Delta O2 Research Articles

The Potential Predictive Role of Oxidative Stress and Antioxidant Parameters Regarding Mortality and the Type of Causative Agent in Sepsis.

Oxidative stress represents an imbalance between oxidants and antioxidants, with a predominance of oxidants leading to cellular and tissue damage. Given the limited number of studies showing the predictive value of oxidative stress factors regarding sepsis type, the objectives of this study emerged as follows: to determine whether pro-oxidant and antioxidant values could predictively differentiate between Gram-positive (GP) and Gram-negative (GN) sepsis. Additionally, the study sought to assess whether bacterial type impacts treatment outcomes in sepsis patients. This prospective, observational cohort longitudinal study included 87 patients diagnosed with sepsis according to the Third International Consensus on Sepsis and Septic Shock (Sepsis-3) criteria. Following the sepsis diagnosis, blood, urine, bronchoalveolar lavage (BAL), and swabs/punctures were sampled and microbiologically analyzed. Sampling was repeated 24 hours after the first collection. Based on the microbiological results, four groups of subjects were formed: the GP group included septic patients in whom one or more GPbacteriawere isolated by microbiological analysis; the GN group included septic patients in whom one or more GN bacteria were isolated; the GP/GN group included septic patients with both GP and GN bacteria isolated; and the negative culture (NC) groupincluded septic patients in whom no pathogenic microorganisms were detected by microbiological analysis. Additionally, after sepsis diagnosis, oxidative stress markers, i.e., thiobarbituric acid reactive substances (TBARS), nitrite ion radical (NO₂⁻), hydrogen peroxide (H₂O₂), superoxide ion radical (O₂⁻),and antioxidants:superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) were determined from blood samples. Blood sampling was repeated 24 hours after the first collection. On comparing pro-oxidant values relative to the type of infection in septic patients, measured on the first and second days, no statistically significant differences were observed for the analyzed parameters, except for delta (Δ) O₂⁻. A statistically significant increase was noted in the GN group of septic patients (p = 0.02). On comparing antioxidant values relative to infection type in septic patients, measured on the first and second days, no statistically significant differences were found for the analyzed parameters. Based on the measured values of pro-oxidants and antioxidants in this study, it is evident that they do not have predictive significance for the final treatment outcome and the type of sepsis-causing pathogen.These results underscore the need for further research on the predictive role of oxidative stress in sepsis.

Abstract 13710: Cardiac Platypnea-Orthodeoxia Syndrome: How the Stars Aligned

Case description: A 79-year-old man with recurrent falls, dyslipidemia and recent exercise intolerance presented after a fall. He was putting on shoes, lost his balance and fell. There was no pre-syncope, syncope, dyspnea, chest pain, palpitations or dizziness. On admission, vital signs were normal except oxygen saturation (O2 sat) 79% on room air (and no improvement with supplemental O2). An arterial blood gas (ABG) revealed partial pressure of oxygen 42 mmHg with oxygen saturation 80%. He had lower thoracic spine tenderness, normal respiratory and cardiac exam. CT head showed no acute intracranial abnormalities. CTA chest had no pulmonary embolism, arterio-venous malformations or parenchymal lung disease. There was a thoracic aorta aneurysm (4.5cm at aortic root and 5.1cm at posterior arch). Subsequently, O2 sat was 92% supine and 79% standing. He also had a compression fracture of T12 and spinal asymmetry. A transesophageal echocardiogram (TEE) showed an aneurysmal, hypermobile interatrial septum with early right to left shunt with agitated saline due to a large patent foramen ovale (PFO). Right heart catheterization revealed no pulmonary hypertension and confirmed a step down from the pulmonary vein to left atrium (delta O2 sat 6%). A 30mm Gore Cardioform occluder was used to close the defect and immediately supplemental oxygen was removed, and O2 sat on room air was 95%. Follow up echocardiogram showed no residual shunt and exercise intolerance resolved. Discussion: Unexplained positional hypoxemia raised our suspicion for cardiac POS. Hypoxemia is caused by right to left shunting via the PFO, exacerbated by the thoracic aortic aneurysm and spinal changes such as the T12 fracture and spinal asymmetry. Going from being recumbent to erect there is stretching of the atria causing his PFO to enlarge, increasing the shunt. Additionally, the dilated thoracic aorta exerts mechanical pressure on the right atrium (RA) and interatrial septum, increasing PFO patency and augmenting flow from the inferior vena cava through the PFO. The spinal abnormality may cause more aortic distortion and exert forces on the RA, exacerbating shunting. Percutaneous PFO closure is the treatment of choice with closure immediately leading to significant improvement of hypoxemia.

P6267Novel direct effects of SGLT2 inhibitor, Canagliflozin, on myocardial redox state in humans

Abstract Background Sodium glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic drugs that control plasma glucose levels by inhibiting reabsorption of glucose in kidney. Recent clinical trials have suggested a class effect of SGLT2 inhibitors in preventing hospitalization due to heart failure. However, the underlying mechanism has not been fully elucidated. Purpose We investigated the direct effect of the SGLT2 inhibitor, Canagliflozin (Cana), on myocardial redox state in humans. Methods The study included 48 patients undergoing cardiac surgery. Fresh myocardial tissues were incubated ex vivo with or without Cana and then used for superoxide quantification and Western immunoblotting. NADPH-oxidases activity was evaluated with NADPH 100μM stimulation, while nitric oxide synthase (NOS) coupling was assessed by using N(ω)-nitro-L-arginine methyl ester (L-NAME, a NOS inhibitor). A human cardiomyocyte (HCM) cell line was also used for in vitro validation of the effects of Cana on myocardium. Results Ex vivo incubation of myocardium with Cana significantly reduced baseline (A) and NADPH-oxidase-derived O2·− (B) and improved NOS coupling reflected by positive L-NAME delta O2·− values (C). Regulation of NADPH-oxidases activity by Cana was found to result from reduced GTP-activation (D) and consequent membrane translocation (E) of Rac1, a key subunit of NADPH-oxidases. Cana also reduced tetrahydrobiopterin (BH4) oxidation, increasing its bioavailability (F), which is a key mechanism to improve NOS coupling. Incubation with Cana enhanced phosphorylation of AMPK, and the downstream signalling, ACC (not shown). Additional Compound C, which is inhibitor of AMPK, significantly reversed these effects of Cana (A, B, C, D, E, F). These findings were replicated in HCM (not shown). In line with these, Cana increased the ADP/ATP ratio of cytoplasm in HCM, which could provide an upstream mechanism for AMPK activation. Conclusions We demonstrate for the first time in humans, that Cana suppresses myocardial NADPH-oxidases activity and improves NOS coupling through an AMPK-mediated pathway. This could be an underlying mechanism for the cardioprotective effects of SGLT2 inhibitors.

Pre-discharge Bedside Exercise Gas Exchange Measurements Predict 30 Day Heart Failure Patient Readmissions

Thirty day hospital readmissions for heart failure (HF) are associated with high morbidity, mortality and costs. Based on evidence relating a growing array of submaximum exercise gas exchange (Gx) measurements to outcomes in HF we hypothesized that submaximum Gx testing at the time of discharge would be an effective tool to identify which patients have high risk of readmission. Patients hospitalized for acute decompensated HF (N=50, mean age 65±14; 78% male) from 3 participating centers who met inclusion criteria (age> 18, NYHA II-IV chronic HF, and capable of exercise) provided informed consent were enrolled in the study. Subjects performed submax exercise on the day of hospital discharge. Heart and respiratory rate, Gx and O2 saturation were monitored continuously during a 6 min protocol consisting of 2 min of rest, 3 min of step exercise and 1 minute of recovery. A 6- parameter multi-metric Shape Score consisting of resting and exercise delta ETCO2, VE slope and O2 uptake efficiency slope (OUES), pulmonary capacitance (GxCap), and end exercise SaO2 were computed. RER, HR, VO2, and O2 pulse were also assessed during rest and exercise. The overall readmission (RA) rate for those Shape tested was 11 of 50 or 22%. Comparing those HF patients who were RA within 30 days vs. those who were not readmitted (NRA), volitional effort, based on peak RER, was equivalent between groups (0.94±.07 and 0.94±.10, respectively, p=.99). Patients with RA had higher Shape Scores than the NRA group (2.4±1.0 vs. 1.1±1.1, p< .005). Individual gas exchange parameters known to prognosticate in patients with chronic HF also tended to be more impaired in the RA group (Table, i.e. lower achieved VO2, higher VE/VCO2 slope, lower OUES). In this pilot study, exercise Gx using a simple, 6 min. bedside step protocol prior to discharge offers an objective means to predict likelihood for 30 day readmission in patients hospitalized with ADHF. A multi-metric Shape Gx score that integrates sub-maximum exercise Gx parameters outperforms individual Gx variables in predicting hospital readmission. While larger, definitive studies are required, bedside measurement of Gx in HF patients may represent an inexpensive, non-invasive practical clinical tool to track functional status and to effectively indentify HF patients at risk for readmission.Table 1Gas exchange variables at the time of dischargeStudy groupShape Multivariate Composite ScoreVO2 peakVE/VCO2 slopeGxCAP peakOUESΔETCO2End exercise SaO230 day readmitN= 112.4±1.0p=.0029.4±1.5p=.02441.6±16.7NS363±208NS1.12±.34p=0.06-1.0±3.8NS91±5NSNo 30 day readmitN=391.1±1.111.1±2.835.4±10.4432±1631.42±.51-.44±3.093±4 Open table in a new tab

The Displacive Phase Transition of Vanadium Dioxide and the Effect of Doping with Tungsten

Static-lattice calculations have been employed to model the phases of VO2 and V1-delta W delta O2. Interatomic potentials were empirically fitted to reproduce the low- and high-temperature phases (monoclinic and tetragonal, respectively) of vanadium dioxide as well as the monoclinic phase of tungsten dioxide. For pure VO2, we located the soft modes of the high-temperature phase, which characterize the initial atomic displacements that lead to the displacive phase transition to the low-temperature phase. The T = 0 structure of the saddle point, where only half of the one-dimensional chains have undergone Peierls distortions, and the ionic motion along the lowest-energy path for the phase transition are described. For V1-delta W delta O2, we found that doping significantly stabilizes the high-temperature phase relative to the low-temperature phase, which explains the observed depression in the transition temperature as delta increases. For the high- and low-temperature phases, the local structures about the dopant, which were obtained by employing a Mott-Littleton approach, resembled those of the low- and high-temperature phases, respectively.

Oxidation of carbon nanotubes by singlet O2.

Chemisorption of singlet (1)Delta(g) O2 on single-walled carbon nanotubes is reexamined by first principles calculations, and the reaction barrier is substantially lower than previously reported when the spin on O2 is correctly treated. The process is initiated by the cycloaddition of a singlet O2 on top of a C-C bond and ended with an epoxy structure with each of the two oxygen atoms occupying a bridge position. The overall process is exothermic, with an activation barrier as low as 0.61 eV for the (8, 0) tube. Our results raise the possibility that carbon nanotubes with small diameters could be degraded after exposure to air and sunlight, similar to the degradation of natural rubber and synthetic plastics.

Right ventricular oxygen supply/demand balance in exercising dogs.

This is the first investigation of right ventricular (RV) myocardial oxygen supply/demand balance in a conscious animal. A novel technique developed in our laboratory was used to collect right coronary (RC) venous blood samples from seven instrumented, conscious dogs at rest and during graded treadmill exercise. Contributions of the RV oxygen extraction reserve and the RC flow reserve to exercise-induced increases in RV oxygen demand were measured. Strenuous exercise caused a 269% increase in RV oxygen consumption. Expanded arteriovenous oxygen content difference (A-V(Delta)O2) provided 58% of this increase in oxygen demand, and increased RC blood flow (RCBF) provided 42%. At less strenuous exercise, expanded A-V(Delta)O2 provided 60-80% of the required oxygen, and increases in RCBF were small and driven by increased aortic pressure. RC resistance fell only at strenuous exercise after the extraction reserve had been mobilized. Thus RC resistance was unaffected by large decreases in RC venous PO2 until an apparent threshold at 20 mmHg was reached. Comparisons of RV findings with published left ventricular data from exercising dogs demonstrated that increased O2 demand of the left ventricle is met primarily by increasing coronary flow, whereas increased O2 extraction makes a greater contribution to RV O2 supply.

Mechanism of lower oxidizability of eicosapentaenoate than linoleate in aqueous micelles.

The aerobic oxidation kinetics of methyl eicosapentaenoate (20:5n-3) and methyl linoleate (18:2n-6) were compared in homogeneous chlorobenzene solution and in Triton X-100 aqueous micelles at 37 degrees C. The rate of disappearance of 20:5n-3 was two times faster than that of 18:2n-6 in chlorobenzene, while the former was five times slower than the latter in aqueous micelles. It was also observed that delta O2 = delta 18:2n-6 and delta O2 = 2 delta 20:5n-3 in aqueous micelles. In the oxidation of a 1:1 mixture of 20:5n-3 and 18:2n-6 in micelles, the rate of disappearance of 20:5n-3 was 3.6 times faster than that of 18:2n-6, and the rate of total substrate disappearance was reduced by a factor of 5 as compared with 18:2n-6 oxidation. These data suggest that the peroxyl radical derived from 20:5n-3 is more polar than that from 18:2n-6, and the former is likely to diffuse from the core to the micelle surface. This lowers the oxidizability for 20:5n-3 in aqueous micelles by enhancing the termination reaction rate for peroxyl radicals and by reducing the rate of propagation since there may be more 20:5n-3 peroxyl radicals at the surface than in the micelle core.

Receptor inactivation by dye-neuropeptide conjugates: 2. Characterization of the quantum yield of singlet oxygen generated by irradiation of dye-neuropeptide conjugates.

Different neuropeptide analogues of the neurotransmitter FMRFamide were covalently attached to a tethered dye, forming dye-neuropeptide conjugates capable of stably binding to the FMRFamide receptors. Singlet oxygen (1 delta O2) generated by laser irradiation of the conjugates bound to this receptor should inactivate it if (a) the distance 1 delta O2 must diffuse to reach the photo-sensitized receptor is less than 1000 A, (b) the conjugate binds the receptor with the same affinity as the indigenous neurotransmitter, and (c) the quantum yield (phi) of 1 delta O2 is sufficient. Previous studies determined that the first two constraints are satisfied. The results of the present study confirm that the third constraint is also satisfied, as the phi of 1 delta O2 resulting from the laser irradiation of the conjugates were uniformly large, exceeding those for the dye itself, ranging from 0.25 at pD 6.0 to 0.93 at pD 9.0.

Effect of sputum induction on arterial oxygen saturation and spirometry in HIV-infected patients

We wanted to study the effect of sputum induction on forced expiratory volume in one second (FEV1) and on oxygen saturation in normal controls, asymptomatic human immunodeficiency virus (HIV)-seropositive individuals, and HIV-seropositive patients under investigation for suspected Pneumocystis carinii pneumonia (PCP). Over a five month period, sputum induction with ultrasonically nebulized 3% saline was performed on 110 HIV-seropositive patients with suspected PCP, 10 asymptomatic HIV-seropositive patients, and 15 normal controls. Oxygen saturation (peak, trough and change in oxygen saturation (delta O2)) was measured throughout the procedure using pulse oximetry, and these results compared with the chest radiograph and the final pulmonary diagnosis. In addition, the effect of sputum induction on FEV1 was measured in the 15 control subjects and 10 asymptomatic HIV-seropositive patients. Compared with bronchoalveolar lavage, sputum induction had a diagnostic sensitivity for PCP of 76%. Chest radiography was 79% sensitive, and had specificity of 83%. Patients with PCP had lower peak and trough oxygen saturation values compared with the non-PCP group (mean peak 95 vs 97%; mean trough 88 vs 91%), and greater falls in O2 saturation during the procedure (mean delta O2 7.6 vs 5.5%). One subject desaturated to 76%, requiring supplemental oxygen. Sputum induction caused significant but temporary falls in FEV1 both in control and HIV-seropositive groups (mean maximum fall in FEV1 10.4 vs 12.5%). We conclude that although sputum induction causes significant falls in oxygen saturation and FEV1, it remains sensitive and safe, and provides a useful alternative to bronchoscopy for the diagnosis of PCP.

Pulmonary function tests in HIV-infected patients.

To evaluate alterations in lung function during the course of HIV infection. Total lung capacity (TLC), the ratio of forced expiratory volume in one second to vital capacity (FEV1/VC), the carbon monoxide transfer factor (TLCO) and the alveolar-arterial oxygen gradient [delta (A-a)O2] were determined in this retrospective study. Pulmonary function tests (PFT) were performed on 331 patients at various stages of HIV infection. Patients with a history of intravenous drug use or Kaposi's sarcoma were excluded. No significant differences were observed between the results for asymptomatic patients and those with AIDS-related complex (ARC). TLC, delta (A-a)O2 and TLCO were greatly altered in patients with acute Pneumocystis carinii pneumonia (PCP). No significant differences were observed in the TLC, delta(A-a)O2 or TLCO results between AIDS patients with no history of PCP and those with a history of a single episode of PCP. TLCO was significantly lower (P < 0.001) in AIDS patients with one previous episode of PCP than in the patients with ARC. Interestingly, both TLC and TLCO were significantly lower in the AIDS patients with no history of PCP than in the patients with ARC. Follow-up of 28 patients at different stages of HIV infection confirmed the alteration of PFT results in the late stages. The reasons for alterations in PFT results in PCP-free AIDS patients remain to be determined. Our findings suggest that PFT can provide valuable information throughout the course of HIV infection, particularly with regard to the indication for bronchoalveolar lavage.

Energetics of isometric contractions as a function of muscle temperature.

The energetic cost of generating isometric force in isolated frog muscle was examined at 10, 20, and 30 degrees C. Recovery O2 consumption (delta O2) and recovery lactate production (delta Lact) were measured under conditions in which O2 was not limiting metabolism. Both increased linearly with the force-time integral (integral of Fdt) generated by the muscle. The slopes of the regression equations for both delta O2 and delta Lact as a function of integral of Fdt increased with increasing temperature with a temperature coefficient (Q10) near 3. Total high-energy phosphate resynthesis from recovery metabolism was calculated by scaling the delta O2 regression equation and the delta Lact regression equation into equivalent ATP units and summing them. This total recovery metabolism was modeled as the sum of two components, a "cost of maintaining force" (slope of the equation) and a saturable "start up cost" (intercept of the equation). The cost of maintaining force increased with temperature with a Q10 near 3 over the whole temperature range, whereas the start up cost was nearly independent of temperature between 0 and 20 degrees C and fell to near zero at 30 degrees C. Delta O2 measurements from a series of tetani given in rapid succession showed that for contractions subsequent to the first, no start up cost was incurred and that the "cost of generating force" for these contractions was equal to the slope of the regression line for single tetani. The practical consequence of these facts is that, in series of tetani, the cost of generating force increases with a Q10 of 3.

Helium meter correction equations for oxygen and nitrous oxide.

Helium detectors utilizing thermal conductivity are sensitive to the presence of nitrous oxide (N2O) and oxygen (O2). Measurement of the level of these gases within the spirometer may be used to obtain the true helium concentration for use in the calculation of functional residual capacity (FRC). Linear relationships were obtained relating the change (delta) in reading of the helium meter by nitrous oxide and oxygen. The regression equations are: delta O2 = 0.027 (%O2) - 0.513; delta N2O = -0.276 (%N2O). Failure to correct the helium reading for N2O will overestimate lung volume; elevations of O2 above 21% will underestimate the lung volume.

Continuous spectrophotometric measurements of arteriovenous oxygen difference.

A relatively inexpensive dual-beam optical absorbance monitor was tested and adapted to measure arterio-enous oxygen difference ((a - v)delta O2). Since the molar extinction coefficients of oxy- and deoxyhemoglobin are markedly different at 660 nm, the difference in optical density between arterial and venous blood, as measured by the absorbance monitor, was shown to be linearly related to (a - v)delta02. When appropriate cuvettes (optical path length = 0.5 mm) were used, the instrument's 90% response time (4.4 s) was sufficiently rapid for most physiological applications such as Fick determinations of the rate of an organ's oxygen consumption. The theoretical basis of this spectrophotometric (a - v)deltaO2 measurement and sources of error are discussed in detail.