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Aerobic metabolism relies on external oxygen production through photosynthesis and its subsequent transport into each cell of the body via the cardiorespiratory system. This mechanism has successfully evolved over millions of years, enabling animals to inhabit most environments on Earth. However, the insufficient oxygen supply leads to several clinical problems, ranging from non-healing wounds to tumor resistance to therapy. Given that photosynthetic microorganisms are capable of producing oxygen and removing carbon dioxide from the environment, over the last decade, several groups worldwide have proposed their potential use as an alternative tissue oxygenation approach. While most studies have demonstrated safety and efficacy after local tissue administration, recent studies have also suggested that systemic administration could trigger intravascular photosynthesis. If successful, the development of a new generation of circulating cells, known as chlorocytes, may partially replace the role of erythrocytes in gas exchange within the body, without relying on external supply and vascular flow. This work reviews the existing literature on local and systemic administration of photosynthetic microorganisms, highlighting the main challenges in the field and potential solutions to unleash the enormous potential clinical impact of chlorocytes and intravascular photosynthesis. Key points: • Circulating photosynthetic microorganisms could deliver oxygen to tissues • Microalgae and cyanobacteria have shown safety and efficacy for oxygen delivery • Several key challenges need to be addressed for the clinical success of chlorocytes [ABSTRACT FROM AUTHOR]

Targeted oxygen delivery during cardiopulmonary bypass (CPB) has received significant attention due to its influence on patient outcomes, especially in mitigating acute kidney injury. While it has gained popularity in select institutions, there remains a gap in establishing it globally across multiple centers. The purpose of this investigation was to describe the development of a quality improvement process of targeted oxygen delivery during CPB across hospitals throughout the United States. A systematic approach to utilize oxygen delivery index (DO2i) as a key performance indicator within hospitals serviced by a national provider of perfusion services. The process included a review of the current literature on DO2i, which yielded a target nadir value (272 mL/min/m2) and an area under the curve (DO2i272AUC) cut off of 632. All data is displayed on a dashboard with results categorized across multiple levels from system-wide to individual clinician performance. From January 2020 through December 2022, DO2i data from 91 hospitals and 11,165 coronary artery bypass graft procedures were collected. During this period the monthly proportion of DO2i measurements above the target nadir DO2i272 ranged from 60.5% to 78.4% with a mean+/−SD of 70.8 +/- 4.2%. Binary logistic regression for the first 7 months following monthly DO2i performance reporting has shown a statistically significant positive linear trend in the probability of achieving the target DO2i272 (p <.001), with a crude increase of approximately 7.8% for DO2i272AUC, and a 73.8% success rate (p <.001). A survey was sent to all individuals measuring oxygen delivery during CPB to assess why a target DO2i272 could not be reached. The two most common responses were an 'inability to improve CPB flow rates' and 'restrictive allogeneic red blood cell transfusion policies'. This study demonstrates that targeting a minimum level of oxygen delivery can serve as a key performance indicator during CPB using a structured quality improvement process. [ABSTRACT FROM AUTHOR]

Background: Retinopathy of prematurity (ROP) is a leading cause of avoidable blindness in children, particularly in Latin America, where hyperoxia is a significant risk factor. This study evaluated resource availability and use for administering and monitoring supplemental oxygen in Mexico. Methods: In 2011, an observational study in which 32 government neonatal intensive care units (NICUs) across Mexico were visited. Data collected included occupancy, staffing levels, and equipment to deliver and monitor supplemental oxygen. Preterm infants receiving oxygen were observed. In 2023, 13 NICUs were revisited, and similar data collected. Staffing levels were benchmarked against Argentinian and US recommendations. Results: In 2011, only 38% of NICUs had adequate medical and staffing levels to meet recommended cot-to-staff ratios for all shifts. Staffing ratios were worse during weekends and at night than during weekdays. Only 25.5% of cots had blenders, and 80.1% had saturation monitors. 153 infants were observed 87% of whom were being monitored. Upper and lower oxygen saturations were ≥ 96% in 53%, and ≤ 89% in 8%, respectively. Alarm settings were inadequate, as 38% and 32% of upper and lower alarms were switched off and 16% and 53% were incorrectly set, respectively. In the 13 NICUs with data from 2011 and 2023, cot-to-staff ratios deteriorated over time, and in 2023 no unit had recommended ratios for all shifts. Equipment provision did not change, with similar proportions of babies in oxygen being monitored (79% 2011; 75% 2023). Rates of hyperoxia decreased slightly from 54% in 2011 to 49% in 2023. More upper alarms were set (46% 2011; 75% 2023), but a higher proportion were incorrectly set (52% 2011; 68% 2023). Conclusions: Between 2011 and 2023, cot-to-staff ratios worsened, and equipment for safe oxygen delivery and monitoring remained insufficient. Despite available monitoring equipment, oxygen saturations often exceeded recommended levels, and alarms were frequently not set or incorrectly configured. Urgent improvements are needed in healthcare workforce numbers and practices, along with ensuring adequate equipment for safe oxygen delivery. [ABSTRACT FROM AUTHOR]

The presence of hypoxics, bacterial infection, and the creation of bacterial biofilms are significant obstacles that hinder the healing of diabetic wounds. Calcium peroxide (CaO2) can be hydrolyzed to produce oxygen (O2) and hydrogen peroxide (H2O2), resulting in the simultaneous creation of oxygen and an antimicrobial effect. However, oxygen delivery is limited by the skin and bacterial biofilm barrier. Herein, we proposed a microneedles patch loading CaO2 nanoparticles (abbreviated as CaO2 NPs@MN). The microneedles can puncture the skin and destroy the biofilm barrier. Meanwhile, upon contact with the biological fluid, the microneedles would be dissolved, and CaO2 NPs would be released into the wound site, further being hydrolyzed to O2 and H2O2 to achieve antibacterial effect and local deep oxygen delivery. Notably, in order to encapsulate CaO2 powders evenly into the microneedle tips and avoid their hydrolysis during the preparation process, we fabricated the nanoscaled CaO2 particles and encapsulated them in microneedles in an ethanol system for the first time. The in vitro experiments demonstrated that CaO2 NPs@MN possessed the desired oxygen delivery and antibacterial effect. Furthermore, the elimination of bacteria, reduction in inflammation, promotion of collagen formation, stimulation of blood vessel growth, and subsequent acceleration of wound healing were observed in in vivo experiments. In conclusion, we provided a simple process for the application of CaO2 in wound healing and also a promising strategy for infected diabetic ulcer treatment. [ABSTRACT FROM AUTHOR]

This article discusses the concept of the Laffer curve, which was popularized by economist Arthur Laffer in the 1970s. The Laffer curve illustrates the relationship between tax rates and tax revenue, suggesting that there is an optimal tax rate that maximizes government revenue. The article then applies this concept to the study of lactate kinetics in physiology. Lactate is produced by cells during anaerobic metabolism and is used as a measure of tissue perfusion. The article suggests that there may be two states of perfusion that result in the same blood lactate concentration, which could have implications for the interpretation of lactate levels in clinical practice. [Extracted from the article]

Purpose: Oxygen delivery (DO2) and its monitoring are highlighted to aid postoperative goal directed therapy (GDT) to improve perioperative outcomes such as acute kidney injury (AKI) after high-risk cardiac surgeries associated with multiple morbidities and mortality. However, DO2 monitoring is neither routine nor done postoperatively, and current methods are invasive and only produce intermittent DO2 trends. Hence, we proposed a novel algorithm that simultaneously integrates cardiac output (CO), hemoglobin (Hb) and oxygen saturation (SpO2) from the Edwards Life Sciences ClearSight System® and Masimo SET Pulse CO-Oximetry® to produce a continuous, real-time DO2 trend. Methods: Our algorithm was built systematically with 4 components – machine interface to draw data with PuTTY, data extraction with parsing, data synchronization, and real-time DO2 presentation using a graphic-user interface. Hb readings were validated. Results: Our algorithm was implemented successfully in 93% (n = 57 out of 61) of our recruited cardiac surgical patients. DO2 trends and AKI were studied. Conclusion: We demonstrated a novel proof-of-concept and feasibility of continuous, real-time, non-invasive DO2 monitoring, with each patient serving as their own control. Our study also lays the foundation for future investigations aimed at identifying personalized critical DO2 thresholds and optimizing DO2 as an integral part of GDT to enhance outcomes in perioperative cardiac surgery. [ABSTRACT FROM AUTHOR]

Background: Recent advances on cardiorespiratory monitoring applied in ARDS patients undergoing invasive mechanical ventilation and noninvasive ventilatory support are available in the literature and may have potential prognostic implication in ARDS treatment. Main body: The measurement of oxygen saturation by pulse oximetry is a valid, low-cost, noninvasive alternative for assessing arterial oxygenation. Caution must be taken in patients with darker skin pigmentation, who may experience a greater incidence of occult hypoxemia. Dead space surrogates, which are easy to calculate, have important prognostic implications. The mechanical power, which can be automatically computed by intensive care ventilators, is an important parameter correlated with ventilator-induced lung injury and outcome. In patients undergoing noninvasive ventilatory support, the use of esophageal pressure can measure inspiratory effort, avoiding possible delays in endotracheal intubation. Fluid responsiveness can also be evaluated using dynamic indices in patients ventilated at low tidal volumes (< 8 mL/kg). In patients ventilated at high levels of positive end expiratory pressure (PEEP), the PEEP test represents a valid alternative to passive leg raising. There is growing evidence on alternative parameters for evaluating fluid responsiveness, such as central venous oxygen saturation variations, inferior vena cava diameter variations and capillary refill time. Conclusion: Careful cardiorespiratory monitoring in patients affected by ARDS is crucial to improve prognosis and to tailor treatment via mechanical ventilatory support. Keypoints: The SpO2/FiO2 ratio, corrected minute ventilation and ventilatory ratio are valid surrogates for estimating gas exchange in ARDS patients, and caution should be taken in patients with darker skin pigmentation and moderate–severe ARDS. Changes in esophageal pressure during noninvasive respiratory support and mechanical power must be carefully monitored to estimate PSILI and VILI in ARDS patients undergoing mechanical ventilation. The use of dynamic indexes of fluid responsiveness should be encouraged in ARDS patients. Pulse pressure variation and stroke volume variation have also been validated in mechanically ventilated patients with low tidal volume. A possible alternative to passive leg raising in a mechanically ventilated patient is the PEEP test. Two minimally invasive alternatives to predict fluid responsiveness are changes in central venous oxygen saturation and capillary refill time after a passive leg raising or a fluid challenge. [ABSTRACT FROM AUTHOR]

OBJECTIVES The multifactorial dynamic perfusion index was recently introduced as a predictor of cardiac surgery-associated acute kidney injury. The multifactorial dynamic perfusion index was developed based on retrospective data retrieved from the patient files. The present study aims to prospectively validate this index in an external series of patients, through an on-line measure of its various components. METHODS Inclusion criteria were adult patients undergoing cardiac surgery with cardiopulmonary bypass. Data collection included preoperative factors and cardiopulmonary bypass-related factors. These were collected on-line using a dedicated monitor. Factors composing the multifactorial dynamic perfusion index are the nadir haematocrit, the nadir oxygen delivery, the time of exposure to a low oxygen delivery, the nadir mean arterial pressure, cardiopulmonary bypass duration, the use of red blood cell transfusions and the peak arterial lactates. RESULTS Two hundred adult patients were investigated. The multifactorial dynamic perfusion index had a good (c-statistics 0.81) discrimination for cardiac surgery-associated acute kidney injury (any stage) and an excellent (c-statistics 0.93) discrimination for severe patterns (stage 2–3). Calibration was modest for cardiac surgery-associated acute kidney injury (any stage) and good for stage 2–3. The use of vasoconstrictors was an additional factor associated with cardiac surgery-associated acute kidney injury. CONCLUSIONS The multifactorial dynamic perfusion index is validated for discrimination of cardiac surgery-associated acute kidney injury risk. It incorporates modifiable risk factors, and may help in reducing the occurrence of cardiac surgery-associated acute kidney injury. [ABSTRACT FROM AUTHOR]

Background: Anemia, characterized by low hemoglobin levels, is a global public health concern. Anemia is an independent factor worsening outcomes in various patient groups. Blood transfusion has been the traditional treatment for anemia; its triggers, primarily based on hemoglobin levels; however, hemoglobin level is not always an ideal trigger for blood transfusion. Additionally, blood transfusion worsens clinical outcomes in certain patient groups. This narrative review explores alternative triggers for red blood cell transfusion and their physiological basis. Main Text: The review delves into the physiology of oxygen transport and highlights the limitations of using hemoglobin levels alone as transfusion trigger. The main aim of blood transfusion is to optimize oxygen delivery, necessitating an individualized approach based on clinical signs of anemia and the balance between oxygen delivery and consumption, reflected by the oxygen extraction rate. The narrative review covers different alternative triggers. It presents insights into their diagnostic value and clinical applications, emphasizing the need for personalized transfusion strategies. Conclusion: Anemia and blood transfusion are significant factors affecting patient outcomes. While restrictive transfusion strategies are widely recommended, they may not account for the nuances of specific patient populations. The search for alternative transfusion triggers is essential to tailor transfusion therapy effectively, especially in patients with comorbidities or unique clinical profiles. Investigating alternative triggers not only enhances patient care by identifying more precise indicators but also minimizes transfusion-related risks, optimizes blood product utilization, and ensures availability when needed. Personalized transfusion strategies based on alternative triggers hold the potential to improve outcomes in various clinical scenarios, addressing anemia's complex challenges in healthcare. Further research and evidence are needed to refine these alternative triggers and guide their implementation in clinical practice. [ABSTRACT FROM AUTHOR]

Background: ECPELLA, a combination of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) and Impella, a percutaneous left ventricular (LV) assist device, has emerged as a novel therapeutic option in patients with severe cardiogenic shock (CS). Since multiple cardiovascular and pump factors influence the haemodynamic effects of ECPELLA, optimising ECPELLA management remains challenging. In this study, we conducted a comprehensive simulation study of ECPELLA haemodynamics. We also simulated global oxygen delivery (DO2) under ECPELLA in severe CS and acute respiratory failure as a first step to incorporate global DO2 into our developed cardiovascular simulation. Methods and results: Both the systemic and pulmonary circulations were modelled using a 5-element resistance‒capacitance network. The four ventricles were represented by time-varying elastances with unidirectional valves. In the scenarios of severe LV dysfunction, biventricular dysfunction with normal pulmonary vascular resistance (PVR, 0.8 Wood units), and biventricular dysfunction with high PVR (6.0 Wood units), we compared the changes in haemodynamics, pressure–volume relationship (PV loop), and global DO2 under different VA-ECMO flows and Impella support levels. Results: In the simulation, ECPELLA improved total systemic flow with a minimising biventricular pressure–volume loop, indicating biventricular unloading in normal PVR conditions. Meanwhile, increased Impella support level in high PVR conditions rendered the LV–PV loop smaller and induced LV suction in ECPELLA support conditions. The general trend of global DO2 was followed by the changes in total systemic flow. The addition of veno-venous ECMO (VV-ECMO) augmented the global DO2 increment under ECPELLA total support conditions. Conclusions: The optimal ECPELLA support increased total systemic flow and achieved both biventricular unloading. The VV-ECMO effectively improves global DO2 in total ECPELLA support conditions. [ABSTRACT FROM AUTHOR]

Hypoxia is known to increase muscle fatigue via both central and peripheral mechanisms. Females are typically less fatigable than males during isometric fatiguing contractions due to greater peripheral blood flow. However, sex differences in fatigue are blunted during dynamic fatiguing tasks. Thus, this study determined the interactions of sex and hypoxia on knee extensor muscle contractile function during a dynamic, ischemic fatiguing contraction. Electrical stimulation was used to determine contractile properties of the knee extensor muscles in eight males and eight females before and after an ischemic, dynamic fatiguing task while inspiring room air or a hypoxic gas mixture (10% O2:90% N2). Fatigue (assessed as time-to-task failure) was ~10% greater during the hypoxic condition (94.3 ± 33.4 s) compared with normoxic condition (107.0 ± 42.8 s, P = 0.041) and ~40% greater for females than males (77.1 ± 18.8 vs. 124.2 ± 38.7, P < 0.001). Immediately after the dynamic fatiguing task, there were reductions in maximal voluntary contraction force (P = 0.034) and electrically evoked twitch force (P < 0.001), and these reductions did not differ based on sex or inspirate. Cerebral tissue oxygenation showed a significant interaction of time and inspirate (P = 0.003) whereby it increased during normoxia and remained unchanged in hypoxia. No sex-related differences in the changes of cerebral tissue oxygenation were observed (P = 0.528). These data suggest that acute hypoxia increases central fatigue during ischemic single-leg exercise resulting in earlier exercise termination, but the effect does not differ based on sex. [ABSTRACT FROM AUTHOR]

Introduction: cardiac surgery associated acute kidney injury (CSA-AKI) has a number of preoperative and intraoperative risk factors. Cardiopulmonary bypass (CPB) factors have not yet been elucidated in a single multivariate model. The aim of this study is to develop a dynamic predictive model for CSA-AKI. Methods: retrospective study on 910 consecutive adult cardiac surgery patients. Baseline data were used to settle a preoperative CSA-AKI risk model (static risk model, SRM); CPB related data were assessed for association with CSA-AKI. CPB duration, nadir oxygen delivery, time of exposure to a low oxygen delivery, nadir mean arterial pressure, peak lactates and red blood cell transfusion were included in a multivariate dynamic perfusion risk (DPR). SRM and DPR were merged into a final logistic regression model (multifactorial dynamic perfusion index, MDPI). The three risk models were assessed for discrimination and calibration. Results: the SRM model had an AUC of 0.696 (95% CI 0.663–0.727), the DPR model of 0.723 (95% CI 0.691–0.753), and the MDPI model an AUC of 0.769 (95% CI 0.739–0.798). The difference in AUC between SRM and DPR was not significant (p = 0.495) whereas the AUC of MDPI was significantly larger than that of SRM (p = 0.004) and DPR (p = 0.015). Conclusions: inclusion of dynamic indices of the quality of CPB improves the discrimination and calibration of the preoperative risk scores. The MDPI has better predictive ability than the existing static risk models and is a promising tool to integrate different factors into an advanced concept of goal-directed perfusion. [ABSTRACT FROM AUTHOR]

The management of severe burns remains a complex challenge. Adenosine, lidocaine, and magnesium (ALM) resuscitation therapy has been shown to protect against hemorrhagic shock and traumatic injury. The aim of the present study was to investigate the early protective effects of small-volume ALM fluid resuscitation in a rat model of 30% total body surface area (TBSA) thermal injury. Male Sprague–Dawley rats (320–340 g; n = 25) were randomly assigned to: 1) Sham (surgical instrumentation and saline infusion, without burn, n = 5), 2) Saline resuscitation group (n = 10), or 3) ALM resuscitation group (n = 10). Treatments were initiated 15-min after burn trauma, including 0.7 mL/kg 3% NaCl ± ALM bolus and 0.25–0.5 mL/kg/h 0.9% NaCl ± ALM drip, with animals monitored to 8.25-hr post-burn. Hemodynamics, cardiac function, blood chemistry, hematology, endothelial injury markers and histopathology were assessed. Survival was 100% for Shams and 90% for both ALM and Saline groups. Shams underwent significant physiological, immune and hematological changes over time as a result of surgical traums. ALM significantly reduced malondialdehyde levels in the lungs compared to Saline (P =.023), and showed minimal alveolar destruction and inflammatory cell infiltration (P <.001). ALM also improved cardiac function and oxygen delivery (21%, P =.418 vs Saline), reduced gut injury (P <.001 vs Saline), and increased plasma adiponectin (P <.001 vs baseline). Circulating levels of the acute phase protein alpha 1-acid glycoprotein (AGP) increased 1.6-times (P <.001), which may have impacted ALM's therapeutic efficacy. We conclude that small-volume ALM therapy significantly reduced lung oxidative stress and preserved alveolar integrity following severe burn trauma. Further studies are required to assess higher ALM doses with longer monitoring periods. [ABSTRACT FROM AUTHOR]

Hypoxia has the potential to impair cognitive function; however, it is still uncertain which cognitive domains are adversely affected. We examined the effects of acute hypoxia (∼7 h) on central executive (Go/No‐Go) and non‐executive (memory) tasks and the extent to which impairment was potentially related to regional cerebral blood flow and oxygen delivery (CDO2). Twelve male participants performed cognitive tasks following 0, 2, 4 and 6 h of passive exposure to both normoxia and hypoxia (12% O2), in a randomized block cross‐over single‐blinded design. Middle cerebral artery (MCA) and posterior cerebral artery (PCA) blood velocities and corresponding CDO2 were determined using bilateral transcranial Doppler ultrasound. In hypoxia, MCA DO2 was reduced during the Go/No‐Go task (P = 0.010 vs. normoxia, main effect), and PCA DO2 was attenuated during memorization (P = 0.005 vs. normoxia) and recall components (P = 0.002 vs. normoxia) in the memory task. The accuracy of the memory task was also impaired in hypoxia (P = 0.049 vs. normoxia). In contrast, hypoxia failed to alter reaction time (P = 0.19 vs. normoxia) or accuracy (P = 0.20 vs. normoxia) during the Go/No‐Go task, indicating that selective attention and response inhibition were preserved. Hypoxia did not affect cerebral blood flow or corresponding CDO2 responses to cognitive activity (P > 0.05 vs. normoxia). Collectively, these findings highlight the differential sensitivity of cognitive domains, with memory being selectively vulnerable in hypoxia. New Findings: What is the central question of this study?We sought to examine the effects of acute hypoxia on central executive (selective attention and response inhibition) and non‐executive (memory) performance and the extent to which impairments are potentially related to reductions in regional cerebral blood flow and oxygen delivery.What is the main finding and its importance?Memory was impaired in acute hypoxia, and this was accompanied by a selective reduction in posterior cerebral artery oxygen delivery. In contrast, selective attention and response inhibition remained well preserved. These findings suggest that memory is selectively vulnerable to hypoxia. [ABSTRACT FROM AUTHOR]

Late gestational supine positioning reduces maternal cardiac output due to inferior vena caval (IVC) compression, despite increased collateral venous return. However, little is known about the impact of maternal position on oxygen (O2) delivery and consumption of the gravid uterus, fetus, placenta and lower limbs. We studied the effects of maternal positioning on these parameters in 20 healthy pregnant subjects at 36 ± 2 weeks using magnetic resonance imaging (MRI); a follow‐up MRI was performed 6‐months postpartum (n = 16/20). MRI techniques included phase‐contrast and T1/T2 relaxometry for blood flow and oximetry imaging, respectively. O2 transport was measured in the following vessels (bilateral where appropriate): maternal abdominal descending aorta (DAoabdo), IVC, ovarian, paraspinal veins (PSV), uterine artery (UtA) and external iliacs, and umbilical. Maternal cardiac output was measured by summing DAothoracic and superior vena cava flows. Supine mothers (n = 6) had lower cardiac output and O2 delivery in the DAoabdo, UtA and external iliac arteries, and higher PSV flow than those in either the left (n = 8) or right (n = 6) lateral positions during MRI. However, O2 consumption in the gravid uterus, fetus, placenta and lower limbs was unaffected by maternal positioning. The ratio of IVC/PSV flow decreased in supine mothers while ovarian venous flow and O2 saturation were unaltered, suggesting a major route of pelvic venous return unaffected by maternal position. Placental–fetal O2 transport and consumption were similar between left and right lateral maternal positions. In comparison to non‐pregnant findings, DAoabdo and UtA O2 delivery and pelvic O2 consumption increased, while lower‐limb consumption remained constant , despite reduced external iliac artery O2 delivery in late gestation. Key points: Though sleeping supine during the third trimester is associated with an increased risk of antepartum stillbirth, the underlying biological mechanisms are not fully understood.Maternal cardiac output and uteroplacental flow are reduced in supine mothers due to inferior vena caval compression from the weight of the gravid uterus.This MRI study provides a comprehensive circulatory assessment, demonstrating reduced maternal cardiac output and O2 delivery (uteroplacental, lower body) in supine compared to lateral positioning; however, O2 consumption (gravid uterus, fetus, placenta, lower limbs) was preserved.Unlike other mammalian species, the ovarian veins conduct substantial venous return from the human pregnant uterus that is unaffected by maternal positioning. Lumbar paraspinal venous flow increased in supine mothers. These observations may have important considerations during major pelvic surgery in pregnancy (i.e. placenta percreta).Future studies should address the importance of maternal positioning as a potential tool to deliver improved perinatal outcomes in pregnancies with compromised uteroplacental O2 delivery. [ABSTRACT FROM AUTHOR]

The article focuses on cerebral physiology, covering topics such as cerebral metabolic rate, cerebral circulation, and factors affecting cerebral blood flow. It discusses how various physiological variables such as cerebral autoregulation, neurovascular coupling, and vasomotor reactivity influence cerebral blood flow and oxygen delivery.

Background: Abdominal normothermic regional perfusion (A‐NRP) allows in‐situ reperfusion and recovery of abdominal organs metabolism in donors after circulatory death (DCD). Besides improving liver transplantation outcomes, liver injury and function can be assessed during A‐NRP. Methods: To refine liver viability assessment during A‐NRP, prospectively collected data of controlled DCD donors managed at our Institution between October 2019 and May 2022 were retrospectively analyzed. Baseline characteristics, procedural variables and A‐NRP parameters of donors whose liver was successfully transplanted were compared to those of donors whose liver was discarded. Results: Twenty‐seven donors were included and in 20 (74%) the liver was accepted (positive outcome). No differences between study groups were observed concerning baseline characteristics and warm ischemia times (WIT). Initial lactate levels were positively correlated with functional WIT (r2 = 0.4, p = 0.04), whereas transaminase levels were not. Blood flow during A‐NRP was comparable, whereas oxygen consumption (VO2) was significantly higher in the positive outcome group after 1 h. Time courses of lactate, AST and ALT were significantly different between study groups (p < 0.001). Donors whose liver was accepted showed faster lactate clearance, a difference which was amplified by normalizing lactate clearance to oxygen delivery (DO2) and VO2. Lactate clearance was correlated to transaminase levels and DO2‐normalized lactate clearance was the parameter best discriminating between study groups. Conclusions: DO2‐normalized lactate clearance may represent an element of liver viability assessment during A‐NRP. [ABSTRACT FROM AUTHOR]

Tumor hypoxia, which is mainly caused by the inefficient microvascular systems induced by rapid tumor growth, is a common characteristic of most solid tumors and has been found to hinder treatment outcomes for many types of cancer therapeutics. In this study, an amphiphilic block copolymer, poly (ethylene glycol) methyl ether acrylate-block-n-butyl acrylate (PEGA-BA), was prepared via the ATRP method and self-assembled into core-shell micelles as nano radiosensitizers. These micelles encapsulated a photosensitizer, Chlorin e6 (Ce6), and demonstrated well-defined morphology, a uniform size distribution, and high oxygen loading capacity. Cell experiments showed that PEGA-BA@Ce6@PFCE micelles could effectively enter cells. Further in vitro anticancer studies demonstrated that the PEGA-BA@Ce6@PFCE micelles significantly suppressed the tumor cell survival rate when exposed to a laser. [ABSTRACT FROM AUTHOR]

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The benefits of exercise involve skeletal muscle redox state alterations of nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD). We determined the fiber-specific effects of acute exercise on the skeletal muscle redox state in healthy adults. Muscle biopsies were obtained from 19 participants (11 M, 8 F; 26 ± 4 yr) at baseline (fasted) and 30 min and 3 h after treadmill exercise at 80% maximal oxygen consumption (VO2max). Muscle samples were probed for autofluorescence of NADH (excitation at 340-360 nm) and oxidized flavoproteins (Fp; excitation at 440-470 nm) and subsequently, fiber typed to quantify the redox signatures of individual muscle fibers. Redox state was calculated as the oxidation-to-reduction redox ratio: Fp/(Fp + NADH). At baseline, pair-wise comparisons revealed that the redox ratio of myosin heavy chain (MHC) I fibers was 7.2% higher than MHC IIa (P = 0.023, 95% CI: 5.2, 9.2%) and the redox ratio of MHC IIa was 8.0% higher than MHC IIx (P = 0.035, 95% CI: 6.8, 9.2%). MHC I fibers also displayed greater NADH intensity than MHC IIx (P = 0.007) and greater Fp intensity than both MHC IIa (P = 0.019) and MHC IIx (P < 0.0001). Fp intensities increased in all fiber types (main effect, P = 0.039) but redox ratios did not change (main effect, P ¼ 0.483) 30 min after exercise. The change in redox ratio was positively correlated with capillary density in MHC I (rho = 0.762, P = 0.037), MHC IIa fibers (rho = 0.881, P = 0.007), and modestly in MHC IIx fibers (rho = 0. 771, P ¼ 0.103). These findings support the use of redox autofluorescence to interrogate skeletal muscle metabolism. [ABSTRACT FROM AUTHOR]

Cerebral hypoxic vasodilation is poorly understood in humans, which undermines the development of therapeutics to optimize cerebral oxygen delivery. Across four investigations (total n = 195) we investigated the role of nitric oxide (NO) and hemoglobin-based S -nitrosothiol (RSNO) and nitrite ( NO 2 − ) signaling in the regulation of cerebral hypoxic vasodilation. We conducted hemodilution (n = 10) and NO synthase inhibition experiments (n = 11) as well as hemoglobin oxygen desaturation protocols, wherein we measured cerebral blood flow (CBF), intra-arterial blood pressure, and in subsets of participants trans-cerebral release/uptake of RSNO and NO 2 − . Higher CBF during hypoxia was associated with greater trans-cerebral RSNO release but not NO 2 − , while NO synthase inhibition reduced cerebral hypoxic vasodilation. Hemodilution increased the magnitude of cerebral hypoxic vasodilation following acute hemodilution, while in 134 participants tested under normal conditions, hypoxic cerebral vasodilation was inversely correlated to arterial hemoglobin concentration. These studies were replicated in a sample of polycythemic high-altitude native Andeans suffering from excessive erythrocytosis (n = 40), where cerebral hypoxic vasodilation was inversely correlated to hemoglobin concentration, and improved with hemodilution (n = 6). Collectively, our data indicate that cerebral hypoxic vasodilation is partially NO-dependent, associated with trans-cerebral RSNO release, and place hemoglobin-based NO signaling as a central mechanism of cerebral hypoxic vasodilation in humans. [ABSTRACT FROM AUTHOR]

Background: Isolated limb perfusion (ILP) is a regional surgical treatment for localized metastatic disease. High doses of chemotherapeutic agents are administered within an extracorporeal circulated isolated extremity, treating the metastasis, while systemic toxicity is avoided. To our knowledge, indexed oxygen supply/demand relationship during ILP has not previously been described. Our aim was to measure and describe oxygen metabolism, specifically oxygen delivery, consumption, and extraction, in an isolated leg/arm during ILP. Also investigate whether invasive oxygenation measurement during ILP correlates and can be used interchangeable with the non-invasive method, near infrared spectroscopy (NIRS). Methods: Data from 40 patients scheduled for ILP were included. At six time points blood samples were drawn during the procedure. DO2, VO2, and O2ER were calculated according to standard formulas. NIRS and hemodynamics were recorded every 10 min. Results: For all observations, the mean of DO2 was 190±59 ml/min/m2, VO2 was 35±8 ml/min/m2, and O2ER was 21±8%. VO2 was significantly higher in legs compared to arms (38±8 vs. 29±7 ml/min/m2, p=0.02). Repeated measures showed a significant decrease in DO2 in legs (209±65 to 180±66 ml/min/m2, p=<0.01) and in arms (252±72 to 150±57 ml/min/m2, p=<0.01). Significant increase in O2ER in arms was also found (p=0.03). Significant correlation was detected between NIRS and venous extremity oxygen saturation (SveO2) (rrm=0.568, p=<. 001, 95% CI 0.397–0.701). When comparing SveO2 and NIRS using a Bland–Altman analysis, the mean difference (bias) was 8.26±13.03 (p=<. 001) and the limit of agreement was − 17.28–33.09, with an error of 32.5%. Conclusion: DO2 above 170 ml/min/m2 during ILP kept O2ER below 30% for all observations. NIRS correlates significant to SveO2; however, the two methods do not agree sufficiently to work interchangeable. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT04460053 and NCT03073304. [ABSTRACT FROM AUTHOR]

Nanocarriers for oxygen delivery have been the focus of extensive research to ameliorate the therapeutic effects of current anti-cancer treatments and in the organ transplant field. In the latter application, the use of oxygenated cardioplegic solution (CS) during cardiac arrest is certainly beneficial, and fully oxygenated crystalloid solutions may be excellent means of myocardial protection, albeit for a limited time. Therefore, to overcome this drawback, oxygenated nanosponges (NSs) that can store and slowly release oxygen over a controlled period have been chosen as nanocarriers to enhance the functionality of cardioplegic solutions. Different components can be used to prepare nanocarrier formulations for saturated oxygen delivery, and these include native α-cyclodextrin (αCD), αcyclodextrin-based nanosponges (αCD-NSs), native cyclic nigerosyl-nigerose (CNN), and cyclic nigerosyl-nigerose-based nanosponges (CNN-NSs). Oxygen release kinetics varied depending on the nanocarrier used, demonstrating higher oxygen release after 24 h for NSs than the native αCD and CNN. CNN-NSs presented the highest oxygen concentration (8.57 mg/L) in the National Institutes of Health (NIH) CS recorded at 37 °C for 12 h. The NSs retained more oxygen at 1.30 g/L than 0.13 g/L. These nanocarriers have considerable versatility and the ability to store oxygen and prolong the amount of time that the heart remains in hypothermic CS. The physicochemical characterization presents a promising oxygen-carrier formulation that can prolong the release of oxygen at low temperatures. This can make the nanocarriers suitable for the storage of hearts during the explant and transport procedure. [ABSTRACT FROM AUTHOR]

Background: Prehospital anesthesia may lead to circulatory collapse after severe hemorrhage. It is possible that permissive hypoventilation, refraining from tracheal intubation and accepting spontaneous ventilation, decreases this risk, but it is not known if oxygen delivery can be maintained. We investigated the feasibility of permissive hypoventilation after class III hemorrhage and whole blood resuscitation in three prehospital phases: 15 min on‐scene, 30 min whole blood resuscitation, and 45 min after. Study Design and Methods: 19 crossbred swine, mean weight 58.5 kg, were anesthetized with ketamine/midazolam and hemorrhaged to a mean (SD) 1298 (220) mL (33%) and randomized to permissive hypoventilation (n = 9) or positive pressure ventilation with FiO2 21% (n = 10). Results: In permissive hypoventilation versus positive pressure ventilation, indexed oxygen delivery (DO2I) decreased to mean (SD) 4.73 (1.06) versus 3.70 (1.13) mL min−1 kg−1 after hemorrhage and increased to 8.62 (2.09) versus 6.70 (1.56) mL min−1 kg−1 at completion of resuscitation. DO2I, indexed oxygen consumption (VO2I), and arterial saturation (SaO2) did not differ. Permissive hypoventilation increased the respiratory rate and increased pCO2. Positive pressure ventilation did not deteriorate circulation. Cardiac index (CI), systolic arterial pressure (SAP), hemoglobin (Hb), and heart rate did not differ. Discussion: Permissive hypoventilation and positive pressure ventilation were equally effective to maintain oxygen delivery in all phases. A respiratory rate of 40 was feasible, showing no signs of respiratory fatigue for 90 min, indicating that whole blood resuscitation may be prioritized in select patients with severe hemorrhage and spontaneous breathing. [ABSTRACT FROM AUTHOR]

Background: Prehospital anesthesia may lead to circulatory collapse after severe hemorrhage. It is possible that permissive hypoventilation, refraining from tracheal intubation and accepting spontaneous ventilation, decreases this risk, but it is not known if oxygen delivery can be maintained. We investigated the feasibility of permissive hypoventilation after class III hemorrhage and whole blood resuscitation in three prehospital phases: 15 min on‐scene, 30 min whole blood resuscitation, and 45 min after. Study Design and Methods: 19 crossbred swine, mean weight 58.5 kg, were anesthetized with ketamine/midazolam and hemorrhaged to a mean (SD) 1298 (220) mL (33%) and randomized to permissive hypoventilation (n = 9) or positive pressure ventilation with FiO2 21% (n = 10). Results: In permissive hypoventilation versus positive pressure ventilation, indexed oxygen delivery (DO2I) decreased to mean (SD) 4.73 (1.06) versus 3.70 (1.13) mL min−1 kg−1 after hemorrhage and increased to 8.62 (2.09) versus 6.70 (1.56) mL min−1 kg−1 at completion of resuscitation. DO2I, indexed oxygen consumption (VO2I), and arterial saturation (SaO2) did not differ. Permissive hypoventilation increased the respiratory rate and increased pCO2. Positive pressure ventilation did not deteriorate circulation. Cardiac index (CI), systolic arterial pressure (SAP), hemoglobin (Hb), and heart rate did not differ. Discussion: Permissive hypoventilation and positive pressure ventilation were equally effective to maintain oxygen delivery in all phases. A respiratory rate of 40 was feasible, showing no signs of respiratory fatigue for 90 min, indicating that whole blood resuscitation may be prioritized in select patients with severe hemorrhage and spontaneous breathing. [ABSTRACT FROM AUTHOR]

Reduced oxygen consumption (VO2), either due to insufficient oxygen delivery (DO2), microcirculatory hypoperfusion and/or mitochondrial dysfunction, has an impact on the adverse short- and long-term survival of patients after cardiac surgery. However, it is still unclear whether VO2 remains an efficient predictive marker in a population in which cardiac output (CO) and consequently DO2 is determined by a left ventricular assist device (LVAD). We enrolled 93 consecutive patients who received an LVAD with a pulmonary artery catheter in place to monitor CO and venous oxygen saturation. VO2 and DO2 of in-hospital survivors and non-survivors were calculated over the first 4 days. Furthermore, we plotted receiver-operating curves (ROC) and performed a cox-regression analysis. VO2 predicted in-hospital, 1- and 6-year survival with the highest area under the curve of 0.77 (95%CI: 0.6–0.9; p = 0.0004). A cut-off value of 210 mL/min VO2 stratified patients regarding mortality with a sensitivity of 70% and a specificity of 81%. Reduced VO2 was an independent predictor for in-hospital, 1- and 6-year mortality with a hazard ratio of 5.1 (p = 0.006), 3.2 (p = 0.003) and 1.9 (p = 0.0021). In non-survivors, VO2 was significantly lower within the first 3 days (p = 0.010, p < 0.001, p < 0.001 and p = 0.015); DO2 was reduced on days 2 and 3 (p = 0.007 and p = 0.003). In LVAD patients, impaired VO2 impacts short- and long-term outcomes. Perioperative and intensive care medicine must, therefore, shift their focus from solely guaranteeing sufficient oxygen supply to restoring microcirculatory perfusion and mitochondrial functioning. [ABSTRACT FROM AUTHOR]

Clinical outcomes, including the primary outcome of day 28 mortality, were not statistically different but there were more deaths by day 90 in patients assigned to conservative oxygen therapy (44/99 I v i 31/102 patients; difference, 14.0 percentage points; 95% CI, 0.7-27.2). Keywords: Intensive care; Resuscitation; Shock; Oxygen delivery; Neurocognitive disorders; Grief EN Intensive care Resuscitation Shock Oxygen delivery Neurocognitive disorders Grief 153 156 4 03/08/23 20230301 NES 230301 Recent advances in critical care relevant to a broad range of clinicians Global interest in the management of critically ill patients has increased significantly with the coronavirus disease 2019 (COVID-19) pandemic. Intensive care, Resuscitation, Shock, Oxygen delivery, Neurocognitive disorders, Grief Evaluation of early administration of simvastatin in the prevention and treatment of delirium in critically ill patients undergoing mechanical ventilation (MODUS): a randomised, double-blind, placebo-controlled trial. [Extracted from the article]

Extracorporeal membrane oxygenation (ECMO) can be delivered in veno-arterial (VA) and veno-venous (VV) configurations based on the cannulation strategy. VA and VV ECMO are delivered primarily for haemodynamic and respiratory support in patients with severe heart and lung failure, respectively. The Fick principle describes the relationship between blood flow and oxygen consumption – key parameters in the physiological management of extracorporeal support. This review will discuss the application of the Fick principle in: (i) recirculation in VV ECMO; (ii) the quantification of oxygen delivery (DO2) in VV ECMO and (iii) the quantification of transpulmonary blood flow and systemic arterial oxygen saturation in VA ECMO. [ABSTRACT FROM AUTHOR]

A bag-valve-mask (BVM) is a portable handheld medical device commonly used in airway management and manual ventilation. Outside of the operating theatre, BVM devices are often used to pre-oxygenate spontaneously breathing patients before intubation to reduce the risk of hypoxaemia. Pre-oxygenation is considered adequate when the end-tidal expiratory fraction of oxygen is greater than 0.85. There are reports that some BVM devices fail to deliver a satisfactory inspired oxygen (FiO2) in spontaneously breathing patients due to variability in design. The primary aim of this study was to evaluate the efficacy of oxygen delivery of a broad range of adult and paediatric BVM devices at increasing tidal volumes using a mechanical lung to simulate spontaneous ventilation. The secondary aim was to evaluate the effect of BVM design on performance. Forty BVM devices were evaluated in a laboratory setting as part of a safety assessment requested by HealthShare New South Wales. The oxygen inlet of each BVM device was primed with 100% oxygen (15 l/min) for two min. The BVM device was then attached to the mechanical lung and commenced spontaneous breathing at a fixed respiratory rate of 12 breaths/min with an inspiratory: expiratory ratio of 1:2. For each device FiO2 was measured after two min of spontaneous breathing. This process was repeated with small (250 ml), medium (500 ml) and large (750 ml) tidal volumes simulating adult breathing in adult BVM devices, and small (150 ml), medium (300 ml) and large (450 ml) tidal volumes simulating paediatric breathing in paediatric BVM devices. The test was repeated using up to five BVM devices of the same model (where supplied) at each tidal volume as a manufacturing quality control measure. Eight of the 40 devices tested failed to deliver a FiO2 above 0.85 for at least one tidal volume, and five models failed to achieve this at any measured tidal volume. Concerningly, three of these devices delivered a FiO2 below 0.55. Six of the eight poorly performing devices delivered reducing concentrations of inspired oxygen with increasing tidal volumes. Devices which performed the worst were those with a duckbill non-rebreather valve and without a dedicated expiratory valve. Several BVM devices available for clinical use in Australia did not deliver sufficient oxygen for reliable pre-oxygenation in a spontaneously breathing in vitro model. Devices with a duckbill non-rebreather valve and without a dedicated expiratory valve performed the worst. It is imperative that clinicians using BVM devices to deliver oxygen to spontaneously breathing patients are aware of the characteristics and limitations of the BVM devices, and that the standards for manufacture are updated to require safe performance in all clinical circumstances. [ABSTRACT FROM AUTHOR]

Alterations of aerobic fitness and muscle deoxygenation during a ramp incremental exercise test (GXT) were assessed on two occasions within a time-frame of 2.9 ± 0.1y in competitive youth cyclists. Nine cyclists (age, 14.5 ± 1.1y; peak oxygen uptake ( V ˙ O2peak), 62.6 ± 4.2 mL.min−1.kg−1) participated in this investigation. V ˙ O2peak, the gas exchange threshold (GET) and the respiratory compensation point (RCP), as well as the muscle deoxygenation response pattern were determined during a GXT using open circuit spirometry and near-infrared spectroscopy, respectively. T-tests and Pearson's correlations were used to assess effects of time on the dependent variables and relationships between changes of parameter estimates of aerobic fitness and the muscle deoxygenation response, respectively. Workrate and metabolic rate at GET (33 ± 20 and 42 ± 23%) and RCP (36 ± 20 and 40 ± 22%), and V ˙ O2peak (30 ± 18%) significantly increased throughout the study (P < 0.05). The muscle deoxygenation response showed a significant rightward shift from occasion one to two (P < 0.05). Alterations in the workrate/metabolic rate at RCP, and V ˙ O2peak, were correlated with alterations of the muscle deoxygenation response (R = 0.71–0.89, P < 0.05). Together, this is thought to indicate a superior muscle perfusion within the tissue of interrogation at the same metabolic rate on occasion two vs. one, which partially contributed to the improved aerobic fitness in the cyclists herein. [ABSTRACT FROM AUTHOR]

Cell transplantation aims to regenerate damaged tissues and cure currently incurable diseases, such as Type 1 diabetes. Post‐transplantation cell survival is highly limited by the lack of suitable support matrix (anoikis) and insufficient oxygen supply (hypoxia), which is aggravated when using macroencapsulation devices. Graft failure can be overcome by encapsulation in extracellular matrix (ECM)‐based hydrogels with high oxygen capacity. Estimation of the oxygen durability in these systems is critical for the design of hydrogel loaded macroencapsulation devices aimed to increase graft survival. In this study, a novel hyaluronic acid/perfluorocarbon biomaterial (Oxygel) is formulated, oxygenated, and characterized. Oxygel exhibits shear thinning and self‐healing properties while it can carry high oxygen payloads and slowly release them for 90 h, exhibiting a 14.5 times smaller oxygen diffusivity than PBS. In parallel, a model able to predict the oxygen durability within Oxygel upon cell encapsulation is developed and experimentally validated in vitro. Correlations between model estimations and experimental results are found, demonstrating the validity of the model to analyze oxygen durability. The application of this mathematical model to oxygenated cell scaffolds (such as Oxygel) holds great promise to improve cell transplantation success. [ABSTRACT FROM AUTHOR]

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Purpose: The hematocrit-to-whole blood viscosity ratio (Hct/WBV) reflects the blood O2 delivery potential (O2-DP). WBV is variable to the dynamic vascular shear rate (SR), 1–5/s at microcirculation and 300/s at larger vessels. To estimate the impact of hemodilution on the blood O2-DP to the myocardium, we analyzed the hemodilution-induced change of Hct/WBV at SR 5/s (Hct/WBV5) during off-pump coronary bypass (OPCAB) surgery. Methods: During OPCAB surgery (n = 21), 10% acute normovolemic hemodilution (HD 10%) was applied. Arterial blood samples were taken: one before and two after HD 10%. One of which after HD 10% underwent an additional 33% in vitro hemodilution (reaching 40% hemodilution in total, HD 40%). WBV of all blood samples was determined using a scan-capillary tube viscometer (Hemovister™). The changes of Hct/WBV5 were analyzed as a primary measure of the study and compared with those of Hct/WBV at SR 300/s (Hct/WBV300). Results: Median[IQR] of Hct/WBV5 [3.5 (2.8–4.2)%/cPoise] was significantly increased by HD 10 and HD 40% [3.6 (3.2–4.6)%/cPoise and 4.2 (3.3–5.2)%/cPoise, respectively, all P < 0.001], but the degrees of changes after HD 10 and HD 40% were not different. Median[IQR] of Hct/WBV300 [10.3(8.6‒10.8)%/cPoise] was not changed by HD 10% [10.3(9.1–11.1)%/cPoise], but it was significantly decreased by HD 40% [8.4(7.4‒9.2)%/cPoise, P < 0.001]. Conclusion: The increased Hct/WBV5 suggests that 10–40% hemodilution improves the blood O2-DP to the myocardium during OPCAB surgery. The SR-specific discrepancy in Hct/WBV changes advocates using microvascular WBV and Hct/WBV to evaluate the blood O2-DP changes to the myocardium. Further study is warranted to assess the actual changes in myocardial O2 delivery. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is one of most common comorbidities in acute respiratory distress syndrome (ARDS). There are few specific studies on the appropriate ventilation strategy for patients with ARDS comorbid with COPD, especially regarding on positive end-expiratory pressure (PEEP) titration. Methods: To compare the respiratory mechanics in mechanical ventilated ARDS patients with or without COPD and to determine whether titration of PEEP based on electrical impedance tomography (EIT) is superior to the ARDSnet protocol. This is a single center, perspective, repeated measure study. ARDS patients requiring mechanical ventilation who were admitted to the intensive care unit between August 2017 and December 2020 were included. ARDS patients were divided according to whether they had COPD into a COPD group and a non-COPD group. Respiratory mechanics, gas exchange, and hemodynamics during ventilation were compared between the groups according to whether the PEEP level was titrated by EIT or the ARDSnet protocol. Results: A total of twenty-seven ARDS patients including 14 comorbid with and 13 without COPD who met the study eligibility criteria were recruited. The PEEP levels titrated by EIT and the ARDSnet protocol were lower in the COPD group than in the non-COPD group (6.93 ± 1.69 cm H2O vs. 12.15 ± 2.40 cm H2O, P < 0.001 and 10.43 ± 1.20 cm H2O vs. 14.0 ± 3.0 cm H2O, P < 0.001, respectively). In the COPD group, the PEEP level titrated by EIT was lower than that titrated by the ARDSnet protocol (6.93 ± 1.69 cm H2O vs. 10.43 ± 1.20 cm H2O, P < 0.001), as was the global inhomogeneity (GI) index (0.397 ± 0.040 vs. 0.446 ± 0.052, P = 0.001), plateau airway pressure (16.50 ± 4.35 cm H2O vs. 20.93 ± 5.37 cm H2O, P = 0.001), dead space ventilation ratio (48.29 ± 6.78% vs. 55.14 ± 8.85%, P < 0.001), ventilation ratio (1.63 ± 0.33 vs. 1.87 ± 0.33, P < 0.001), and mechanical power (13.92 ± 2.18 J/min vs. 15.87 ± 2.53 J/min, P < 0.001). The cardiac index was higher when PEEP was treated by EIT than when it was titrated by the ARDSnet protocol (3.41 ± 0.50 L/min/m2 vs. 3.02 ± 0.43 L/min/m2, P < 0.001), as was oxygen delivery (466.40 ± 71.08 mL/min/m2 vs. 411.10 ± 69.71 mL/min/m2, P = 0.001). Conclusion: Titrated PEEP levels were lower in patients with ARDS with COPD than in ARDS patients without COPD. In ARDS patient comorbid with COPD, application of PEEP titrated by EIT was lower than those titrated by the ARDSnet protocol, which contributed to improvements in the ventilation ratio, mechanical energy, cardiac index, and oxygen delivery with less of an adverse impact on hemodynamics. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is one of most common comorbidities in acute respiratory distress syndrome (ARDS). There are few specific studies on the appropriate ventilation strategy for patients with ARDS comorbid with COPD, especially regarding on positive end-expiratory pressure (PEEP) titration.Methods: To compare the respiratory mechanics in mechanical ventilated ARDS patients with or without COPD and to determine whether titration of PEEP based on electrical impedance tomography (EIT) is superior to the ARDSnet protocol. This is a single center, perspective, repeated measure study. ARDS patients requiring mechanical ventilation who were admitted to the intensive care unit between August 2017 and December 2020 were included. ARDS patients were divided according to whether they had COPD into a COPD group and a non-COPD group. Respiratory mechanics, gas exchange, and hemodynamics during ventilation were compared between the groups according to whether the PEEP level was titrated by EIT or the ARDSnet protocol.Results: A total of twenty-seven ARDS patients including 14 comorbid with and 13 without COPD who met the study eligibility criteria were recruited. The PEEP levels titrated by EIT and the ARDSnet protocol were lower in the COPD group than in the non-COPD group (6.93 ± 1.69 cm H2O vs. 12.15 ± 2.40 cm H2O, P < 0.001 and 10.43 ± 1.20 cm H2O vs. 14.0 ± 3.0 cm H2O, P < 0.001, respectively). In the COPD group, the PEEP level titrated by EIT was lower than that titrated by the ARDSnet protocol (6.93 ± 1.69 cm H2O vs. 10.43 ± 1.20 cm H2O, P < 0.001), as was the global inhomogeneity (GI) index (0.397 ± 0.040 vs. 0.446 ± 0.052, P = 0.001), plateau airway pressure (16.50 ± 4.35 cm H2O vs. 20.93 ± 5.37 cm H2O, P = 0.001), dead space ventilation ratio (48.29 ± 6.78% vs. 55.14 ± 8.85%, P < 0.001), ventilation ratio (1.63 ± 0.33 vs. 1.87 ± 0.33, P < 0.001), and mechanical power (13.92 ± 2.18 J/min vs. 15.87 ± 2.53 J/min, P < 0.001). The cardiac index was higher when PEEP was treated by EIT than when it was titrated by the ARDSnet protocol (3.41 ± 0.50 L/min/m2 vs. 3.02 ± 0.43 L/min/m2, P < 0.001), as was oxygen delivery (466.40 ± 71.08 mL/min/m2 vs. 411.10 ± 69.71 mL/min/m2, P = 0.001).Conclusion: Titrated PEEP levels were lower in patients with ARDS with COPD than in ARDS patients without COPD. In ARDS patient comorbid with COPD, application of PEEP titrated by EIT was lower than those titrated by the ARDSnet protocol, which contributed to improvements in the ventilation ratio, mechanical energy, cardiac index, and oxygen delivery with less of an adverse impact on hemodynamics. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?In electrically stimulated skeletal muscle, force production is downregulated when oxygen delivery is compromised and rapidly restored upon oxygen delivery restoration. Whether 'oxygen conforming' of force production occurs during voluntary muscle activation in humans and whether it is exercise intensity dependent remains unknown.What is the main finding and its importance?Here, we show in humans that force at a given voluntary muscle activation does conform to a decrease in oxygen delivery and recovers rapidly and completely with restoration of oxygen delivery. This oxygen‐conforming response of contraction force appears to happen only at higher intensities. In electrically stimulated skeletal muscle, force production is downregulated when oxygen delivery is compromised and rapidly restored upon restoration of oxygen delivery in the absence of cellular disturbance. Whether this 'oxygen‐conforming' response of force occurs and is exercise intensity dependent during stable voluntary muscle activation in humans is unknown. In 12 participants (six female), handgrip force, forearm muscle activation (EMG), muscle oxygenation and forearm blood flow (FBF) were measured during rhythmic handgrip exercise at forearm EMG achieving 50, 75 or 90% critical impulse (CI). Four minutes of brachial artery compression to reduce FBF by ∼60% (Hypoperfusion) or sham compression (adjacent to artery; Control) was performed during exercise. Sham compression had no effect. Hypoperfusion rapidly reduced muscle oxygenation at all exercise intensities, resulting in contraction force per muscle activation (force/EMG) progressively declining over 4 min by ∼16% at both 75 and 90% CI. No force/EMG decline occurred at 50% CI. Rapid restoration of muscle oxygenation after compression was closely followed by force/EMG such that it was not different from Control within 30 s for 90% CI and after 90 s for 75% CI. Our findings reveal that an oxygen‐conforming response does occur in voluntary exercising muscle in humans. Within the exercise modality and magnitude of fluctuation of oxygenation in this study, the oxygen‐conforming response appears to be exercise intensity dependent. Mechanisms responsible for this oxygen‐conforming response have implications for exercise tolerance and warrant investigation. [ABSTRACT FROM AUTHOR]

Background: Rapid fluid administration may decrease hemoglobin concentration (Hb) by a diluting effect, which could limit the increase in oxygen delivery (DO2) expected with a positive response to fluid challenge in critically ill patients. Our aim was to quantify the decrease in Hb after rapid fluid administration.Methods: Our protocol was registered in PROSPERO (CRD42020165146). We searched PubMed, the Cochrane Database, and Embase from inception until February 15, 2022. We selected studies that reported Hb before and after rapid fluid administration (bolus fluid given over less than 120 min) with crystalloids and/or colloids in adults. Exclusion criteria were studies that included bleeding patients, or used transfusions or extracorporeal circulation procedures. Studies were divided according to whether they involved non-acutely ill or acutely ill (surgical/trauma, sepsis, circulatory shock or severe hypovolemia, and mixed conditions) subjects. The mean Hb difference and, where reported, the DO2 difference before and after fluid administration were extracted. Meta-analyses were conducted to assess differences in Hb before and after rapid fluid administration in all subjects and across subgroups. Random-effect models, meta-regressions and subgroup analyses were performed for meta-analyses. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic.Results: Sixty-five studies met our inclusion criteria (40 in non-acutely ill and 25 in acutely ill subjects), with a total of 2794 participants. Risk of bias was assessed as "low" for randomized controlled trials (RCTs) and 'low to moderate' for non-RCTs. Across 63 studies suitable for meta-analysis, the Hb decreased significantly by a mean of 1.33 g/dL [95% CI - 1.45 to - 1.12; p < 0.001; I2 = 96.88] after fluid administration: in non-acutely ill subjects, the mean decrease was 1.56 g/dL [95% CI - 1.69 to - 1.42; p < 0.001; I2 = 96.71] and in acutely ill patients 0.84 g/dL [95% CI - 1.03 to - 0.64; p = 0.033; I2 = 92.91]. The decrease in Hb was less marked in patients with sepsis than in other acutely ill patients. The DO2 decreased significantly in fluid non-responders with a significant decrease in Hb.Conclusions: Hb decreased consistently after rapid fluid administration with moderate certainty of evidence. This effect may limit the positive effects of fluid challenges on DO2 and thus on tissue oxygenation. [ABSTRACT FROM AUTHOR]

Background: Studies have demonstrated the efficacy of oxygen delivery-guided perfusion (ODGP) in preventing postoperative acute kidney injury, but the benefit of ODGP for delirium has not been confirmed. We retrospectively investigated the risk factors for postoperative delirium in patients who underwent ODGP (with oxygen delivery index [DO2i] > 300 mL/min/m2).Methods: Consecutive patients who underwent on-pump cardiovascular surgery with ODGP from January 2018 to December 2020 were retrospectively analyzed. In addition to examining patients' DO2i during cardiopulmonary bypass (CPB), we quantified the two primary DO2 components-hematocrit (Hct) and pump flow. Delirium was defined based on the Intensive Care Delirium Screening Checklist (ICDSC). Patients were divided into three groups: no delirium (ICDSC score = 0), subsyndromal delirium (ICDSC score = 1-3), and clinical delirium (ICDSC score ≥ 4).Results: Multivariate analysis identified only the number of red blood cell (RBC) units transfused, intubation time, and the cumulative time below the Hct threshold of 25% as predictive factors of postoperative delirium. Although patients with higher ICDSC scores had greater hemodilution during CPB, ODGP resulted in a higher pump flow, and DO2i was maintained above 300 mL/min/m2, with no significant difference between the three groups.Conclusions: A low Hct level during CPB with ODGP, the number of RBC units transfused, and intubation time were associated with postoperative delirium. Further investigations are needed to determine the ability of ODGP to prevent low Hct during CPB. [ABSTRACT FROM AUTHOR]

After major surgery, longitudinal changes in resting energy expenditure (REE) as well as imbalances in oxygen delivery (DO2) and distribution and processing (VO2) may occur due to dynamic metabolic requirements, an impaired macro- and microcirculatory flow and mitochondrial dysfunction. However, the longitudinal pattern of these parameters in critically ill patients who die during hospitalization remains unknown. Therefore, we analyzed in 566 patients who received a pulmonary artery catheter (PAC) their REE, DO2, VO2 and oxygen extraction ratio (O2ER) continuously in survivors and non-survivors over the first 7 days post cardiac surgery, calculated the percent increase in the measured compared with the calculated REE and investigated the impact of a reduced REE on 30-day, 1-year and 6-year mortality in a uni- and multivariate model. Only in survivors was there a statistically significant transition from a negative to a positive energy balance from day 0 until day 1 (Day 0: −3% (−18, 14) to day 1: 5% (−9, 21); p < 0.001). Furthermore, non-survivors had significantly decreased DO2 during the first 4 days and reduced O2ER from day 2 until day 6. Additionally, a lower REE was significantly associated with a worse survival at 30 days, 1 year and 6 years (p = 0.009, p < 0.0001 and p = 0.012, respectively). Non-survivors seemed to be unable to metabolically adapt from the early (previously called the 'ebb') phase to the later 'flow' phase. DO2 reduction was more pronounced during the first three days whereas O2ER was markedly lower during the following four days, suggesting a switch from a predominantly limited oxygen supply to prolonged mitochondrial dysfunction. The association between a reduced REE and mortality further emphasizes the importance of REE monitoring. [ABSTRACT FROM AUTHOR]

Background: This study aimed to describe the efficacy of veno-arterial extracorporeal life support (VA-ECLS) through early lactate clearance and pH restoration and assess the potential association with 30-day survival following hospital discharge. Methods: Data of patients receiving VA-ECLS for at least 24 h were retrospectively compiled. Blood lactate levels, liver enzymes, and kidney parameters prior to VA-ECLS initiation and at 2, 8, 14, 20, and 26 h of support had been recorded as part of clinical care. The primary outcome was 30-day survival. Results: Of 77 patients who underwent VA-ECLS for refractory cardiogenic shock, 44.2% survived. For all non-survivors, ECLS was initiated after eight hours (p =.008). Blood pH was significantly higher in survivors compared to non-survivors at all time points except for pre-ECLS. Lactate levels were significantly lower in survivors (median range 1.95-4.70 vs 2.90-6.70 mmol/L for survivors vs non-survivors, respectively). Univariate and multivariate analyses indicated that blood pH at 24 h (OR 0.045, 95% CI: 0.005-0.448 for pH <7.35, p =.045) and lactate concentration pre-ECLS (OR 0.743, 95% CI: 0.590-0.936, p =.012) were reliable predictors for 30-day survival. Further, ischemic cardiogenic shock as ECLS indication showed 36.2% less lactate clearance compared to patients with other indications such as arrhythmia, postcardiotomy, and ECPR. Conclusion: ECLS showed to be an effective treatment in reducing blood lactate levels in patients suffering from refractory cardiogenic shock in which the outcome is influenced by the initial lactate level and pH in the early phase of the intervention. [ABSTRACT FROM AUTHOR]

For example, Bentley et al. ([2]) showed that compromising exercising forearm muscle perfusion evoked compensatory vasodilatation in 13 out of 21 participants and that the other 8 experienced an absence of compensatory vasodilatation and impaired exercise tolerance (Bentley et al., [2]). Keywords: critical power; exercise; muscle blood flow; oxygen delivery; oxygen demand EN critical power exercise muscle blood flow oxygen delivery oxygen demand 1705 1707 3 05/17/23 20230515 NES 230515 The current line of reasoning within the field of cardiovascular exercise physiology is that skeletal muscle oxygen delivery is tightly matched to oxygen demand. [Extracted from the article]

High End-Surgery Arterial Lactate Concentration (ES-ALC) predicts poor outcome after hepatectomy. The aim of this study was to identify intraoperative hemodynamic parameters predicting high ES-ALC during elective liver resection. Patients who underwent liver resection between 2017 and 2018, under FloTrac/EV1000TM hemodynamic monitoring, were included. The ES-ALC cutoff best predicting severe postoperative complications was identified. Association between high ES-ALC and preoperative and intraoperative variables was assessed. 108 patients were included; 90-day mortality was 0.9% and severe morbidity 14.8%. ES-ALC cutoff best discriminating severe complications was 5.05 mmol/L. Patients with ES-ALC > 5.0 mmol/L had a relative risk of severe complications of 2.8% (p = 0.004). High ES-ALC patients had longer surgery and ischemia duration, larger blood losses and higher requirements of fluids and blood transfusions. During surgery, hemoglobin concentration and oxygen delivery (DO2) decreased more significantly in patients with high ES-ALC, although they had similar values of stroke volume and cardiac output to those of other patients. At multivariate analysis, surgery duration and lowest recorded DO2 value were the strongest predictors of high ES-ALC. ES-ALC > 5.0 mmol/L in elective liver resection predicts postoperative morbidity and is essentially driven by the impaired DO2. Timely correction of blood losses might prevent the ES-ALC increase. [ABSTRACT FROM AUTHOR]

Co-delivery of cancer therapeutics improves efficacy and encourages synergy, but delivery faces challenges, including multidrug resistance and spatiotemporal distribution of therapeutics. To address these, we added paclitaxel to previously developed acoustically labile, oxygen-core, surfactant-stabilized microbubbles encapsulating lonidamine, with the aim of developing an agent containing both a therapeutic gas and two drugs acting in combination. Upon comparison of unloaded, single-loaded, and dual-loaded microbubbles, size (~1.7 µm) and yield (~2 × 109 microbubbles/mL) (~1.7) were not statistically different, nor were acoustic properties (maximum in vitro enhancements roughly 18 dB, in vitro enhancements roughly 18 dB). Both drugs encapsulated above required doses calculated for head and neck squamous cell carcinoma, the cancer of choice. Interestingly, paclitaxel encapsulation efficiency increased from 1.66% to 3.48% when lonidamine was included. During preparation, the combination of single drug-loaded micelles gave higher encapsulation (µg drug/g microbubbles) than micelles loaded with either drug alone (lonidamine, 104.85 ± 22.87 vs. 87.54 ± 16.41), paclitaxel (187.35 ± 8.38 vs. 136.51 ± 30.66). In vivo intravenous microbubbles produced prompt ultrasound enhancement within tumors lasting 3–5 min, indicating penetration into tumor vasculature. The ability to locally destroy the microbubble within the tumor vasculature was confirmed using a series of higher intensity ultrasound pulses. This ability to locally destroy microbubbles shows therapeutic promise that warrants further investigation. [ABSTRACT FROM AUTHOR]

New Findings: What is the topic of this review?This review focuses on the physiological impact of abdominal aortic aneurysm (AAA) on cardiorespiratory fitness and the negative consequences of low fitness on clinical outcomes in AAA. We also discuss the efficacy of exercise training for improving cardiorespiratory fitness in AAA.What advances does it highlight?We demonstrate the negative impact of low fitness on disease progression and clinical outcomes in AAA. We highlight potential mechanistic determinants of low fitness in AAA and present evidence that exercise training can be an effective treatment strategy for improving cardiorespiratory fitness, postoperative mortality and disease progression. An abdominal aortic aneurysm (AAA) is an abnormal enlargement of the aorta, below the level of the renal arteries, where the aorta diameter increases by >50%. As an aneurysm increases in size, there is a progressive increase in the risk of rupture, which ranges from 25 to 40% for aneurysms >5.5 cm in diameter. People with AAA are also at a heightened risk of cardiovascular events and associated mortality. Cardiorespiratory fitness is impaired in people with AAA and is associated with poor (postoperative) clinical outcomes, including increased length of hospital stay and postoperative mortality after open surgical or endovascular AAA repair. Although cardiorespiratory fitness is a well‐recognized prognostic marker of cardiovascular health and mortality, it is not assessed routinely, nor is it included in current clinical practice guidelines for the management of people with AAA. In this review, we discuss the physiological impact of AAA on cardiorespiratory fitness, in addition to the consequences of low cardiorespiratory fitness on clinical outcomes in people with AAA. Finally, we summarize current evidence for the effect of exercise training interventions on cardiorespiratory fitness in people with AAA, including the associated improvements in postoperative mortality, AAA growth and cardiovascular risk. Based on this review, we propose that cardiorespiratory fitness should be considered as part of the routine risk assessment and monitoring of people with AAA and that targeting improvements in cardiorespiratory fitness with exercise training might represent a viable adjunct treatment strategy for reducing postoperative mortality and disease progression. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI), triggered by blockage of a coronary artery, remains the most common cause of death worldwide. After MI, the capability of providing sufficient blood and oxygen significantly decreases in the heart. This event leads to depletion of oxygen from cardiac tissue and consequently leads to massive cardiac cell death due to hypoxemia. Over the past few decades, many studies have been carried out to discover acceptable approaches to treat MI. However, very few have addressed the crucial role of efficient oxygen delivery to the injured heart. Thus, various strategies were developed to increase the delivery of oxygen to cardiac tissue and improve its function. Here, we have given an overall discussion of the oxygen delivery mechanisms and how the current technologies are employed to treat patients suffering from MI, including a comprehensive view on three major technical approaches such as oxygen therapy, hemoglobin-based oxygen carriers (HBOCs), and oxygen-releasing biomaterials (ORBs). Although oxygen therapy and HBOCs have shown promising results in several animal and clinical studies, they still have a few drawbacks which limit their effectiveness. More recent studies have investigated the efficacy of ORBs which may play a key role in the future of oxygenation of cardiac tissue. In addition, a summary of conducted studies under each approach and the remaining challenges of these methods are discussed. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Older patients have a higher cardiac surgery-associated acute kidney injury (CSA-AKI) related mortality. Low oxygen delivery (DO2) during cardiopulmonary bypass (CPB) is a risk factor for CSA-AKI, but critical DO2 thresholds for older patients are unknown. This study investigated critical DO2 thresholds for CSA-AKI in patients ≥70 years undergoing on-pump cardiac surgery. METHODS Patients were enrolled from July 2015 until August 2017. CPB data from 432 patients were collected, and DO2 values were calculated per minute. The primary outcome was CSA-AKI. The association between DO2 and CSA-AKI was analysed with multivariable regression analysis. Multiple DO2 thresholds were analysed. The association between CSA-AKI and the area below the DO2 thresholds (DO2 deficit) was evaluated, as was the association between frailty and CSA-AKI. RESULTS CSA-AKI occurred in 63 (14.6%) patients. Mean and nadir (lowest) DO2 values were lower in patients with CSA-AKI (283 vs 312 ml/min/m2; P -value <0.001 and 238 vs 270 ml/min/m2; P -value <0.001, respectively). The adjusted relative risk for CSA-AKI was 1.006 [99% confidence interval (CI) 1.001–1.012] per ml/min/m2 nadir DO2 decrease. The critical DO2 threshold was 270 ml/min/m2 [adjusted relative risk 2.06 (99% CI 1.33–2.80)]. The DO2 deficit below 270 ml/min/m2 was associated with CSA-AKI [adjusted relative risk 2.84 (99% CI 1.87–3.81)]. No association between frailty and CSA-AKI was found (P  = 0.82). CONCLUSIONS Low DO2 increased the risk for CSA-AKI in older patients who had cardiac surgery. A critical DO2 threshold of 270 ml/min/m2 was applicable for frail and non-frail patients. The efficacy of a DO2 >270 ml/min/m2 to reduce CSA-AKI in older patients needs further evaluation. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers remain one of the most difficult-to-treat complications of diabetes and may seriously threaten the life of patients since it frequently results in limb loss due to amputation, suggesting that an effective therapeutic strategy is still urgently needed. In this study, a chitosan-based heterogeneous composite hydrogel encapsulating perfluorocarbon emulsions, epidermal growth factor (EGF)-loaded chitosan nanoparticles, and polyhexamethylene biguanide (PHMB) named PEENPPCH was developed for diabetic wound healing. The PEENPPCH could sustainably release EGF and PHMB in an ion-rich environment to exert antibacterial effects and promote cell growth for wound repair. In addition, the PEENPPCH can provide anti-inflammatory effects functioned by its main constituent of chitosan. Moreover, the PEENPPCH can proactively offer oxygen delivery through the incorporation of perfluorocarbon and, therefore, is able to alleviate hypoxia conditions on diabetic wounds. These functionalities enabled a markedly enhanced wound healing efficacy on diabetic rats treated with the PEENPPCHs, including thorough re-epithelization, a reduced inflammatory response, faster collagen deposition, and advanced collagen maturation resulting in a 95% of wound closure degree after 15 days that was 12.6% (p < 0.05) higher than the value of the group treated with the commercial dressing HeraDerm. Given the aforementioned advantages, together with the known merits of hydrogels, the developed PEENPPCH is anticipated to be a feasible tool for clinical diabetic wound treatment. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) is a procedure used to aid respiratory function in critical patients, involving extracorporeal circulation (ECC) of blood. There is a limited number of studies quantifying the hemodynamic effects of ECC procedures on the microcirculation. We sought to mimic veno-arterial-ECMO flow conditions by use of a scaled-down circuit primed with either lactate Ringer (LR) or 5% human serum albumin (HSA). The circuit was first tested using benchtop runs with blood, and subsequently used for in vivo experiments in Golden Syrian hamsters instrumented with a dorsal window chamber to allow for quantification of microvascular hemodynamics and functional capillary density (FCD). Results showed significant impairment in FCD, and a reduction of arteriolar and venular blood flow, with HSA providing significant higher blood flows and FCD compared with LR. Changes in hematocrit and RBC labeling after ECC reflected a shift in plasma volume, which may stem from a loss in intravascular oncotic pressure due to priming fluids. The distribution of hemoglobin oxygen saturation in the microvasculature showed a significant decrease in venules after ECC. In addition, major organs such as the kidney and heart showed increases in both inflammatory and damage markers. These results suggest that ECC impairs microvasculature function and promotes ischemia and hypoxia in the tissues, which can be vital to understanding comorbid clinical outcomes from ECC procedures such as acute kidney injury and multiorgan dysfunction [ABSTRACT FROM AUTHOR]

Currently, there is an unmet therapeutic need for the medical management of cardiac arrest, as is evident from the high mortality rate associated with this condition. These dire outcomes can be attributed to the severe nature and poor prognosis of this disorder. However, the current treatment modalities, while helping to augment survival, are limited and do not offer adequate improvements to outcomes. Treatment modalities are particularly lacking when considering the underlying pathophysiology of the metabolic phase of cardiac arrest. In this study, we explore the three phases of cardiac arrest and assess the factors related to positive clinical outcomes and survival for these events. Furthermore, we evaluate the present guidelines for resuscitation and recovery, the issues related to ischemia and tissue reperfusion, and the benefit of oxygen-delivery therapeutic methods including blood transfusion therapy and synthetic hemoglobins (HBOCs). The current therapy protocols are limited specifically by the lack of an efficient method of oxygen delivery to address the metabolic phase of cardiac arrest. In this article, we investigate the next generation of HBOCs and review their properties that make them attractive for their potential application in the treatment of cardiac arrest. These products may be a viable solution to address complications associated with ischemia, reperfusion injury, and organ damage. [ABSTRACT FROM AUTHOR]

Keywords: chronic hypoxia; exercise; oxygen delivery; sympathetic vasoconstriction EN chronic hypoxia exercise oxygen delivery sympathetic vasoconstriction 381 383 3 01/17/23 20230115 NES 230115 We read with great interest the work by Hansen and colleagues ([1]) investigating mechanisms responsible for reduced exercising muscle vasodilatation and blood flow after high altitude acclimatization (HA). Using a sub-maximal forearm exercise model the data confirm reduced vasodilatation in HA I vs i . sea level (SL), but importantly demonstrate that this does not compromise the increase in oxygen delivery relative to consumption ( O SB 2del sb : HT ht ) because arterial oxygen content was normalized and oxygen cost of exercise was decreased. [Extracted from the article]