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

Hedner, Thomas; Hedner, Jan; Bergman, B; Iversen, Knut; Jonason, Jan

doi:10.1159/000241620

Cited by 16 publications

(7 citation statements)

References 23 publications

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“…Our results are in agreement with those of a study on chloride hydrate sedated piglets during the 1st week of postnatal life in which bicuculline had no respiratory effects [14]. However, they are contrary to the GABAevoked decrease in V T in anesthetized preterm rabbits [11] and the bicuculline-evoked increase in phrenic nerve activity in anesthetized kittens 1 day of age [26].…”

Section: Ventilatory Effects Of Aoaasupporting

confidence: 91%

“…Consistent with the presence of tonic GABA A receptor mediated inhibition of inspiratory neurons, bicuculline, a GABA A receptor antagonist, increases inspiratory activity [9] and the rate of breathing [7] in anesthetized adult cats and rabbits. In anesthetized preterm rabbits, newborn kittens and opossums, and in a neonatal rat brainstem-spinal cord preparation in vitro, respiratory effects of GABA and bicuculline resemble those in adult animals [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Increased Brain GABA Concentrations on Breathing in Unanesthetized Newborn Rabbits

Monin

Aranda²,

Bansal³

et al. 1999

Neonatology

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Evidence suggests that γ-aminobutyric acid (GABA) is involved in control of breathing and in the hypoxia-related ventilatory depression in newborns. However, this evidence is obtained mainly from studies on anesthetized animals. Because anesthesia may interfere with the GABA system, the objectives of our study were to examine effects of GABA on ventilation (V_E) and ventilatory response to hypoxia and to reveal effects of repeated hypoxia on GABA concentrations in unanesthetized newborns. The study was performed in rabbits in two age groups: 1–3 days old (group I) and 10–14 days old (group II). To increase brain endogenous GABA concentrations, rabbits were injected with an inhibitor of GABA transaminase, aminooxyacetic acid (AOAA; 20 mg/kg i.p.). To prevent postmortem formation of GABA, at the end of experiments the rabbits received an inhibitor of glutamic acid decarboxylase, IP-3-mercaptopropionic acid (100 mg/kg i.p.). Animals were studied in normoxia alone, or they were exposed for 15 min to 8% O₂ before and 10 and 35 min after saline or AOAA. GABA concentrations were measured in brainstem, cerebrum, and cerebellum by means of a capillary electrophoresis. In group I, AOAA had no respiratory effects. In group II, AOAA decreased V_E, tidal volume, and mean inspiratory flow in normoxia and reversed V_E decline during hypoxia 10 min after the injection, GABA concentrations were not age dependent and the highest in the brainstem. Repeated hypoxia increased the cerebellar GABA concentrations and had no effect in group I. These results imply that in unanesthetized rabbits, GABAergic neurotransmission in the respiratory control network becomes functional by the 2nd week of life, but it does not contribute to the biphasic ventilatory response to moderate hypoxia. In contrast, GABA-evoked block of the cerebellar inhibitory input during hypoxia may be responsible for the reversal of the V_E decline in unanesthetized newborns.

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Section: Ventilatory Effects Of Aoaasupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Effect of Increased Brain GABA Concentrations on Breathing in Unanesthetized Newborn Rabbits

Monin

Aranda²,

Bansal³

et al. 1999

Neonatology

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“…Numerous studies have attempted to elucidate the mechanisms responsible for the ventilatory depression that is seen after a few minutes of hypoxia in the neonate (2)(3)(4)(5)(7)(8)(9)(10)(11)(12)(13)(14). Some investigators have suggested that the ventilatory depression during sustained hypoxia could be due to a relative alkalosis of the brain stem structures produced by a washout of carbon dioxide that result from the increase in brain blood flow that occurs during hypoxia (1 5, 20).…”

Section: Resultsmentioning

confidence: 99%

“…The mechanism responsible for this biphasic response to hypoxia has not been completely elucidated. Various neurotransmitters or modulators released during hypoxia such as endorphins, y-aminobutyric acid, prostaglandins, and adenosine have been suggested as possible mediators of the late decrease in ventilation (2,(7)(8)(9)(10). Other possible explanations have included changes in lung mechanics, a decrease in the metabolic rate, respiratory muscle fatigue, and inhibition of peripheral chemoreceptors (3, 1 1 -14).…”

mentioning

confidence: 99%

Brain Blood Flow and Ventilatory Response to Hypoxia in Sedated Newborn Piglets

1990

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ABSTRACT. To evaluate the relationship between brain blood flow and ventilatory response to hypoxia, seventeen sedated, spontaneously breathing newborn piglets were studied. Minute ventilation (VE) was measured by pneumotachograph, cardiac output by thermodilution and total brain and brain stem blood flows with radiolabeled microspheres. Measurements were performed while the animals were breathing room air and after 10 min of hypoxia induced by breathing 10% Oz. Two patterns of ventilatory response to hypoxia were observed in the study animals. All animals increased VE during the 1st min of hypoxia, but nine (mean 2 SD; age 5 2 1.3 d; wt 1828 2 437 g) sustained increased VE after 10 min of hypoxia (T VE group). The remaining eight animals (age 5 f 1.2 d; wt 1751 k 168 g) had decreased VE at 10 rnin of hypoxia to values less than their room air baseline (J VE group). The decrease in Paoz during hypoxia was similar in both groups, however the Pacoz decreased significantly only in the TVE group. Although cardiac output increased significantly during hypoxia in both groups, the,values during normoxia and hypoxia were lower in the JVE group (p < 0.001). Arterial blood pressure increased significantly during hypoxia only in the TVE group. The increase in total brain and brain stem blood flows with hypoxia was similar in both groups, despite the two different patterns of ventilatory response to hypoxia. These data suggest that in this animal model the distinct patterns of ventilatory response to hypoxia are not related to the changes in total brain or brain stem blood flows that occur during hypoxia. (Pediatr Res 27: 327-331,1990) Abbreviations vE, minute ventilation CO, cardiac output BBF, total brain blood flow BSBF, brain stem blood flow RA, room air ABP, arterial blood pressure V,, tidal volume Cdyn, dynamic lung compliance Rb pulmonary resistanceThe ventilatory response to hypoxia during the first days after birth is characterized in humans and several animal species by a transient initial increase in ventilation (1-2 min), followed by a marked decline in vE to values slightly above or below prehypoxia basal values (1-6). The mechanism responsible for this biphasic response to hypoxia has not been completely elucidated. Various neurotransmitters or modulators released during hypoxia such as endorphins, y-aminobutyric acid, prostaglandins, and adenosine have been suggested as possible mediators of the late decrease in ventilation (2,7-10). Other possible explanations have included changes in lung mechanics, a decrease in the metabolic rate, respiratory muscle fatigue, and inhibition of peripheral chemoreceptors (3, 1 1 -14). The increase in cerebral blood flow that occurs in response to hypoxia can induce a decrease in P C O~ and Hf in the CNS extracellular fluid and this may also account for the decrease in respiratory drive (15). Conversely, the absence of a normal cardiovascular response and the increase in cerebral blood flow that normally occurs during hypoxemia can aggravate CNS hypoxia and lead to CNS de...

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“…which may be a respiratory inhibitor (1 1-16). Branched-chain AA may also compete with glutamate for decarboxylation, resulting in increased glutamate levels and consequently reducing the production of GABA, which is a n important respiratory depressant (17)(18)(19). Because a late ventilatory depression occurs in neonates during hypoxia (20)(21)(22)(23) and because this depression may in part be caused by an increase in inhibitory neurotransmitters, counterbalancing their effect by dietary intervention could reverse the ventilatory depression.…”

Section: Divisiorl O F R'c~ot~atolo~~~ Dcpurtrnolt ~Fmentioning

confidence: 99%

Effect of Amino Acid Infusion on the Ventilatory Response to Hypoxia in Protein-Deprived Neonatal Piglets

et al. 1994

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Divisiorl o f R'c~ot~atolo,~.~~, Dcpurtrnolt ~f Pcdiutrics, Utliver.sitj3 ojl2liut~1i School oj'.\lc~clic.it~c~. ,\liut?~i, FIori(l(1 33101 ABSTRACT. Several amino acids (AA) act a s neurotransmitters and mediate the ventilatory response to carbon dioxide and hypoxia in adult human beings and animals.To evaluate the influence of AA on the neonatal ventilatory response to hypoxia, 29 newborn piglets less than 5 d old were randomly assigned to a control diet or protein-free diet for 7-10 d. Minute ventilation, arterial blood pressure, oxygen consumption, and arterial blood gases were measured in sedated, spontaneous breathing piglets while they breathed room air and at 1, 5 and 10 min of hypoxia p < 0.05). Changes in arterial blood pressure, oxygen consumption, and arterial blood gases during hypoxia were similar before and after AA infusion. The ventilatory response to hypoxia in both protein-free and control diet animals were similar before and after the 10% dextrose infusion. These results stress the importance of nutritional factors in the neonatal control of breathing. (Pediatr Res 35: 316-320, 1994) Abbreviations AA, amino acids D,oW, 10% dextrose ABP, arterial blood pressure BD, base deficit GABA, y-aminobutyric acid VE, minute ventilation Vo2, oxygen consumption VT, tidal volume hypercarbia (1). Furthermore, these respiratory changes were reversed by the administration of enteral or parenteral protein (1-3). In preterm infants, the basal VE and the ventilatory response to hypercarbia were increased after the administration of a standard AA solution (9). The mechanisms that can explain the ventilatory changes during nutritional intervention are not fully defined. Some of these changes may be mediated by the increase and/or decrease in inhibitory or excitatory neurotransmitters in the CNS (4, 10). One of the latter is glutamate, a central excitatory neurotransmitter that participates in the ventilatory response to hypoxia (5). Other AA that are not neurotransmitters may also influence the central respiratory output. For example, the administration of branched-chain AA to adult human beings resulted in an increase in basal ventilation and the ventilatory response to hypercarbia (6, 7). Branched-chain AA may compete with tryptophan at the blood brain bamer, limiting the entry of tryptophan to the CNS and thereby decreasing the production of serotonin. which may be a respiratory inhibitor (1 1-16). Branched-chain AA may also compete with glutamate for decarboxylation, resulting in increased glutamate levels and consequently reducing the production of GABA, which is a n important respiratory depressant (17)(18)(19). Because a late ventilatory depression occurs in neonates during hypoxia (20)(21)(22)(23) and because this depression may in part be caused by an increase in inhibitory neurotransmitters, counterbalancing their effect by dietary intervention could reverse the ventilatory depression. T o our knowledge, no studies have been conducted to evaluate the influence of AA infusion on the ventilatory re...

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

Cited by 16 publications

References 23 publications

Effect of Increased Brain GABA Concentrations on Breathing in Unanesthetized Newborn Rabbits

Effect of Increased Brain GABA Concentrations on Breathing in Unanesthetized Newborn Rabbits

Brain Blood Flow and Ventilatory Response to Hypoxia in Sedated Newborn Piglets

Effect of Amino Acid Infusion on the Ventilatory Response to Hypoxia in Protein-Deprived Neonatal Piglets

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