A narrative review of the mechanisms and consequences of intermittent hypoxia and the role of advanced analytic techniques in pediatric autonomic disorders

Ramirez, Jan‐Marino; Carroll, Michael S.; Burgraff, Nicholas; Rand, Casey M.; Weese‐Mayer, Debra E.

doi:10.1007/s10286-023-00958-6

Cited by 7 publications

(3 citation statements)

References 181 publications

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“…CIH models the frequent hypoxic episodes that occur in humans with obstructive sleep apnea ( Barnes et al, 2022 ) and other disorders of dysautonomia ( Ramirez et al, 2023 ). In the present study, mice that underwent the CIH protocol exhibited higher baseline respiratory rate with reduced expiratory duration, as well as increased cervical sympathetic nerve activity ( Figure 1 ).…”

Section: Discussionmentioning

confidence: 99%

Postinspiratory and preBötzinger complexes contribute to respiratory-sympathetic coupling in mice before and after chronic intermittent hypoxia

Karlen-Amarante,

Glovak,

Huff

et al. 2024

Front. Neurosci.

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The sympathetic nervous system modulates arterial blood pressure. Individuals with obstructive sleep apnea (OSA) experience numerous nightly hypoxic episodes and exhibit elevated sympathetic activity to the cardiovascular system leading to hypertension. This suggests that OSA disrupts normal respiratory-sympathetic coupling. This study investigates the role of the postinspiratory complex (PiCo) and preBötzinger complex (preBötC) in respiratory-sympathetic coupling under control conditions and following exposure to chronic intermittent hypoxia (CIH) for 21 days (5% O2–80 bouts/day). The surface of the ventral brainstem was exposed in urethane (1.5 g/kg) anesthetized, spontaneously breathing adult mice. Cholinergic (ChAT), glutamatergic (Vglut2), and neurons that co-express ChAT and Vglut2 at PiCo, as well as Dbx1 and Vglut2 neurons at preBötC, were optogenetically stimulated while recording activity from the diaphragm (DIA), vagus nerve (cVN), and cervical sympathetic nerve (cSN). Following CIH exposure, baseline cSN activity increased, breathing frequency increased, and expiratory time decreased. In control mice, stimulating PiCo specific cholinergic-glutamatergic neurons caused a sympathetic burst during all phases of the respiratory cycle, whereas optogenetic activation of cholinergic-glutamatergic PiCo neurons in CIH mice increased sympathetic activity only during postinspiration and late expiration. Stimulation of glutamatergic PiCo neurons increased cSN activity during the postinspiratory phase in control and CIH mice. Optogenetic stimulation of ChAT containing neurons in the PiCo area did not affect sympathetic activity under control or CIH conditions. Stimulating Dbx1 or Vglut2 neurons in preBötC evoked an inspiration and a concomitant cSN burst under control and CIH conditions. Taken together, these results suggest that PiCo and preBötC contribute to respiratory-sympathetic coupling, which is altered by CIH, and may contribute to the hypertension observed in patients with OSA.

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Section: Discussionmentioning

confidence: 99%

Postinspiratory and preBötzinger complexes contribute to respiratory-sympathetic coupling in mice before and after chronic intermittent hypoxia

Karlen-Amarante,

Glovak,

Huff

et al. 2024

Front. Neurosci.

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“…Intermittent hypoxemia (IH) in the NICU has been widely studied (Ramirez et al 2023, Dormishian et al 2023a, 2023b. Definitions of IH events require fixed parameters including SPO2 threshold (e.g.…”

Section: Intermittent Hypoxemiamentioning

confidence: 99%

Highly comparative time series analysis of oxygen saturation and heart rate to predict respiratory outcomes in extremely preterm infants

Qiu,

Di Fiore,

Krishnamurthi

et al. 2024

Physiol. Meas.

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Objective: Highly comparative time series analysis (HCTSA) is a novel approach involving massive feature extraction using publicly available code from many disciplines. The Prematurity-Related Ventilatory Control (Pre-Vent) observational multicenter prospective study collected bedside monitor data from >700 extremely preterm infants to identify physiologic features that predict respiratory outcomes. We calculated a subset of 33 HCTSA features on >7M 10-minute windows of oxygen saturation (SPO2) and heart rate (HR) from the PreVent cohort to quantify predictive performance. This subset included representatives previously identified using unsupervised clustering on >3500 HCTSA algorithms. Performance of each feature was measured by individual area under the receiver operating curve (AUC) at various days of life and binary respiratory outcomes. We hypothesized that the best HCTSA algorithms would compare favorably to optimal PreVent physiologic predictor IH90_DPE (duration per event of intermittent hypoxemia events below 90%).Main Results: The top HCTSA features were from a cluster of algorithms associated with the autocorrelation of SPO2 time series and identified low frequency patterns of desaturation as high risk. These features had comparable performance to and were highly correlated with IH90_DPE but perhaps measure the physiologic status of an infant in a more robust way that warrants further investigation. The top HR HCTSA features were symbolic transformation measures that had previously been identified as strong predictors of neonatal mortality. HR metrics were only important predictors at early days of life which was likely due to the larger proportion of infants whose outcome was death by any cause. A simple HCTSA model using 3 top features outperformed IH90_DPE at day of life 7 (.778 versus .729) but was essentially equivalent at day of life 28 (.849 versus .850). These results validated the utility of a representative HCTSA approach but also provides additional evidence supporting IH90\_DPE as an optimal predictor of respiratory outcomes.

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“…Intermittent hypoxemia (IH) in the NICU has been widely studied (Ramirez et al 2023, Dormishian, Schott, Aguilar, Jimenez, Bancalari, Tolosa & Claure 2023, Dormishian, Schott, Aguilar, Bancalari & Claure 2023). Definitions of IH events require fixed parameters including SPO2 threshold (e.g.…”

Section: Introductionmentioning

confidence: 99%

Highly comparative time series analysis of oxygen saturation and heart rate to predict respiratory outcomes in extremely preterm infants

Qiu,

Di Fiore,

Krishnamurthi

et al. 2024

Preprint

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Abstract. Objective: Highly comparative time series analysis (HCTSA) is a novel approach involving massive feature extraction using publicly available code from many disciplines. The Prematurity-Related Ventilatory Control (Pre-Vent) observational multicenter prospective study collected bedside monitor data from > 700 extremely preterm infants to identify physiologic features that predict respiratory outcomes. We calculated a subset of 33 HCTSA features on > 7M 10-minute windows of oxygen saturation (SPO2) and heart rate (HR) from the Pre-Vent cohort to quantify predictive performance. This subset included representatives previously identified using unsupervised clustering on > 3500 HCTSA algorithms. Performance of each feature was measured by individual area under the receiver operating curve (AUC) at various days of life and binary respiratory outcomes. These were compared to optimal PreVent physiologic predictor IH90 DPE, the duration per event of intermittent hypoxemia events with threshold of 90%. Main Results: The top HCTSA features were from a cluster of algorithms associated with the autocorrelation of SPO2 time series and identified low frequency patterns of desaturation as high risk. These features had comparable performance to and were highly correlated with IH90 DPE but perhaps measure the physiologic status of an infant in a more robust way that warrants further investigation. The top HR HCTSA features were symbolic transformation measures that had previously been identified as strong predictors of neonatal mortality. HR metrics were only important predictors at early days of life which was likely due to the larger proportion of infants whose outcome was death by any cause. A simple HCTSA model using 3 top features outperformed IH90 DPE at day of life 7 (.778 versus .729) but was essentially equivalent at day of life 28 (.849 versus .850). These results validated the utility of a representative HCTSA approach but also provides additional evidence supporting IH90 DPE as an optimal predictor of respiratory outcomes.

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A narrative review of the mechanisms and consequences of intermittent hypoxia and the role of advanced analytic techniques in pediatric autonomic disorders

Cited by 7 publications

References 181 publications

Postinspiratory and preBötzinger complexes contribute to respiratory-sympathetic coupling in mice before and after chronic intermittent hypoxia

Postinspiratory and preBötzinger complexes contribute to respiratory-sympathetic coupling in mice before and after chronic intermittent hypoxia

Highly comparative time series analysis of oxygen saturation and heart rate to predict respiratory outcomes in extremely preterm infants

Highly comparative time series analysis of oxygen saturation and heart rate to predict respiratory outcomes in extremely preterm infants

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