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Biomedical subjects

C Roman

Publications and source records attributed to C Roman.

At least 91 records · Page 5Linked to original sources

Effects of antenatal glucocorticoid administration on ductus arteriosus of preterm lambs.

We have previously shown that the incidence of patent ductus arteriosus (PDA) in premature infants whose mothers received prenatal glucocorticoid therapy was significantly lower than that of an untreated group. In addition, the incidence of respiratory distress syndrome was lower in the treated than in the untreated group. To determine whether glucocorticoids affect the ductus arteriosus itself, we studied the effects of a 48-h intravenous infusion of 1 mg/h hydrocortisone in prematurely born lambs (120-129 days, 0.84 gestation). Estimations of ductus patency were made on 1-h-old lambs by radioactive microsphere injections. We found that hydrocortisone infusions facilitate the closure of the ductus without altering the severity of respiratory distress in premature lambs. In the lamb, prostaglandin E2 (PGE2) inhibits the ability of the ductus to contract in response to O2. Because production of PGE2 has been shown to be inhibited by hydrocortisone in several isolated organ systems, we measured PGE2 plasma concentrations in treated and untreated animals. We found circulating PGE2 concentrations to be similar in the two groups; furthermore, release of PGE2 by isolated ductal rings in vitro was similar in treated and untreated animals. This contradicts the hypothesis that diminished PGE2 concentrations, either circulating or in the tissue, are the cause for ductus arteriosus closure in hydrocortisone-treated animals. However, hydrocortisone treatment decreases the sensitivity of the ductus arteriosus in vitro to the relaxing action of PGE2. These findings suggest that glucocorticoid treatment decreases the incidence of PDA in premature infants by affecting the interaction of PGE2 with ductal tissue.

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Circulating prostaglandin E2 concentrations and patent ductus arteriosus in fetal and neonatal lambs.

We used pregnant sheep and their fetuses as well as newborn lambs (with and without severe respiratory distress due to prematurity) to study the differences in plasma clearance rate, production rate, and circulating concentrations of immunoreactive PGE2. Fetal PGE2 concentrations were significantly higher than simultaneous maternal concentrations. After delivery by cesarean section, all newborn animals were paralyzed and mechanically ventilated. The PGE2 concentrations fell in those lambs that required only minimal ventilatory support (FIO2 < 0.25) and were similar to maternal concentrations by two to three hours. Newborn lambs that developed severe respiratory distress (FIO2 < 0.55) continued to have concentrations that were even greater than fetal concentrations. The elevated PGE2 concentrations in severely distressed lambs were due not only to a decreased plasma clearance rate but also to an increased production rate of PGE2. Since PGE2 appears to maintain the patency of the ductus arteriosus in the fetus and preterm neonate, we examined the patency of the ductus arteriosus in 3-hour-old newborn lambs by radioactive microsphere injections. The ductus was more widely patent in lambs with higher concentrations of PGE2. The increased circulating concentrations of PGE2 in newborn lambs with severe respiratory distress may contribute to the pathogenesis of patent ductus arteriosus by exerting an additional vasodilatory effect on the vessel.

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Mechanism of the noradrenergic motor control on the lower oesophageal sphincter in the cat.

1. The release of labelled acetylcholine has been measured on lower oesophageal sphincter (l.o.s.) muscular strips previously loaded with tritiated choline. 2. This release was greatly increased by noradrenaline 10(-5) g/ml. and unaffected by atropine 10(-6) g/ml., but it was practically abolished if hemicholinium 5.2 X 10(-4) M was added to the incubating bath containing the tritiated choline. 3. A radioautographic study of sections of l.o.s. strips loaded with tritiated choline showed that the radioactivity was mainly located in the nervous cells of the enteric plexuses and that the muscular cells were very poorly labelled. 4. The increased release of acetylcholine induced by noradrenaline did not occur in a Ca2+-free or in a hypermagnesic Tyrode (12 mM). 5. Tetrodotoxin 10(-6) G/ml. had no effect on the increased release of acetylcholine induced by noradrenaline. In addition, sucrose gap recordings showed that the depolarizing effect of noradrenaline on l.o.s. muscular strips was unaffected by tetrodotoxin 10(-6) g/ml. 6. It is concluded that acetylcholine released in the l.o.s. under the action of noradrenaline originated from the synaptic endings of the cholinergic intramural neurones.

Acetylcholine↗

[Horseradish peroxidase localization of the cell bodies of the sympathetic and parasympathetic neurones controlling the lower oesophageal sphincter in the cat (author's transl)].

The localization of the parasympathetic preganglionic and sympathetic postganglionic neuronal cell bodies innervating the lower oesophageal sphincter (l.o.s.) has been investigated in cats, using the technique of horseradish peroxidase (HRP) retrograde axonal transport. HRP was injected into the sphincteric muscle layers (under aseptic conditions). The animals were sacrificed 72 hours later and fixed by perfusion via the aorta. The medulla oblongata and the sympathetic chains from the stellate to T12 ganglia were removed and processed for HRP identification. 1. Labelled cell bodies were identified in the medulla, the stellate and other thoracic ganglia and in the caeliac ganglia. 2. In the medulla, the labelled neurones were located mainly in the vagal dorsal motor nucleus and, to a lesser extent, in the nucleus ambiguus. A few cell bodies were observed between both nuclei. The medullary labelled cell bodies are presumably those of the preganglionic vagal neurones innervating the l.o.s. 3. In the stellate ganglia, the labelled neurones were exclusively located in the ventromedial area. It is likely that they correspond to the postganglionic adrenergic neurones of the sympathetic pathway controlling the lower oesophageal sphincter, the axons of which leave the ganglia through cardiac branches and pass in the thoracic vagus nerve to reach the sphincter (see GONELLA et al., 1979). 4. Labelled neurones were no longer observed in the medulla and in the stellate ganglia when HRP was injected in the l.o.s. after a thoracic bilateral vagotomy. 5. Labelled neurones were also observed in other thoracic ganglia from T3 to T11, most of them lying in T9 and T10. They are probably the postganglionic neurones of a second sympathetic pathway controlling the lower oesophageal sphincter, via the splanchnic nerve (see GONELLA et al., 1979). 6. A homogenous distribution of labelled neurones has been observed in the caeliac ganglia. Its functional significance is discussed.

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Developmental response to indomethacin: a comparison of isometric tension with PGE2 formation in the lamb ductus arteriosus.

We studied the effects of oxygen and indomethacin on the isometric contractile response and the production of PGE2 in isolated rings of lamb ductus arteriosus from animals of different gestational ages (100 to 144 days; term is 150 days). Rings of ductus arteriosus from animals less than 110 days released significantly less PGE2 than did rings from animals greater than 120 days. The indomethacin-induced increase in muscle tension in relation to the decrease in endogenous PGE2 production in preparations from animals less than 110 days gestation was greater than in animals older than 120 days. These findings do not support the hypothesis that immature animals have a larger indomethacin-induced contraction due to an increased production of PGE2 earlier in gestation. They are, however, consistent with a decreased sensitivity to PGE2 in the more mature animals; they also support the hypothesis that the decreased effectiveness of indomethacin on the ductus arteriosus from later gestation animals reflects primarily a decrease in the sensitivity of the vessel to PGE2 during development.

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Sympathetic control of lower oesophageal sphincter motility in the cat.

1. The action of adrenaline, noradrenaline and efferent sympathetic fibres on the smooth muscle of the lower oesophageal sphincter (l.o.s.) was studied in vivo on the anaesthetized cat and in vitro with the sucrose gap method. 2. Adrenaline and noradrenaline produce a marked depolarization of the circular muscle of the l.o.s. This effect is suppressed by dihydroergotamine or phentolamine, and greatly reduced by atropine; it remains unaltered by hexamethonium. 3. Sympathetic fibres are excitatory for the l.o.s. They come from the stellate ganglion or run along the splanchnic nerve: the fibres arising from the stellate ganglion (mainly by the cardiac branch of the ganglion) join the vagus nerve at the thoracic level; the fibres running along the splanchnic nerve pass through the coeliac ganglion without synapsing; their cellular bodies lie probably in the ganglia of the sympathetic chain. 4. Repetitive stimulation (20--40 Hz) of these fibres induce, with a latency of 5--8 sec, a sustained or rhythmic contraction of the l.o.s. This response is suppressed by dihydroergotamine, and greatly reduced by atropine, while hexamethonium has no effect. 5. Stimulation of sympathetic fibres induces a facilitation of the vagal excitatory responses and an inhibition of the vagal inhibitory responses of the l.o.s. 6. Our data show that the sympathetic response of the l.o.s. results from the stimulation of adrenergic receptors which are located not only on muscular fibres but also, and chiefly, on intrinsic neurones. Thus, the sympathetic control of the l.o.s. is mainly exerted through cholinergic myenteric neurones which could be excited either directly or indirectly by inhibition of inhibitory intrinsic neurones.

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PGE2 is a more potent vasodilator of the lamb ductus arteriosus than is either PGI2 or 6 keto PGF1alpha.

It has been shown in vitro that the lamb ductus arteriosus forms prostaglandins PGE2, PGF2alpha, 6 keto PGF1alpha (and its unstable precursor PGI2). In this study the relative potencies of these endogenous prostaglandins were investigated on isolated lamb ductus arteriosus preparations contracted by exposure to elevated PO2 and indomethacin. All the prostaglandins (except PGF2alpha) relaxed the vessel. This is consistent with the hypothesis that endogenous prostaglandins inhibit the tendency of the vessel to contract in response to oxygen. Only PGE2, however, relaxed the vessel at concentrations below 10(-8)M. PGI2 and 6 keto PGF1alpha had approximately 0.001 and 0.0001 times the activity of PGE2. Although PGE2 has been observed to be a minor product of prostaglandin production in the lamb ductus arteriosus, the tissue's marked sensitivity to PGE2 might make it the most significant prostaglandin in regulating the patency of the vessel.

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[Activity of vagal efferent fibres innervating the smooth muscle of the dog's cardia].

Our experiments were performed on dogs in which the central end of the left thoracic vagus had been sutured to the peripheral end of the left phrenic nerve. In such preparations, the activity of motor units of the re-innervated left hemidiaphragm indicated the activity of the vagal efferent fibres. After the left hemidiaphragm had been transformed into subcutaneous muscle, we studied, (using electromyography in the unanesthetized dog), the discharge of vagal fibres which originally supplied the lower oesophageal sphincter (cardia). The present paper only deals with fibres showing low frequency tonic discharge. 1. For some fibres (VIC type ; N = 42), the spontaneous firing rate (1.5 less than f less than 4.5 spikes/s) is suddenly enhanced just after the buccopharyngeal stage of swallowing (12 less than f less than 16 spikes/s). The this discharge stops abruptly just before the end of oesophageal peristalsis and starts again 2 to 3 seconds later at a low frequency (15 less than f less than 4.5 spikes/s). 2. Other fibres (VEC ; N = 18), which also have a slow discharge frequency (1 less than f less than 3 spikes/s) stop firing soon after the onset of swallowing and remain silent until the end of oesophageal peristalsis. At this time, i.e. when the bolus enters the stomach, the discharge starts again with an increased frequency (5 less than mean frequency less than 9 spikes/s). 3. The behaviour of the tonic vagal fibres during swallowing, as well as their low discharge frequency, strongly suggest that these fibres originally controlled the smooth muscle of the lower oesophageal sphincter and excited either an inhibitory (VIC = vagal inhibitory fibres of cardia) or an excitatory control (VEC = vagal excitatory fibres of cardia) upon this area.

Action Potentials↗

Vagal control of lower oesophageal sphincter motility in the cat.

1. The effects of vagal efferent fibre stimulation on the smooth muscle of the lower oesophageal sphincter have been studied on the anaesthetized animal and on the isolated and perfused organ.2. In both muscle layers (longitudinal and circular) vagal stimulation elicits two types of electromyographic (e.m.g.) potentials: (a) excitatory junction potentials (e.j.p.s) where there is a depolarization of the smooth muscle fibres. E.j.p.s can give rise to spike potentials inducing a contraction of the sphincter; (b) inhibitory junction potentials (i.j.p.s) where there is hyperpolarization of the smooth muscle fibres, often followed by a transient depolarization which may initiate spikes (post-inhibitory rebound).3. Pure i.j.p.s are observed after atropine treatment which suppresses e.j.p.s. Under these conditions, a long lasting vagal stimulation induces a long duration hyperpolarization concomitant with an opening of the lower oesophageal sphincter followed after the cessation of stimulation by a powerful rebound leading to a strong contraction which closes the sphincter.4. Several arguments, pharmacological (action of acetylcholine (ACh), atropine and hexamethonium) and physiological (threshold and latency of responses) lead to the following conclusions. Preganglionic vagal fibres are cholinergic and they activate (a) intramural excitatory cholinergic neurones; (b) intramural non-adrenergic inhibitory neurones (purinergic neurones). Preganglionic fibres leading to inhibition have a higher threshold than those leading to excitation. Both excitatory and inhibitory pathways are interconnected inside the intramural network. In particular, activation of intramural inhibitory neurones, by relaxing the oesophagus orally to the lower oesophageal sphincter, inhibits intramural excitatory neurones and subsequently blocks vagal excitatory responses.5. Two functions may be attributed to the vagal extrinsic innervation: (a) closure of the lower oesophageal sphincter by maintaining the basal tone of the sphincter; this would imply that at rest the inhibitory control is supplanted by the excitatory one; (b) sphincter opening during swallowing by suppressing the excitatory stimulus and reinforcing the inhibitory one (it may be recalled that after bilateral vagotomy, swallowing is no longer followed by a relaxation of the sphincter).

Acetylcholine↗

A pontine primary relay for ascending projections of the superior laryngeal nerve,.

1. In sheep anaesthetized with fluothane, electrical stimulation of the superior laryngeal nerve (SLN), which contains most of the afferent fibres for swallowing, evokes potentials in the medial part of the ipsilateral thalamic VPM (nucleus ventro-postero-medialis) within about 5 msec. This region constitutes the secondary synaptic relay for the laryngeal impulses projecting to the frontal cortex concerned with swallowing. 2. SLN fibres are synaptically connected with cells of the NTS (nucleus of the tractus solitarius), 2-4 mm rostral to the obex (see Car and Jean, 1971). Coagulation of this region abolishes reflexly and cortically induced swallowing, but does not influence the thalamic or cortical responses induced by SLN stimulation. 3. SLN stimulation evokes potentials with a short latency (2 msec) in a restricted pontine area localized 5 mm from the midline and above the trigeminal motor nucleus, just in front of the central emergence of the facial nerve (i.e; about 12 mm rostral to obex). Restricted coagulation of this pontine region eliminates both the thalamic and the cortical projection of SLN. 4. Repetitive stimulation (2 V; 0.2 msec; 20-30 Hz) of this same pontine region produces rhythmic swallowing with characteristics quite similar to those of swallowing induced by SLN or bulbar stimulation. 5. Other data show that SLN fibres, or at least part of them, bifurcate after entering the brain stem (about 6 mm in front of the obex), and give a caudal branch, which reaches the bulbar swallowing centre (3 mm rostral to the obex) by running through the tractus solitarius; and a rostral branch terminating in the pons where the primary synaptic relay for the ascending laryngeal pathway is localized.

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Comparison of activity in pontine versus medullary neurones during swallowing.

1. On decerebellectomized sheep lightly anaesthetized with fluothane, the activity of 49 neurones in the pontine relay (see Car et al., 1975) was recorded with microelectrodes following stimulation of afferents in the superior laryngeal nerve (SLN), 2. These pontine neurones (PN) exhibited an "initial activity" (one or a few spikes) for stimulation either of the homolateral SLN (35 PN) or glossopharyngeal nerve (14 PN). This initial activity had a latency between 1.5 and 4 msec. When swallowing was induced by SLN stimulation, a later discharge appeared. This "swallowing activity" consisted of a variable burst of spikes. 3. The effect of curarization was tested for 13 PN. It always eliminated the "swallowing activity". 4. A clear antidromic response of 16 PN (26 tested PN) was induced by stimulating the thalamic VPM nucleus. This stimulation failed to elicit an antidromic response in medullary neurones (14 tested) located in the nucleus of the tractus solitarius. 5. It is concluded that PN are probably sensory relay neurones which inform higher nervous centres of the state of oropharyngeal receptors; whereas medullary swallowing neurones are really interneurones involved in the programming of the wallowing motor sequence.

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