Changes in respiratory timing induced by hypercapnia in maturing rats

Abu-Shaweesh, Jalal M.; Dreshaj, Ismail A.; Thomas, Alicia; Haxhiu, Musa A.; Strohl, Kingman P.; Martin, Richard J.

doi:10.1152/jappl.1999.87.2.484

Cited by 48 publications

(21 citation statements)

References 37 publications

(42 reference statements)

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“…Early reports indicated that the hypercapnic response was very modest in the first 2 postnatal weeks (Bamford et al, 1996). There was little effect of CO 2 on frequency early in development (VT did increase), but the frequency response increased by P18, and the development of an increased ventilatory response to CO 2 over the first weeks of life tracked the emergence of a frequency response to CO 2 (Bamford et al, 1996;Abu-Shaweesh et al, 1999). Stunden et al (2001) described changes in ventilation during hypercapnia in neonatal rats ranging in age from P1 to P21 and in animals greater than 100 days of age.…”

Section: The Acute Response To Hypercapniamentioning

confidence: 99%

“…However, there are conflicting reports about whether or not GABA is excitatory early in development. Some investigators have interpreted the poor frequency response to inhaled CO 2 in the early postnatal period as evidence of inhibitory GABAergic effects, since bicuculline, a GABA A antagonist, enhanced the frequency response to CO 2 even in P5 rats (Abu-Shaweesh et al, 1999). Furthermore, Kim et al (1997) showed that GABA occasionally depolarizes rostral NTS neurons from young rats, while Grabauskas and Bradley (2001) found that rostral NTS neurons from young rats hyperpolarized in the same manner as adult neurons in response to GABA.…”

Section: Maturation Of 'Inhibitory' Chemical Synapses-mentioning

confidence: 99%

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Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity

Putnam

Conrad

Gdovin

et al. 2005

Respiratory Physiology & Neurobiology

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The ventilatory response to CO 2 changes as a function of neonatal development. In rats, a ventilatory response to CO 2 is present in the first 5 days of life, but this ventilatory response to CO 2 wanes and reaches its lowest point around postnatal day 8. Subsequently, the ventilatory response to CO 2 rises towards adult levels. Similar patterns in the ventilatory response to CO 2 are seen in some other species, although some animals do not exhibit all of these phases. Different developmental patterns of the ventilatory response to CO 2 may be related to the state of development of the animal at birth. The triphasic pattern of responsiveness (early decline, a nadir, and subsequent achievement of adult levels of responsiveness) may arise from the development of several processes, including central neural mechanisms, gas exchange, the neuromuscular junction, respiratory muscles and respiratory mechanics. We only discuss central neural mechanisms here, including altered CO 2 sensitivity of neurons among the various sites of central CO 2 chemosensitivity, changes in astrocytic function during development, the maturation of electrical and chemical synaptic mechanisms (both inhibitory and excitatory mechanisms) or changes in the integration of chemosensory information originating from peripheral and multiple central CO 2 chemosensory sites. Among these central processes, the maturation of synaptic mechanisms seems most important and the relative maturation of synaptic processes may also determine how plastic the response to CO 2 is at any particular age.

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Section: The Acute Response To Hypercapniamentioning

confidence: 99%

Section: Maturation Of 'Inhibitory' Chemical Synapses-mentioning

confidence: 99%

Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity

Putnam

Conrad

Gdovin

et al. 2005

Respiratory Physiology & Neurobiology

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“…The ventilatory response to a single hypercapnic exposure has been extensively studied and is diminished in apneic preterm infants [2,3] and during early postnatal life in both preterm infants and rat pups [4][5][6] . The characteristic increase in tidal volume is accompanied by a decrease in respiratory frequency during hypercapnic exposure in preterm infants [7,8] .…”

Section: Introductionmentioning

confidence: 99%

Effect of Intermittent Hypercapnia on Respiratory Control in Rat Pups

et al. 2009

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Preterm infants are subject to fluctuations in blood gas status associated with immature respiratory control. Intermittent hypoxia during early postnatal life has been shown to increase chemoreceptor sensitivity and destabilize the breathing pattern; however, intermittent hypercapnia remains poorly studied. Therefore, to test the hypothesis that intermittent hypercapnia results in altered respiratory control, we examined the effects of daily exposure to intermittent hypercapnia on the ventilatory response to subsequent hypercapnic and hypoxic exposure in neonatal rat pups. Exposure cycles consisted of 5 min of intermittent hypercapnia (5% CO₂, 21% O₂, balance N₂) followed by 10 min of normoxia. Rat pups were exposed to 18 exposure cycles each day for 1 week, from postnatal day 7 to 14. We analyzed diaphragm electromyograms (EMGs) from pups exposed to subsequent acute hypercapnic (5% CO₂) and hypoxic (12% O₂) challenges. In response to a subsequent hypercapnia challenge, there was no significant difference in the ventilatory response between control and intermittent hypercapnia-exposed groups. In contrast, intermittent hypercapnia-exposed rat pups showed an enhanced ventilatory response to hypoxic challenge with an increase in minute EMG to 118 ± 14% of baseline versus 107 ± 13% for control pups (p < 0.05). We speculate that prior hypercapnic exposure may increase peripheral chemoreceptor response to subsequent hypoxic exposures and result in perturbed neonatal respiratory control.

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“…Based upon these data, it is possible that a maturation of hypothalamic circuits could contribute to changes in respiratory regulation that occur during the first week of development of the rat (28). It is known that levels of arcuate neurotransmitters do not reach adult levels until several weeks after birth (29).…”

Section: Discussionmentioning

confidence: 99%

The Basomedial Hypothalamus Modulates the Ventilatory Response to Hypoxia in Neonatal Rats

et al. 2003

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We sought to examine the role of the basomedial hypothalamus in the regulation of breathing in neonatal rats. Small basomedial hypothalamic lesions were produced by a lesioning agent, goldthioglucose, in 5-d-old male rat pups, and 2 d later, baseline ventilation and the ventilatory responses to hypoxia and hypercapnia were examined. When compared with vehicleinjected controls, goldthioglucose-lesioned rat pups had a significantly slower respiratory rate and longer expiratory time at baseline. Lesioned rats displayed an impaired increase in breathing frequency in response to hypoxia, and augmented increases in tidal volume and respiratory drive (the ratio of tidal volume to inspiratory time) during hypoxia relative to controls. Hypercapnic responses were not affected. These data demonstrate that cells in a restricted area of the hypothalamus specifically influence the respiratory response to hypoxia. It is well established that ventilatory responses to hypoxia are mediated by discrete neural pathways involving peripheral chemoreceptors, primary afferents, and brainstem respiratoryrelated neurons. The characteristics of the response, however, depend on complex interactions at multiple levels of the neuraxis, including suprapontine structures. Several studies have suggested that the caudal hypothalamus modulates responses to hypoxia and hypercapnia (1, 2). For example, one study showed that 21% of hypothalamic units are activated by hypoxia and 31% by hypercapnic loading (3). Furthermore, hypoxia and hypercapnia stimulate neurons in various hypothalamic nuclei (paraventricular, supraoptic, and dorsomedial) to synthesize the transcription-regulating protein Fos (4 -6). Binding of the adipocyte hormone leptin to receptors in either the hypothalamus or area postrema modulates respiration and may underlie the respiratory abnormalities observed in genetically obese rodents (7-9). Finally, electrolytic lesions that destroy extensive amounts of perifornical cells in the posterior hypothalamus enhance the ventilatory response to hypoxia (10). However, the role of these structures in regulating ventilatory responses to chemical drive is not well understood.Functional effects of relatively large electrolytic lesions of the hypothalamus are instructive, but are less helpful in pinpointing the precise location of hypothalamic cells critical for respiratory control. Likewise, unit recording or examination of Fos expression throughout the hypothalamus during hypoxia does not identify cells initiating a hypothalamic response to hypoxia because of multisynaptic projections among activated neuronal pools. These techniques also do not determine the functional role of hypothalamic cells in the regulation of respiratory responses to changes in chemical drive. One approach to this problem is to examine the effects of relatively restricted hypothalamic damage. This can be achieved via the systemic administration of a toxin, GTG, which diffuses into the hypothalamus via the permeable capillaries of the median eminence and which damages o...

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Changes in respiratory timing induced by hypercapnia in maturing rats

Cited by 48 publications

References 37 publications

Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity

Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity

Effect of Intermittent Hypercapnia on Respiratory Control in Rat Pups

The Basomedial Hypothalamus Modulates the Ventilatory Response to Hypoxia in Neonatal Rats

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