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

Fewell, James E.; Smith, Francine G.; Ng, Vienna K. Y.; Wong, Vanessa; Wang, Yinghong

doi:10.1152/ajpregu.2000.279.1.r39

Cited by 40 publications

(71 citation statements)

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“…The bradycardia associated with sleep apnea is likely mediated, at least in part, by increases in parasympathetic cardioinhibitory activity because atropine, a blocker of cardiac vagal activity, is partially effective in preventing the majority of arrhythmias during and after obstructive sleep apnea (35). Although the cause of the severe bradycardia associated with sleep apnea is unknown, the results from this study suggest that it may be the result of excitation of parasympathetic cardiac neurons that typically occurs during autoresuscitation (36).…”

Section: Discussionmentioning

confidence: 80%

“…Although the cause(s) for SIDS remains unknown, chronic fetal nicotine exposure by maternal smoking dramatically increases the risk for SIDS by two to four times (19,20). Infants who succumb to SIDS typically have gasp-like respiratory patterns as well as intrathoracic petechial hemorrhages, which are an indication of rigorous respiratory efforts (36,38). Prenatal exposure to nicotine exaggerates the bradycardia response to hypoxia (22), although the mechanisms have not previously been studied.…”

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confidence: 99%

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Prenatal Nicotine Exposure Recruits an Excitatory Pathway to Brainstem Parasympathetic Cardioinhibitory Neurons during Hypoxia/Hypercapnia in the Rat: Implications for Sudden Infant Death Syndrome

et al. 2005

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Maternal cigarette smoking and prenatal nicotine exposure increase the risk for sudden infant death syndrome (SIDS) by 2-to 4-fold, yet despite adverse publicity, nearly one of four pregnant women smoke tobacco. Infants who succumb to SIDS typically experience a severe bradycardia that precedes or is accompanied by centrally mediated life-threatening apneas and gasping. Although the causes of the apnea and bradycardia prevalent in SIDS victims are unknown, it has been hypothesized that these fatal events are exaggerated cardiorespiratory responses to hypoxia or hypercapnia. Changes in heart rate are primarily determined by the activity of cardiac vagal neurons (CVNs) in the brainstem. In this study, we tested whether hypoxia/hypercapnia evokes synaptic pathways to CVNs and whether these cardiorespiratory interactions are altered by prenatal exposure to nicotine. Spontaneous rhythmic inspiratoryrelated activity was recorded from the hypoglossal rootlet of 700-to 800-m medullary sections. CVNs were identified in this preparation by retrograde fluorescent labeling, and excitatory synaptic inputs to CVNs were isolated and studied using patchclamp electrophysiologic techniques. Hypoxia/hypercapnia did not elicit an increase in excitatory neurotransmission to CVNs in unexposed animals, but in animals that were exposed to nicotine in the prenatal period, hypoxia/hypercapnia recruited an excitatory neurotransmission to CVNs. This study establishes a likely neurochemical mechanism for the exaggerated decrease in heart rate in response to hypoxia/hypercapnia that occurs in SIDS victims. There are at least two major physiologic interactions between the respiratory system and the neural control of heart rate. The most ubiquitous cardiorespiratory interaction is respiratory sinus arrhythmia. During each respiratory cycle, the heart beat slows during postinspiration/expiration, and heart rate increases during inspiration. Such increases in heart rate during inspiration are observed in a wide variety of mammals, including both neonatal (1) and adult humans (2) and rats (3). Respiratory sinus arrhythmia helps match pulmonary blood flow to lung inflation and maintain the appropriate diffusion gradient for oxygen in the lungs (4).Although feedback from pulmonary stretch receptors, direct respiratory related-changes in venous return, and cardiac stretch can evoke respiratory-related fluctuations in heart rate, the dominant source of respiratory sinus arrhythmia originates from the brainstem (4,5). Respiratory sinus arrhythmia persists when the lungs are stationary (caused by muscle paralysis or constant flow ventilation), and the respiratory modulation of heart rate remains synchronized with brainstem respiratory rhythms even when artificial ventilation of the lungs and chemoreceptor activation occur at different intervals (6,7). In animals, including humans, respiratory sinus arrhythmia is mediated via cardiac vagal activity. Respiratory sinus arrhythmia persists in experimental animals upon sectioning sympathetic pathways and in...

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Section: Discussionmentioning

confidence: 80%

mentioning

confidence: 99%

Prenatal Nicotine Exposure Recruits an Excitatory Pathway to Brainstem Parasympathetic Cardioinhibitory Neurons during Hypoxia/Hypercapnia in the Rat: Implications for Sudden Infant Death Syndrome

et al. 2005

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“…Supporting this hypothesis, the results from other animal studies suggest that the cardiorespiratory responses to hypoxia strongly depend on the postnatal age of animals. For example, postnatal age influences the ability of rats to autoresuscitate from apnea (Fewell et al 2000). In particular, increases in postnatal age, up to 20 days of postnatal age, decreases the time to last gasp and the number of successful autoresuscitations following repeated hypoxic exposures (Fewell et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Developmental changes in GABAergic neurotransmission to presympathetic and cardiac parasympathetic neurons in the brainstem

Dergacheva

Boychuk

Mendelowitz

2013

Journal of Neurophysiology

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Cardiovascular function is regulated by a dynamic balance composed of sympathetic and parasympathetic activity. Sympathoexcitatory presympathetic neurons (PSNs) in the rostral ventrolateral medulla project directly to cardiac and vasomotor sympathetic preganglionic neurons in the spinal cord. In proximity to the PSNs in the medulla, there are preganglionic cardiac vagal neurons (CVNs) within the nucleus ambiguus, which are critical for parasympathetic control of heart rate. Both CVNs and PSNs receive GABAergic synaptic inputs that change with challenges such as hypoxia and hypercapnia (H/H). Autonomic control of cardiovascular function undergoes significant changes during early postnatal development; however, little is known regarding postnatal maturation of GABAergic neurotransmission to these neurons. In this study, we compared changes in GABAergic inhibitory postsynaptic currents (IPSCs) in CVNs and PSNs under control conditions and during H/H in postnatal day 2–5 (P5), 16–20 (P20), and 27–30 (P30) rats using an in vitro brainstem slice preparation. There was a significant enhancement in GABAergic neurotransmission to both CVNs and PSNs at age P20 compared with P5 and P30, with a more pronounced increase in PSNs. H/H did not significantly alter this enhanced GABAergic neurotransmission to PSNs in P20 animals. However, the frequency of GABAergic IPSCs in PSNs was reduced by H/H in P5 and P30 animals. In CVNs, H/H elicited an inhibition of GABAergic neurotransmission in all ages studied, with the most pronounced inhibition occurring at P20. In conclusion, there are critical development periods at which significant rearrangement occurs in the central regulation of cardiovascular function.

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“…The ability of respiratory neurones to generate rhythmic activity using anaerobic metabolism is a specific feature of neonates (23), because in mature mammals, rhythmic respiratory drive potentials cease in medullary respiratory neurones (24,25) in the absence of oxygen. These characteristics of neonatal respiratory neurones undoubtedly contribute to the remarkable high tolerance to hypoxia, assistance in the maintenance of rhythmic activity, and successful autoresuscitation of newborns (26).…”

Section: Discussionmentioning

confidence: 99%

“…This coupled with a forced inspiratory effort would provide adequate ventilation (12). Thus, this pattern can be seen as an attempt of the respiratory network to overcome hypoxia and may play a crucial role for autoresuscitation (12,26). However, in group 1 rats, the more frequently found paradoxic inspiratory upper airway constriction would clearly impair any attempt for re-oxygenation.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Changes in Glottal Resistance during Exposure to Severe Hypoxia in Neonatal Rats In Situ

Dutschmann

Paton

2005

Pediatr Res

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The neural control of respiratory airflow via the vocal fold is characterized by inspiratory abduction and postinspiratory (early expiratory) adduction causing decreases and increases in glottal resistance, respectively. The postinspiratory increase in glottal resistance plays a major role in braking the speed of expiratory airflow, to act against the high recoil pressure of the neonatal rat lung. In the present study, we investigated changes in upper airway patency during severe hypoxia in neonatal rats. We measured dynamic changes in subglottal pressure during normoxic and hypoxic conditions in an arterially perfused brainstem preparation in which we could control gas tensions accurately. Initially, hypoxia (5% O 2 , 5% CO 2 , and 90% nitrogen) produced an excitatory response in phrenic nerve activity accompanied by augmentation of both inspiratory-related glottal dilation and postinspiratory glottal constriction. Later, during the early stages of hypoxia-induced respiratory depression and initiation of gasping, we observed a massive reduction of the respiratory modulation of glottal resistance. In most preparations, this was transient and replaced by a paradoxic inspiratory-related glottal constriction. We propose that during severe hypoxia in the in situ preparation, paradoxic inspiratory glottal constriction can be observed during gasping, and this may impair ventilation despite the persistence of rhythmic contractions of the respiratory muscles. The latter is of clinical interest, because this may relate to the finding of cot death victims who died as a result of upper airway obstruction but without apparent apnea or rebreathing. Classically, hypoxia triggers a biphasic respiratory response that consists of an initial augmentation, then a marked depression of ventilation; this is followed by gasping until death (1). The characteristics of the hypoxic ventilatory response undergoes postnatal maturation (2). For example, in neonates, the early increase in respiration in response to hypoxia is less pronounced (2). However, neonates have a remarkable tolerance to hypoxia and robust mechanisms for autoresuscitation after hypoxia-induced respiratory depression (3-5). A major component for successful autoresuscitation is gasping (4,5), a breathing pattern triggered during marked hypoxia or anoxia. Because hypoxia is a common complication in the human neonate (3), a knowledge of the precise physiologic response to hypoxia is of clinical interest.Gasping is a unique breathing pattern defined as having a decrementing inspiratory discharge (as opposed to the augmenting pattern of eupnea) and a synchronization of inspiratory discharges in cranial (vagal, hypoglossal) and phrenic motor outflows (6 -8). In eupnea, there is a highly coordinated initiation of the motor pattern sequence of upper airway and respiratory pump motor activity such that the latter is temporally delayed so that decrease of upper airway resistance can precede the onset of lung inflation. This being the case, the respiratory cycle can be divided in...

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

Cited by 40 publications

References 38 publications

Prenatal Nicotine Exposure Recruits an Excitatory Pathway to Brainstem Parasympathetic Cardioinhibitory Neurons during Hypoxia/Hypercapnia in the Rat: Implications for Sudden Infant Death Syndrome

Prenatal Nicotine Exposure Recruits an Excitatory Pathway to Brainstem Parasympathetic Cardioinhibitory Neurons during Hypoxia/Hypercapnia in the Rat: Implications for Sudden Infant Death Syndrome

Developmental changes in GABAergic neurotransmission to presympathetic and cardiac parasympathetic neurons in the brainstem

Dynamic Changes in Glottal Resistance during Exposure to Severe Hypoxia in Neonatal Rats In Situ

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