Oxygen regulation in biological systems

Evans, Roger G.

doi:10.1152/ajpregu.00004.2016

Cited by 3 publications

(4 citation statements)

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“…Newborn infants undergo dramatic developmental changes during the first weeks of life; some of these changes, like the transition from fetal to adult hemoglobin (which is often accelerated in the NICU setting by frequent transfusions) significantly alter the physiology of tissue transfer oxygen for any given SpO 2 . [28] Coming from a moderately hypoxic intrauterine environment, the newborn infant is likely to have residual tolerance to hypoxemia, at least during the early postnatal period. [29] Perhaps most importantly, the adverse outcomes we are trying to prevent (e.g., ROP and NEC) have different postnatal vulnerability periods; since the “optimal” SpO 2 target is a balance between competing outcomes, differences in pathophysiologic timing for different adverse outcomes suggest that the optimal SpO 2 will also depend on postnatal and developmental age.…”

Section: Optimal Spo2 As a “Moving Target”mentioning

confidence: 99%

Oxygen saturation targeting by pulse oximetry in the extremely low gestational age neonate: a quixotic quest

Cummings

Lakshminrusimha

2017

Current Opinion in Pediatrics

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Purpose of review A collaboration of comparative effectiveness research trials of pulse oximeter saturation (SpO2) targeting in extremely low gestational age neonates (ELGANs) have begun to report their aggregate results. We will examine the results of those trials, collectively referred to as the Neonatal Oxygenation Prospective Meta-analysis, or NeOProM. We will also discuss the uncertainties that remain and the clinical challenges that lie ahead. Recent findings The primary outcome from NeOProM was a composite of death or disability at 18–24 months corrected age. Earlier this year, the last of these reports was published. Although there were no differences in the primary outcome overall, analyses of secondary outcomes and data subsets following a pulse oximeter revision show significant treatment differences between targeting a lower compared to a higher SpO2. Summary NeOProM represents the largest collaborative clinical research study of SpO2 targets in ELGANs. While aggregate results give us some insight into the feasibility and efficacy of SpO2 targeting in this population, many questions remain. A patient-level analysis, tracking individual outcomes based on actual SpO2 experienced, may shed some light on these questions. However, finding a single optimal SpO2 range seems unlikely.

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Section: Optimal Spo2 As a “Moving Target”mentioning

confidence: 99%

Oxygen saturation targeting by pulse oximetry in the extremely low gestational age neonate: a quixotic quest

Cummings

Lakshminrusimha

2017

Current Opinion in Pediatrics

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“…Oxygen, whilst vital, can also be toxic, with both oxidative stress and cellular hyperoxia identified as major contributors to multiple pathological states (Evans, 2016).…”

Section: Physiological Interpretation Of Findingsmentioning

confidence: 99%

“…Oxygen, whilst vital, can also be toxic, with both oxidative stress and cellular hyperoxia identified as major contributors to multiple pathological states (Evans, 2016). Historically, under-oxygenation was (and still remains) the key concern in patients undergoing cardiac surgery, although recent studies are starting to highlight the pathological dangers of over-oxygenation during CPB, with an ongoing debate around the level of damage (Jakutis et al, 2017; Young 2012; Abou-Arab et al, 2020).…”

Section: Physiological Interpretation Of Findingsmentioning

confidence: 99%

A Dynamic Time-Series Model of Oxygen Consumption during Paediatric Cardiopulmonary Bypass

Sharabiani,

Issitt,

Mahani

et al. 2024

Preprint

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BackgroundDuring cardiopulmonary bypass (CPB), maintaining adequate oxygen consumption (VO2i) can only be achieved indirectly either by modifying oxygen delivery (DO2i) through its component parts or by modulating metabolic demand through altering body temperature. The body reacts to these actions by changing OER and consequently VO2i. Understanding the body’s adaptive OER dynamics can elucidate its oxygen consumption goals during CPB and help improve our ability to safely manage the patient’s journey.MethodsAn autoregressive, integrated time-series model was trained on granular perfusion data from 879 paediatric patients (age: newborn to 18 years old) undergoing 963 CPB operations, with the outcome variable being the minute-by-minute changes in the logit transformation of OER. Variables were cardiac index, haemoglobin concentration, oxygen saturation of arterial haemoglobin and temperature. An explicit ‘disequilibrium term group’ was also included, proportional to the difference between the logarithm of VO2i and logarithm of a ‘latent’ (i.e. unobserved) oxygen demand - or ‘target’ VO2(tVO2i) - term, with the logarithm of tVO2i assumed to be a linear function of body temperature (the Van’t Hoff model). The trained time-series models were studied using permutation-based variable importance, deterministic and stochastic simulations, and subgroup analysis by acute kidney injury (AKI) grade and by temperature.ResultsModel coefficients are consistent with an adaptive OER response to keep VO2i in line with tVO2i, according to body temperature. This adaptation consists of a primary rapid response for 5-10 minutes, and a secondary slow response that is estimated to last up to several hours. The model reproduces the hyperbolic shape of DO2i-VO2i curves - first published in 1982 - as an artefact of insufficient wait times between equilibrium-state transitions. Asymptotically, however, the model converges to a piecewise linear relationship between DO2i and VO2i, with supply-independence of oxygen consumption occurring above a threshold DO2i. Subgroup analysis by temperature suggests that the dependence of tVO2i on temperature (expressed as Q10) may be significantly stronger at low temperatures (< 28C) than at high temperatures (> 28C).ConclusionsThis study proposes a physiologically plausible model of OER changes during CPB that is consistent with past experimental data. While during CPB, under-oxygenation is the dominant risk in the long term, slow adaptation of OER during CPB creates short-term opportunities for over-oxygenation following significant changes in variables such as cardiac index. The model provides well-defined values for tVO2i at a given temperature, paving the way for further research into the effects of over- and under-oxygenation during CPB on postoperative outcomes such as AKI, and hence improvements in goal-directed perfusion protocols.Clinical PerspectiveWhat Is New?This study is the first to present a data-driven, analytical framework for predicting OER changes in response to clinical interventions during CPB.Changes in the components of oxygen delivery cause an adaptive OER response to keep oxygen consumption in line with oxygen demand, according to body temperature.The dependence of oxygen demand on temperature decreases as temperature increases towards normothermia, inconsistent with the accepted Van’t Hoff equation.Children developing AKI exhibit a dampened response to changes in haemoglobin during CPB, with this dampening of response intensifying with AKI severity.What Are the Clinical Implications?This proposed, dynamic model of OER provides a novel framework for goal-directed perfusion by identifying periods of over- and under-oxygenation.The observed, dampened response to haemoglobin changes in patients that develop AKI can be the foundation of an intraoperative tool for early diagnosis of at-risk patients.

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“…Mitochondria are also taking center stage as critical elements in multiple disease processes, including neurodegenerative (2) and cardiac (1) diseases. Such diverse areas of "oxygen research" have also generated considerable interest in the pages of the journal in recent years (3). The impetus for this call for papers is to build on this interest among the readers and authors of the journal.…”

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confidence: 99%