During acute hypoxic exposure, cerebral blood flow (CBF) increases to compensate for the reduced arterial oxygen content (CaO
). Nevertheless, as exposure extends, both CaO
and CBF progressively ...normalize. Haemoconcentration is the primary mechanism underlying the CaO
restoration and may therefore explain, at least in part, the CBF normalization. Accordingly, we tested the hypothesis that reversing the haemoconcentration associated with extended hypoxic exposure returns CBF towards the values observed in acute hypoxia. Twenty-three healthy lowlanders (12 females) completed two identical 4-day sojourns in a hypobaric chamber, one in normoxia (NX) and one in hypobaric hypoxia (HH, 3500 m). CBF was measured by ultrasound after 1, 6, 12, 48 and 96 h and compared between sojourns to assess the time course of changes in CBF. In addition, CBF was measured at the end of the HH sojourn after hypervolaemic haemodilution. Compared with NX, CBF was increased in HH after 1 h (P = 0.001) but similar at all later time points (all P > 0.199). Haemoglobin concentration was higher in HH than NX from 12 h to 96 h (all P < 0.001). While haemodilution reduced haemoglobin concentration from 14.8 ± 1.0 to 13.9 ± 1.2 g·dl
(P < 0.001), it did not increase CBF (974 ± 282 to 872 ± 200 ml·min
; P = 0.135). We thus conclude that, at least at this moderate altitude, haemoconcentration is not the primary mechanism underlying CBF normalization with acclimatization. These data ostensibly reflect the fact that CBF regulation at high altitude is a complex process that integrates physiological variables beyond CaO
. KEY POINTS: Acute hypoxia causes an increase in cerebral blood flow (CBF). However, as exposure extends, CBF progressively normalizes. We investigated whether hypoxia-induced haemoconcentration contributes to the normalization of CBF during extended hypoxia. Following 4 days of hypobaric hypoxic exposure (corresponding to 3500 m altitude), we measured CBF before and after abolishing hypoxia-induced haemoconcentration by hypervolaemic haemodilution. Contrary to our hypothesis, the haemodilution did not increase CBF in hypoxia. Our findings do not support haemoconcentration as a stimulus for the CBF normalization during extended hypoxia.
This study compared the brachial artery blood flow (Q̇BA) and microvascular oxygen delivery responses during handgrip exercise above vs. below critical force (CF; the isometric analog of critical ...power). Q̇BA and microvascular oxygen delivery are important determinants of oxygen utilization and metabolite accumulation during exercise, both of which increase progressively during exercise above CF. However the Q̇BA and microvascular oxygen delivery responses above vs. below CF remain unknown. We hypothesized that Q̇BA, deoxygenated-heme (deoxy-heme; an estimate of microvascular fractional oxygen extraction), and total-heme concentrations (total-heme; an estimate of changes in microvascular hematocrit) would demonstrate physiological maximums above CF despite increases in exercise intensity. Seven men and six women performed 1) a 5-min rhythmic isometric-handgrip maximal-effort test (MET) to determine CF and 2) two constant target-force tests above (severe-intensity; S1 and S2) and two constant target-force tests below (heavy-intensity; H1 and H2) CF. CF was 189.3 ± 16.7 N (29.7 ± 1.6%MVC). At end-exercise, Q̇BA was greater for tests above CF (S1: 418 ± 147 mL/min; S2: 403 ± 137 mL/min) compared to tests below CF (H1: 287 ± 97 mL/min; H2: 340 ± 116 mL/min; all p < 0.05) but was not different between S1 and S2. Further, end-test Q̇BA during both tests above CF was not different from Q̇BA estimated at CF (392 ± 37 mL/min). At end-exercise, deoxy-heme was not different between tests above CF (S1: 150 ± 50 μM; S2: 155 ± 57 μM), but was greater during tests above CF compared to tests below CF (H1: 101 ± 24 μM; H2: 111 ± 21 μM; all p < 0.05). At end-exercise, total-heme was not different between tests above CF (S1: 404 ± 58 μM; S2: 397 ± 73 μM), but was greater during tests above CF compared to H1 (352 ± 58 μM; p < 0.01) but not H2 (371 ± 57 μM). These data suggest limb blood flow limitations exist and maximal levels of muscle microvascular oxygen delivery and extraction occur during exercise above, but not below, CF.
•Limb blood flow reached a physiological maximum above critical force.•Microvascular O2 delivery reached a physiological maximum above critical force.•Maximal-effort force declined despite reaching task-specific maximal microvascular O2 delivery.•High muscular force generation may limit muscle perfusion above critical force.
Hypoxemia during a failed airway scenario is life threatening. A dual-lumen pharyngeal oxygen delivery device (PODD) was developed to fit inside a traditional oropharyngeal airway for undisrupted ...supraglottic oxygenation and gas analysis during laryngoscopy and intubation. We hypothesized that the PODD would provide oxygen as effectively as high-flow nasal cannula (HFNC) while using lower oxygen flow rates.
We compared oxygen delivery of the PODD to HFNC in a preoxygenated, apneic manikin lung that approximated an adult functional residual capacity. Four arms were studied: HFNC at 20 and 60 liters per minute (LPM) oxygen, PODD at 10 LPM oxygen, and a control arm with no oxygen flow after initial preoxygenation. Five randomized 20-minute trials were performed for each arm (20 trials total). Descriptive statistics and analysis of variance were used with statistical significance of
< 0.05.
Mean oxygen concentrations were statistically different and decreased from 97% as follows: 41 ± 0% for the control, 90 ± 1% for HFNC at 20 LPM, 88 ± 2% for HFNC at 60 LPM, and 97 ± 1% (no change) for the PODD at 10 LPM.
Oxygen delivery with the PODD maintained oxygen concentration longer than HFNC in this manikin model at lower flow rates than HFNC.
New Findings
What is the topic of this review?
The manuscript collectively combines the experimental observations from >100 publications focusing on the regulation of cerebral blood flow and ...metabolism during exercise from 1945 to the present day.
What advances does it highlight?
This article highlights the importance of traditional and historical assessments of cerebral blood flow and metabolism during exercise, as well as traditional and new insights into the complex factors involved in the integrative regulation of brain blood flow and metabolism during exercise. The overarching theme is the importance of quantifying cerebral blood flow and metabolism during exercise using techniques that consider multiple volumetric cerebral haemodynamics (i.e. velocity, diameter, shear and flow).
Cerebral function in humans is crucially dependent upon continuous oxygen delivery, metabolic nutrients and active regulation of cerebral blood flow (CBF). As a consequence, cerebrovascular function is precisely titrated by multiple physiological mechanisms, characterized by complex integration, synergism and protective redundancy. At rest, adequate CBF is regulated through reflexive responses in the following order of regulatory importance: fluctuating arterial blood gases (in particularly, partial pressure of carbon dioxide), cerebral metabolism, arterial blood pressure, neurogenic activity and cardiac output. Unfortunately, the magnitude that these integrative and synergistic relationships contribute to governing the CBF during exercise remains unclear. Despite some evidence indicating that CBF regulation during exercise is dependent on the changes of blood pressure, neurogenic activity and cardiac output, their role as a primary governor of the CBF response to exercise remains controversial. In contrast, the balance between the partial pressure of carbon dioxide and cerebral metabolism continues to gain empirical support as the primary contributor to the intensity‐dependent changes in CBF observed during submaximal, moderate and maximal exercise. The goal of this review is to summarize the fundamental physiology and mechanisms involved in regulation of CBF and metabolism during exercise. The clinical implications of a better understanding of CBF during exercise and new research directions are also outlined.
The relationship between low oxygen delivery (DO2) on cardiopulmonary bypass and morbidity and mortality following cardiac surgery remains unexamined.
We reviewed patients undergoing Society of ...Thoracic Surgeons index procedures from March 2019 to July 2020, coincident with implementation of a new electronic perfusion record that provides for continuous recording of DO2 and flow parameters. Continuous perfusion variables were analyzed using area-over-the-curve (AOC) calculations below predefined thresholds (DO2 <280 mL O2/min/m2, cardiac index <2.2 L/min, hemoglobin < baseline, and mean arterial pressure <65 mm Hg) to quantify depth and duration of potentially harmful exposures. Multivariable logistic regression adjusted by Society of Thoracic Surgeons predicted-risk scores were used to assess for relationship of perfusion variables with the primary composite outcome of any Society of Thoracic Surgeons index procedure, as well as individual Society of Thoracic Surgeons secondary outcomes (eg, mortality, renal failure, prolonged ventilation >24 hours, stroke, sternal wound infection, and reoperation).
Eight hundred thirty-four patients were included; 42.7% (356) underwent isolated coronary artery bypass grafting (CABG), whereas 57.3% underwent nonisolated CABG (eg, valvular or combined CABG/valvular operations). DO2 <280-AOC trended toward association with the primary outcome across all cases (P = .07), and was significantly associated for all nonisolated CABG cases (P = .02)—more strongly than for cardiac index <2.2-AOC (P = .04), hemoglobin <7-AOC (P = .51), or mean arterial pressure <65-AOC (P = .11). Considering all procedures, DO2 <280-AOC was independently associated prolonged ventilation >24 hours (P = .04), an effect again most pronounced in nonisolated-CABG cases (P = .002), as well as acute kidney injury <72 hours (P = .04). Patients with glomerular filtration rate <65 mL/min and baseline hemoglobin <12.5 g/dL appeared especially vulnerable.
Low DO2 on bypass may be associated with morbidity/mortality following cardiac surgery, particularly in patients undergoing nonisolated CABG. These results underscore the importance of goal-directed perfusion strategies.
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OBJECTIVES:We sought to characterize 1) the difference in the diffusion gradient of cellular oxygen delivery and 2) the presence of diffusion limitation physiology in hypoxic-ischemic brain injury ...patients with brain hypoxia, as defined by parenchymal brain tissue oxygen tension less than 20 mm Hg versus normoxia (brain tissue oxygen tension > 20 mm Hg).
DESIGN:Post hoc subanalysis of a prospective study in hypoxic-ischemic brain injury patients dichotomized into those with brain hypoxia versus normoxia.
SETTING:Quaternary ICU.
PATIENTS:Fourteen adult hypoxic-ischemic brain injury patients after cardiac arrest.
INTERVENTIONS:Patients underwent monitoring with brain oxygen tension, intracranial pressure, cerebral perfusion pressure, mean arterial pressure, and jugular venous bulb oxygen saturation. Data were recorded in real time at 300Hz into the ICM+ monitoring software (Cambridge University Enterprises, Cambridge, United Kingdom). Simultaneous arterial and jugular venous bulb blood gas samples were recorded prospectively.
MEASUREMENTS AND MAIN RESULTS:Both the normoxia and hypoxia groups consisted of seven patients. In the normoxia group, the mean brain tissue oxygen tension, jugular venous bulb oxygen tension, and cerebral perfusion pressure were 29 mm Hg (SD, 9), 45 mm Hg (SD, 9), and 80 mm Hg (SD, 7), respectively. In the hypoxia group, the mean brain tissue oxygen tension, jugular venous bulb oxygen to brain tissue oxygen tension gradient, and cerebral perfusion pressure were 14 mm Hg (SD, 4), 53 mm Hg (SD, 8), and 72 mm Hg (SD, 6), respectively. There were significant differences in the jugular venous bulb oxygen tension–brain oxygen tension gradient (16 mm Hg sd, 6 vs 39 mm Hg SD, 11; p < 0.001) and in the relationship of jugular venous bulb oxygen tension–brain oxygen tension gradient to cerebral perfusion pressure (p = 0.004) when comparing normoxia to hypoxia. Each 1 mm Hg increase in cerebral perfusion pressure led to a decrease in the jugular venous bulb oxygen tension–brain oxygen tension gradient by 0.36 mm Hg (95% CI, –0.54 to 0.18; p < 0.001) in the normoxia group, but no such relation was demonstrable in the hypoxia group.
CONCLUSIONS:In hypoxic-ischemic brain injury patients with brain hypoxia, there is an elevation in the jugular venous bulb oxygen tension–brain oxygen tension gradient, which is not modulated by changes in cerebral perfusion pressure.
To determine whether a goal-directed perfusion (GDP) strategy aimed at maintaining oxygen delivery (DO2) at ≥280 mL·min−1·m−2 reduces the incidence of acute kidney injury (AKI).
This multicenter ...randomized trial enrolled a total of 350 patients undergoing cardiac surgery in 9 institutions. Patients were randomized to receive either GDP or conventional perfusion. A total of 326 patients completed the study and were analyzed. Patients in the treatment arm were treated with a GDP strategy during cardiopulmonary bypass (CPB) aimed to maintain DO2 at ≥280 mL·min−1·m−2. The perfusion strategy for patients in the control arm was factored on body surface area and temperature. The primary endpoint was the rate of AKI. Secondary endpoints were intensive care unit length of stay, major morbidity, red blood cell transfusions, and operative mortality.
Acute Kidney Injury Network (AKIN) stage 1 was reduced in patients treated with GDP (relative risk RR, 0.45; 95% confidence interval CI, 0.25-0.83; P = .01). AKIN stage 2-3 did not differ between the 2 study arms (RR, 1.66; 95% CI, 0.46-6.0; P = .528). There were no significant differences in secondary outcomes. In a prespecified analysis of patients with a CPB time between 1 and 3 hours, the differences in favor of the treatment arm were more pronounced, with an RR for AKI of 0.49 (95% CI, 0.27-0.89; P = .017).
A GDP strategy is effective in reducing AKIN stage 1 AKI. Further studies are needed to define perfusion interventions that may reduce more severe levels of renal injury (AKIN stage 2 or 3).
An imbalance in oxygen delivery to demand in solid tumors results in local areas of hypoxia leading to poor prognosis for the patient. We hypothesize that aerobic exercise increases tumor blood flow, ...recruits previously nonperfused tumor blood vessels, and thereby augments blood-tumor O2 transport and diminishes tumor hypoxia. When combined with conventional anticancer treatments, aerobic exercise can significantly improve the outcomes for several types of cancers.
Microparticles have demonstrated value for regenerative medicine. Attempts in this field tend to focus on the development of intelligent multifunctional microparticles for tissue regeneration. Here, ...inspired by erythrocytes-associated self-repairing process in damaged tissue, we present novel biomimetic erythrocyte-like microparticles (ELMPs). These ELMPs, which are composed of extracellular matrix-like hybrid hydrogels and the functional additives of black phosphorus, hemoglobin, and growth factors (GFs), are generated by using a microfluidic electrospray. As the resultant ELMPs have the capacity for oxygen delivery and near-infrared-responsive release of both GFs and oxygen, they would have excellent biocompatibility and multifunctional performance when serving as microscaffolds for cell adhesion, stimulating angiogenesis, and adjusting the release profile of cargoes. Based on these features, we demonstrate that the ELMPs can stably overlap to fill a wound and realize controllable cargo release to achieve the desired curative effect of tissue regeneration. Thus, we consider our biomimetic ELMPs with discoid morphology and cargo-delivery capacity to be ideal for tissue engineering.
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