Vulnerability of neonatal respiratory neural control to sustained hypoxia during a uniquely sensitive window of development

2014 ◽  
Vol 116 (5) ◽  
pp. 514-521 ◽  
Author(s):  
C. A. Mayer ◽  
J. M. Di Fiore ◽  
R. J. Martin ◽  
P. M. MacFarlane
Keyword(s):  
Critical Period ◽  
Neural Control ◽  
Sudden Infant Death ◽  
Whole Body ◽  
Sudden Infant ◽  
Environmental Stressor ◽  
Rat Pups ◽  
Comparable Effect ◽  
Whole Body Plethysmography ◽  
Sustained Hypoxia

The first postnatal weeks represent a period of development in the rat during which the respiratory neural control system may be vulnerable to aberrant environmental stressors. In the present study, we investigated whether sustained hypoxia (SH; 11% O2) exposure starting at different postnatal ages differentially modifies the acute hypoxic (HVR) and hypercapnic ventilatory response (HCVR). Three different groups of rat pups were exposed to 5 days of SH, starting at either postnatal age 1 (SH1–5), 11 (SH11–15), or 21 (SH21–25) days. Whole body plethysmography was used to assess the HVR and HCVR the day after SH exposure ended. The primary results indicated that 1) the HVR and HCVR of SH11–15 rats were absent or attenuated (respectively) compared with age-matched rats raised in normoxia; 2) there was a profoundly high (∼84% of pups) incidence of unexplained mortality in the SH11–15 rats; and 3) these phenomena were unique to the SH11–15 group with no comparable effect of the SH exposure on the HVR, HCVR, or mortality in the younger (SH1–5) or older (SH21–25) rats. These results share several commonalities with the risk factors thought to underlie the etiology of sudden infant death syndrome, including 1) a vulnerable neonate; 2) a critical period of development; and 3) an environmental stressor.

Brain stem serotonin protects blood pressure in neonatal rats exposed to episodic anoxia

2013 ◽  
Vol 115 (12) ◽  
pp. 1733-1741 ◽  
Author(s):  
Hsiao T. Yang ◽  
Kevin J. Cummings
Keyword(s):  
Tidal Volume ◽  
Brain Stem ◽  
Sudden Infant Death ◽  
Whole Body ◽  
Sudden Infant ◽  
Breathing Frequency ◽  
Body Plethysmography ◽  
Rat Pups ◽  
Time Required ◽  
Whole Body Plethysmography

In neonatal rodents, a loss of brain stem serotonin [5-hydroxytryptamine (5-HT)] in utero or at birth compromises anoxia-induced gasping and the recovery of heart rate (HR) and breathing with reoxygenation (i.e., autoresuscitation). How mean arterial pressure (MAP) is influenced after an acute loss of brain stem 5-HT content is unknown. We hypothesized that a loss of 5-HT for ∼1 day would compromise MAP during episodic anoxia. We injected 6-fluorotryptophan (20 mg/kg ip) into rat pups (postnatal days 9–10 or 11–13, n = 22 treated, 24 control), causing a ∼70% loss of brain stem 5-HT. Pups were exposed to a maximum of 15 anoxic episodes, separated by 5 min of room air to allow autoresuscitation. In younger pups, we measured breathing frequency and tidal volume using “head-out” plethysmography and HR from the electrocardiogram. In older pups, we used whole body plethysmography to detect gasping, while monitoring MAP. Gasp latency and the time required for respiratory, HR, and MAP recovery following each episode were determined. Despite normal gasp latency, breathing frequency and a larger tidal volume ( P < 0.001), 5-HT-deficient pups survived one-half the number of episodes as controls ( P < 0.001). The anoxia-induced decrease in MAP experienced by 5-HT-deficient pups was double that of controls ( P = 0.017), despite the same drop in HR ( P = 0.48). MAP recovery was delayed ∼10 s by 5-HT deficiency ( P = 0.001). Our data suggest a loss of brain stem 5-HT leads to a pronounced, premature loss of MAP in response to episodic anoxia. These data may help explain why some sudden infant death syndrome cases die from what appears to be cardiovascular collapse during apparent severe hypoxia.

Influence of adenosine A1-receptor blockade and vagotomy on the gasping and heart rate response to hypoxia in rats during early postnatal maturation

2007 ◽  
Vol 103 (4) ◽  
pp. 1234-1241 ◽  
Author(s):  
James E. Fewell ◽  
Chunfen Zhang ◽  
Anne M. Gillis
Keyword(s):  
Heart Rate ◽  
Heart Rate Response ◽  
Parasympathetic Nervous System ◽  
Age Groups ◽  
Sudden Infant Death ◽  
Severe Hypoxia ◽  
Sudden Infant ◽  
Postnatal Life ◽  
Postnatal Maturation ◽  
Rat Pups

Failure to autoresuscitate from apnea has been suggested to play a role in sudden infant death. Little is known, however, about factors that influence the gasping and heart rate response to severe hypoxia that are fundamental to successful autoresuscitation in the newborn. The present experiments were carried out on 184 rat pups to investigate the influence of the parasympathetic nervous system, as well as adenosine, in mediating the profound bradycardia that occurs with the onset of hypoxic-induced primary apnea and in modulating hypoxic gasping. On days 1 to 2, days 5 to 6, and days 10 to 11 postpartum and following bilateral cervical vagotomy (VAG) or administration of a selective adenosine A1 receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine; DPCPX), each pup was exposed to a single period of severe hypoxia produced by breathing an anoxic gas mixture (97% N2-3% CO2). Exposure to severe hypoxia resulted in an age-dependent decrease in heart rate ( P < 0.001), accentuated with increasing postnatal age, that was attenuated in all age groups by DPCPX but not by VAG. Furthermore, DPCPX but not VAG decreased the time to last gasp but increased the total number of gasps in the 1- to 2-day-old and 5- to 6-day-old pups but not in the 10- to 11-day-old pups during exposure to severe hypoxia. Thus our data provide evidence that adenosine acting via adenosine A1 receptors plays a role in modulating hypoxic gasping and in mediating the profound bradycardia that occurs coincident with hypoxic-induced primary apnea in rats during early postnatal life.

scholarly journals Maternal dietary tryptophan deficiency alters cardiorespiratory control in rat pups

2011 ◽  
Vol 110 (2) ◽  
pp. 318-328 ◽  
Author(s):  
Eliana M. Penatti ◽  
Alexis E. Barina ◽  
Sharat Raju ◽  
Aihua Li ◽  
Hannah C. Kinney ◽  
...  
Keyword(s):  
Brain Stem ◽  
Sudden Infant Death ◽  
Normal Weight ◽  
Sudden Infant ◽  
Postnatal Life ◽  
Cardiorespiratory Control ◽  
Cardiorespiratory Function ◽  
Rat Pups ◽  
Neuronal Number

Malnutrition during pregnancy adversely affects postnatal forebrain development; its effect upon brain stem development is less certain. To evaluate the role of tryptophan [critical for serotonin (5-HT) synthesis] on brain stem 5-HT and the development of cardiorespiratory function, we fed dams a diet ∼45% deficient in tryptophan during gestation and early postnatal life and studied cardiorespiratory variables in the developing pups. Deficient pups were of normal weight at postnatal day (P)5 but weighed less than control pups at P15 and P25 ( P < 0.001) and had lower body temperatures at P15 ( P < 0.001) and P25 ( P < 0.05; females only). Oxygen consumption (V̇o2) was unaffected. At P15, deficient pups had an altered breathing pattern and slower heart rates. At P25, they had significantly lower ventilation (V̇e) and V̇e-to-V̇o2 ratios in both air and 7% CO2. The ventilatory response to CO2 (% increase in V̇e/V̇o2) was significantly increased at P5 (males) and reduced at P15 and P25 (males and females). Deficient pups had 41–56% less medullary 5-HT ( P < 0.01) compared with control pups, without a difference in 5-HT neuronal number. These data indicate important interactions between nutrition, brain stem physiology, and age that are potentially relevant to understanding 5-HT deficiency in the sudden infant death syndrome.

scholarly journals Perinatal nicotine exposure impairs ability of newborn rats to autoresuscitate from apnea during hypoxia

1998 ◽  
Vol 85 (6) ◽  
pp. 2066-2074 ◽  
Author(s):  
James E. Fewell ◽  
Francine G. Smith
Keyword(s):  
Sleep Apnea ◽  
Infant Death ◽  
Sudden Infant Death ◽  
Repeated Exposure ◽  
Hypoxic Exposure ◽  
Sudden Infant ◽  
Perinatal Exposure ◽  
Newborn Rats ◽  
Pregnant Rats ◽  
Rat Pups

Failure to autoresuscitate by hypoxic gasping during prolonged sleep apnea has been suggested to play a role in sudden infant death. Furthermore, maternal smoking has been repeatedly shown to be a risk factor for sudden infant death. The present experiments were carried out on newborn rat pups to investigate the influence of perinatal exposure to nicotine (the primary pharmacological and addictive agent in tobacco) on their time to last gasp during a single hypoxic exposure and on their ability to autoresuscitate during repeated exposure to hypoxia. Pregnant rats received either nicotine (6 mg ⋅ kg−1 ⋅ 24 h−1) or vehicle continuously from day 6 of gestation to days 5 or 6 postpartum via an osmotic minipump. On days 5 or 6 postpartum, pups were exposed either to a single period of hypoxia (97% N2-3% CO2) and their time to last gasp was determined, or they were exposed repeatedly to hypoxia and their ability to autoresuscitate from primary apnea was determined. Perinatal exposure to nicotine did not alter the time to last gasp, but it did impair the ability of pups to autoresuscitate from primary apnea. After vehicle, the pups were able to autoresuscitate from 18 ± 1 (SD) periods of hypoxia, whereas, after nicotine, the pups were able to autoresuscitate from only 12 ± 2 periods ( P < 0.001) of hypoxia. Thus our data provide evidence that perinatal exposure to nicotine impairs the ability of newborn rats to autoresuscitate from primary apnea during repeated exposure to hypoxia, such as may occur during episodes of prolonged sleep apnea.

Laryngeal apnea in rat pups: effects of age and body temperature

2008 ◽  
Vol 104 (1) ◽  
pp. 269-274 ◽  
Author(s):  
Luxi Xia ◽  
James C. Leiter ◽  
Donald Bartlett
Keyword(s):  
Body Temperature ◽  
Sudden Infant Death ◽  
Developmental Changes ◽  
Sudden Infant ◽  
Human Infants ◽  
The Past ◽  
Rat Pups ◽  
Respiratory Disturbance ◽  
Temporal Profiles ◽  
Stimulation Of

In neonatal mammals of many species, including human infants, apnea and other reflex responses frequently arise from stimulation of laryngeal receptors by ingested or regurgitated liquids. These reflexes, mediated by afferents in the superior laryngeal nerves (SLNs), are collectively known as the laryngeal chemoreflex (LCR) and are suspected to be responsible for some cases of the sudden infant death syndrome (SIDS). The LCR is strongly enhanced by mild increases in body temperature in decerebrate piglets, a finding that is of interest because SIDS victims are often found in overheated environments. Because of the experimental advantages of studying reflex development and mechanisms in neonatal rodents, we have developed methods for eliciting laryngeal apnea in anesthetized rat pups and have examined the influence of mild hyperthermia in animals ranging in age from 3 to 21 days. We found that apnea and respiratory disruption, elicited either by intralaryngeal water or by electrical stimulation of the SLN, occurred at all ages studied. Raising body temperature by 2–3°C prolonged the respiratory disturbance in response to either stimulus. This effect of hyperthermia was prominent in the youngest animals and diminished with age. We conclude that many studies of the LCR restricted to larger neonatal animals in the past can be performed in infant rodents using appropriate methods. Moreover, the developmental changes in the LCR and in the thermal modulation of the LCR seem to follow different temporal profiles, implying that distinct neurophysiological processes may mediate the LCR and thermal prolongation of the LCR.

Postnatal age influences the ability of rats to autoresuscitate from hypoxic-induced apnea

2000 ◽  
Vol 279 (1) ◽  
pp. R39-R46 ◽  
Author(s):  
James E. Fewell ◽  
Francine G. Smith ◽  
Vienna K. Y. Ng ◽  
Vanessa H. Wong ◽  
Yinghong Wang
Keyword(s):  
Sleep Apnea ◽  
Infant Death ◽  
Acute Hypoxia ◽  
Sudden Infant Death ◽  
Repeated Exposure ◽  
Hypoxic Exposure ◽  
Sudden Infant ◽  
Gas Mixture ◽  
Rat Pups ◽  
Temperature Controlled

Failure to autoresuscitate from apnea by gasping has been suggested to have a role in sudden infant death. Little is known, however, about the factors that influence the ability of gasping to sustain life during acute hypoxia in the newborn. The present experiments were carried out on 105 rat pups to investigate the influence of postnatal age on the time to last gasp during a single hypoxic exposure and on the ability to autoresuscitate from primary apnea during repeated hypoxic exposures. On days 1–2, 5–6, 10–11, 15–16, and 19–20 postpartum, each pup was placed into a temperature-controlled chamber regulated to 37 ± 1°C and was exposed either to a single period of hypoxia produced by breathing an anoxic gas mixture (97% N2-3% CO2), and the time to last gasp was determined, or repeated exposure to hypoxia was performed, and the ability to autoresuscitate from primary apnea was determined. Increases in postnatal age decreased the time to last gasp following a single hypoxic exposure and decreased the number of successful autoresuscitations following repeated hypoxic exposures. Thus our data provide evidence that postnatal age influences protective responses that may prevent death during hypoxia as may occur during episodes of prolonged sleep apnea.

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