of gross tumor volume (GTV) and MaxSUVATSM was positively correlated with hypoxic volume (R = 0.674; P = 0.0001), but not GTV (P = 0.182). Tumor hypoxic volume was heterogeneous in location and distribution. 64Cu-ATSM-avid regions were associated with differential CT attenuation. Hypoxic volume did not predict CNV-NT germination. 64Cu-ATSM PET scanning predicts hypoxia patterns within spontaneously occurring tumors of dogs as measured by direct oxymetry. Total tumor volume does not accurately predict degree or proportion of tumor hypoxia.

Intra-operative and early post-operative prediction of cardiac surgery-associated acute kidney injury: Urinary oxygen tension compared with plasma and urinary biomarkers.

Acute kidney injury (AKI) is a common and serious post-operative complication of cardiac surgery. The value of a predictive biomarker is determined not only by its predictive efficacy, but also by how early this prediction can be made. For a biomarker of cardiac surgery-associated AKI, this is ideally during the intra-operative period. Therefore, in 82 adult patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB), we prospectively compared the predictive efficacy of various blood and urinary biomarkers with that of continuous measurement of urinary oxygen tension (UPO2 ) at pre-determined intra- and post-operative time-points. None of the blood or urine biomarkers we studied showed predictive efficacy for post-operative AKI when measured intra-operatively. When treated as a binary variable (≤ or > median for the whole cohort), the earliest excess risk of AKI was predicted by an increase in urinary neutrophil gelatinase-associated lipocalin (NGAL) at 3h after entry into the intensive care unit (odds ratio [95% confidence limits], 2.86 [1.14-7.21], p=0.03). Corresponding time-points were 6h for serum creatinine (3.59 [1.40-9.20], p=0.008), and 24h for plasma NGAL (4.54 [1.73-11.90], p=0.002) and serum cystatin C (6.38 [2.35-17.27], p=0.001). In contrast, indices of intra-operative urinary hypoxia predicted AKI after weaning from CPB, and in the case of a fall in UPO2 to ≤10mmHg, during the rewarming phase of CPB (3.00 [1.19-7.56], p=0.02). We conclude that continuous measurement of UPO2 predicts AKI earlier than plasma or urinary NGAL, serum cystatin C, or early post-operative changes in serum creatinine.

Predicting oxygen tension along the ureter

Continuous measurement of bladder urine oxygen tension (Po2) is a method to potentially detect renal medullary hypoxia in patients at risk of acute kidney injury (AKI). To assess its practicality, we developed a computational model of the peristaltic movement of a urine bolus along the ureter and the oxygen exchange between the bolus and ureter wall. This model quantifies the changes in urine Po2 as urine transits from the renal pelvis to the bladder. The model parameters were calibrated using experimental data in rabbits, such that most of the model predictions are within ±1 SE of the reported mean in the experiment, with the average percent difference being 7.0%. Based on parametric experiments performed using a model scaled to the geometric dimensions of a human ureter, we found that bladder urine Po2 is strongly dependent on the bolus volume (i.e., bolus volume-to-surface area ratio), especially at a volume less than its physiological (baseline) volume (<0.2 mL). For the model assumptions, changes in peristaltic frequency resulted in a minimal change in bladder urine Po2 (<1 mmHg). The model also predicted that there exists a family of linear relationships between the bladder-urine Po2 and pelvic urine Po2 for different input conditions. We conclude that it may technically be possible to predict renal medullary Po2 based on the measurement of bladder urine Po2, provided that there are accurate real-time measurements of model input parameters.NEW & NOTEWORTHY Measurement of bladder urine oxygen tension has been proposed as a new method to potentially detect the risk of acute kidney injury in patients. A computational model of oxygen exchange between urine bolus and ureteral tissue shows that it may be technically possible to determine the risk of acute kidney injury based on the measurement of bladder urine oxygen tension, provided that the measurement data are properly interpreted via a computational model.

Optical Oxygen Sensor Patch Printed with Polystyrene Microparticles-based Ink on Flexible Substrate.

Optical oxygen sensors based on photoluminescence quenching have gained increasing attention as a superior method for continuous monitoring of oxygen in a growing number of applications. A simple and low-cost fabrication technique was developed to produce sensor arrays capable of two-dimensional oxygen tension measurement. Sensor patches were printed on polyvinylidene chloride film using an oxygen-sensitive ink cocktail, prepared by immobilizing Pt(II) mesotetra(pentafluorophenyl)porphine (PtTFPP) in monodispersed polystyrene microparticles. The dispersion media of the ink cocktail, high molecular weight polyvinyl pyrrolidone suspended in 50% ethanol (v/v in water), allowed adhesion promotion and compatibility with most common polymeric substrates. Ink phosphorescence intensity was found to vary primarily with fluorophore concentration and to a lesser extent with polystyrene particle size. The sensor performance was investigated as a function of oxygen concentrations employing two different techniques: a multi-frequency phase fluorometer and smart phone-based image acquisition. The printed sensor patch showed fast and repetitive response over 0-21% oxygen concentrations with high linearity (with R2 >0.99) in a Stern-Volmer plot, and sensitivity of I0/I21 >1.55. The optical sensor response on a surface was investigated further using two-dimensional images which were captured and analyzed under different oxygen environment. Printed sensor patch along with imaging read-out technique make an ideal platform for early detection of surface wounds associated with tissue oxygen.

Right ventricular myocardial oxygen tension is reduced in monocrotaline-induced pulmonary hypertension in the rat and restored by myo-inositol trispyrophosphate

Pulmonary hypertension (PH) initially results in compensatory right ventricular (RV) hypertrophy, but eventually in RV failure. This transition is poorly understood, but may be triggered by hypoxia. Measurements of RV oxygen tension (pO2) in PH are lacking. We hypothesized that RV hypoxia occurs in monocrotaline-induced PH in rats and that myo-inositol trispyrophosphate (ITPP), facilitating oxygen dissociation from hemoglobin, can relieve it. Rats received monocrotaline (PH) or saline (control) and 24 days later echocardiograms, pressure–volume loops were obtained and myocardial pO2 was measured using a fluorescent probe. In PH mean pulmonary artery pressure more than doubled (35 ± 5 vs. 15 ± 2 in control), RV was hypertrophied, though its contractility was augmented. RV and LV pO2 was 32 ± 5 and 15 ± 8 mmHg, respectively, in control rats. In PH RV pO2 was reduced to 18 ± 9 mmHg, while LV pO2 was unchanged. RV pO2 correlated with RV diastolic wall stress (negatively) and LV systolic pressure (positively). Acute ITPP administration did not affect RV or LV pO2 in control animals, but increased RV pO2 to 26 ± 5 mmHg without affecting LV pO2 in PH. RV oxygen balance is impaired in PH and as such can be an important target for PH therapy. ITPP may be one of such potential therapies.

The influence of low- intensity laser irradiation versus hyperbaric oxygen therapy on transcutaneous oxygen tension in chronic diabetic foot ulcers: a controlled randomized trial.

Evaluation of the stage and severity of the chronic diabetic foot ulcer (CDFU) is vital to increase the healing rate andto select the suitable treatment. We aim to assess the influence of low-intensity laser irradiation (LILI) and hyperbaric oxygenation therapy (HBOT) to acceleratethe CDFU healing thru the transcutaneous oxygen tension (TcPO2) measurements. Seventy-five diabetic patients (type 2) of both genders, their ages ranged from 40-65years with CDFUs (duration of ulcer < 6weeks). All patients were randomly assigned into LILI, HBOT, and the control group. Measurement of TcPO2 using transcutaneous oximetry was performed for all patients once in the baseline and consequently in the second, fourth, and sixth- weeks duration. LILI utilized by a 33-diode cluster contact applicator with output power 1440 mW, energy density (fluency) was adjusted for 4J/Cm2 at 10kHz, and for 8min per session, three times per week for a total of consecutive 6weeks. HBOT was pressurized up to 2.5 ATA and patients delivered 100% oxygen for 60min per session for 30 sessions. The Control group received conventional wound care only, twice daily, with saline and apply a new bandage after cleaning. MANOVA revealed a statistically insignificant difference in the control group, while statistically significant improvement in both the LILI and HBOT groups. The intergroup comparisons showed an insignificant statistical difference in the pre-test, while highly statistically significant differences for the three post-measures in favor of HBOT and LILI groups. The percentage of improvement of the HBOT group was higher than LILI. Post-hoc test using the least significant difference (LSD) revealed statistically significant differences of HBOT in favor of the LILI group. Both LILI and HBOT may be used as adjunctive methods to improve TcPO2 that accelerate healing in CDFUs. HBOT may be favorable in the improvement of TcPO2 than LILI.

Feasibility of Photo-Optical Transcutaneous Oxygen Tension Measurement During Revascularization of the Lower Extremity

ObjectivesA novel approach in the evaluation of peripheral arterial disease is the photo-optical oxygen tension measurement (pTCpO2). This modality is suggested to be more practical in use in comparison to standard electro-chemical oxygen tension measurement. Hence, pTCpO2 might be of added value to evaluate revascularization of the lower extremities peri-procedural. We conducted a preliminary feasibility study to analyze the potential of pTCpO2 during revascularization. MethodsTen patients scheduled for revascularization of the lower extremities were enrolled. pTCpO2 values of the affected lower extremity were measured pre-operatively, during revascularization and after revascularization. Results were compared to the pre- and postoperative ankle-brachial index (ABI) and to perioperative angiography. Primary endpoint was the feasibility of perioperative pTCpO2 measurement. Secondary endpoints were concordance between pTCpO2, ABI, angiography and clinical outcome. ResultsTwo out of twelve measurements were unsuccessful. Eight out of ten patients experienced significant clinical improvement and pTCpO2 increase. Two patients that did not experience clinical improvement corresponded with no changes in intraoperative angiography and without increase in ABI or pTCpO2. A significant and strong correlation was found between prior and after revascularization ABI and pTCpO2 measurements (r = 0.82 P = 0.04). ConclusionsPhoto-optical transcutaneous oxygen tension measurement may serve as an intraoperative tool to evaluate the success of revascularization. pTCpO2 could be an alternative for the ABI to determine the success of lower extremity revascularization.

Comparison of Photo-optical Transcutaneous Oxygen Tension Measurement with Electro-chemical Transcutaneous Oxygen Tension Measurement in Patients with Arterial Claudication

Photo-optical TCpO2 (pTCpO2) has been proposed as a new method to determine the partial oxygen pressure of the lower extremity in patients with peripheral arterial disease. It is aimed to determine the level of agreement between pTCpO2 and the traditional electro-chemical transcutaneous oxygen tension measurement (eTCpO2). Eighteen patients with intermittent claudication underwent simultaneous ankle-brachial index measurement, toe-pressure, pTCpO2 and eTCpO2 tests. Oxygen tension levels were measured on anterior chest and calf prior in rest (T0), during induced ischemia (T1) and after blood flow restoration (T2). TCpO2 agreement was assessed according to the principles of Bland and Altman. Absolute average TCpO2 values differed between eTCpO2 and pTCpO2 for calf in T2 (38,1 mmHg (σ 14,4) vs. 49,8 (σ 22.3) with P=0.35). The Bland-Altman plots demonstrated eTCpO2 and pTCpO2 bias of 3,7 mmHg (σ 18,8), 11,6 mmHg (σ 17,6) and 6,7 mmHg (σ 23,5) for T0, T1 and T2 for the calf. pTCpO2 is in agreement with eTCpO2 in measuring pO2 levels of the lower extremity in rest and during induced ischemia in patients with vascular claudication. The large variability between eTCpO2 and pTCpO2 should be accounted for, while pTCpO2 values have a tendency to demonstrate higher values in comparison to eTCpO2.

Soil oxygen and water dynamics underlying hypoxic conditions in the root-zone of avocado irrigated with treated wastewater in clay soil

Alternative water sources for agriculture are in high demand in a world with diminishing fresh water (FW) availability. Treated wastewater (TWW) offers a reliable alternative, but increasing evidence is pointing to damage to TWW irrigated orchards planted in clay soils related to soil hypoxia. The mechanisms responsible for this hypoxia have not been extensively studied to date. The aim of this study was to elucidate meaningful insights into the mechanisms responsible for the hypoxia in TWW irrigated orchards planted in clay soils using a novel approach whereby parameters describing the soil oxygen and water temporal dynamics are analyzed. To that end, soil oxygen and soil water tension (SWT) measurements from a two year field experiment comparing TWW to FW irrigation in an avocado orchard planted in a clay soil (60 % clay) were used. The deterioration in oxygen levels occurred as the irrigation season progressed, and the oxygen availability decreased with depth (10–35 cm depth). During August-September, when the lowest oxygen concentrations were measured, the water content at which oxygen supply matched oxygen consumption at 35-cm depth did not differ between treatments (∼50 mbar), but the TWW irrigated soil experienced ∼47 % more time at wetter conditions. Lower oxygen decline rates were observed in the TWW irrigated plots which countered the previous concept that TWW leads to increased soil oxygen consumption. The findings point towards the rate of soil drying as the prime cause of differences – TWW irrigated plots dried in a rate which is nearly 4-times smaller than that in FW irrigated plots during the dark and light hours, reflecting slower drainage and water uptake respectively. It is suggested that soil hypoxia induced by the low soil drainage in TWW irrigated clay soils impairs tree water uptake, which further hinders the soil oxygen levels. Based on these results management tools are suggested to allow sustainable irrigation with TWW in the future. Furthermore, the work demonstrates how analysis of parameters describing the oxygen hourly changes can be utilized to gain mechanistic insights unto processes affecting the oxygen regime in the soil.

Individualized Brain Tissue Oxygen-Monitoring Probe Placement Helps to Guide Therapy and Optimizes Outcome in Neurocritical Care

Background/ObjectiveIn order to monitor tissue oxygenation in patients with acute neurological disorders, probes for measurement of brain tissue oxygen tension (ptO2) are often placed non-specifically in a right frontal lobe location. To improve the value of ptO2 monitoring, placement of the probe into a specific area of interest is desirable. We present a technique using CT-guidance to place the ptO2 probe in a particular area of interest based on the individual patient’s pathology.MethodsIn this retrospective cohort study, we analyzed imaging and clinical data from all patients who underwent CT-guided ptO2 probe placement at our institution between October 2017 and April 2019. Primary endpoint was successful placement of the probe in a particular area of interest rated by two independent reviewers. Secondary outcomes were complications from probe insertion, clinical consequences from ptO2 measurements, clinical outcome according to the modified Rankin Scale (mRS) as well as development of ischemia on follow-up imaging. A historical control group was selected from patients who underwent conventional ptO2 probe placement between January 2010 and October 2017.ResultsEleven patients had 16 CT-guided probes inserted. In 15 (93.75%) probes, both raters agreed on the correct placement in the area of interest. Each probe triggered on average 0.48 diagnostic or therapeutic adjustments per day. Only one infarction within the vascular territory of a probe was found on follow-up imaging. Eight out of eleven patients (72.73%) reached a good outcome (mRS ≤ 3). In comparison, conventionally placed probes triggered less diagnostic and therapeutic adjustment per day (p = 0.007). Outcome was worse in the control group (p = 0.024).ConclusionCT-guided probe insertion is a reliable and easy technique to place a ptO2 probe in a particular area of interest in patients with potentially reduced cerebral oxygen supply. By adjusting treatment aggressively according to this individualized monitoring data, clinical outcome may improve.