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Biomedical subjects

S Delpierre

Publications and source records attributed to S Delpierre.

At least 37 records · Page 2Linked to original sources

[Experimental study of the pleural effects of the pulverization, under thoracoscopic control, of a fibrin glue (Tissucol)].

The instillation of a fibrin sealant (Tissucol) has been proposed in the treatment of recurrent spontaneous pneumothorax. The present work is devoted to an experimental study in the dog of the effects of this substance on the pleural cavity one and two weeks after instillation under thoracoscopic control. Its action is compared to that of placebo (methylene blue). The instillation of a placebo (n = 5) did not alter the ventilatory mechanics or the structure of the pleura. On the other hand Tissucol (n = 6) led to a fall in the thoraco-pulmonary compliance (-14%), corresponding to that of the vital capacity (-10%). In these animals, no pleural symphysis was noted, but the histological analysis gave evidence of changes in the layers of the parietal and visceral pleura: an inflammatory mononuclear reaction (71% of cases) and/or polymorphonuclear (54%), recent fibrosis (67%) and more rarely a mesothelial hyperplasia (21%). The maintenance of the integrity of the mesothelial cellular layer would explain the absence of pleural symphysis after instillation of Tissucol. These results as well as those recently obtained in the human situation prompt us to advise other methods of pleural symphysis which have been tried and tested, such as talcage or surgery.

Animals↗

The effects of electrical stimulation of myelinated and non-myelinated vagal motor fibres on airway tone in the rabbit and the cat.

The bronchomotor effects of repetitive electrical stimulation of the peripheral end of the cervical vagus nerves were studied in anaesthetized and paralysed rabbits and cats. Stimulation of either myelinated or of all motor vagal fibres was obtained by varying the duration of electrical square pulses. In rabbits, selective stimulation of myelinated vagal fibres induced a bronchoconstriction, strongly potentiated by the recruitment of non-myelinated fibres. This potentiation was absent in cats. After ganglionic blockade with hexamethonium, the vagally mediated bronchoconstriction was abolished in rabbits, while a slight and transient effect persisted in cats. Propranolol did not modify the bronchoconstrictor response to vagal stimulation, which was abolished after further injection of atropine in both species. When propranolol plus atropine was administered and airway tone was increased by continuous i.v. injection of bronchoconstrictor agonists, the stimulation of vagal motor fibres was devoid of any bronchomotor effect in rabbits. However, in cats this resulted in a strong bronchodilation, which was doubled after recruitment of non-myelinated fibres. Thus, in the latter species preganglionic vagal motor fibres participate in the non-adrenergic-non-cholinergic vagal system. Amongst them, non-myelinated fibres play an important role.

Airway Resistance↗

Cholinergic responsiveness of respiratory and vascular tissues in two different rat strains.

The airway and systemic arterial smooth muscle responsiveness to cholinergic agents of two strains of rats, Rat Albino (RA) and Brown Norway (BN), was compared in vivo and in vitro. In vivo, we measured the doses of carbachol that induced a 100% increase in lung resistance (PD100 RL), a 50% decrease in dynamic lung compliance (PD50 Cdyn), and the value of systolic blood pressure at the carbachol dose of 10 micrograms (Pa 10 micrograms). In vitro airway smooth muscle and systemic arterial smooth muscle responsiveness was assessed by measuring the maximal response to acetylcholine, the slope of the linear portion of the dose-response curve, and the negative logarithm of the molar concentration of acetylcholine producing 50% of the maximal response (pD2). PD100 and PD50 were about four times greater in BN rats than in RA rats. In contrast, Pa 10 micrograms was 1.5 lower in the BN rats. These differences persisted after bivagotomy. Tracheal pD2 was 25% greater in the RA than in the BN strain. The mean dose-response curve of parenchymal strips of RA rats was situated upward and to the left of the BN curve, but the reverse was observed for aortic smooth muscle dose-response curves. Thus 1) airway smooth muscle responsiveness to cholinergic agents is greater in RA strain than in BN, but the reverse is true for systemic arterial smooth muscle responsiveness; and 2) these differences are not due to factors extrinsic to the smooth muscle, since they occurred in vitro and may depend on different densities of muscarinic receptors.

Acetylcholine↗

The effects of ischemia, lactic acid and hypertonic sodium chloride on phrenic afferent discharge during spontaneous diaphragmatic contraction.

In 9 sodium pentobarbital anaesthetized cats, 50 single-unit phrenic afferent recordings were determined during spontaneous ventilation, retrograde carotid arterial injection of lactic acid (LA, 0.1 N) and NaCl (5%), and a 2-min occlusion of the superior thoracic aorta. Fifty percent of the units had tonic low-frequency spontaneous discharge; 50% had phasic high-frequency discharge. Tonic fiber activity increased significantly with LA, NaCl and occlusion, while phasic fiber activity decreased in all 3 conditions. These results suggest that the diaphragm contains sensory endings sensitive to ischemia and extracellular metabolic changes.

Animals↗

Role of vagal and spinal sensory pathways on eupneic diaphragmatic activity.

The interactions between vagal and spinal afferents in the control of eupneic diaphragmatic activity were studied in two groups of cats anesthetized either with pentobarbital sodium (SPB) or with ethyl carbamate-alpha-chloralose (ECC), which enhanced spinal reflexes. Under both conditions of anesthesia two experimental protocols were performed: 1) bilateral cervical vagotomy followed by spinal section at C8 level or 2) spinal section followed by vagotomy. Changes in integrated diaphragmatic activity (Edi) were studied during eupneic ventilation and tracheal occlusion at end expiration. Vagotomy always significantly increased the amplitude of Edi during eupnea (SPB + 30%; ECC + 15%) and prolonged its duration (Tdi) (SPB + 110%; ECC + 75%) but did not modify the overall shape of the Edi vs. time relationship. Spinal section induced reverse changes in the amplitude of Edi, whether vagal afferents were present or suppressed and modified the shape of the Edi wave, but did not significantly modify Tdi. These results indicate that both vagal and spinal afferents may participate in the control of eupneic inspiration but exert different and interdependent influences on the recruitment and firing time of phrenic motoneurons. In addition, Tdi measured during tracheal occlusion (Todi) was markedly prolonged under ECC anesthesia. In this situation spinal section reduced Todi, which became close to the values obtained in intact or spinal cats under SPB anesthesia. Thus the response to tracheal occlusion at end expiration cannot be interpreted as resulting from the sole suppression of volume related vagal information.

Afferent Pathways↗

Phrenic afferents and their role in inspiratory control.

In anesthetized cats, with vagi cut and the spinal cord severed at the C8 level, phrenic motor and/or sensory discharge was recorded. Small afferent phrenic fibers were identified through their activation by lactic acid, hyperosmotic NaCl solution, or phenyl diguanide. They exhibited a spontaneous but irregular low-frequency discharge. Block of their conduction by procaine had no effect on eupneic motor phrenic activity. Large afferent phrenic fibers showed a spontaneous rhythmic discharge, and cold block (6 degrees C) of these fibers significantly prolonged the phrenic discharge time (Tphr) and total breath duration (TT) during eupnea. The stimulation of all afferent phrenic fibers lowered the impulse frequency of phrenic motoneurons (f impulses) and shortened both Tphr and TT. When the stimulation was performed during cold block all of the effects on phrenic output persisted, but changes in timing were less pronounced. Under procaine block, only the effects of phrenic nerve stimulation on Tphr persisted. These results suggest that both large and small afferent phrenic fibers control the inspiratory activity with a prominent role of small fibers on phrenic motoneuron impulse frequency.

Afferent Pathways↗

Ventilatory effects of domperidone, a new dopamine antagonist, in anaesthetized rabbits.

The ventilatory effects of domperidone (DP), a dopamine antagonist that does not cross the blood-brain barrier, were studied on rabbits anaesthetized with pentobarbitone. DP induced hyperventilation (+20%), which was not dose-dependent, without any marked change in arterial blood gases. This effect was abolished by previous transection of both carotid sinus nerves. On an average, steady state hypoxia (PaO2 approximately 45 mmHg for 5 min) doubled ventilation before, and increased itself threefold after DP (0.10 mg kg-1 i.v.). Prazosin (PZ, 0.1 mg kg-1 i.v.), an alpha 1-adrenoceptor antagonist, induced hyperventilation (+16%) but decreased systemic arterial blood pressure. PZ did not modify the ventilatory response to steady state hypoxia. In short, DP has a slight stimulating effect on resting ventilation and potentiates the ventilatory response to steady state hypoxia. This last effect would not depend on additional alpha 1-adrenoceptor antagonism of DP, as PZ does not change the ventilatory response to hypoxia.

Anesthesia↗

Respiratory effects of cold air breathing in anesthetized cats.

Respiratory effects of cold air breathing were studied in anesthetized cats. Two different protocols were used: the air temperature was either lowered in an isolated segment, constituted by the larynx and oropharynx or in lower airways, so that the cats inspired the cold air directly. Temperatures ranged between 37 and 8 degrees C (first protocol) or between 37 and 15 degrees C (second protocol). When the temperature fell below 15 degrees C in the upper segment, marked increase in lung resistance occurred, without any significant changes in ventilatory variables nor in diaphragmatic electrical activity. The section of superior laryngeal nerves abolished this bronchomotor effect. In present experimental circumstances, thermal changes measured in lower airways when cats breathed cold air were mainly located in the cervical trachea. An increase in lung resistance and weak but significant changes in the diaphragmatic electromyogram began when the inspired air temperature fell below 25 degrees C. A selective local block of conduction in small vagal fibres by procaine or section of vagus nerves suppressed all these effects. In all cases the cold-induced changes in lung mechanics began very early (less than 10 sec) but continued for few minutes after the physiological temperature range had been restored in airways. The present data strongly suggest that the bronchomotor response to cold air breathing is a reflex, mediated by afferent fibres in the superior laryngeal nerves and in the vagus nerves.

Anesthesia, General↗

Airway response of asthmatics to carbachol and to deep inspiration.

Dose-response curves were established in asthmatics by using graded doses of aerosolized carbachol and specific airway conductance (SGaw) measurements. After carbachol inhalation, we evaluated the influence on SGaw of a deep inspiration to total lung capacity followed by a passive expiration to functional residual capacity. When SGaw had returned to its pre-deep-inspiration value, forced expiratory volume in one second (FEV1) was obtained. Two groups of patients were selected according to the effect of deep inspiration on SGaw: group A (22 patients) with a less than 25% SGaw increase after deep inspiration, and group B (21 patients) with a more than 75% SGaw increase. Both groups were comparable in age and initial SGaw and FEV1 values. Carbachol inhalation induced a similar SGaw decrease in both groups, whereas FEV1 decreased more (p less than 0.05) in group A than in group B. The two groups did not differ significantly regarding the dose of carbachol causing a 25% SGaw decrease and in the slope of the dose-response curve. We conclude that, in asthmatic patients, airway response to an inhaled broncho-constrictor agent is not related to the airway response to deep inspiration. This suggests that previous studies of airway response to bronchoconstrictor agents which have been performed by using only FEV1 measurements, may need to be reassessed.

Adult↗

Changes in activity of vagal bronchopulmonary C fibres by chemical and physical stimuli in the cat.

1. In eighteen anaesthetized cats, action potentials in non-myelinated vagal afferent neurones were recorded in the nodose ganglion by means of extracellular micro-electrodes. 2. The pulmonary or bronchial origin of these C fibres was assessed in closed chest preparations by injecting phenyl diguanide into either the right atrium or the ascending aorta (bronchial circulation). This was confirmed in two animals by local mechanical stimulation. 3. Eighty per cent of bronchopulmonary C fibres increased their discharge frequency when the end-tidal CO2 concentration (FA,CO2) increased from 0.02 to 0.10. Most of these C endings showed a maximal response when FA,CO2 reached 0.04. For the others a further increase in discharge occurred when CO2 concentration reached 0.08-0.10. Continuous measurement of C fibre discharge frequency indicated that they detected preferentially changes in the inspired CO2 content, but adapted when a high CO2 level was maintained. Their activation by hypercapnia was followed by an increase in lung resistance. 4. Lowering the O2 content of the inspired gas had no effect on the spontaneous activity of bronchopulmonary C endings. 5. When the stroke volume of the pump was doubled, the spontaneous activity of bronchopulmonary C fibres decreased in intact chest preparations. Inflation of the lungs had the opposite effect after the chest was opened. In both cases hyperdeflation was a potent stimulus to these receptors. 6. In tracheotomized cats, the tracheal temperature was 28-29 degrees C. When normal thermal conditions were restored in the tracheal lumen (33-34 degrees C) the spontaneous discharge frequency of some bronchial C fibres was greatly increased. 7. It is concluded that the spontaneous activity of most of the bronchial or pulmonary C fibres was maximal when chemical and physical physiological conditions were restored in the lungs. It appears that changes in alveolar CO2 concentration constitute the usual stimulus for these fibres.

Action Potentials↗

Influence of anxiolytic drugs (Prazepam and Diazepam) on respiratory center output and CO2 chemosensitivity in patients with lung diseases.

Occlusion pressure at 0.1 s (P0.1) and its evolution during progressive hyperoxic hypercapnia (CO2 chemosensitivity) were measured in 40 patients. Most of them (26) were affected by asthma and /or chronic bronchitis and had mild obstruction and hypoxemia. Measurements were made after 2 days of oral prazepam, diazepam or a placebo (single-blind study). Diazepam induced a significant decrease in P0.1 without affecting CO2 chemosensitivity. In contrast, prazepam did not significantly modify P0.1 or CO2 chemosensitivity. However, P0.1 decreased in 5/18 individual cases. 1 week of treatment by prazepam has advantages over diazepam by not depressing respiratory center output.

Asthma↗

Influence of the previous deep inspiration on the spirometric measurement of provoked bronchoconstriction in asthma.

The measurement of the forced expiratory volume in one second (FEV1) after a maximal inspiration is often used to assess the effect of inhaled bronchoconstrictor agents. In persons with asthma, a deep inspiration transiently alters the bronchial tone in a variable way. This may result in a variable decrease of FEV1 despite a similar degree of pharmacologically induced bronchospasm. In 71 patients with asthma we induced a comparable increase (approximating 200%) in airway resistance (Raw) with aerosolized carbachol. We then measured the change in Raw induced by one deep inspiration; when Raw had returned to the value observed before deep inspiration, the FEV1 was measured. A significant correlation (r = 0.74; p less than 0.001) was found between the transient changes in Raw induced by a deep inspiration (ranging individually from a 33% increase to a 70% decrease) and the decrease in FEV1 (from 0 to 70%). The decrease in FEV1 was greatest in patients in whom a deep inspiration increased Raw and least in those in whom Raw decreased. The initial and post-carbachol Raw values of the 17 patients exhibiting a less than 20% decrease in FEV1 were similar to those of the 54 patients with a decrease in FEV1 of more than 20%. Because a prior deep inspiration prevents changes in FEV1 in some patients with asthma, the use of the FEV1 for bronchial provocation tests can be misleading.

Asthma↗

Pulmonary mechanics during hypoxia in spontaneously breathing anesthetized rabbits.

Changes in lung mechanics were measured during hypoxia (FIO2 = 0.10 during 5 min) in spontaneously breathing anesthetized rabbits. In intact animals, hypoxia induced scattered variations in total lung resistance (RL) (decrease, increase or no alteration) and dynamic lung compliance (CL), whereas in carotid body denervated animals it was accompanied by an almost constant decrease in RL (-12%); but if a subsequent vagotomy was performed, there was no significant variation in RL. In animals which had been only vagotomized, CL decreased significantly during hypoxia (-23%) without any associated change in RL. So, the arterial chemoreceptor mediated bronchoconstrictor effects due to hypoxia could be normally masked by the dilator effects (metabolic and/or sympathetic) on the airways.

Airway Resistance↗

Functional evaluation of the transplanted lung after long-term preservation.

In dogs the immediate value of transplanted lungs was tested after preservation in Collins 3 solution and administration of aprotinin. 15 animals received a left or right homograft, which had been preserved for 24 h. In 3 cases preservation time was prolonged to 48 h, and in another 2 dogs both of the lungs were replaced by 24-hour preserved organs in a one-stage operation. The value of the transplants was tested by several physiological, morphological and clinical phenomena. (1) A positive O2 uptake of the transplant after a temporary occlusion of the opposite pulmonary artery documented its capacity for gaseous exchange. (2) Scintigraphic visualization of perfusion and ventilation in 3 dogs demonstrated satisfactory results. (3) A positive response to acetylcholine of the bronchial muscular system was observed in all transplants. (4) Normal light microscopy showed a lack of obvious morphological change. (5) Only slight alterations in electron microscopy were found when compared to those found before preservation. (6) The absence of acute bronchial edema excludes the possibility of irreversible altertions of the alveolocapillary wall. The results demonstrate that preservation of the lung is possible up to a period of 48 h.

Acetylcholine↗

[Assessment of the reflex vagal origin of broncho-constrictor effects of hypercapnia in cats (author's transl)].

Breath-by-breath measurements of pulmonary resistance (RL) were used to study the bronchomotor effects produced by the inhalation of a CO2-enriched gas mixture in anaesthetized, spontaneously breathing cats. A significant increase in RL occurred from the second inhalation of the hypercapnic gas mixture. This bronchoconstrictor effect lasted about 18 seconds, then a marked decrease in RL was observed. The secondary bronchodilatation persisted during the entire hypercapnic test (4 min). After surgical suppression of the sensory vagal component at the level of the nodose ganglion (bilateral sensory vagotomy), the early bronchoconstrictor effect of CO2 disappeared, but the secondary bronchodilatation was unchanged. In other experiments, after procaine block of the nervous conduction in non-myelinated vagal fibers, the bronchomotor effects of CO2 were the same as those observed after sensory vagotomy. In contrast, an electrotonic block of both vagus nerves, which abolished nervous conduction in myelinated fibers, did not suppress the bronchoconstrictor response to hypercapnia. Thus, the early increase in RL, which follows inhalation of a hypercapnic gas mixture, seems to be reflexly mediated by vagal afferents, especially by non-myelinated fibers.

Animals↗

Transient hypoxia: ventilatory response after vagotomy and during artificial phasic inflation.

The early ventilatory response to transient hypoxia was examined in the anaesthetized rabbit. In intact spontaneously breathing animals, an increase in tidal volume (VT) with an accompanying slight increase in inspiratory duration (TI) and a decrease in the expiratory duration (TE) was observed. After vagotomy, the ventilatory response was distinguished by a greater increase in VT and a significant decrease in TI and TE. In another group of artificially ventilated rabbits, an increase in inspiratory volume with a simultaneous decrease in breathing frequency was found to involve a smaller reflex increase in phrenic inspiratory discharge after onset of transient hypoxia. These observations suggest that afferents from pulmonary vagal stretch receptors inhibit those from arterial chemoreceptors.

Animals↗