Tissue Oxygen Content Research Articles

Hyperbaric oxygen therapy improves motor symptoms, sleep, and cognitive dysfunctions in Parkinson's disease.

To systematically analyze the therapeutic effectiveness of hyperbaric oxygen therapy compared with conventional drug therapy in patients with Parkinson's disease. PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Database, searched to the end of March 2023. Two authors independently screened and abstracted data from each trial. The primary outcome measures included the efficacy rate and the Unified Parkinson's Disease Rating Scale III (UPDRS III). Secondary outcome measures included the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Hamilton Depression Scale (HAMD), Minimum Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Hoehn-Yahr staging. Thirteen studies with a total of 958 participants were included in the meta-analysis. After intervention, the experimental group exhibited a higher treatment efficacy rate compared to the control group [OR=3.18, 95%CI (1.60, 6.33), P<0.01], a lower UPDRS III score [MD=-2.96, 95%CI (-4.31, -1.61), P<0.01], and lower Hoehn-Yahr staging [MD=-0.14, 95%CI (-0.26, -0.02), P<0.01]. The experimental group also outperformed the control group in non-motor symptoms, with higher scores in MoCA, PSQI, and ESS [SMD=0.65, 95%CI (0.45, 0.85), P<0.01], [MD=-2.52, 95%CI (-2.85, -2.18), P<0.01], and [MD=-3.30, 95%CI (-3.77, -2.83), P<0.01], respectively. Hyperbaric oxygen therapy improves motor function, relieves the severity of the disease, ameliorates cognitive function, and improves sleep quality while alleviating excessive daytime sleepiness in patients with Parkinson's disease. The therapeutic mechanism of hyperbaric oxygen therapy may be related to increased cerebral tissue oxygen content, which contributes to anti-hypoxic, anti-inflammatory, anti-apoptotic, and antioxidant stress.

Validation of dual-energy CT-based composition analysis using fresh animal tissues and composition-optimized tissue equivalent samples

Objective. Proton therapy allows for highly conformal dose deposition, but is sensitive to range uncertainties. Several approaches currently under development measure composition-dependent secondary radiation to monitor the delivered proton range in-vivo. To fully utilize these methods, an estimate of the elemental composition of the patient’s tissue is often needed. Approach. A published dual-energy computed tomography (DECT)-based composition-extraction algorithm was validated against reference compositions obtained with two independent methods. For this purpose, a set of phantoms containing either fresh porcine tissue or tissue-mimicking samples with known, realistic compositions were imaged with a CT scanner at two different energies. Then, the prompt gamma-ray (PG) signal during proton irradiation was measured with a PG detector prototype. The PG workflow used pre-calculated Monte Carlo simulations to obtain an optimized estimate of the sample’s carbon and oxygen contents. The compositions were also assessed with chemical combustion analysis (CCA), and the stopping-power ratio (SPR) was measured with a multi-layer ionization chamber. The DECT images were used to calculate SPR-, density- and elemental composition maps, and to assign voxel-wise compositions from a selection of human tissues. For a more comprehensive set of reference compositions, the original selection was extended by 135 additional tissues, corresponding to spongiosa, high-density bones and low-density tissues. Results. The root-mean-square error for the soft tissue carbon and oxygen content was 8.5 wt% and 9.5 wt% relative to the CCA result and 2.1 wt% and 10.3 wt% relative to the PG result. The phosphorous and calcium content were predicted within 0.4 wt% and 1.1 wt% of the CCA results, respectively. The largest discrepancies were encountered in samples whose composition deviated the most from tabulated compositions or that were more inhomogeneous. Significance. Overall, DECT-based composition estimations of relevant elements were in equal or better agreement with the ground truth than the established SECT-approach and could contribute to in-vivo dose verification measurements.

Long-Term Luminescence Kinetics of Erythrosine in Breast Tissue in vitro

The kinetics of delayed fluorescence and phosphorescence of the photosensitizer erythrosine in fragments of normal tissues and malignant breast tumors of patients at an oncology clinic was studied in vitro. It has been shown that the kinetics of delayed fluorescence of the dye is formed as a superposition of signals of thermally activated luminescence and luminescence resulting from singlet-triplet annihilation of photosensitizer molecules and singlet oxygen. The quenching of the annihilation component of delayed fluorescence was discovered when molecules were excited by a series of n pulses with a frequency of 5–10 Hz. The shape of the delayed fluorescence curve, the intensity and duration of the afterglow of dye molecules are determined by the ratio of the rates of consumption/regeneration of oxygen content in tissues. A correlation between delayed fluorescence indicators and the clinical and morphological characteristics of tumors has been established, and the application of the results in rapid optical diagnostics of tissues is discussed.

Sodium-dependent glucose transporter 2 inhibitor alleviates renal lipid deposition and improves renal oxygenation levels in newly diagnosed type 2 diabetes mellitus patients: a randomized controlled trial

BackgroundSodium-dependent glucose transporter 2 inhibitor (SGLT2i) has the advantages of effectively lowering blood glucose levels and improving renal outcomes in diabetic patients. This study evaluated the effect of canagliflozin on intrarenal lipid content and oxygenation in newly diagnosed type 2 diabetes mellitus (T2DM) patients.MethodsA total of 64 newly diagnosed T2DM patients with normal renal function were randomly divided into canagliflozin (n = 33) and glimepiride control (n = 31) groups. All patients underwent functional magnetic resonance imaging (fMRI) scanning to assay patients' intrarenal lipid content and oxygenation level before and after 24 weeks of treatment. Furthermore, the relationship between body mass index and intrarenal lipid content in T2DM patients was analyzed and the correlation between changes in intrarenal lipid content and improvements in renal hypoxia was further assessed.ResultsThe canagliflozin group had a greater decrease in body weight and blood uric acid level than the glimepiride group (all P < 0.05). The intrarenal lipid content could be significantly reduced after canagliflozin treatment for 24 weeks. The R2* values, a parameter for quantifying the oxygen content in tissues and is inversely related to the oxygen content, of the renal cortex and medulla in the canagliflozin group decreased from the baseline by 6.40% (P < 0.01) and 12.09% (P = 0.000007), respectively. In addition, the degree of reduction of fat fraction (ΔFF) in the kidneys of the canagliflozin group was correlated with the degree of improvement of oxygenation level (ΔR2*) in the renal cortex (r = 0.422, P = 0.014).ConclusionsThe early renal protective effect of SGLT2i in newly diagnosed T2DM patients may be partly attributed to the amelioration of renal hypoxia via the alleviation of ectopic lipid deposition in the kidneys.Trial Registration: Chu Hsien-I Memorial Hospital of Tianjin Medical University (ChiCTR2000037951).

A physicochemical model of X-ray induced photodynamic therapy (X-PDT) with an emphasis on tissue oxygen concentration and oxygenation

X-PDT is one of the novel cancer treatment approaches that uses high penetration X-ray radiation to activate photosensitizers (PSs) placed in deep seated tumors. After PS activation, some reactive oxygen species (ROS) like singlet oxygen (1O2) are produced that are very toxic for adjacent cells. Efficiency of X-PDT depends on 1O2 quantum yield as well as X-ray mortality rate. Despite many studies have been modeled X-PDT, little is known about the investigation of tissue oxygen content in treatment outcome. In the present study, we predicted X-PDT efficiency through a feedback of physiological parameters of tumor microenvironment includes tissue oxygen and oxygenation properties. The introduced physicochemical model of X-PDT estimates 1O2 production in a vascularized and non-vascularized tumor under different tissue oxygen levels to predict cell death probability in tumor and adjacent normal tissue. The results emphasized the importance of molecular oxygen and the presence of a vascular network in predicting X-PDT efficiency.

Microneedle-assisted transdermal delivery of perfluorotripropylamine-based oxygenated emulsion gel loaded with 5-aminolevulinic acid for enhanced photodynamic therapy of cutaneous squamous cell carcinoma

Topical photodynamic therapy (TPDT) is a clinical treatment for cutaneous squamous cell carcinoma (CSCC). However, the therapeutic efficacy of TPDT for CSCC is significantly weakened by hypoxia, which is caused by the oxygen-poor environment of the skin and CSCC and by the high oxygen consumption of TPDT itself. To overcome these problems, we developed a topically applied perfluorotripropylamine-based oxygenated emulsion gel loaded with the photosensitizer 5-ALA (5-ALA-PBOEG) by a simple ultrasound-assisted emulsion method. With the aid of the microneedle roller, 5-ALA-PBOEG dramatically increased the accumulation of 5-ALA in the epidermis and the dermis, as well as throughout the dermis; a total of 67.6% ± 9.97% of the applied dose penetrated into and through the dermis, which is 19.1±3.2-fold that of the 5-ALA-PBOEG without microneedle treatment group, and 16.9±0.3-fold that of the aminolevulinic acid hydrochloride topical powder treatment group (p<0.001). Meanwhile, PBOEG enhanced the singlet oxygen yield of 5-ALA-induced protoporphyrin IX. The results of in vivo antitumor activity in human epidermoid carcinoma (A431) bearing mice showed that by increasing the oxygen content in tumor tissues, the developed 5-ALA-PBOEG plus microneedle treatment and laser irradiation showed better tumor growth inhibition than the respective control formulations. In addition, the results of safety studies, including the multiple-dose skin irritation study, allergy tests, and skin H&E staining, demonstrated the safety of 5-ALA-PBOEG plus microneedle treatment. In conclusion, the 5-ALA-PBOEG plus microneedle treatment shows great potential in the fight against CSCC and other skin cancers.

Effect of hyperbaric oxygen on post-stroke depression.

In patients with post-stroke depression (PSD) in diabetes, the situation may be more complex, requiring simultaneous treatment of blood glucose, depressive symptoms, and neurological dysfunction. Hyperbaric oxygen (HBO) therapy can improve tissue oxygen content and improve the situation of ischemia and hypoxia, thus playing a role in protecting brain cells and restoring the function of brain cells. However, there are few studies on HBO therapy for patients with PSD. This study explores the clinical efficacy of such therapy for stroke complicated with depression and diabetes mellitus, and to provide reference and basis for clinical treatment and development through the application of relevant rating scales and laboratory test indicators. To evaluate the clinical effects of HBO therapy on patients with diabetes with PSD. A total of 190 diabetic patients with PSD were randomly divided into observation and control groups (95 patients per group). The control group received escitalopram oxalate 10mg once a day for eight weeks. In addition, the ob-servation group was also given HBO therapy, once a day, five times a week, for eight weeks. The Montgomery Depression Rating Scale (MADRS), National Institutes of Health Stroke Scale (NIHSS), hypersensitive C-reactive protein, tumor necrosis factor (TNF)-α, and fasting glucose levels were compared. There were no significant differences in age, sex, or depression course between the groups (P > 0.05). After HBO treatment, MADRS scores in both groups decreased significantly (14.3 ± 5.2), and were significantly lower in the control group (18.1 ± 3.5). After HBO treatment, NIHSS scores in both groups decreased significantly, and scores in the observation group (12.2 ± 4.0) decreased more than in the control group (16.1 ± 3.4), the difference was statistically significant (P < 0.001). The levels of hypersensitive C-reactive protein and TNF-α in both groups were significantly decreased, and the observation group was significantly lower than the control group (P < 0.001). Fasting blood glucose levels in both groups decreased significantly, and those in the observation group decreased more (8.02 ± 1.10) than in the control group (9.26 ± 1.04), with statistical significance (t = -7.994, P < 0.001). HBO therapy can significantly improve depressive symptoms and neurological dysfunction in patients with PSD, and reduce the levels of hypersensitive C-reactive protein, TNF-α and fasting blood glucose.

Canagliflozin could improve the levels of renal oxygenation in newly diagnosed type 2 diabetes patients with normal renal function

ObjectiveTo evaluate the effects of canagliflozin on the renal oxygen level and blood perfusion in newly diagnosed type 2 diabetes mellitus (T2DM) patients with normal renal function. MethodsWe conducted a prospective, randomised, and drug-controlled trial to determine the reno-protective effect exerted by canagliflozin in newly diagnosed T2DM patients with normal renal function using blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) and arterial spin labelling MRI (ASL-MRI). This provides an experimental basis for a first-line of defence for the prevention of diabetic nephropathy. ResultsCanagliflozin induced a significant decrease in body weight and diastolic blood pressure compared with glimepiride (all p < 0.05). The high baseline mean estimated glomerular filtration rate (eGFR) in both groups was indicative of a GFR level at a relatively high status that was significantly alleviated after 24 weeks of canagliflozin treatment (change from baseline, p = 0.04, and change versus glimepiride control, p = 0.048). However, neither drug regimen significantly affected renal blood perfusion. The R2* values were inversely proportional to the tissue oxygen content. Compared to the baseline, 24 weeks of canagliflozin treatment decreased the R2* values of the renal cortex and medulla by 22.3% (p = 0.005) and 29.2% (p = 0.0002) respectively, and these decreases were significantly greater than in the glimepiride control group (p = 0.0004 and p = 0.02). ConclusionsCanagliflozin improved the levels of renal oxygenation in newly diagnosed T2DM patients with normal renal function independent of changes in renal blood perfusion.

Oxygen-release microspheres capable of releasing oxygen in response to environmental oxygen level to improve stem cell survival and tissue regeneration in ischemic hindlimbs

Stem cell transplantation has been extensively explored to promote ischemic limb vascularization and skeletal muscle regeneration. Yet the therapeutic efficacy is low due to limited cell survival under low oxygen environment of the ischemic limbs. Therefore, continuously oxygenating the transplanted cells has potential to increase their survival. During tissue regeneration, the number of blood vessels are gradually increased, leading to the elevation of tissue oxygen content. Accordingly, less exogenous oxygen is needed for the transplanted cells. Excessive oxygen may induce reactive oxygen species (ROS) formation, causing cell apoptosis. Thus, it is attractive to develop oxygen-release biomaterials that are responsive to the environmental oxygen level. Herein, we developed oxygen-release microspheres whose oxygen release was controlled by oxygen-responsive shell. The shell hydrophilicity and degradation rate decreased as the environmental oxygen level increased, leading to slower oxygen release. The microspheres were capable of directly releasing molecular oxygen, which are safer than those oxygen-release biomaterials that release hydrogen peroxide and rely on its decomposition to form oxygen. The released oxygen significantly enhanced mesenchymal stem cell (MSC) survival without inducing ROS production under hypoxic condition. Co-delivery of MSCs and microspheres to the mouse ischemic limbs ameliorated MSC survival, proliferation and paracrine effects under ischemic conditions. It also significantly accelerated angiogenesis, blood flow restoration, and skeletal muscle regeneration without provoking tissue inflammation. The above results demonstrate that the developed microspheres have potential to augment cell survival in ischemic tissues, and promote ischemic tissue regeneration in a safer and more efficient manner.

4-Octyl Itaconate Alleviates Lipopolysaccharide-Induced Acute Lung Injury in Mice by Inhibiting Oxidative Stress and Inflammation.

BackgroundAcute lung injury (ALI) is a fatal disease in the absence of pharmacological treatment. Oxidative stress and inflammation are closely related to ALI. Innate immune cells are the main source of reactive oxygen species (ROS). Macrophages play an extremely important role in ALI through the activation of inflammation and oxidative stress. Itaconate, a metabolite of tricarboxylic acid, has been reported to have strong antioxidant and anti-inflammatory effects. However, the role of itaconate in ALI is unclear. Herein, we use 4-octyl itaconate (OI), the cellular permeable derivate of itaconate, to study the effects of itaconate in vivo and in vitro.MethodsWe used OI to pretreat C57BL/6 mice and LPS-induced ALI models to illustrate the role of itaconate in acute lung injury. The mice were randomly divided into four groups: control group, OI (100 mg/kg) group, ALI Group, ALI + OI (50 mg/kg) group, and ALI + OI (100 mg/kg) group. RAW264.7 cells were used to further prove the role and mechanism of itaconate in vitro.ResultsAccording to the H&E staining of the lung, OI was observed to significantly reduce lung inflammation. The active oxygen content of tissues was also significantly reduced (P<0.05). OI reduced the accumulation of neutrophils and secretion of inflammatory factors in LPS-induced ALI (P<0.05). At the cellular level, OI also reduced oxidative stress and inflammation. Intervention with OI was also observed to upregulate the expression of nuclear factor erythroid 2-related factor-2 (Nrf-2) and Nrf-2 target genes in the lung tissue and RAW264.7 cells.ConclusionOI alleviates LPS-induced ALI. Moreover, the antioxidant and anti-inflammatory effects of OI might depend on the activation of Nrf-2. Therefore, OI might have therapeutic potential for the treatment of ALI.

The Use of Multispectral Imaging in DIEP Free Flap Perforator Selection: A Case Study.

SummaryPerforator selection is of paramount importance when performing a Deep Inferior Epigastric Perforator flap. Technological advancements within imaging modalities have proved invaluable in preoperative planning and intraoperative assessment. Computed tomographic angiography remains the gold standard for preoperative perforator mapping, while color ultrasound Doppler is considered more reliable for determining vessel caliber. Intraoperatively, an imaging modality that provides sequential, real-time assessment of various perforators’ supply to the flap would provide helpful insight to determine which perforator will optimize flap viability, especially of the most distal, lateral margins. Multispectral imaging, a variant of near infrared imaging, has emerged as an alternative method to assess tissue viability in the operating room as well as postoperatively. Unlike Spy technology, which is invasive and cost ineffective, the SnapshotNIR (KD203) is a handheld multispectral imaging device utilizing NIR to measure the oxygenation of the hemoglobin in the area to calculate the tissue oxygen content (StO2) displayed in a color image. The following case of a 46-year-old woman undergoing tertiary breast reconstruction for treatment of progressive grade 2 capsular contracture illustrates the utility and ease of KD203 application to intra-operative perforator determination in deep inferior epigastric perforator flap assessment.

Development of an International, Multicenter, Hyperbaric Oxygen Treatment Registry and Research Consortium: Protocol for Outcome Data Collection and Analysis.

BackgroundHyperbaric oxygen (HBO2)—oxygen at pressures higher than atmospheric—is approved for 14 indications by the Undersea and Hyperbaric Medical Society. HBO2’s main effect is to increase oxygen content in plasma and body tissues, which can counteract hypoxia or ischemia. Laboratory studies show that HBO2 has effects beyond relieving hypoxia (eg, promoting angiogenesis in irradiated tissue, anti-inflammatory effects, radiosensitization of tumors, hypoxia preconditioning, and fungal growth inhibition) and has potential to treat conditions such as inflammatory bowel disease and pyoderma gangrenosum. Lack of consistently collected outcome data on a large cohort of individuals receiving HBO2 therapy limits its use for both established and new indications. A course of therapy often involves 30-40 visits to a hyperbaric chamber, so the number of patients seen at any given center is constrained by chamber capacity. As a result, published HBO2 outcome data tend to be from small case series because few patients with a particular condition are treated at a given center. To solve this problem, a registry that collects and pools data systematically from multiple institutions has been established.ObjectiveThe aim of this study is to collect consistent outcome data across multiple hyperbaric centers to assess treatment effectiveness and establish a research consortium.MethodsA consortium of hyperbaric centers who have agreed to collect consistent outcome data on all patients seen has been assembled. Data are collected at each participating center using Research Electronic Data Capture (REDCap), a web-based, data collection system used frequently for research. Standard outcome measures have been defined for each condition, which are programmed into the REDCap data collection templates. Governance is through a consortium agreement that defines data security, data sharing, publications, liability, and other issues. Centers obtain Institutional Review Board (IRB) and ethics approval to participate, either from their own institutions or by relying on the IRB at the coordinating center at Dartmouth College. Dissemination will occur through a yearly report and by publications based on the data in the registry.ResultsEarly results from some common indications show significant pretreatment to posttreatment changes. Additional indications and outcome measures are being added using the procedures outlined in the consortium agreement.ConclusionsThe registry collects consistent outcome information for a therapy that needs further study and a stronger evidence base. It also overcomes the challenge of collecting data from an adequate number of patients for both established and emerging indications by combining data collection from multiple centers. The data entry requirements should be within the capabilities of existing staff at any given hyperbaric center. By using REDCap, the registry can be expanded to include detailed information on particular indications and long-term follow-up on selected patients without significantly increasing the basic data entry requirements. Through the registry, a network of enrolled hyperbaric centers has been established that provides the basis for a clinical trial network.International Registered Report Identifier (IRRID)DERR1-10.2196/18857

P1782INFLUENCE OF IMMUNOSUPPRESSIVE REGIMEN ON OXYGENATION AND DIFFUSIVITY OF KIDNEY TRANSPLANTS - ANALYSIS OF FUNCTIONAL MRI DATA FROM THE RANDOMIZED ZEUS STUDY

Abstract Background and Aims The ZEUS study was a multi-center open-label randomized controlled trial designed to investigate the effect of an early conversion from a calcineurin-inhibitor-based immunosuppression to a mammalian-target-of-rapamycin inhibitor-based regimen on graft function twelve months post-transplantation. Persistent improvement of renal function up to five years together with albeit higher rejection rates were found in the intervention group. In the context of an investigator-initiated local sub-study, functional magnetic resonance imaging (fMRI) was prospectively performed in a subset of the study population in order to non-invasively assess differences in renal graft oxygenation, diffusion and perfusion between groups and time-points using blood-oxygen level-dependent (BOLD)- and diffusion-weighted (DWI) MRI respectively. Method In the ZEUS trial, 300 de novo kidney graft recipients were randomized to continue ciclosporin (CsA) or be converted to everolimus (EVE) at 4.5 months post-transplant. Concomitant immunosuppression contained enteric-coated mycophenolic acid, steroids and basiliximab. From the 36 subjects included in the ZEUS study at our study center, sixteen were enrolled in the MRI sub-study. FMRI including BOLD-MRI and DWI was prospectively performed at month 4.5 and 12 post-transplantation on a 3 Tesla and 1.5 Tesla (n=3) MR scanner. Blinded image analysis was done by placing up to 24 regions of interest in cortex and medulla. BOLD-MRI yielded the relaxation rate R2*, a parameter indirectly proportional to tissue oxygen content, DWI yielded the perfusion-cleared apparent diffusion coefficient ADCD, a marker of tissue diffusivity, and the perfusion fraction FP, a marker of microperfusion. All data were analyzed using in-house custom-scripts written in IDL® and MATLAB®. Results After exclusion of subjects due to image quality, outlier values or missing data, BOLD data was analyzed in eight, DWI in ten subjects. Mean absolute values and standard deviations corresponded to published values. A clear cortico-medullary gradient was shown for R2* and FP values, but not for ADCD, corresponding to previous results. For all fMRI parameters, there was no change for the whole population from 4.5 to 12 months post-transplantation in cortex and medulla. FMRI parameters did not differ significantly between both medication groups at month 4.5. In BOLD, R2* values increased (decreased tissue oxygen) over time in the CsA-treated and decreased in the EVE-treated group in cortex and medulla. Similarly, R2* values at month 12 were higher in the CsA- vs. EVE-treated group; the low number of subjects having completed BOLD-MRI at month 12 precluded formal statistical testing. In DWI, ADCD decreased in the CsA-group over time, whereas it increased in the EVE-group in cortex and medulla (p=0.046). Likewise, ADCD at month 12 was lower by trend in the CsA- vs. EVE-treated group in both medulla and cortex. The change in ADCD from month 4.5 to month 12 significantly differed in cortex (p=0.033) and medulla (p=0.019) between treatment groups. There was no significant difference for FP between medication groups nor over time. Baseline renal function and blood pressure were comparable in both groups. Conclusion The R2* values obtained by BOLD point to reduced graft oxygenation on CsA and ameliorated graft oxygenation on EVE, possibly due to the known vasoconstrictor effect of calcineurin inhibitors. The observed decreased diffusivity by DWI on CsA might be due to increased tissue density in the context of beginning calcineurin inhibitor-induced interstitial fibrosis. There was no clear trend for microperfusion as assessed by FP. Limitations of this study are the low number of subjects available for analysis. In conclusion, this prospective sub-study of the ZEUS trial suggests an impact of immunosuppressive regimen on fMRI parameters of the renal graft.

Involvement of Recovery Processes in the Effects of Radioprotectors at the Cellular and Organismal Levels

A correlation between the effectiveness of the radioprotective action of cysteamine with the radiosensitivity of cells and their ability to recover from radiation damage was demonstrated for diploid yeast cells of S. cerevisiae. To demonstrate the involvement of the recovery processes in the mechanism for radioprotective action of the T1023 compound in animals, data on the survival of clonogenic bone marrow cells of mice exposed to ionizing radiation are presented. It is shown that the radioprotective effect of this compound can be realized not only at the physicochemical stage of formation of radiation damage due to a decrease in the oxygen content in tissues but also due to the post-radiation cell recovery at the biochemical stage. This is confirmed by the presence of the sigmoid part of the dose-response curve in the region of low doses of ionizing radiation.

The attenuated effect of remote ischemic conditioning on tissue oxygen saturation and heart rate variability in the patient undergoing cardiac surgery: a pilot study

Introduction Remote ischemic conditioning (RIC) has been proven to have organ-protective effects but clinical results for RIC have been inconsistent among cardiac surgery patients. Although there has been several hypothesis for these inconsistent result in cardiac surgery patient, it has not been proven, yet. Tissue oxygen saturation (StO2) and heart rate variability (HRV) reflect peripheral micro-circulation and autonomic nervous system activity, respectively. However, changes in these metrics have not been well-documented during RIC. We hypothesized that RIC effect may be attenuated in the patients undergoing cardiac surgery and that may be reflected on StO2 changes and HRV. We measured and analyzed the changes in StO2 and HRV during RIC in cardiac surgery patients and healthy volunteers. Methods Ten patients undergoing cardiac surgery and ten healthy male volunteers were included in this pilot study. Exclusion criteria were as follows: systolic or diastolic blood pressure >150 or >100 mmHg, body mass index 30 kg/m2, uncontrolled hypertension or diabetes mellitus, use of beta-blockers, any anomaly in the upper extremities, peripheral vascular disease or coagulopathy, and refusal to participate. Subjects received RIC treatment, consisting of four cycles of 5-min ischemia with cuff inflation to 200 mmHg followed by 5-min reperfusion by deflation of the cuff (which was applied to the upper arm). Changes in StO2, measured at the thenar eminence, and HRV, according to R-R intervals of the electrocardiogram, were recorded during RIC. Results During RIC, there was no difference between the two groups in baseline StO2, occlusion or recovery slope. The lowest StO2 during the ischemic period of RIC decreased in cardiac surgery patients (adjusted p = 0.042) but increased in healthy volunteers (adjusted p = 0.006). The mean difference between the groups in the percentage change of the lowest StO2 value was 20% (95% CI, 9–32%, p = 0.002). Among HRV parameters, the low-frequency domain, which corresponds to sympathetic system activity, increased after RIC in healthy volunteers, but not in the patient group (p = 0.028 and p = 0.169, respectively). Discussion Our results suggest that tissue oxygen content is depleted during RIC in cardiac surgery patients, but preserved in healthy volunteers. Sympathetic system activity seems to increase during RIC in healthy volunteers, while not being affected in cardiac surgery patients. These results show that RIC mechanisms may be attenuated in cardiac surgery patients.

Effects of ischaemic conditioning on tissue oxygen saturation and heart rate variability: an observational study.

ObjectiveIschaemic conditioning (IC) has organ-protective effects, but its clinical results have been inconsistent. Tissue oxygen saturation (StO2) and heart rate variability (HRV) reflect peripheral microcirculation and autonomic nervous system activity, but their changes during IC have not been well documented. We assessed StO2 and HRV during IC in patients undergoing cardiac surgery and healthy volunteers.MethodsTen patients undergoing cardiac surgery and 10 healthy male volunteers underwent remote IC (four 5-minute cycles of ischaemia/reperfusion) applied to the upper arm. Changes in StO2 at the thenar eminence and HRV according to the R-R intervals were recorded during IC.ResultsThe lowest StO2 during ischaemia significantly decreased in patients and significantly increased in volunteers. Among the HRV parameters, the low-frequency domain, which corresponds to sympathetic activity, significantly increased after IC in volunteers but not in patients. Other variables were similar between the groups.ConclusionsThese results suggest that the minimum tissue oxygen content is depleted during ischaemia in patients and preserved in healthy volunteers. Sympathetic nervous activity seems to increase after IC in healthy volunteers but remains unaffected in patients. Thus, IC may act differently between patients undergoing cardiac surgery and healthy subjects.

Injectable Oxygen Sensitive Chitosan Complex with High Oxygen Sensitivity and Stability to Oxidoreductants.

Various therapeutic approaches have been developed for vascularization of diseased tissues. To quickly and accurately evaluate efficacy of a therapy, reproducible monitoring of tissue oxygen concentration changes at the same tissue location by a minimally invasive or noninvasive spectroscopic approach represents a compelling strategy. Yet this cannot be achieved by any clinically available approaches. Magnetic-resonance-based method, electron paramagnetic resonance (EPR), has the potential to accomplish the goal. However, the existing small molecule EPR probes cannot maintain a consistent concentration at the same tissue location during vascularization period to acquire a stable EPR signal, and they cannot be implanted and/or retrieved by a minimally invasive approach such as injection. Herein, a polymeric, injectable, and degradable EPR probe was developed. The probe was based on the complex of chitosan and tetrathiatriarylmethyl (TAM) radical. The probe had high oxygen sensitivity and reproducibility. It was more stable than free TAM radical when exposed to oxidoreductants that commonly appear in diseased tissues. The probe maintained EPR signal intensity for 4 weeks in vitro and in vivo without changing oxygen sensitivity. It also exhibited excellent biocompatibility. The developed TAM/chitosan complex may be used for long-term detection of tissue oxygen content during therapies.

Injectable, thermosensitive, fast gelation, bioeliminable, and oxygen sensitive hydrogels

The decrease of tissue oxygen content due to pathological conditions leads to severe cell death and tissue damage. Restoration of tissue oxygen content is the primary treatment goal. To accurately and efficiently assess efficacy of a treatment, minimally invasive, and long-term detection of oxygen concentration in the same tissue location represents a clinically attractive strategy. Among the different oxygen concentration measurement approaches, electron paramagnetic resonance (EPR) has the potential to accomplish this. Yet there lacks injectable EPR probes that can maintain a consistent concentration at the same tissue location during treatment period to acquire a stable EPR signal, and can finally be eliminated from body without retrieval. Herein, we developed injectable and bioeliminable hydrogel-based polymeric EPR probes that exhibited fast gelation rate, slow weight loss rate, and high oxygen sensitivity. The probe was based on N-Isopropylacrylamide (NIPAAm), 2-hydroxyethyl methacrylate (HEMA), dimethyl-γ-butyrolactone acrylate (DBA), and tetrathiatriarylmethyl (TAM) radical. The injectable probes can be implanted into tissues using a minimally invasive injection approach. The high gelation rate (~10 s) allowed the probes to quickly solidify upon injection to have a high retention in tissues. The polymeric probes overcame the toxicity issue of current small molecule EPR probes. The probes can be gradually hydrolyzed. Upon complete hydrolysis, the probes became water soluble at 37 °C, thus having the potential to be removed from the body by urinary system. The probes showed slow weight loss rate so as to maintain EPR signal intensity for extended periods while retaining in a certain tissue location. The probes remained their high oxygen sensitivity after in vitro hydrolysis and in vivo implantation for 4 weeks. These hydrogel-based EPR probes have attractive properties for in vivo oxygen detection.

Blood oxygen level–dependent functional magnetic resonance imaging can evaluate the efficiency of transcatheter arterial chemoembolization in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is among the most common malignant tumors worldwide, and transcatheter arterial chemoembolization (TACE) technology has become the first-line treatment for advanced HCC. Another important, recently developed technique is blood oxygen level–dependent functional magnetic resonance imaging (BOLD-fMRI), which utilizes hemoglobin as an endogenous contrast agent and measures deoxygenated hemoglobin content by sampling the oxygen content of tissues, thus reflecting the hemodynamics and pathophysiologic changes in body organs. Currently this technology is being used in patients with liver tumors; that is, it serves as an important tool in follow-up after TACE. The present paper summarizes these developments.

Continuous In Vivo Monitoring of the Oxygen Concentration in Tissues

Abstract—The kinetics of delayed fluorescence and phosphorescence of xanthene dyes in mouse tissues under the pulse-periodic excitation of molecules was studied in vivo and in vitro. The advantages of continuous monitoring of oxygen content in tissues by the kinetics of delayed fluorescence caused by singlet–triplet annihilation of singlet oxygen with triplet excitation of fluorophore are demonstrated. A method is proposed for determining the time of recovery of the concentration of oxygen consumed in tissues in vivo and in vitro during photodynamic processes.