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Biomedical subjects

T Hedner

Publications and source records attributed to T Hedner.

At least 379 records · Page 21Linked to original sources
PubMed1983

Effects of GABA and some GABA analogues on respiratory regulation in the preterm rabbit.

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 VT/TI and TI/TTOT, respectively. GABA and muscimol reduced both VT/TI and TI/TTOT while GHBA only reduced TI/TTOT. 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.

Animals↗
PubMed1983

Haemodynamic adjustment to weight reduction--separate effects of energy versus salt restriction.

Repeated invasive haemodynamic investigations were performed in two matched groups of patients before and after weight reduction. The patients in Group I had an individually adjusted energy restricted diet and daily dietary sodium supplementation to keep the sodium intake unchanged from baseline. In Group II the patients had the same energy reduced diet but also sodium restriction from 183 +/- 48 to 87 +/- 34 mmol/24 h (P less than 0.001). The energy intake was reduced by about 50% in both groups and the mean reduction in body weight in Group I was 9.2 kg and in Group II 8.8 kg. In Group II the patients had significant reduction of cardiac output, cardiac index, heart rate and blood pressure. No increase in total peripheral resistance was noted. The patients in Group I had a significant reduction of heart rate only. We suggest that the failure of a blood pressure to fall was caused by the relative increase in blood volume observed in patients on a normal sodium intake during weight reduction. The cardiovascular response observed after concomitant sodium and energy restriction is consistent with a reduction of sympathetic nervous system activity and this conclusion is supported by reduced circulating norepinephrine and urinary excretion of norepinephrine.

Adult↗
PubMed1982

Evidence for a dopamine interaction with the central respiratory control system in the rat.

Respiratory activity was studied in adult rats during light halothane anesthesia. Dopamine agonists and antagonists were injected intracerebroventricularly (i.c.v.) or systemically. The respiratory parameters were recorded after exposure to O2 or to CO2 in O2. Apomorphine (i.c.v. 300 microgram) induced a biphasic response with an initial decrease in respiratory frequency (f) followed by pronounced tachypnoea after 5 min. The changes in tidal volume (VT) showed an inverse pattern. When apomorphine was administered into the fourth ventricle, only the later phase of the biphasic response was observed. Haloperidol (2 mg/kg i.p.) antagonized the apomorphine-induced response in contrast to domperidone (2 mg/kg i.v.), a dopamine receptor blocking agent which does not pass the blood brain barrier. Administered i.c.v., haloperidol as well as domperidone induced a decrease in f while VT was increased. The same response was observed after the presynaptic dopamine receptor agonist 3-PPP, 3-(3-hydroxyphenyl)-N-n-propylpiperidine. Hypercapnea was found to decrease the tachypnea in apomorphine-treated animals. Apomorphine also induced a decrease in blood pressure and heart rate, which was not reversed by haloperidol. It is concluded that there is a centrally located, tonically activated dopamine system involved in respiratory regulation. The predominant effect seems to be of a respiratory stimulating nature. The possible role of presynaptic and different postsynaptic dopamine receptor mechanisms is discussed.

Animals↗
PubMed1982

Effect of gammahydroxybutyric acid on catecholamine synthesis and utilization in the developing rat brain.

Gammahydroxybutyric acid (GHBA) was administered subcutaneously, 750 mg/kg, to 1, 4, 14 and 28 days old rats 30 or 90 min before sacrifice. Whole brain and regional brain levels of tyrosine, dopamine (DA) and noradrenaline (NA) were measured. In some experiments the tyrosine hydroxylase activity was studied by measuring the accumulation of dihydroxyphenylalanine (DOPA) after inhibition of aromatic L-aminoacid decarboxylase. GHBA induced an increase in tyrosine and DA levels at the various ages except at 1 day of postnatal age. The effect of GHBA on the accumulation of DOPA after inhibition of aromatic L-aminoacid decarboxylase varied with age. Thus, tyrosine hydroxylase activity seemed to be enhanced in the 4 days old rats after 90 min and after 30 min in the 28 days old rats. Ninety minutes after GHBA administration to the 28 days old animals, DOPA accumulation reached or was slightly below control levels. Brain NA levels were not affected by GHBA administration. Regional analysis of DA and NA after inhibition of tyrosine hydroxylase with alpha-methyltyrosine demonstrated a reduced disappearance of DA after GHBA in the striatum region already from 4 days of postnatal age. GHBA administration did not affect the nerve impulse release of NA in any of the brain regions studied. It may be concluded that GHBA acts inhibitory on brain DA neurons during early postnatal development.

Aging↗
PubMed1982

gamma-Aminobutyric acid concentrations in the cerebrospinal fluid of newborn infants.

gamma-Aminobutyric acid (GABA) concentrations in cerebrospinal fluid (CSF) were measured in 20 neonates with various gestational and postnatal ages. These concentrations varied between 9 and 45 nmol/ml which is approximately 20-100 times the concentrations found in adults. CSF GABA concentrations tended to decrease with advancing gestational age. No apparent alterations were noted with increasing postnatal age (until 6 weeks of age). Asphyxia but not neonatal sepsis was accompanied by an increase in CSF GABA concentrations compared to respective controls.

Asphyxia Neonatorum↗
PubMed1982

Monoamine synthesis and concentration in neonatal rat brain during hypercapnia and recovery.

One-day-old rats were exposed to a gas mixture of 15% CO2-21% O2-64% N2 for a 30-min period. Monoamine synthesis in whole brain was measured during, and at various intervals after, hypercapnia by estimating the accumulation of dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) after inhibition of aromatic L-amino-acid decarboxylase with NSD 1015. Endogenous concentrations of tyrosine, dopamine (DA), noradrenaline (NA), tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were measured at the same intervals. Exposure to CO2 induced an increased synthesis of catecholamines and 5-HT. Further, an increase in DA concentration was seen during hypercapnia, while NA and 5-HT were unchanged. After the CO2 exposure the increased in vivo synthesis rates of catecholamines and 5-HT were rapidly normalized, as was the endogenous DA concentration. A slight increase in 5-HT and 5-HIAA concentrations was seen immediately after CO2 exposure. These results indicate that in neonatal animals, hypercapnia induces changes in central monoamine neurons, primarily an increased synthesis. These alterations may be relevant to some physiological changes seen during CO2 exposure, such as the alteration in central respiratory performance.

5-Hydroxytryptophan↗
PubMed1982

Survival of neonatal rats during hypoxia after monoamine stimulating agents.

Survival of 4 days old rats exposed to 6% O2-94% N2 was studied. Administration of L-DOPA (100 mg/kg) or L-5-HTP (100 mg/kg) reduced survival during hypoxia to about 30% of controls. A further reduction of survival time was noted after combined administration of L-DOPA and L-5-HTP. Administration of increasing doses of L-DOPA or L-5-HTP resulted in a dose-related decrease in neonatal survival time. After inhibition of the peripheral L-aminoacid decarboxylase with MK-486, L-DOPA caused the same reduction of survival time during hypoxia as after L-DOPA alone. Clonidine (2 mg/kg) was found to reduce hypoxic survival time to about 60%, while apomorphine had no effect compared to controls. Clonidine and apomorphine together had the same effect as clonidine alone. It is suggested that central monoamine neurotransmitters are involved in the mechanisms determining survival during neonatal oxygen deprivation.

5-Hydroxytryptophan↗
PubMed1982

Cardiovascular effects in the rat of ketanserin, a novel 5-hydroxytryptamine receptor blocking agent.

Following intravenous administration of ketanserin (0.3-10 mg kg-1) to conscious or anaesthetized normotensive and spontaneously hypertensive rats there were dose-dependent blood pressure reductions but no compensatory tachycardia. Intracerebroventricular administration of ketanserin (25-500 microgram) had inconsistent and largely insignificant cardiovascular effects. In a dose range where it produces hypotension ketanserin antagonized the pressor responses to adrenaline and noradrenaline as well as to 5-hydroxytryptamine in monoamine depleted and spinalized rats. It is suggested that the hypotensive action of ketanserin in the rat does not involve a central mechanism but a peripheral alpha-adrenolytic action is implicated.

Animals↗
PubMed1982

Terbutaline and pulmonary surfactant release in the rabbit fetus.

The influence of terbutaline on content of phospholipids and their fatty acid composition in fetal lung wash and lung homogenates was studied in 28-day-old rabbit fetuses. To obtain both the fatty acid composition and the quantity of lecithin and sphingomyelin gas-liquid chromatography (GLC) was used, which gave a linear relationship when compared to standard solutions of the phospholipids. The amount of lecithin was significantly increased in the lung wash in terbutaline-treated fetuses compared to controls, while the sphingomyelin content was unchanged. In the lung homogenates no quantitative differences were noted between the two groups. The fatty acid composition of lecithin and sphingomyelin did not alter neither in lung wash nor in lung homogenate after terbutaline administration. The present results indicate that beta-mimetics mainly act by favouring the release of preformed surfactant and not by stimulating the synthetic capacity of type II cells in the alveolar lining layer.

Animals↗
PubMed1982

Respiratory effects of TRH in preterm rabbits.

The respiratory activity in newborn preterm (29 days gestation) rabbits was studied after administration of thyrotropic releasing hormone. Intraperitoneal injection induced an increase in respiratory frequency (f) and a decrease in tidal volume (VT) resulting in a slight increase in pulmonary ventilation (VE). These effects were seen in parallel to a decrease in expiratory time (TE) and respiratory time (TTOT). An increase in the TI/TTOT ratio but (unaffected) VT/TI ratio indicates that thyrotropic releasing hormone affects "respiratory timing" mechanisms rather than "inspiratory drive." The changes in respiratory parameters are most probably due to an effect on the central respiratory controlling centers in the brain stem.

Animals↗
PubMed1981

Central respiratory stimulant effect by thyrotropin in releasing hormone in the rat.

Anaesthetized male rats were injected intracerebroventricularly with the tripeptide, thyrotropin releasing hormone (TRH). Respiratory frequency (f), tidal volume (VT) and minute volume (VE) were measured in a closed whole body plethysmograph by a low pressure transducer connected to a Grass polygraph. TRH induced an approximately 50% increase in f, while VT was not altered. VE increased in the same proportion as f. Our results indicate that TRH neurons or TRH-sensitive receptors may be involved in the regulation of central respiratory activity.

Animals↗
PubMed1981

GABA-ergic mechanisms in central respiratory control in the anesthetized rat.

Rats lightly anesthetized with halothane were injected intracerebroventricularly (i.c.v.) with gamma aminobutyric acid (GABA) and the GABA-like drugs muscimol, baclofen, and gamma-hydroxybutyric acid (GHBA). Respiratory frequency (f) was reduced after GABA (1 mg) but increased after baclofen (0.5 microgram), while muscimol (0.5 microgram) or GHBA (1 mg) did no affect f. However, GHBA administered repeatedly caused a dose-dependent increase in f. Tidal volume (VT) decreased in a dose-dependent fashion after i.c.v. administration of all the drugs used. Taken together, these changes in f and VT resulted mainly in a dose dependent decrease in minute volume (VE) after GABA and muscimol while after baclofen and GHBA VE was increased due to the marked stimulation of f after repeated administration. Mean arterial pressure (MAP) decreased after GABA and muscimol while no effect or a slight increase was seen after baclofen and GHBA. Heart rate (HR) was unaltered after muscimol, decreased after gaba but slightly increased after GHBA and baclofen. No alterations were seen in blood gases except after administration of GABA which induced a slight hypoxia, hypercapnia and acidosis. The data indicate that an activation of GABA-ergic mechanisms results in a respiratory depression. Moreover, the effects of GABA and muscimol are probably due to a direct GABA-ergic receptor activation while the effects elicited by baclofen and GHBA are due to other mechanisms than direct GABA receptor activation or indirect effects via other system on respiratory regulating centers.

Animals↗
PubMed1981

Transient apnea after an enkephalin analogue in the preterm rabbit.

FK 33-824, a potent enkephalin analogue was administered systemically, 0.5-5 mg/kg to preterm neonatal rabbits. A marked decrease in respiratory frequency as well as irregular breathing and apneic spells was recorded at 5 mg/kg. Tidal volume was not affected. The enkephalin-induced respiratory depression was restored immediately after naloxone (10 mg/kg). Bases on the results it may be speculated upon whether brain stem enkephalin neurons are involved in the pathogenesis of neonatal transient apnea and irregular breathing.

Animals↗