Effect of Postnatal Intermittent Hypoxia on Growth and Cardiovascular Regulation of Rat Pups

Abstract

Background: Intermittent hypoxic episodes are common among preterm infants, although longer term consequences on growth pattern and cardiovascular regulation are unclear. Furthermore, the effects of intermittent hypoxia (IH) may depend on the pattern of hypoxia-reoxygenation. Objectives: We tested the hypothesis that a clustered versus dispersed pattern of repetitive IH during early postnatal life would induce differential long-term alteration in growth and cardiovascular regulation. Methods: Sprague-Dawley rat pups were exposed to room air or to one of two patterns of IH (clustered vs. dispersed) from 1 to 7 days of life. Body weight was measured daily for the first 8 days and weekly from weeks 2 to 8. Blood pressure (BP) and heart rate were measured weekly from weeks 4 to 8 using a noninvasive tail-cuff method for awake, nonanesthetized animals. Results: Exposure to both patterns of repetitive IH induced early growth restriction followed by later catch-up of growth to controls 3 weeks after completion of IH exposures. IH-exposed rats exhibited a sustained decrease in heart rate regardless of the hypoxic exposure paradigm employed. In contrast, a differential response was seen for arterial pressure; the clustered paradigm was associated with a significantly lower BP versus controls, while the pups exposed to the dispersed paradigm showed no effect on BP. Conclusion: We speculate that repetitive IH during a critical developmental window and regardless of IH exposure paradigm contributes to prolonged changes in sympathovagal balance of cardiovascular regulation.

Programming of the Hypothalamic-Pituitary-Adrenal Axis by Neonatal Intermittent Hypoxia: Effects on Adult Male ACTH and Corticosterone Responses Are Stress Specific

“…It has also been noted that prior to IH-exposed rats reaching maturity, weight gain is not parallel between IH-and non-IH-exposed groups and after reaching maturity, both groups reach similar body weights due to growth catch-up (8,26). This study found similar body weights between treatment and control groups at 100 days of age, reinforcing this previously documented body weight phenomenon.…”

“…Neonatal IH has previously been associated with a decreased growth rate during the neonatal period (8,10,26). It has also been noted that prior to IH-exposed rats reaching maturity, weight gain is not parallel between IH-and non-IH-exposed groups and after reaching maturity, both groups reach similar body weights due to growth catch-up (8,26).…”

Patterns of Oxygenation, Mortality, and Growth Status in the Surfactant Positive Pressure and Oxygen Trial Cohort

“…They are typically a consequence of impaired respiratory control and may occur in spontaneously breathing or ventilated preterm infants 3, 19, 20 . Intermittent hypoxia and/or related apnea events during early postnatal life have been linked to neurodevelopmental impairment 21, 22, 23, 24 , attention deficit disorder 25 , neurotransmitter imbalance 25 , retinopathy of prematurity 3, 26 , cardiovascular regulation 27 and growth restriction 27 in both human infants and neonatal animal models. We are only beginning to appreciate that patterns of IH may play a role in both detrimental and beneficial effects on the respiratory, cardiovascular, and nervous systems among others 26, 28 .…”

Hypoxic Episodes in Bronchopulmonary Dysplasia

“…IH effects on cardiovascular control are more complex and longer lasting. Changes in arterial blood pressure are dependent on the timing of the IH events with a clustered pattern associated with lower blood pressure than equaling dispersed events 40 with no recovery in either IH paradigm after 7 weeks of exposure. Interestingly, there is an association between extreme prematurity, increased blood pressure in adolescence and functional vascular changes, although it is speculative whether intermittent hypoxic episodes in early life might be contributory 41 .…”

“…In rodent models, IH exposure during early postnatal life restricts both body 40 and brain growth 19 , however, these effects were reversed after a few weeks of recovery. IH effects on cardiovascular control are more complex and longer lasting.…”