Voxelotor as a Treatment of Persistent Hypoxia in the ICU.

Hypoxia is encountered frequently in the ICU as a result of a wide range of pathologic characteristics. The oxygen-hemoglobin dissociation curve describes hemoglobin's affinity for a given Po2 and factors affecting uptake and offload. Research in manipulating this relationship between hemoglobin and oxygen is sparing. Voxelotor is a hemoglobin oxygen-affinity modulator that is approved by the US Food and Drug Association for use in the management of sickle cell disease. We present two patients without sickle cell disease who underwent treatment with this novel agent to assist with chronic hypoxia and weaning of mechanical support.

Oxygen transport across tank-treading red blood cell: Individual and joint roles of flow convection and oxygen-hemoglobin reaction.

Gas, especially oxygen, transport in the microcirculation is a complex phenomenon, however, of critical importance for maintaining normal biological functions, and the cytoplasm fluid in red blood cells (RBCs) is the major vehicle for transporting oxygen from lungs to tissues via the circulatory system. Existing theoretical and numerical studies have neglected the cytoplasm convection effect by treating RBCs as rigid particles undergoing a constant translation velocity. As a consequence, the influence and mechanism of the cytoplasm flow on oxygen transport are still not clear in microcirculation research. In this study, we consider a tank-treading capsule in shear flow, which is generated with two parallel plates moving in opposite directions: the top plate of a higher oxygen pressure (PO2) representing the RBC core in the central region of a microvessel and the bottom plate of a lower PO2 representing the microvessel wall. Numerical simulations are conducted to investigate the individual and combined effects of cytoplasm convection and oxygen-hemoglobin (O2-Hb) reaction on the oxygen transport efficiency across the tank-treading capsule, and different PO2 situations and shear rates are also tested. Due to the lower oxygen diffusivity in cytoplasm, the presence of the capsule reduces the oxygen transfer flux across the gap by 7.34 % in the pure diffusion system where the flow convection and O2-Hb reaction are both neglected. Including the flow convection or the O2-Hb reaction has little influence on the oxygen flux; however, when they act together as in real microcirculation situations, the enhancement in oxygen transport could be significant, especially in the low PO2 and high shear rate situations. In particular, with the respective PO2 at 60 and 30 mmHg on the top and bottom plates and a 400 s-1 shear rate, the oxygen flux reduction is only 0.02 %, suggesting that the cytoplasm convection can improve the oxygen transport across RBCs considerably. The simulation results are scrutinized to explore the underlying mechanism for the enhancement, and a new nondimensional parameter is introduced to characterize the importance of cytoplasm convection in oxygen transport. These simulation results, discussion and analysis could be helpful for a better understanding of the complex oxygen transport process and therefor valuable for relevant studies.

Artocarpus Altilis (Breadfruit) could Reverse Myocardial Infarction Through the Normalization of the Oxygen Haemoglobin Dissociation Curve.

OBJECTIVE: The study was performed to assess if hematological mechanisms such as blood flow modulation, P50 and Oxygen haemoglobin dissociation are involved in Artocarpus altilis leaf extract amelioration of Isoproterenol-Induced Myocardial Damage in rats. METHODS: Twenty (20) adult male Sprague-Dawley rats were randomly divided into 5 groups. Group 1 served as the control, group 3 and 5 received 50 and 100 mg/kg Artocarpus altilis water extract, respectively, after being induced with Isoproterenol twice (85 mg/ kg) at a 24-hour period. Group 2 received 85mg/kg isoproterenol only, while group 4 received 50 mg/kg Artocarpus altilis extract only for 6 days. The Hematological parameters were assessed using an automatic Coulter Counter, blood flow was assessed with the CODA machine using the tail cuff method, while blood viscosity was measured at native hematocrit and the oxygen haemoglobin dissociation curves were assessed with the BioProfiler and Hemox Analyzer at the end of seven days. RESULTS: Artocarpus altilis treatment ameliorated the ISO induced increases in viscosity, increased the ISO induced decreased blood flow and influenced oxygen release through its effects on the P50 of the oxygen hemoglobin dissociation curve, AA treatment also reversed the ISO induced weight loss. Apart from the changes in MCH, MCV, there were no significant differences in hematological parameters. CONCLUSION: This study reported the effects of Artocarpus atilis on the improvement of oxygen availability, the reduction of blood viscosity, and the improvement of blood flow through its influence on endothelial functions and NO availability. Our study further highlights The usefulness of A.atilis, as having a beneficial cardiovascular and haematological outcome in experimental myocardial infarction and as such, potential drug discovery for diseases of cardiovascular & hematological involvement.

Precision pinch force control via brain and spinal motor neuron excitability during motor imagery.

This study presents a novel approach for identifying neural substrates underlying the beneficial effects of motor imagery. For motor imagery, participants were instructed to imagine contraction of the left thenar muscle at 50 % maximal voluntary contraction (MVC). The participants then performed isometric contractions of the thumb and index finger at 50 % MVC as accurately as possible after motor imagery and without motor imagery. F-waves and oxygen-hemoglobin levels were examined with and without motor imagery relative to the resting condition. These data were analyzed using structural equation modeling. The degree of changes in the excitability of spinal motor neurons using F-waves during motor imagery may be modulated by inputs from the supplementary motor area. F-waves were analyzed with respect to persistence and the F-wave/maximum M-wave amplitude ratio. We found an association between precision pinch force control after motor imagery and spinal motor neuron excitability during motor imagery. The excitability of the supplementary motor area was not directly associated with precision pinch force control. However, spinal motor neuron excitability was adjusted by the supplementary motor area. Thus, the ability to perform precision pinch force control may be influenced by the supplementary motor area through the excitability of spinal motor neurons.

Relationship Between Exercise Capacity and Muscle O2Hb Saturation in Patients Before Hematopoietic Stem-Cell Transplantation.

Patients with hematological malignancy might already have decreased muscle oxygen saturation at rest and exercise capacity before undergoing hematopoietic stem cell transplantation (HSCT). However, to date, no studies have investigated the relationship between exercise capacity and muscle oxygen saturation at rest in these patients. Therefore, purpose of this study was to investigate the relationship between exercise capacity and muscle oxygen-hemoglobin (O2Hb) saturation (SmO2) at rest and patients' hemoglobin level before undergoing HSCT. METHODS: This study included 60 men with hematologic disease who underwent allo-HSCT. Patients performed a 6-minute walk test (6MWT) to determine exercise capacity, and muscle O2Hb saturation at rest was evaluatabed using near-infrared spectroscopy (BOM-L1TRW, Omegawave Inc., Japan); hemoglobin levels in hematological malignancy patients before undergoing HSCT were also evaluated. RESULTS: There was a significant correlation between the 6MWT and muscle O2Hb saturation at rest in hematological malignancy patients (p < 0.05). Additionally, the 6MWT was significantly correlated to the hemoglobin level (p < 0.05). Furthermore, muscle O2Hb saturation at rest was significantly related to hemoglobin level (p < 0.05). CONCLUSION: In patients with hematological malignancy, a relationship exists between exercise capacity, muscle O2Hb saturation, and hemoglobin level before they undergo HSCT. Therefore, rehabilitation staff, nurses, and physicians should recognize these relationships in patients who undergo allo-HSCT. Moreover, physiotherapists may need to promote muscle oxidative metabolism through exercise to increase exercise capacity in these patients.

Modulation of Cortical Activity by High-Frequency Whole-Body Vibration Exercise: An fNIRS Study.

CONTEXT: Whole-body vibration (WBV) has shown many positive effects on the human body in rehabilitation and clinical settings in which vibration has been used to elicit muscle contractions in spastic and paretic muscles. OBJECTIVE: The purpose of this study was to investigate whether WBV exercise (WBVe) differently modulates the cortical activity associated with motor and prefrontal function based on its frequency. METHODS: A total of 18 healthy male adults (mean age: 25.3 [2.4] y) participated in this study and performed WBVe (Galileo Advanced plus; Novotec Medical, Pforzheim, Germany) under 3 different vibration frequency conditions (4-mm amplitude with 10-, 20-, and 27-Hz frequencies) and a control condition (0-mm amplitude with 0-Hz frequency). Each condition consisted of 2 alternating tasks (squatting and standing) every 30 seconds for 5 repetitions. All subjects performed the 4 conditions in a randomized order. MAIN OUTCOME MEASURE: Cortical activation during WBVe was measured by relative changes in oxygenated hemoglobin concentration over the primary motor cortex, premotor cortex, supplementary motor area, and prefrontal and somatosensory cortices using functional near-infrared spectroscopy. RESULTS: Oxygenated hemoglobin concentration was higher during the 27-Hz vibration condition than the control and 10-Hz vibration conditions. Specifically, these changes were pronounced in the bilateral primary motor cortex (P < .05) and right prefrontal cortex (P < .05). In contrast, no significant changes in oxygenated hemoglobin concentration were observed in any of the cortical areas during the 10-Hz vibration condition compared with the control condition. CONCLUSION: This study provides evidence that the motor network and prefrontal cortical areas of healthy adult males can be activated by 27-Hz WBVe. However, WBVe at lower frequencies did not induce significant changes in cortical activation.

Application of functional near-infrared spectroscopy in schizophrenia / 上海交通大学学报（医学版）

Functional near-infrared spectroscopy (fNIRS) is a relatively new technique that can measure the hemoglobin changes in brain tissue. Depending on the absorption for different wavelength, relative changes in the concentration of hemoglobin in brain can be measured, obtaining the hemodynamic characteristics of brain to understand the brain functional state in real-time. Compared with other neuroimaging techniques, it has some advantages and has been used in psychiatry rapidly. Schizophrenia is one of the most common mental disorders, researches on its pathogenesis have focused on collection of structural and functional alteration in brain. Existing techniques can provide only indirect evidence, while fNIRS can perform brain function monitoring in real-time. A number of studies have suggested that fNIRS signal could be used as a biomarker for schizophrenia identification and adjuvant diagnosis. This paper reviewed the research progress in the application of fNIRS in schizophrenia.

Application of functional near-infrared spectroscopy in schizophrenia / 上海交通大学学报（医学版）

Functional near-infrared spectroscopy (fNIRS) is a relatively new technique that can measure the hemoglobin changes in brain tissue. Depending on the absorption for different wavelength, relative changes in the concentration of hemoglobin in brain can be measured, obtaining the hemodynamic characteristics of brain to understand the brain functional state in real-time. Compared with other neuroimaging techniques, it has some advantages and has been used in psychiatry rapidly. Schizophrenia is one of the most common mental disorders, researches on its pathogenesis have focused on collection of structural and functional alteration in brain. Existing techniques can provide only indirect evidence, while fNIRS can perform brain function monitoring in real-time. A number of studies have suggested that fNIRS signal could be used as a biomarker for schizophrenia identification and adjuvant diagnosis. This paper reviewed the research progress in the application of fNIRS in schizophrenia.

Sildenafil Increases the p50 and Shifts the Oxygen-Hemoglobin Dissociation Curve to the Right.

INTRODUCTION: Sildenafil (Viagra®) is a selective phosphodiesterase type 5 (PDE5) inhibitor that block the breakdown of cyclic guanyl monophosphate (cGMP) leading to relaxation of the smooth muscles of the corpus cavernous and an increase in blood flow resulting in penile erection. It is hypothesized that sildenafil will increase the release of oxygen from erythrocytes and shift the oxygen-hemoglobin curve to the right. AIM: The aim of this study was to investigate the effect of varying doses of sildenafil on the p50 of the oxygen-hemoglobin dissociation curve in blood samples from eight (8) healthy adult male volunteers with normal hemoglobin HbAA. METHOD: The hemox-analyzer was used to generate the p50 and the oxygen-hemoglobin dissociation curves. MAIN OUTCOME MEASURES: The effect of different doses of sildenafil on the p50 values and shift of the oxygen-hemoglobin curve were the main outcome measures. RESULT: Sildenafil caused a statistically significant increase in the p50 values and rightward shift of the oxygen-hemoglobin dissociation curve. CONCLUSION: Sildenafil caused a dose-dependent increase in the release of oxygen from the erythrocytes as shown by the increased p50 values and rightward shift of the oxygen-hemoglobin dissociation curve. Ellis SS and Pepple DJ. Sildenafil increases the p50 and shifts the oxygen-hemoglobin dissociation curve to the right.

Effect of cilostazol on the p50 of the oxygen-hemoglobin dissociation curve.

Cilostazol is a drug used for the treatment of intermittent claudication caused by narrowing of the blood vessels and reduced oxygen supply, characterized by intense pain in the leg when walking. This study was designed to investigate the effect of cilostazol on the P50 of the oxygen hemoglobin dissociation curve. A total of eight healthy adult subjects were studied. Blood samples (0.5 mL) from each subject were mixed with 5, 10, and 20 µL of the 0.5 mg/mL stock solution of cilostazol to give concentrations of 10, 20, and 40 µg/mL equivalent to adult doses of 50, 100, and 200 mg, respectively. The control sample had no drug added. The oxygen hemoglobin dissociation curve of each sample was plotted and the P50 determined with a Hemox-Analyzer (TCS, Medical Products Division, Southampton, PA). The mean P50 for the control samples was 28.27 ± 0.43 mm Hg. The values of the samples exposed to 10, 20, and 40 µg/mL cilostozol were 29.63 ± 0.66, 30.15 ± 0.77, and 31.66 ± 0.62 mm Hg, respectively. There was a statistically significant difference (p < 0.01) between the control and samples exposed to 40 µg/mL cilostazol. This study suggests that cilostazol caused an increase in the release of oxygen from hemoglobin as shown in the P50 values. This effect was significant at the highest concentration of 40 µg/mL.

Exercise-induced oxygen desaturation in COPD patients without resting hypoxemia.

Exercise-induced oxygen desaturation (EID) is associated with increased risk of mortality in chronic obstructive pulmonary disease (COPD). Several screening tests have been proposed to predict EID, including FEV1, DLCO and baseline-SpO2. We aimed to validate a proposed cut-off of baseline-SpO2 ≤95% as simple screening procedure to predict EID during six-minute walk test (6MWT). In addition, we studied the prevalence and characteristics of patients exhibited EID to SpO2nadir ≤88%. 402 non-hypoxemic COPD patients performed 6MWT. Sensitivity and specificity of baseline SpO2 ≤95% as a cut-off to predict EID and determinants of EID were investigated. 158 patients (39%) exhibited EID. The sensitivity of baseline-SpO2 ≤95% to predict EID was 81.0%, specificity 49.2%, positive and negative predictive values were 50.8% and 80.0%, respectively. In a multivariate model, DLCO <50%, FEV1 <45%, PaO2 <10kPa, baseline-SpO2 <95%, and female sex were the strongest determinants of EID. Baseline oxygen saturation solely is inaccurate to predict EID. A combination of clinical characteristics (DLCO, FEV1, PaO2, baseline-SpO2, sex) increases the odds for EID in COPD.

Insights from venous oxygen profiles: oxygen utilization and management in diving California sea lions.

The management and depletion of O2 stores underlie the aerobic dive capacities of marine mammals. The California sea lion (Zalophus californianus) presumably optimizes O2 store management during all dives, but approaches its physiological limits during deep dives to greater than 300 m depth. Blood O2 comprises the largest component of total body O2 stores in adult sea lions. Therefore, we investigated venous blood O2 depletion during dives of California sea lions during maternal foraging trips to sea by: (1) recording venous partial pressure of O2 (P(O2)) profiles during dives, (2) characterizing the O2-hemoglobin (Hb) dissociation curve of sea lion Hb and (3) converting the P(O2) profiles into percent Hb saturation (S(O2)) profiles using the dissociation curve. The O2-Hb dissociation curve was typical of other pinnipeds (P50=28±2 mmHg at pH 7.4). In 43% of dives, initial venous S(O2) values were greater than 78% (estimated resting venous S(O2)), indicative of arterialization of venous blood. Blood O2 was far from depleted during routine shallow dives, with minimum venous S(O2) values routinely greater than 50%. However, in deep dives greater than 4 min in duration, venous S(O2) reached minimum values below 5% prior to the end of the dive, but then increased during the last 30-60 s of ascent. These deep dive profiles were consistent with transient venous blood O2 depletion followed by partial restoration of venous O2 through pulmonary gas exchange and peripheral blood flow during ascent. These differences in venous O2 profiles between shallow and deep dives of sea lions reflect distinct strategies of O2 store management and suggest that underlying cardiovascular responses will also differ.

High thermal sensitivity of blood enhances oxygen delivery in the high-flying bar-headed goose.

The bar-headed goose (Anser indicus) crosses the Himalaya twice a year at altitudes where oxygen (O2) levels are less than half those at sea level and temperatures are below -20°C. Although it has been known for over three decades that the major hemoglobin (Hb) component of bar-headed geese has an increased affinity for O2, enhancing O2 uptake, the effects of temperature and interactions between temperature and pH on bar-headed goose Hb-O2 affinity have not previously been determined. An increase in breathing of the hypoxic and extremely cold air experienced by a bar-headed goose at altitude (due to the enhanced hypoxic ventilatory response in this species) could result in both reduced temperature and reduced levels of CO2 at the blood-gas interface in the lungs, enhancing O2 loading. In addition, given the strenuous nature of flapping flight, particularly in thin air, blood leaving the exercising muscle should be warm and acidotic, facilitating O2 unloading. To explore the possibility that features of blood biochemistry in this species could further enhance O2 delivery, we determined the P50 (the partial pressure of O2 at which Hb is 50% saturated) of whole blood from bar-headed geese under conditions of varying temperature and [CO2]. We found that blood-O2 affinity was highly temperature sensitive in bar-headed geese compared with other birds and mammals. Based on our analysis, temperature and pH effects acting on blood-O2 affinity (cold alkalotic lungs and warm acidotic muscle) could increase O2 delivery by twofold during sustained flapping flight at high altitudes compared with what would be delivered by blood at constant temperature and pH.

Effect from local vibration stimulus on hemoglobin change of biceps muscles / 医用生物力学

Objective To investigate the effect from local vibration stimulus on the total hemoglobin and oxygen hemoglobin change of biceps muscles. Methods Arm Vibration Massage Band was used by twelve volunteers(female college students) to receive the local vibration stimulus. By using the Near Infrared Spectroscopy, the total hemoglobin and oxygen hemoglobin of biceps muscles were measured at 10th minute before vibration, 10th minute during vibration and at 15th minute after vibration, respectively, to get the variation tendency at each minute. Repeated measured one-way ANOVA was used to compare the differences in the test Results. Results The total hemoglobin of biceps muscles was significantly increased at 15th minute after vibration (P<0.05), and the total oxygen hemoglobin of biceps muscles was significantly increased at 10th minute during vibration and 15th minute after vibration (P<0.05). The maximum value of the total hemoglobin and oxygen hemoglobin occurred at 5th minute during 10-minute vibration stimulus, and compared with 10th minute before vibration, the total hemoglobin and oxygen hemoglobin could continue to be higher at 15th minute after vibration with a stable tendency. Conclusions The local vibration stimulus can acutely increase the total hemoglobin and oxygen hemoglobin of biceps muscles, which can reach the maximum value with sustained vibration stimulus for at least 5 minutes.

The Erythrocyte 2,3-diphosphoglycerate Concentration and Its Related Factors in Patients with End-stage Liver Disease / 대한마취과학회지

BACKGROUND: It is believed that an increase in the level of erythrocyte 2,3-diphosphoglycerate is an important compensatory mechanism that allows satisfactory tissue oxygenation in hypoxic patients. This study measured the level of 2,3-diphophoglycerate and the factors affecting its concentration, as well as the position of the oxygen-hemoglobin dissociation curve in patients with end-stage liver disease. METHODS: Fifty patients receiving liver transplantation (experimental group) and forty-five healthy donors (control group) were enrolled in this study. Arterial-mixed venous oxygen content difference, whole body oxygen delivery and consumption were measured after determining the hemodynamic parameters including cardiac output in the experimental group. The erythrocyte 2,3-diphosphoglycerate level was measured using assay procedures. The P50 value was used to determine the position of the oxygen-hemoglobin dissociation curve. RESULTS: The 2,3-diphosphoglycerate level was higher in patients with end-stage liver disease than in the controls. A 0.3 g/L increase in the 2,3-diphosphoglycerate concentration corresponded to a P50 increase in 1.2 mmHg with a rightward displacement of the oxygen-hemoglobin dissociation curve. The 2,3-diphosphoglycerate concentration showed a significant correlation with the PaO2, Ca-vO2, P50, and blood lactate level, but not with the hemodynamic parameters such as the cardiac index, oxygen delivery index, and pH. CONCLUSIONS: End-stage liver disease is associated with an increase in the level of the erythrocyte 2,3-diphosphoglycerate and P50. This is believed to be an important compensatory mechanism to allow better tissue oxygenation. An increase in the 2,3-diphosphoglycerate level correlates well with the oxygenation parameters, rather than with the hemodynamic parameters.