Transient Apnea after an Enkephalin Analogue in the Preterm Rabbit

Hedner, Thomas; Hedner, Jan; Bergman, B; Lundberg, Dag

doi:10.1159/000241450

Cited by 17 publications

(4 citation statements)

References 10 publications

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“…serotonin, GABA and enkephal ins) [6,7,10,23] and stimulating (e.g. dopa mine, substance P and TRH) [8,9,11,12,21 ] systems as previously proposed [6].…”

Section: Introductionmentioning

confidence: 99%

Effects of GABA and Some GABA Analogues on Respiratory Regulation in the Preterm Rabbit

Hedner¹,

Hedner²,

Bergman³

et al. 1983

Neonatology

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Preterm neonatal rabbits (gestational age 29 days) were given GABA (750 mg/kg) or the GABA-like drugs muscimol (2 mg/kg) and GHBA (375 mg/kg) intraperitoneally. Basal respiration and the ventilatory response to 10% CO₂ were studied, before and after drug administration, in a whole body plethysmograph during halothane anesthesia. The three drugs tested all caused a decrease in minute volume. The decrease in minute volume was mainly due to a decrease in tidal volume after GABA and muscimol, while GHBA reduced minute volume due to a decrease in respiratory frequency. A decrease in respiratory frequency was also seen after muscimol administration. Changes in the respiratory time intervals were seen after muscimol and GHBA both causing significant increases in expiratory and respiratory time. ‘Inspiratory drive’ and ‘respiratory timing mechanisms’ were evaluated by V_τ/T_I and T_ι/T_TOT, respectively. GABA and muscimol reduced both V_T/T_I and Tι/T_TOT while GHBA only reduced T_I/T_TOT Addition of 10% CO₂ to the inhalation gas caused an increase in tidal volume and minute volume during control conditions. This response to CO₂ was abolished by GABA and GHBA treatment. Our findings demonstrate that GABA and GABA-like drugs cause respiratory depression in the preterm neonate. Central mechanisms are most likely involved in this response. These findings may be relevant to the irregular or apneic breathing sometimes seen in the preterm human infant.

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“…serotonin, GABA and enkephal ins) [6,7,10,23] and stimulating (e.g. dopa mine, substance P and TRH) [8,9,11,12,21 ] systems as previously proposed [6].…”

Section: Introductionmentioning

confidence: 99%

Effects of GABA and Some GABA Analogues on Respiratory Regulation in the Preterm Rabbit

Hedner¹,

Hedner²,

Bergman³

et al. 1983

Neonatology

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“…Acute increases in the [ME], for instance, depress respiration in adult [30], term [17], and preterm [16] animals and may be involved in the newborn's ventilatory re sponse to hypoxia [31]. In útero hypoxia-in duced increases in the brainstem [ME] in re gions which integrate cardiorespiratory func tion, as seen in the pons of fetal animals, may have important acute effects during early adaptation to extrauterine life.…”

Section: Discussionmentioning

confidence: 99%

“…ME (an inhibitory and/or modulatory neuropeptide) is found in high concentrations within brainstem nuclei involved in cardiorespiratory control [14,15]. Within these nuclei, the concentration of ME is higher in younger animals than older animals [15], In addition, ME produces apnea in both preterm [16] and term [17] ex perimental animals. The respiratory depres sion induced by ME is reversed by naloxone to a greater degree in younger animals [17].…”

Section: Introductionmentioning

confidence: 99%

Chronic Maternal Hypoxia

Gingras

Long²

1988

Dev Neurosci

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We examined the effect of chronic maternal hypoxia on methionine-enkephalin concentrations in fetal (gestational day E-28) and neonatal (postnatal days 3, 7, 21) brainstem regions. Pregnant rabbits were housed in environmental chambers at gestational day E-10. Between E-14 and E-28 the pregnant rabbits were separated into two groups. Group I were controls (C) and breathed 21% 02/79% N2 and group II, hypoxia (H), breathed 12–14% 02/86–88% N2. Sacrifice occurred at various days depending on the experimental paradigm. On gestational day E-28, the first group of 6 pregnant animals (3 C, 3 H) were delivered by hysterotomy and the pups were immediately sacrificed. On and after gestational day E-28, the remaining 12 pregnant animals breathed room air. These animals delivered spontaneously between 30 and 32 days of gestation. The pups remained with their mothers until sacrifice. On postnatal days 3, 7, or 21, methionine-enkephalin was measured by radioimmunoassay in the colliculi (fetal animals), superior and inferior colliculi (postnatal animals), pons and medulla (both groups). In both normoxia-exposed and hypoxia-exposed animals, methionine-enkephalin was highest in the medulla, intermediate in the pons, and lowest in the colliculi. Chronic maternal hypoxia significantly increased the methionine-enkephalin concentration in the pons of E-28 fetuses (p < 0.02). Levels were increased in the medulla as well but these did not reach significance (p = 0.09). In contrast, chronic maternal hypoxia had no effect on brainstem methionine-enkephalin concentrations at 3 and 7 days postnatally, but did decrease the methionine-enkephalin concentrations in the superior colliculi, pons and medulla (but not the inferior colliculi) at postnatal day 21. These data support the concept that regional differences exist in basal methionine-enkephalin concentrations within the brainstem regions of fetal and neonatal animals, and show that maternal hypoxia has both immediate and long-term effects on brain methionine-enkephalin concentrations. Both fetal and postnatal animals show regional susceptibility to changes in brainstem methionine-enkephalin concentrations after exposure to chronic maternal mid-gestational hypoxia.

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“…(Pediatr Res 20: 655-657,1986) Abbreviations ME, methionine-enkephalin [ME], methionine-enkephalin concentration ME has been implicated in modulation of a number of physiologic functions particularly nocioception and cardiovascular control (1,2). Recently, its role in respiratory control has been suggested by both direct and indirect studies under basal conditions as well as under conditions of hypoxia and asphyxia (3)(4)(5). Indeed, ME may play a particularly important role in respiratory modulation of the fetus and newborn (6)(7)(8).…”

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confidence: 99%

Age-Dependent Influence of Hypoxia on Methionine-Enkephalin Concentration within Rabbit Brainstem Nuclei

1986

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ABSTRACT. We examined the effect of hypoxia (F102 = 0.10) on methionine-enkephalin concentrations in brainstem nuclei involved in the integration of cardiopulmonary control in 3-and 21-day-old rabbits. Rabbit pups were confined in environmental chambers for 6 h and exposed to one of four conditions. Control, 21% Oz for 6 h; intermittent hypoxia, 12 cycles of 20 min 21% O2 followed by 10 min of 10% 02; acute hypoxia, 4 h of 21% Oz followed by 2 h of 10% 02; recovery, 2 h of 10% Oz followed by 4 h of 21% 02. Methionine-enkephalin was measured by radioimmunoassay in the nucleus tractus solitarius, nucleus ambiguus, nucleus parabrachialismedialis, and nucleus reticulogigantocellularis. In 3-day-old rabbits, exposure to 10% O2 did not affect methionine-enkephalin concentrations in any brainstem nuclei studied. In contrast, 21-dayold pups demonstrated a decrease in methionine-enkephalin concentration in three of the four nuclei studied when exposed to intermittent hypoxia, as well as a n apparent ability to recover from an acute hypoxic exposure (p < 0.05). These data support an age-, nucleus-, and stimulusspecific effect of hypoxia on methionine-enkephalin concentration within specific brainstem nuclei and suggest a possible mechanism for the newborn's increased cardiopulmonary instability under hypoxia. (Pediatr Res 20: [655][656][657]1986) Abbreviations ME, methionine-enkephalin [ME], methionine-enkephalin concentration ME has been implicated in modulation of a number of physiologic functions particularly nocioception and cardiovascular control (1, 2). Recently, its role in respiratory control has been suggested by both direct and indirect studies under basal conditions as well as under conditions of hypoxia and asphyxia (3-5). Indeed, ME may play a particularly important role in respiratory modulation of the fetus and newborn (6-8). This concept is supported by studies showing that naloxone, an opiate antagonist, decreases the duration of primary apnea in neonatal rabbits (9), reverses neonatal depression caused by fetal asphyxia (lo), and reverses the hypoxic respiratory depressant effects in neonatal but not older animals (1 1). ME receptors are found in high concentration within brainstem areas involved in cardiopulmonary control (12, 13), and, more specifically, studies from our laboratory have shown ME levels to be higher in young versus old rabbit brainstem nuclei involved in integration of cardiopulmonary control (14).Hypoxia produces alterations in the concentration of classical neurotransmitters in the brains of adult and neonatal animals (1 5-18). However, little is known about the effects of hypoxia on levels of the neuropeptide ME. To determine whether hypoxia affects brainstem levels of the inhibitory opiate transmitter ME, we measured [ME] within specific brainstem nuclei in 3-and 2 1-day-old animals after exposure to hypoxia. This study was undertaken in an effort to assess the central biochemical events that may influence the newborn's response to hypoxia. Our specific hypotheses were: 1) variou...

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Transient Apnea after an Enkephalin Analogue in the Preterm Rabbit

Cited by 17 publications

References 10 publications

Effects of GABA and Some GABA Analogues on Respiratory Regulation in the Preterm Rabbit

Effects of GABA and Some GABA Analogues on Respiratory Regulation in the Preterm Rabbit

Chronic Maternal Hypoxia

Age-Dependent Influence of Hypoxia on Methionine-Enkephalin Concentration within Rabbit Brainstem Nuclei

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