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Background:We have previously shown an increased incidence of intermittent hypoxemia (Ih) events in preterm infants with severe retinopathy of prematurity (ROP). animal models suggest that patterns of Ih events may play a role in ROP severity as well. We hypothesize that specific Ih event patterns are associated with ROP in preterm infants. Methods: Variability in Ih event duration, severity, and the time interval between Ih events (≤80%, ≥10 s, and ≤3 min) along with the frequency spectrum of the oxygen saturation (spO 2 ) waveform were assessed. results: severe ROP was associated with (i) an increased mean and sD of the duration of Ih event (P < 0.005), (ii) more variability (histogram entropy) of the time interval between Ih events (P < 0.005), (iii) a higher Ih nadir (P < 0.05), (iv) a time interval between Ih events of 1-20 min (P < 0.05), and (v) increased spectral power in the range of 0.002-0.008 hz (P < 0.05), corresponding to spO 2 waveform oscillations of 2-8 min in duration. spectral differences were detected as early as 14 d of life. conclusion: severe ROP was associated with more variable, longer, and less severe Ih events. Identification of specific spectral components in the spO 2 waveform may assist in early identification of infants at risk for severe ROP.

In infants, respiratory infection elicits tachypnea. To begin to evaluate the role of brainstem cytokine expression in modulation of breathing pattern changes, we compared the pattern generated after endotracheal instillation of lipopolysaccharide (LPS) in in vivo rat pups to local pro-inflammatory cytokine injection in the nucleus tractus solitarius (nTS) in an in vitro en bloc brainstem spinal cord preparation. We hypothesized that both challenges would elicit similar changes in patterning of respiration. In anesthetized, spontaneously breathing rat pups, lipopolysaccharide (LPS) or saline was instilled in the airway of urethane-anesthetized rats (postnatal day 10–11). We recorded diaphragm EMG over the subsequent 2 hours and saw a 20–30% decrease in interburst interval (Te) at 20–80 min post-injection in LPS-instilled animals with no significant change in Ti. In contrast, IL-1β injections into the nTS of en bloc in vitro brainstem-spinal cord preparations from 0 to 5 day-old pups maintained Ti and caused an increase in Te as early as 20 min later, decreasing frequency for 80 to 120 minutes after injection. Our results suggest that the neonatal respiratory response to the cytokine IL-1β mediated inflammatory response depends on the site of the inflammatory stimulus and that the direct effect of IL-1β in the nTS is to slow rather than increase rate.

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Numerous experimental preparations from neonatal rodents have been developed to study mechanisms responsible for respiratory rhythm generation. Amongst them, the in vivo anesthetized neonatal rat preparation and the in vitro medullary slice preparation from neonatal rat are commonly used. These two preparations not only contain a different extent of the neuroanatomical axis associated with central respiratory control, but they are also studied under markedly different conditions, all of which may affect the complex dynamics underlying the central inspiratory neural network. Here, we evaluated the approximate entropy (ApEn) underlying inspiratory motor bursts as an index of inspiratory neural network complexity from each preparation to address this possibility. Our findings suggest that the central inspiratory neural network of the in vivo anesthetized neonatal rat exhibits lower complexity (i.e., more order) than that observed in the in vitro transverse medullary slice preparation, both of which are substantially lower than that observed in more intact in vitro (e.g., arterially-perfused rat) and mature in vivo (e.g., anesthetized rat, piglet, cat) preparations. We suggest that additional studies be conducted to identify the precise mechanisms responsible for the differences in central inspiratory neural network complexity between these two neonatal rat preparations.

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The in vitro medullary slice preparation from neonatal rodents is capable of generating spontaneous fictive inspiratory rhythm, provided it contains the preBötzinger complex and supporting neural circuitry. Previous work has shown the rhythm‐generating network may differ fundamentally in neonatal rats and mice. To further understand and characterize these differences, we have applied two measures of complexity (predictability), Approximate (ApEn) and Interval Entropy (IntEn), to our neonatal (postnatal days 0–5) rodent recordings. Changes in complexity within respiratory bursts (ApEn) and between bursts (IntEn) are compared for varying K+ concentrations and between species—Sprague Dawley rat and BL6 mouse. Our results show that the mouse recordings, on average, are more complex than those from rat and peak complexity within the mouse network is shifted to a higher potassium level (8mM) than in the rat (5mM). Del Negro et al. (2005) have shown that a very different proportion of ICAN and INaP exists in neonatal rats and mice. We hypothesize that the fundamental architectural differences within the respiratory rhythm‐generating network of differing rodent species can be detected by complexity (entropy) measures. The application of these complexity measures provides a first step in fully describing the various proposed neural network architectures of the brainstem medullary respiratory circuit.

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