Tissue O2 Research Articles

Is flow-mediated dilatation associated with near-infrared spectroscopy-derived magnitude of muscle O2 desaturation in healthy young and individuals at risk for cardiovascular disease?

Vascular occlusion test (VOT)-induced reactive hyperemia in brachial artery is crucial to flow-mediated dilation (FMD). Emerging studies have suggested that reactive hyperemia depends on the magnitude of the O2 desaturation (ischemia) in downstream microvessels. Although near-infrared spectroscopy-derived tissue O2 saturation index (TSI) has been used to assess the magnitude of ischemia, the association between FMD and the magnitude of O2 desaturation has not been addressed. Therefore, the aim of the present study was to evaluate whether FMD correlates with the magnitude of muscle O2 desaturation in healthy young individuals and older adults at risk for cardiovascular disease (CVD). Twenty healthy young individuals and 20 others at risk for CVD participated in the study. The magnitude of ischemic stimulus was determined by calculating the area under curve of TSI signal over 5 min of cuff occlusion period. Oxygen resaturation rate was calculated as the upslope of the TSI signal over 10 s following cuff deflation. There was no significant correlation between FMD and the magnitude of ischemic stimulus in both groups assessed (young: R = 0.327; P = 0.159 and older: R = −0.184; P = 0.436). However, a significant correlation between the magnitude of O2 desaturation and O2 resaturation rate in young (R = 0.555; P = 0.011) and older individuals at risk for CVD (R = 0.539; P = 0.014). In conclusion, FMD response did not correlate with the magnitude of muscle O2 desaturation, although it seems to be partially associated with O2 resaturation rate.

Can molecular markers of oxygen homeostasis and the measurement of tissue oxygen be leveraged to optimize red blood cell transfusions?

The clinical indication for transfusing red blood cells (RBCs) is to restore or maintain adequate oxygenation of respiring tissue. Oxygen (O2) transport, delivery, and utilization following transfusion are impacted by perfusion, hemoglobin (Hb) allosteric saturation/desaturation, and the concentration of tissue O2. Bioavailable O2 maintains tissue utilization and homeostasis; therefore, measuring imbalances in supply and demand could be valuable to assessing blood quality and transfusion effectiveness. O2 homeostasis is critically intertwined with erythropoietic response in blood loss and anemia and the hormones that modulate iron mobilization and RBC production (e.g., erythropoietin, erythroferrone, and hepcidin) are intriguing markers for the monitoring of transfusion effectiveness in acute and chronic settings. The evaluation of RBC donor unit quality and the determination of RBC transfusion needs are emerging areas for biomarker development and minimally invasive O2 measurements. Novel methods for assessing circulatory and tissue compartment biomarkers of transfusion effectiveness are suggested. In addition, monitoring of tissue oxygenation by indirect and direct measurements of O2 is available and applied in experimental settings. Herein, we discuss tissue O2 homeostasis, related aspects of erythropoiesis, molecular markers and measurements of tissue oxygenation, all aimed at optimizing transfusion and assessing blood quality.

Reduced cerebrovascular and cardioventilatory responses to intermittent hypoxia in elderly

BackgroundThe impact of aging on cerebrovascular function and tissue oxygenation during graded hypoxemia is incompletely known. This study compared the age effect on these variables during cyclic hypoxemia-reoxygenation. MethodsHypoxia-induced changes in arterial (SaO2) and cerebral tissue (ScO2) O2 saturation, middle cerebral arterial flow velocity (VMCA), estimated cerebral vascular conductance (CVC), heart rate (HR) and ventilation were compared between 12 elderly (71 ± 2 yr, 7 women) and 13 young (24 ± 3 yr, 5 women) adults during the first and fifth 5-min exposures to 10% O2. ResultsAlthough pre-hypoxia SaO2 did not differ between the groups, ScO2 was lower (P < 0.05) in the elderly (68.4 ± 1.2%) than young (73.8 ± 0.9%) adults, commensurate with a lower resting VMCA (P < 0.05). SaO2 fell less sharply (P < 0.05) in the elderly subjects during the first and fifth hypoxia exposures. Moreover, the responses of ScO2, VMCA, CVC, HR and breathing frequency to hypoxia were attenuated in the elderly subjects. Systolic and diastolic arterial pressures fell by 2–6 mmHg during hypoxia in both young and elderly. Thus, hypoxemia developed more gradually in elderly than young adults during normobaric hypoxia, concordant with a reduced metabolic demand in the elderly. ConclusionsThe elderly adults safely tolerated cyclic, moderate hypoxemia which lowered SaO2 by 20–25%, despite dampening of cerebrovascular and cardiac responses to hypoxemia.

Contribution of prostaglandins to exercise hyperaemia: workload, ethnicity and sex matter!

The contribution of prostaglandins (PGs) to exercise hyperaemia is controversial. In this review, we argue this is partly explained by differences in exercise intensity between studies. The effects of cyclooxygenase (COX) inhibition and PG assays indicate that PGs contribute more at moderate to heavy than at light workloads and are mainly released by low tissue O2 . But, the release and actions of PGs also depend on other O2 -dependent dilators including ATP, adenosine and NO. K+ may inhibit the action of PGs and other mediators by causing hyperpolarization, but contributes to the hyperaemia. Thus, at lighter loads, the influence of PGs may be blunted by K+ , while COX inhibition leads to compensatory increases in other O2 -dependent dilators. In addition, we show that other sources of variability are sex and ethnicity. Our findings indicate that exercise hyperaemia following rhythmic contractions at 60% maximum voluntary contraction, is smaller in young black African (BA) men and women than in their white European (WE) counterparts, but larger in men than in women of both ethnicities. We propose the larger absolute force in men causes greater vascular occlusion and accumulation of dilators, while blunted hyperaemia in BAs may reflect lower oxidative capacity and O2 requirement. Nevertheless, COX inhibition attenuated peak hyperaemia by ∼30% in WE, BA men and WE women, indicating PGs make a substantial contribution in all three groups. There was no effect in BA women. Lack of PG involvement may provide early evidence of endothelial dysfunction, consistent in BA women with their greater risk of cardiovascular disease.

The evolution of surgical treatment for gastrointestinal cancers.

According to the latest Japanese nationwide estimates, over a million Japanese people are newly diagnosed with cancer each year. Since gastrointestinal cancers account for more than 40% of all cancer-related deaths, it is imperative to formulate effective strategies to control them. Basic drug discovery research Our research has revealed that the abnormal expression of regulators of chromosomal stability is a cause of cancers and identified an effective compound against cancers with chromosomal instability. We revealed the molecular mechanism of peritoneal dissemination of cancer cells via the CXCR4/CXCL12 axis to CAR-like cells and identified an MEK inhibitor effective against these tumors. Residual tumor cells after chemotherapy in colorectal cancer are LGR5-positive cancer stem cells and their ability to eliminate reactive oxygen species is elevated. The development of surgical procedures and devices In cases of gastric tube reconstruction for esophageal cancer, we determined the anastomotic line for evaluating the blood flow using ICG angiography and measuring the tissue O2 metabolism. We established a novel gastric reconstruction method (book-binding technique) for gastric cancer and a new rectal reconstruction method focusing on the intra-intestinal pressure resistance for rectal cancer. We established a novel tissue fusion method, which allows contact-free local heating and retains tissue viability with very little damage, and developed an understanding of the collagen-related processes that underpin laser-induced tissue fusion. Strategy to prevent carcinogenesis We succeeded in cleaving hepatitis B virus DNA integrated into the nucleus of hepatocytes using genome editing tools. The development of HCC from non-alcoholic steatohepatitis (NASH) may be prevented by metabolic surgery. We believe that these efforts will help to significantly improve the gastrointestinal cancer treatment and survival.

Life Ascending: Mechanism and Process in Physiological Adaptation to High-Altitude Hypoxia.

To cope with the reduced availability of O2 at high altitude, air-breathing vertebrates have evolved myriad adjustments in the cardiorespiratory system to match tissue O2 delivery with metabolic O2 demand. We explain how changes at interacting steps of the O2 transport pathway contribute to plastic and evolved changes in whole-animal aerobic performance under hypoxia. In vertebrates native to high altitude, enhancements of aerobic performance under hypoxia are attributable to a combination of environmentally induced and evolved changes in multiple steps of the pathway. Additionally, evidence suggests that many high-altitude natives have evolved mechanisms for attenuating maladaptive acclimatization responses to hypoxia, resulting in counter-gradient patterns of altitudinal variation for key physiological phenotypes. For traits that exhibit counteracting environmental and genetic effects, evolved changes in phenotype may be cryptic under field conditions and can only be revealed by rearing representatives of high-and low-altitude populations under standardized environmental conditions to control for plasticity.

Reduced metabolism supports hypoxic flight in the high-flying bar-headed goose (Anser indicus).

The bar-headed goose is famed for migratory flight at extreme altitude. To better understand the physiology underlying this remarkable behavior, we imprinted and trained geese, collecting the first cardiorespiratory measurements of bar-headed geese flying at simulated altitude in a wind tunnel. Metabolic rate during flight increased 16-fold from rest, supported by an increase in the estimated amount of O2 transported per heartbeat and a modest increase in heart rate. The geese appear to have ample cardiac reserves, as heart rate during hypoxic flights was not higher than in normoxic flights. We conclude that flight in hypoxia is largely achieved via the reduction in metabolic rate compared to normoxia. Arterial [Formula: see text] was maintained throughout flights. Mixed venous PO2 decreased during the initial portion of flights in hypoxia, indicative of increased tissue O2 extraction. We also discovered that mixed venous temperature decreased during flight, which may significantly increase oxygen loading to hemoglobin.

Dynamics of benthic metabolism, O2, and pCO2 in a temperate seagrass meadow

AbstractSeagrass meadows play an important role in “blue carbon” sequestration and storage, but their dynamic metabolism is not fully understood. In a dense Zostera marina meadow, we measured benthic O2 fluxes by aquatic eddy covariance, water column concentrations of O2, and partial pressures of CO2 (pCO2) over 21 full days during peak growing season in April and June. Seagrass metabolism, derived from the O2 flux, varied markedly between the 2 months as biomass accumulated and water temperature increased from 16°C to 28°C, triggering a twofold increase in respiration and a trophic shift of the seagrass meadow from being a carbon sink to a carbon source. Seagrass metabolism was the major driver of diurnal fluctuations in water column O2 concentration and pCO2, ranging from 173 to 377 μmol L−1 and 193 to 859 ppmv, respectively. This 4.5‐fold variation in pCO2 was observed despite buffering by the carbonate system. Hysteresis in diurnal water column pCO2 vs. O2 concentration was attributed to storage of O2 and CO2 in seagrass tissue, air–water exchange of O2 and CO2, and CO2 storage in surface sediment. There was a ~ 1:1 mol‐to‐mol stoichiometric relationship between diurnal fluctuations in concentrations of O2 and dissolved inorganic carbon. Our measurements showed no stimulation of photosynthesis at high CO2 and low O2 concentrations, even though CO2 reached levels used in IPCC ocean acidification scenarios. This field study does not support the notion that seagrass meadows may be “winners” in future oceans with elevated CO2 concentrations and more frequent temperature extremes.

In vivo validation of a miniaturized electrochemical oxygen sensor for measuring intestinal oxygen tension.

Recent advances in the fields of electronics and microfabrication techniques have led to the development of implantable medical devices for use within the field of precision medicine. Monitoring visceral surface tissue O2 tension () by means of an implantable sensor is potentially useful in many clinical situations, including the perioperative management of patients undergoing intestinal resection and anastomosis. This concept could provide a means by which treatment could be tailored to individual patients. This study describes the in vivo validation of a novel, miniaturized electrochemical O2 sensor to provide real-time data on intestinal . A single O2 sensor was placed onto the serosal surface of the small intestine of anesthetized rats that were exposed to ischemic (superior mesenteric artery occlusion) and hypoxemic (alterations in inspired fractional O2 concentrations) insults. Control experiments demonstrated that the sensors can function and remain stable in an in vivo environment. Intestinal decreased following superior mesenteric artery occlusion and with reductions in inspired O2 concentrations. These results were reversible after reinstating blood flow or by increasing inspired O2 concentrations. We have successfully developed an anesthetized rat intestinal ischemic and hypoxic model for validation of a miniaturized O2 sensor to provide real-time measurement of intestinal . Our results support further validation of the sensors in physiological conditions using a large animal model to provide evidence of their use in clinical applications where monitoring visceral surface tissue O2 tension is important.NEW & NOTEWORTHY This is the first report of real-time continuous measurements of intestinal oxygen tension made using a microfabricated O2 sensor. Using a developed rodent model, we have validated this sensor's ability to accurately measure dynamic and reversible changes in intestinal oxygenation that occur through ischemic and hypoxemic insults. Continuous monitoring of local intestinal oxygenation could have value in the postoperative monitoring of patients having undergone intestinal surgery.

Absence of cardiovascular drift during prolonged arm-crank exercise in individuals with spinal cord injury.

Observational study OBJECTIVE: To investigate the effects of prolonged arm-crank exercise on cardiovascular drift (CVdrift) in spinal cord injury (SCI). This is a community-based supervision study METHODS: Ten participants with motor -complete or incomplete SCI (lesion level T7-L1), and 10 able-bodied (AB) participants matched for age performed a 40-min arm-crank exercise at an intensity of 50% of peak oxygen uptake (VO2). During the exercise, there were no significant differences between the groups in VO2, tissue O2 saturation in the biceps brachii (active muscle), and chest and arm skin temperature (all P > 0.05). In the AB, heart rate (HR) increased within the first 15 min of the exercise and continued to increase until the end of the exercise; however, in the SCI, HR increased within first 15 min of the exercise and then remained constant until the end of exercise. After 10 min of exercise, thigh skin temperature had increased more in the SCI than in the AB (P < 0.05). Thigh skin blood flow (SkBF) continued to increase after 10 min of exercise in the AB but remained almost stable in the SCI. Relative changes in the thigh SkBF were associated with changes in HR during exercise between the values at 10 min and 40 min in the pooled data (R2 = 0.706, P < 0.001). CVdrift during the prolonged arm-crank exercise was not observed in individuals with SCI. This might be partially explained by different responses in cutaneous circulation within the inactive muscles of these participants.

PS1522 CENTRAL PHYSIOLOGIC MECHANISMS WHICH AUGMENT OXYGEN RELEASE (BOHR EFFECT AND 2,3‐DPG BINDING) ARE PRESERVED IN THE PRESENCE OF VOXELOTOR AT THE THERAPEUTIC TARGET OF 30% HB MODIFICATION

Background:Key physiologic mechanisms that drive O2 offloading to tissues in vivo include the Bohr effect and 2,3‐DPG binding. The Bohr effect is the capacity of Hb to offload more O2 in hypoxic peripheral tissues in response to conditions of increased H+ concentrations (or acidosis). Similarly, the binding of 2,3‐DPG to Hb stabilizes the deoxyHb state, reduces the Hb‐O2 affinity and facilitates O2 release to tissues.Aims:To investigate oxygen off‐loading dynamics from voxelotor‐modified hemoglobin in vitro under increased acidity or increased DPG content.Methods:In this study, the Oxygen Dissociation Assay (ODA) and oxygen equilibrium curves (OECs) were used to determine the effect of voxelotor on Hb‐O2 affinity in response to H+ and 2,3‐DPG (5 mM). The ODA is a spectrophotometric assay that measures the time dependences of O2 release, while Hb‐O2 affinities can be measured using OECs. Studies in the ODA were conducted with purified Hb (3 μM), while OEC determinations were conducted with both purified Hb (25 μM) and whole blood.Results:Relative to Hb alone, voxelotor‐modified Hb dose‐dependently increased the proportion of oxygenated Hb (oxyHb) molecules during two hours of deoxygenation consistent with stabilization of hemoglobin in the oxy, or R‐ state. Under deoxygenated conditions, the percentage of oxygenated voxelotor‐modified Hb decreased over time, demonstrating oxygen release (offloading) by voxelotor‐modified Hb. With increased acidity (down to 6.8), there was an acceleration of oxygen release from voxelotor‐modified Hb under deoxygenated conditions. This resulted in an increase in the p50 of voxelotor‐modified blood and thus demonstrates a pH‐dependent decrease in the affinity of Hb for O2 in the presence of voxelotor at the therapeutic target Hb modification of 30% (Figure 1A). Similarly, the response of Hb to 2,3‐DPG effect was not inhibited in the presence of voxelotor at the 30% modification target (Figure 1B).Summary/Conclusion:The results of this study indicate that the central physiologic mechanisms which augment oxygen release to metabolically active tissues, such as the Bohr effect and 2,3‐DPG binding, are preserved when voxelotor is bound to Hb.image

Efficacy of Novel Multispectral Imaging Device to Determine Anastomosis for Esophagogastrostomy

BackgroundBiomedical imaging devices that utilize the optical characteristics of hemoglobin (Hb) have become widespread. In the field of gastroenterology, there is a strong demand for devices that can apply this technique to surgical navigation. We aimed to introduce our novel multispectral device capable of intraoperatively performing quantitative imaging of the oxygen (O2) saturation and Hb amount of tissues noninvasively and in real time, and to examine its application for deciding the appropriate anastomosis point after subtotal or total esophagectomy. Materials and methodsA total of 39 patients with esophageal cancer were studied. Tissue O2 saturation and Hb amount of the gastric tube just before esophagogastric anastomosis were evaluated using a multispectral tissue quantitative imaging device. The anastomosis point was decided depending on the quantitative values and patterns of both the tissue O2 saturation and Hb amount. ResultsThe device can instantaneously and noninvasively quantify and visualize the tissue O2 saturation and Hb amount using reflected light. The tissue Hb status could be classified into the following four types: good circulation type, congestion type, ischemia type, and mixed type of congestion and ischemia. Postoperative anastomotic failure occurred in 2 cases, and both were mixed cases. ConclusionsThe method of quantitatively imaging the tissue O2 saturation and Hb level in real time and noninvasively using a multispectral device allows instantaneous determination of the anastomosis and related organ conditions, thereby contributing to determining the appropriate treatment direction.

A 4-year follow-up of non-freezing cold injury with cold allodynia and neuropathy in 26 naval soldiers.

Background and aims Non-freezing cold injuries (NFCI), which typically may occur in military personnel, may result from exposure to cold, at temperatures around 0 °C or above, and worsened by wind and moisture. The injury is due to cooling but not freezing of tissue like in frostbite. NFCI may result in in chronic neuropathy and cold hypersensitivity. A recent retrospective study of small-and large fibres has suggested that NFCI results in neuropathic pain due to a sensory neuropathy and question a longitudinal study to verify a possible observation of improvement of NFCI over time. The present study is a 4-year follow-up investigation of large - and small-fibre function in 26 naval cadets and officers who were exposed to cold injury during the same military expedition. Methods The 26 soldiers were investigated clinically (with investigation of motor function, reflexes, sensibility), with nerve conduction studies (NCS) of major nerves in upper- and lower extremity, small fibre testing (QST, measurement of thermal thresholds), measurements of subcutaneous fat tissue and maximal O2 uptake. Investigations found place 2 months following the actual military expedition, with follow-up investigations of affected soldiers at 6-12 months and up to 3-4 years. In order to elucidate possible mechanisms (disinhibition of cold pain by myelinated nerve fibres) of cold allodynia, cold pain thresholds were measured following an ischemic block of conduction of large and small myelinated nerve fibres. Results Of 26 soldiers, 19 complained of numbness in feet and a large majority of 16 of cold hypersensitivity 2 months following injury. There were significant alterations of both large- and small-fibre function, indicating a general large- and small-fibre neuropathy. The most prominent finding was a pronounced cold allodynia, inversely correlated with the amount of subcutaneous fat. During the first year, results of NCS and thermal testing gradually normalized in most. Seven soldiers developed chronic symptoms in the form of cold hypersensitivity and with findings of cold allodynia, which was not further enhanced, but abolished following block of conduction of myelinated nerve fibres. Seven soldiers were free of symptoms from that start of the investigation, probably because they had been more eager to keep their legs moving during the exposure to cold. Conclusions Of a total of 26 soldiers, only seven developed chronic symptoms of cold hypersensitivity, corresponding to the finding of cold allodynia by thermal testing. The cold allodynia may not be explained by disinhibition of cold pain by myelinated fibres as in healthy subjects. A large majority recovered from an initial large-and small fibre neuropathy, demonstrating that recovery from NFCI may occur. Implications Although large-and small fibre neuropathy may be restored following cold injury, there is a risk of a permanent and disabling cold hypersensitivity, corresponding to the findings of cold allodynia. It is of uttermost importance to secure military personnel from the risk of cold injuries. It seems important to avoid immobilisation of extremities during exposure to cold.

Combined effects of exposure to hypoxia and cool on walking economy and muscle oxygenation profiles at tibialis anterior

ABSTRACTWe investigated combined effects of ambient temperature (23°C or 13°C) and fraction of inspired oxygen (21%O2 or 13%O2) on energy cost of walking (Cw: J·kg−1·km−1) and economical speed (ES). Eighteen healthy young adults (11 males, seven females) walked at seven speeds from 0.67 to 1.67 m s−1 (four min per stage). Environmental conditions were set; thermoneutral (N: 23°C) with normoxia (N: 21%O2) = NN; 23°C (N) with hypoxia (H: 13%O2) = NH; cool (C: 13°C) with 21%O2 (N) = CN, and 13°C (C) with 13%O2 (H) = CH. Muscle deoxygenation (HHb) and tissue O2 saturation (StO2) were measured at tibialis anterior. We found a significantly slower ES in NH (1.289 ± 0.091 m s−1) and CH (1.275 ± 0.099 m s−1) than in NN (1.334 ± 0.112 m s−1) and CN (1.332 ± 0.104 m s−1). Changes in HHb and StO2 were related to the ES. These results suggested that the combined effects (exposure to hypoxia and cool) is nearly equal to exposure to hypoxia and cool individually. Specifically, acute moderate hypoxia slowed the ES by approx. 4%, but acute cool environment did not affect the ES. Further, HHb and StO2 may partly account for an individual ES.

Hemodynamic responses to warming in euryhaline rainbow trout: implications of the osmo-respiratory compromise.

In seawater, rainbow trout (Oncorhynchus mykiss) drink and absorb water through the gastrointestinal tract to compensate for water passively lost to the hyperosmotic environment. Concomitantly, they exhibit elevated cardiac output and a doubling of gastrointestinal blood flow to provide additional O2 to the gut and increase convective flux of absorbed ions and water. Yet, it is unknown how warming waters, which elevate tissue O2 demand and the rate of diffusion of ions and water across the gills (i.e. the osmo-respiratory compromise), affects these processes. We measured cardiovascular and blood variables of rainbow trout acclimated to freshwater and seawater during acute warming from 11 to 17°C. Relative to freshwater-acclimated trout, cardiac output was 34% and 55% higher in seawater-acclimated trout at 11 and 17°C, respectively, which allowed them to increase gastrointestinal blood flow significantly more during warming (increases of 75% in seawater vs. 31% in freshwater). These adjustments likely served to mitigate the impact of warming on osmotic balance, as changes in ionic and osmotic blood composition were minor. Furthermore, seawater-acclimated trout seemingly had a lower tissue O2 extraction, explaining why trout acclimated to freshwater and seawater often exhibit similar metabolic rates, despite a higher cardiac output in seawater. Our results highlight a novel role of gastrointestinal blood perfusion in the osmo-respiratory compromise in fish, and improve our understanding of the physiological changes euryhaline fishes must undergo when faced with interacting environmental challenges such as transient warming events.

Regulation of Red Blood Cell Volume with Exercise Training.

Hypervolemia is a hallmark of endurance training (ET) and manifests by similar elevations in plasma (PV) and red blood cell volume (RBCV) so that hematocrit largely remains unaltered following weeks/months of training. While the mechanisms facilitating PV expansion with ET have been previously reviewed extensively this is not the case for RBCV. Endurance champions may have 40% more RBCV than controls and RBCV may increase up to 10% following months of regular exercise training in healthy individuals. Such adaptations are the main factor leading to concomitant changes in maximal oxygen uptake. The increase in RBCV is preceded by that of PV after few ET sessions, which in turn transiently decreases the hematocrit. The "critmeter" theory suggests that O2 sensors located within the juxtamedullary apparatus regulate the hematocrit via modulation of renal erythropoietin (EPO) production according to arterial O2 content-dependent changes in tissue O2 pressure. Hence, the initial decrease in hematocrit can be considered as a primary mechanism facilitating RBCV expansion with ET. Furthermore, after a single endurance exercise bout blood volume-regulating hormones ANGII and VPN increase transiently. Both stimulate renal EPO production. Catecholamines and cortisol, stress hormones acutely increased by endurance exercise, may facilitate the release of red blood cells from the bone marrow, thus possibly contributing to ET-induced erythropoiesis. These and other endocrine effects could be enhanced by the hyperplasia of the hematopoietic bone marrow observed in endurance athletes. © 2019 American Physiological Society. Compr Physiol 9:149-164, 2019.

The disuse effect on canal network structure and oxygen supply in the cortical bones of rats.

In this study, based on the measurements of intracortical vascular canal structure, we investigated the disuse effect on local O2 supply in the cortical bones of growing rats. Hindlimb disuse was produced by unilateral sciatic neurectomy (SN) at 4weeks age. The canal network structures within tibial cortical bone were evaluated in 8- and 12-week-old rats undergoing SN or no treatment (control) by synchrotron radiation micro-CT. Additionally, we developed an intracortical network model by combining the imaged-based canal network with a bone matrix containing theoretical lacunar-canalicular network, and determined the distribution of O2 concentration in bone tissue numerically. In the control bone, canal network was reduced with growth, resulting in decreased blood flow and averaged O2 concentration and increased spatial heterogeneity in tissue O2 concentration. Disuse reduced the canal network, leading to a lower flow rate, lower average O2 concentration and higher heterogeneity of O2 concentrations. However, the rarefaction of the canal network with growth was smaller under the disuse condition, and accordingly, the flow rate, the average O2 concentration and the heterogeneity of O2 concentrations remained stable. In particular, although the fraction of the canal volume was smaller, the densities of canal segments and bifurcation points under disuse condition tended to be higher than those of the control bone. The heterogeneity of O2 concentration was lower. Our results indicated that the disuse may lead to more uniformity in the canal network structure and thereby uniform O2, possibly contributing to O2 supply efficiency.

Systemic Oxygen Transport with Rest, Exercise, and Hypoxia: A Comparison of Humans, Rats, and Mice.

The objective of this article is to compare and contrast the known characteristics of the systemic O2 transport of humans, rats, and mice at rest and during exercise in normoxia and hypoxia. This analysis should help understand when rodent O2 transport findings can-and cannot-be applied to human responses to similar conditions. The O2 -transport system was analyzed as composed of four linked conductances: ventilation, alveolo-capillary diffusion, circulatory convection, and tissue capillary-cell diffusion. While the mechanisms of O2 transport are similar in the three species, the quantitative differences are naturally large. There are abundant data on total O2 consumption and on ventilatory and pulmonary diffusive conductances under resting conditions in the three species; however, there is much less available information on pulmonary gas exchange, circulatory O2 convection, and tissue O2 diffusion in mice. The scarcity of data largely derives from the difficulty of obtaining blood samples in these small animals and highlights the need for additional research in this area. In spite of the large quantitative differences in absolute and mass-specific O2 flux, available evidence indicates that resting alveolar and arterial and venous blood PO2 values under normoxia are similar in the three species. Additionally, at least in rats, alveolar and arterial blood PO2 under hypoxia and exercise remain closer to the resting values than those observed in humans. This is achieved by a greater ventilatory response, coupled with a closer value of arterial to alveolar PO2 , suggesting a greater efficacy of gas exchange in the rats. © 2018 American Physiological Society. Compr Physiol 8:1537-1573, 2018.

Modeling Tissue and Blood Gas Kinetics in Coastal and Offshore Common Bottlenose Dolphins, Tursiops truncatus.

Bottlenose dolphins (Tursiops truncatus) are highly versatile breath-holding predators that have adapted to a wide range of foraging niches from rivers and coastal ecosystems to deep-water oceanic habitats. Considerable research has been done to understand how bottlenose dolphins manage O2 during diving, but little information exists on other gases or how pressure affects gas exchange. Here we used a dynamic multi-compartment gas exchange model to estimate blood and tissue O2, CO2, and N2 from high-resolution dive records of two different common bottlenose dolphin ecotypes inhabiting shallow (Sarasota Bay) and deep (Bermuda) habitats. The objective was to compare potential physiological strategies used by the two populations to manage shallow and deep diving life styles. We informed the model using species-specific parameters for blood hematocrit, resting metabolic rate, and lung compliance. The model suggested that the known O2 stores were sufficient for Sarasota Bay dolphins to remain within the calculated aerobic dive limit (cADL), but insufficient for Bermuda dolphins that regularly exceeded their cADL. By adjusting the model to reflect the body composition of deep diving Bermuda dolphins, with elevated muscle mass, muscle myoglobin concentration and blood volume, the cADL increased beyond the longest dive duration, thus reflecting the necessary physiological and morphological changes to maintain their deep-diving life-style. The results indicate that cardiac output had to remain elevated during surface intervals for both ecotypes, and suggests that cardiac output has to remain elevated during shallow dives in-between deep dives to allow sufficient restoration of O2 stores for Bermuda dolphins. Our integrated modeling approach contradicts predictions from simple models, emphasizing the complex nature of physiological interactions between circulation, lung compression, and gas exchange.

Hydrogen gas inhalation protects against cutaneous ischaemia/reperfusion injury in a mouse model of pressure ulcer.

Pressure ulcer formation depends on various factors among which repetitive ischaemia/reperfusion(I/R) injury plays a vital role. Molecular hydrogen (H2) was reported to have protective effects on I/R injuries of various internal organs. In this study, we investigated the effects of H2 inhalation on pressure ulcer and the underlying mechanisms. H2 inhalation significantly reduced wound area, 8‐oxo‐dG level (oxidative DNA damage) and cell apoptosis rates in skin lesions. H2 remarkably decreased ROS accumulation and enhanced antioxidant enzymes activities by up‐regulating expression of Nrf2 and its downstream components in wound tissue and/or H2O2‐treated endothelia. Meanwhile, H2 inhibited the overexpression of MCP‐1, E‐selectin, P‐selectin and ICAM‐1 in oxidant‐induced endothelia and reduced inflammatory cells infiltration and proinflammatory cytokines (TNF‐α, IL‐1, IL‐6 and IL‐8) production in the wound. Furthermore, H2 promoted the expression of pro‐healing factors (IL‐22, TGF‐β, VEGF and IGF1) and inhibited the production of MMP9 in wound tissue in parallel with acceleration of cutaneous collagen synthesis. Taken together, these data indicated that H2 inhalation suppressed the formation of pressure ulcer in a mouse model. Molecular hydrogen has potentials as a novel and alternative therapy for severe pressure ulcer. The therapeutic effects of molecular hydrogen might be related to its antioxidant, anti‐inflammatory, pro‐healing actions.