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 Arousal from sleep in response to intermittent hypoxia in rat pups is modulated by medullary raphe GABAergic mechanisms

2012 ◽  
Vol 302 (5) ◽  
pp. R551-R560 ◽  
Author(s):  
Robert A. Darnall ◽  
Robert W. Schneider ◽  
Christine M. Tobia ◽  
Benjamin M. Zemel
Keyword(s):  
Heart Rate ◽  
Intermittent Hypoxia ◽  
Receptor Agonist ◽  
Sudden Infant Death ◽  
Sudden Infant ◽  
Autonomic Functions ◽  
Nipecotic Acid ◽  
Oxyhemoglobin Saturation ◽  
Rat Pups ◽  
Medullary Raphe

Arousal is an important defense against hypoxia during sleep. Rat pups exhibit progressive arousal impairment (habituation) with multiple hypoxia exposures. The mechanisms are unknown. The medullary raphe (MR) is involved in autonomic functions, including sleep, and receives abundant GABAergic inputs. We hypothesized that inhibiting MR neurons with muscimol, a GABAA receptor agonist, or preventing GABA reuptake with nipecotic acid, would impair arousal and enhance arousal habituation and that blocking GABAA receptors with bicuculline would enhance arousal and attenuate habituation. Postnatal day 15 (P15) to P25 rat pups were briefly anesthetized, and microinjections with aCSF, muscimol, bicuculline, or nipecotic acid were made into the MR. After a ∼30-min recovery, pups were exposed to four 3-min episodes of hypoxia separated by 6 min of normoxia. The time to arousal from the onset of hypoxia (latency) was determined for each trial. Latency progressively increased across trials (habituation) in all groups. The overall latency was greater after muscimol and nipecotic acid compared with aCSF, bicuculline, or noninjected controls. Arousal habituation was reduced after bicuculline compared with aCSF, muscimol, nipecotic acid, or noninjected pups. Increases in latency were mirrored by decreases in chamber [O2] and oxyhemoglobin saturation. Heart rate increased during hypoxia and was greatest in muscimol-injected pups. Our results indicate that the MR plays an important, not previously described, role in arousal and arousal habituation during hypoxia and that these phenomena are modulated by GABAergic mechanisms. Arousal habituation may contribute to sudden infant death syndrome, which is associated with MR serotonergic and GABAergic receptor dysfunction.

scholarly journals Reversible blunting of arousal from sleep in response to intermittent hypoxia in the developing rat

2010 ◽  
Vol 109 (6) ◽  
pp. 1686-1696 ◽  
Author(s):  
R. A. Darnall ◽  
S. McWilliams ◽  
R. W. Schneider ◽  
C. M. Tobia
Keyword(s):  
Heart Rate ◽  
Intermittent Hypoxia ◽  
Sudden Infant Death ◽  
Sudden Infant ◽  
Hypoxia Exposure ◽  
Rat Pups ◽  
Group A ◽  
Group B ◽  
Arousal Group ◽  
Developing Rat

Arousal is an important survival mechanism when infants are confronted with hypoxia during sleep. Many sudden infant death syndrome (SIDS) infants are exposed to repeated episodes of hypoxia before death and have impaired arousal mechanisms. We hypothesized that repeated exposures to hypoxia would cause a progressive blunting of arousal, and that a reversal of this process would occur if the hypoxia was terminated at the time of arousal. P5 (postnatal age of 5 days), P15, and P25 rat pups were exposed to either eight trials of hypoxia (3 min 5% O2 alternating with room air) ( group A), or three hypoxia trials as in group A, followed by five trials in which hypoxia was terminated at arousal ( group B). In both groups A and B, latency increased over the first four trials of hypoxia, but reversed in group B animals during trials 5–8. Progressive arousal blunting was more pronounced in the older pups. The effects of intermittent hypoxia on heart rate also depended on age. In the older pups, heart rate increased with each hypoxia exposure. In the P5 pups, however, heart rate decreased during hypoxia and did not return to baseline between exposures, resulting in a progressive fall of baseline values over successive hypoxia exposures. In the group B animals, heart rate changes during trials 1–4 also reversed during trials 5–8. We conclude that exposure to repeated episodes of hypoxia can cause progressive blunting of arousal, which is reversible by altering the exposure times to hypoxia and the period of recovery between hypoxia exposures.

scholarly journals 353 HEART RATE VARIABILITY AND SUDDEN INFANT DEATH SYNDROME

1994 ◽  
Vol 36 (1) ◽  
pp. 61A-61A
Author(s):  
Francesco Perticone ◽  
Raffaele Maio ◽  
Carmela Cosco ◽  
Fabiola Pugliese ◽  
Cosima Cloro ◽  
...  
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Sudden Infant Death Syndrome ◽  
Infant Death ◽  
Sudden Infant Death ◽  
Sudden Infant

Periodic Breathing in Preterm Infants: Incidence and Characteristics

PEDIATRICS ◽  
1989 ◽  
Vol 84 (5) ◽  
pp. 785-792
Author(s):  
S. F. Glotzbach ◽  
R. B. Baldwin ◽  
N. E. Lederer ◽  
P. A. Tansey ◽  
R. L. Ariagno
Keyword(s):  
Preterm Infants ◽  
Age Groups ◽  
Periodic Breathing ◽  
Sudden Infant Death ◽  
Respiratory Pattern ◽  
Sudden Infant ◽  
Quiet Time ◽  
Term Infants ◽  
Respiratory Dysfunction ◽  
Postconceptional Age

The prevalence and characteristics of periodic breathing in preterm infants were measured by 24-hour impedance pneumograms in 66 preterm infants before discharge from the nursery. Four periodic breathing parameters (percentage of periodic breathing per quiet time, number of episodes of periodic breathing per 100 minutes of quiet time, mean duration of periodic breathing, and longest episode of periodic breathing) were compared to data available from healthy term infants and from term infants who subsequently died of sudden infant death syndrome (SIDS). Periodic breathing was found in all preterm infants studied and mean periodic breathing parameter values (12.0%, 8.6 episodes, 1.2 minutes, and 7.3 minutes, respectively) in our preterm population were substantially higher than values from healthy term infants and SIDS victims. Most periodic breathing parameters decreased significantly in infants studied at 39 to 41 weeks' postconceptional age compared with earlier postconceptional age groups. No relationship was found between central apneas of ≥15 seconds' duration and postconceptional age or any periodic breathing parameter. Periodic breathing is a common respiratory pattern in preterm infants that is usually not of pathologic significance. Associations between elevated levels of periodic breathing and respiratory dysfunction or SIDS should be made with caution.

Apnea, Hypoxemia, and Aborted Sudden Infant Death Syndrome

PEDIATRICS ◽  
1978 ◽  
Vol 62 (5) ◽  
pp. 686-691
Author(s):  
June P. Brady ◽  
Ronald L. Ariagno ◽  
John L. Watts ◽  
Steven L. Goldman ◽  
Fe M. Dumpit
Keyword(s):  
Heart Rate ◽  
Sudden Infant Death Syndrome ◽  
Infant Death ◽  
Total Duration ◽  
Periodic Breathing ◽  
Sudden Infant Death ◽  
Control Group ◽  
Sudden Infant ◽  
Nasal Catheter ◽  
End Tidal

To find out whether there is any relationship between the ventilatory response to hypoxia and the sudden infant death syndrome (SIDS), we studied the effects of mild induced hypoxia (PIO2, 120 mm Hg = 17% oxygen) in 16 infants aged 2 weeks to 6 months. Eight had recurrent apneic spells (apnea group) (five had aborted SIDS and three had recurrent apnea in the intensive care nursery) and eight were "well" preterm infants about to fly in a pressurized airplane (PIO2, 120 mm Hg) (control group). Mean birth weights were 2,245 and 1,400 gm and mean gestational ages were 35 and 30 weeks. Postconceptual ages (41.8 and 41.3 weeks) were almost identical. Heart rate was obtained from an ECG, and respiratory rate and pattern were obtained from a pneumogram. In addition, end-tidal PCO2 and PN2 or PO2 were obtained with a nasal catheter and gas analyzers. In the apnea group with inhalation of 17% oxygen, we observed an increase in periodic breathing and an increase in both rate and total duration of respiratory pauses. In the control group there were no significant changes. Heart rate and PCO2 did not change in either group. Our findings suggest that infants prone to apnea may have unique respiratory responses to mild induced hypoxia.

Heart rate control in normal and aborted-SIDS infants

1993 ◽  
Vol 264 (3) ◽  
pp. R638-R646 ◽  
Author(s):  
S. M. Pincus ◽  
T. R. Cummins ◽  
G. G. Haddad
Keyword(s):  
Heart Rate ◽  
Rem Sleep ◽  
Rate Control ◽  
Approximate Entropy ◽  
Sudden Infant Death ◽  
Sudden Infant ◽  
Normal Infant ◽  
Quiet Sleep ◽  
Heart Rate Data ◽  
High Risk Subject

Approximate entropy (ApEn), a mathematical formula quantifying regularity in data, was applied to heart rate data from normal and aborted-sudden infant death syndrome (SIDS) infants. We distinguished quiet from rapid-eye-movement (REM) sleep via the following three criteria, refining the notion of REM as more "variable": 1) REM sleep has greater overall variability (0.0374 +/- 0.0138 vs. 0.0205 +/- 0.0090 s, P < 0.005); 2) REM sleep is less stationary (StatAv = 0.742 +/- 0.110) than quiet sleep (StatAv = 0.599 +/- 0.159, P < 0.03); 3) after normalization to overall variability, REM sleep is more regular (ApEnsub = 1.224 +/- 0.092) than quiet sleep (ApEnsub = 1.448 +/- 0.071, P < 0.0001). Fifty percent of aborted-SIDS infants showed greater ApEn instability across quiet sleep than any normal infant exhibited, suggesting that autonomic regulation of heart rate occasionally becomes abnormal in a high-risk subject. There was an association between low ApEn values and aborted-SIDS events; 5 of 14 aborted-SIDS infants had at least one quiet sleep epoch with an ApEn value below the minimum of 45 normal-infant ApEn values.

Alteration in heart rate response to hemorrhage in conscious dogs with volume overload

1978 ◽  
Vol 235 (4) ◽  
pp. H422-H428
Author(s):  
M. M. LeWinter ◽  
J. S. Karliner ◽  
J. W. Covell
Keyword(s):  
Heart Rate ◽  
Central Venous Pressure ◽  
Pulse Pressure ◽  
Pressure Pulse ◽  
Heart Rate Response ◽  
Parasympathetic Nervous System ◽  
Venous Pressure ◽  
Volume Overload ◽  
Conscious Dogs ◽  
Central Venous

The heart rate response to hemorrhage was studied in conscious dogs before and up to 2 mo after the establishment of volume overload due to systemic arteriovenous (a-v) fistulas. Before a-v fistula, heart rate increased markedly during hemorrhage. When hemorrhage was preceded by dextran infusion, bleeding resulted in a gradual reduction in heart rate. The a-v fistula caused marked increases in resting heart rate, central venous pressure, pulse pressure, and blood volume. During hemorrhage, heart rate initially remained constant, but then declined abruptly from the resting value of 121 +/- 3.7 beats/min to a nadir of 89 +/- 6.5 beats/min (P less than 0.01). Although mean arterial pressure decreased markedly, there was no significant change in pulse pressure, and central venous pressure tended to stabilize with the heart rate decline. The abrupt heart rate decline was prevented by atropine but unaltered by propranolol. The response was observed as early as 5 days after a-v fistula. We conclude that an alteration in the heart rate response to hemorrhage appears early during volume overload. This alteration appears to be reflex in nature and to be mediated by the parasympathetic nervous system.

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