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Biomedical subjects

J Hedner

Publications and source records attributed to J Hedner.

140 records · Page 8Linked to original sources
PubMed1983

Neuropharmacological aspects of central respiratory regulation. An experimental study in the rat.

Neuropharmacological mechanisms in central regulation of respiration in anesthetized rats were studied in a whole body plethysmographic model. Neurotransmitter agonists and antagonists were administered intracerebroventricularly or locally into the brain and the respiratory pattern was analysed. The four anesthetics: enflurance (E), halothane (H), pentobarbital sodium (P) and urethane (U) were found to have different effects on central respiratory regulation. Respiratory frequency was higher after H and U compared to after E and P. Animals anesthetized with H exhibited a lower inspiratory drive and a slightly depressed sensitivity to CO2. The responses to the neuropeptides substance P and TRH as well as the amino acid neurotransmitter GABA were partly modified after the different forms of anesthesia. Apomorphine (i.c.v) induced a biphasic, haloperidol reversible, respiratory response in H- and U- (but not in E- and P-) anesthetized rats. The initial bradypnoic response might be due to a decreased sensitivity to afferent vagal signals, while the following tachypnoic phase might be elicited by dopaminergic mechanisms at posterior diencephalic and upper midbrain levels (hypoxic, hypercapnic tachypnea). The tachypnoic response was inhibited by a graded exposure to CO2. The effects of different neurotransmitters were further analysed in H-anesthetized animals. GABA and the GABA agonist muscimol exerted a depressant effect on ventilation in contrast to the GABA-like drugs GHBA an baclofen. Exogenous GABA depressed all respiratory parameters studied exept for inspiratory time and was found to affect mainly respiratory timing mechanisms. An increase in endogenous GABA levels induced by the GABA transaminase inhibitor AOAA blunted the respiratory response to CO2 and induced a ventilatory depression similar to that seen after exogenous GABA. A significance correlation between brain stem GABA levels and respiratory duty cycle was found. The tripeptide TRH induced a marked tachypnea due to the extrahypothalamic actions of the peptide. A delay in the response was seen after local injection into the nucleus tractus solitarius and the tachypnea was abolished by CO2 exposure. The ventilatory effects might be elicited by mechanisms similar to those involved in the tachypnoic response to apomorphine. The tachypnea was potentiated by GABA (possibly due to that both agents act on inspiratory off-switch lowering mechanism) and by methylatropine or naloxone (possibly due to secondary pertubation by cholinergic or enkephalinergic mechanisms). A stimulation of ventilation (increase in tidal volume) was seen after substance P (SP) due to an increase in inspiratory drive and o

Anesthetics↗
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

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

Neuronal and extraneuronal uptake of 3H-noradrenaline in rat portal vein in vitro.

Rat portal veins were incubated with 3 different concentrations of 3H-l-noradrenaline (3H-l-NA) and the radioactive material retained in the tissue as well as that present in the postincubation medium was analyzed after a postincubation period in substrate-free medium. Inhibition of the neuronal amine uptake mechanism (by preincubation with LU 3-010) reduced the retention of radioactivity in the tissue more at low than at high substrate concentrations. At increasing substrate concentrations the relative role of the extraneuronal amine uptake was increased. Corticosterone and hydrocortisone reduced extraneuronal accumulation whereas betamethasone and methylprednisolone in the concentrations used were ineffective, indicating that the inhibition of extraneuronal uptake by the corticosteroids is unrelated to their glucocorticoid potency. When the composition of the retained radioactivity was analyzed, NA was found to be the major component of the retained radioactivity after inhibition of extraneuronal uptake, whereas tritiated catabolites were found to be the predominating constituent of the retained radioactivity after neuronal uptake inhibition. The possible role of inactivation of the adrenergic transmitter by the extraneuronal uptake mechanism in different situations is discussed.

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↗
PubMed1980

Respiratory effects of gamma-hydroxybutyric acid in anesthetized rats.

Rats lightly anesthetized with halothane were treated with graded intraperitoneal doses of gamma-hydroxybutyric acid (GHBA), a GABA analogue. The drug induced a dose dependent decrease in minute ventilation, mainly due to reduced respiratory frequency. A reduced pH in arterial blood was recorded. GHBA also blunted or abolished the respiratory response to CO2 exposure in a dose-related way. Picrotoxin (0.25, 0.5 or 1.0 mg/kg intravenously), a presumed GABA antagonist did not significantly change the respiratory pattern when given alone but clearly antagonized the GHBA-induced respiratory depression. It is concluded that GABA-ergic mechanisms are involved in central respiratory control.

Anesthesia, General↗
PubMed1980

Respiratory depression by GABA-ergic drugs in the preterm rabbit.

Respiratory parameters were studied in preterm rabbits (gestational age 29 days) after intraperitoneal administration of the GABA-like drugs gamma-hydroxybutyric acid and muscimol. The animals were anaesthetized with 0.7% halothane in oxygen and studied in a closed body plethysmograph. Both drugs induced a decreased respiratory frequency and minute volume. Tidal volume decreased after muscimol, but not after gamma-hydroxybutyric acid administration. The present results indicate that an increased GABA-ergic activity causes respiratory depression in the preterm neonatal rabbit, presumably by an action on central nervous frequency and tidal volume modulating systems. Central GABA neurons may thus be involved in the pathogenesis of neonatal respiratory depression and irregular breathing.

Animals↗
PubMed1978

Appendico-cutaneous fistula. A case report.

Fistula formation between the appendix and adjacent organs is a rare condition. Cutaneous fistulas occur even more seldom. In this paper a case will be described where a fistula was formed between the appendix and the right buttock.

Aged↗
PubMedDate not supplied

Changes in cerebrospinal fluid homovanillic acid in children with Ondine's curse.

The cerebrospinal fluid (CSF) concentrations of three acid monoamine metabolites, two purines, and a group of amino acids were determined in two children with chronic central alveolar hypoventilation (Ondine's curse). The levels of all assayed neuroactive substances, metabolites, and amino acids, with one exception, were normal compared to an age-matched group of neurologically healthy children. The levels of the dopamine metabolite homovanillic acid in the children with Ondine's curse were approximately 2.4 times higher than expected for age range. The present findings may indicate a link between central nervous system dopamine activity and chronic central alveolar hypoventilation. Among other possible explanations, the changes seen might represent a primary alteration in dopamine activity or may reflect a change in dopamine turnover resulting from the chronic hypoventilation.

Adenosine↗