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Biomedical subjects

R Matran

Publications and source records attributed to R Matran.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Left single-lung allotransplantation with or without bronchial artery revascularization in pigs. Development of a model with a five-week survival].

After lung transplantation, immunological mechanisms are easier to understand if the pathologist can examine larger pieces of tissues than those obtained by endoscopic biopsies. The purpose of this study was to test the experimental left-lung transplantation in the pig, performed with or without bronchial arterial revascularization and with a survival of 5 weeks. Three animals were only thoracotomised (sham-operated), ten were allotransplanted without and nine with- bronchial arterial revascularization. To optimize survival several clinical and paraclinical parameters were used: laboratory, immunological, endoscopic and flowmetric examinations. Seven of the nineteen transplanted animals survived until the fifth week. Long-term survival is possible and depends mainly on the development of pulmonary sepsis. We observed an increase of the pulmonary vascular resistances and pressures in the allo-transplanted animals. In these animals, histologic examination showed lymphoplasmocytic infiltration in the interalveolar walls and the number of ciliated epithelial cells decreased on the main and lobar bronchi. Our observations suggest that CD8 lymphocytic infiltration is predominant on the bronchi after transplantation and that rejection may occur in the pig. Class 2 DR Swine Leukocyte Antigen does not seem to be expressed on the bronchi in the allo-transplanted pig after 5 weeks. Finally, it is very difficult to demonstrate the patency of bronchial arterial grafts after 5 weeks and therefore to prove the influence of revascularization.

Animals↗
PubMed1994

[Mechanisms of bronchial hyperreactivity. Bronchial edema, mechanical and vascular factors].

Hindrance to gas flow in the bronchi is affected not only by airway smooth muscle tone but also by airway circulation. Congestion and oedema increase airway wall thickness and act in series with airway smooth muscle contraction to reduce airway calibre, an effect which is more marked in small and intermediate bronchi. Many mediators, neuromediators, paracrine mediators produced by resident (epithelium) or migrant (inflammatory cells) cells share bronchomotor and vascular effects. In addition, contraction of airway smooth muscle and vascular phenomena are mechanically coupled. Contraction of airway smooth muscle facilitates vascular congestion and oedema because the diameter of the muscle ring is more reduced than the external diameter of the airways. In addition, a negative intrathoracic pressure, e.g. in asthma, increases the mechanical loading of both ventricles, thereby facilitating pulmonary and bronchial oedema. The effects of this mechanical coupling are enhanced by airway inflammation that facilitates both vascular congestion and leakage. Stimuli such as exercise and hyperventilation cause airway vasodilatation which, in turn, facilitates and, possibly, triggers the post-exercise asthma attack. Conversely, congestion and vasodilatation may have a protective effect through an increase in the clearance of bronchoconstrictor substances, or in reducing the amplitude of airway cooling and water loss in exercise-induced asthma. The relative role in bronchial hyperresponsiveness of airway smooth muscle contraction and vascular phenomena probably depends upon individual factors such as, for instance, both intensity and nature of inflammation of the airway walls.

Airway Obstruction↗
PubMed1992

Effect of airway blood flow on airflow.

Resistance to gas flow of an airway is a function of both airway smooth muscle tone and thickness of the airway wall internal to the outer ring of airway smooth muscle. Schematically, the increase in airway resistance caused by shortening of airway smooth muscle may be potentiated by a concomitant increase in airway wall thickness caused by vasodilation of the bronchial vessels and/or microvascular leakage. Conversely, bronchial vasoconstriction may limit to some extent the increase in resistance to gas flow caused by airway smooth muscle shortening and/or congestion and edema of the airway wall. Many endogenous paracrine mediators, putatively involved in asthma and bronchial hyperresponsiveness, have both bronchomotor and vascular effects. The overall effects on resistance to airflow of endogenous or exogenous agents depend not only upon pre-existing airway smooth muscle tone and pre-existing condition of bronchial vessels but also upon two factors that facilitate microvascular leakage, namely, inflammation of the airway wall and outflow pressure of the bronchial circulation, which is close to left atrial pressure.

Airway Obstruction↗
PubMed1991

Capsaicin-induced local effector responses, autonomic reflexes and sensory neuropeptide depletion in the pig.

Systemic capsaicin pretreatment (total cumulative dose 50 mg/kg administered s.c. over 2h) was performed in pigs under pentobarbitone anaesthesia and the effects on sensory and sympatho-adrenal mechanisms were examined acutely and 2 days after treatment. During pretreatment with capsaicin, pronounced sensory and sympatho-adrenal activation were noticed. This resulted in a several-fold increase in the systemic arterial plasma levels of calcitonin gene-related peptide (CGRP), neurokinin A (NKA), noradrenaline (NA), adrenaline (Adr) and neuropeptide Y (NPY), and a slight increase (39%) in plasma cortisol. Simultaneously, there was marked tachycardia, an increase in blood pressure, total skin erythema and some bronchoconstriction, all lasting for about 30 min. Upon repeated injections tachyphylaxis was observed. 2 days after capsaicin pretreatment, basal plasma levels of the neuropeptides, catecholamines and cortisol as well as basal cardiovascular and pulmonary parameters were similar in control and capsaicin-treated pigs. The tissue content of CGRP and NKA was reduced by 50-65% in the airways and by 80-90% in the skin 2 days after capsaicin pretreatment. In contrast, the CGRP content was unchanged or increased (by 195%) in the nodose and spinal ganglia, respectively. The corresponding tissue levels of vasoactive intestinal polypeptide (VIP) and NPY were basically unchanged in capsaicin-treated pigs. A bolus injection of capsaicin (1 mg/kg i.v.) in control animals resulted in a marked increase in plasma catecholamines and NPY, concomitant with elevation in blood pressure and heart rate. These effects were preceded by an initial bradycardia and decrease in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Association between histamine-containing mast cells and sensory nerves in the skin and airways of control and capsaicin-treated pigs.

The association between mast cells (visualized by routine staining and immunohistochemistry for histamine) and capsaicin-sensitive nerves (containing calcitonin gene-related peptide (CGRP) and substance P (SP] was studied in the pig. In the 1-ethyl-3(3-diethylaminopropyl)carbodiimide (EDCDI)-fixed skin tissue, histamine-containing mast cells and CGRP/SP-positive nerves were found in close association around blood vessels. In the EDCDI-fixed airway mucosa, only single histamine-containing mast cells were detected. However, many alcian blue-positive mast cells were found, sometimes close to the airway epithelium where CGRP SP-containing nerve were abundant. The CGRP/SP-containing nerve fibres were absent 2 days after systemic capsaicin pretreatment, but no changes in the number and distribution of tissue mast cells, granulocytes or lymphocytes, or the number of blood leukocytes were detected. Local injection of allergen, histamine and capsaicin into the skin of pigs actively sensitized with ascaris antigen caused a rapid light red-flare (vasodilation) reaction. Allergen and histamine, but not capsaicin, also produced plasma protein extravasation. In contrast to the absent flare, the protein extravasation response still occurred in capsaicin-treated pigs. The sensitivity to ascaris antigen was mediated by an IgE-like antibody. We conclude that a functional and morphological relationship exists between histamine-containing mast cells and capsaicin-sensitive sensory nerves in the pig skin. Mast cells and sensory nerves are also found in the airway mucosa and appear to be closely associated with the epithelium.

Animals↗
PubMed1991

Effect of nedocromil sodium on allergen-, PAF-, histamine- and bradykinin-induced airways vasodilatation and pulmonary obstruction in the pig.

1. The influence of nedocromil sodium on the nasal and bronchial effects induced by allergen, platelet-activating factor (PAF), capsaicin, histamine and bradykinin aerosol challenge in ascaris-sensitized and pentobarbitone-anaesthetized pigs was studied. Blood flow changes in the bronchial and nasal circulation were measured with ultrasonic flow probes around the supplying arteries, and vascular resistance was calculated. Changes in pulmonary resistance (Rpulm), dynamic compliance (Cdyn), mean arterial pressure (MAP) and heart rate (HR) were also determined. 2. Allergen and PAF aerosol challenge in the lung produced similar effects consisting of both bronchial and nasal vasodilatation, bronchoconstriction (increase in Rpulm and decrease in Cdyn) and increases in MAP and HR. Local pretreatment with nedocromil sodium (80 mg, aerosol) reduced the peak and duration of both the bronchial vasodilatation and increase in Rpulm, while only the duration of the change in Cdyn was significantly decreased. Nedocromil sodium did not alter the increases in MAP and HR. The nasal vasodilatation evoked by PAF, but not allergen, challenge in the lung was reduced by nedocromil sodium. 3. Allergen challenge in the nose induced vasodilatation of long duration which was reduced by local nedocromil sodium pretreatment (50 micrograms kg-1, intra-arterially). 4. The vasodilator response to histamine aerosol was attenuated in the nasal, but not the bronchial circulation by local nedocromil sodium pretreatment. Histamine-induced bronchoconstriction was not altered by nedocromil sodium. 5. Bradykinin aerosol-induced vasodilatation in the nasal and bronchial circulation was markedly and equally reduced by local nedocromil sodium and systemic capsaicin (50 mg kg-1, s.c. 2 days before) pretreatment. 6. In conclusion, nedocromil sodium blocks some local vascular and bronchial effects, but not increases in MAP and HR, induced by allergen and PAF aerosol in the pig. Bradykinin-induced vasodilatation in the airways, which seems to be largely dependent on capsaicin-sensitive sensory nerves, is markedly inhibited by nedocromil sodium pretreatment, whereas capsaicin-induced vasodilatation is not affected by nedocromil sodium. It may be suggested that nedocromil sodium acts by inhibiting some common process involved in the release of mediators from inflammatory cells (when stimulated by allergen and PAF) and sensory nerves (when stimulated by bradykinin and histamine, but not capsaicin).

Allergens↗
PubMed1991

The possible role of prostaglandin D2 in the long-lasting airways vasodilatation induced by allergen in the sensitized pig.

Allergen-induced nasal and bronchial vasodilatation and bronchoconstriction were studied in ascaris-sensitized pigs with and without pretreatment with diclofenac sodium, to evaluate the contribution of prostanoids in these responses. The bronchoconstriction induced by allergen aerosol challenge was enhanced by diclofenac, whereas the duration of the bronchial vasodilatation was reduced from 80 to 30 min, without changing the maximal effect. However, both the maximal effect and the duration of the nasal vasodilatation were reduced upon nasal allergen challenge by 60% (P less than 0.01) and from 72 to 16 min (P less than 0.05), respectively. Bronchial challenge with the allergen also induced nasal vasodilatation of long duration and this response was highly sensitive to diclofenac pretreatment. I.v. injections of prostaglandins (PG) E1, E2, I2 and D2 revealed that only PGD2 induced vasodilatation of long duration in the airways without major effects on the systemic arterial blood pressure. Nebulization of PGD2 (0.7-1.4 mumol) into the pig airways also induced marked vasodilatation of long duration (greater than or equal to 40 min), especially in the nasal circulation. The vasodilatory responses to PGD2 were not changed by systemic pretreatment with capsaicin or diclofenac. Challenge in the airways with platelet-activating factor (PAF) produced bronchial and vascular responses similar to those seen with the allergen and the vasodilatory responses to PAF were partly sensitive to diclofenac. We propose that a long-lasting component of the allergen-induced vasodilatation in the pig airways, especially in the nasal mucosa, may be caused by the release of PGD2, acting independently of sensory nerves. Allergen and PAF aerosol challenge in the lung may also induce the release of a vasodilatory prostaglandin, possibly PGD2 into the systemic circulation, thereby inducing nasal vasodilatation.

Allergens↗
PubMed1991

Differential bronchial and pulmonary vascular responses to vagal stimulation in the pig.

The pulmonary and bronchial vascular responses and changes in bronchial tone upon vagal stimulation (240 impulses at 2 Hz or 10 Hz) were studied in anaesthetized pigs paralyzed with pancuronium. The acetylcholine-evoked vasodilatation in the tracheobronchial circulation had the same magnitude when using pancuronium or succinylcholine as skeletal muscle relaxants. Atropine-sensitive bradycardia, hypotension and bronchoconstriction were observed upon vagal stimulation. A vasoconstrictor response in the pulmonary vascular bed and clear-cut vasodilatation in the bronchial circulation supplied by the bronchial artery also occurred upon vagal stimulation. The vagally-evoked increase in pulmonary vascular resistance was markedly reduced after atropine while the bronchial vasodilatation was unchanged. This suggests that the vagally-induced increase in bronchial blood flow was not secondary to changes in the pulmonary circulation. Furthermore, the pulmonary vasoconstrictor response caused by vagal stimulation under control conditions is probably explained by reflex sympathetic activation due to the fall in systemic blood pressure. These data indicate selective vagal non-cholinergic influence of blood flow in the bronchial vascular bed compared to the pulmonary circulation.

Acetylcholine↗
PubMed1991

Sensory neuropeptide involvement in animal models of airway irritation and of allergen-evoked asthma.

C-fiber afferents in the airways are in close contact with mast cells and are activated both upon allergic reactions and by inhalation of irritants such as capsaicin and cigarette smoke. This evokes both protective reflexes such as cough as well as local release of tachykinins and calcitonin gene-related peptide (CGRP) with subsequent actions on blood vessels (vasodilatation and plasma protein extravasation) and bronchial smooth muscle (bronchoconstriction). After capsaicin pretreatment when peptides have been depleted from the sensory nerves, there is a marked reduction of the vasodilatatory response upon allergen challenge and the protein extravasation evoked by cigarette smoke. Conversely, chronic cigarette smoke exposure is accompanied by increased coughing to capsaicin challenge. Furthermore, aerosol immunization and chronic smoke exposure are both associated with elevated tissue levels of CGRP, suggesting upregulation of C-fiber function and peptide synthesis, which may contribute to airway hyperreactivity.

Aerosols↗
PubMed1991

Neural control of lower airway vasculature. Involvement of classical transmitters and neuropeptides.

1. SP- and CGRP-IR fibres of presumably sensory origin were abundantly located around the vasculature and glands in the laryngotracheal and bronchial mucosae of the pig. A sparse presence of CGRP- and SP-IR nerves in the tracheobronchial smooth muscle layer as well as an atropine-sensitive bronchoconstrictor response to electrical field stimulation suggested that neuropeptides locally released from sensory nerves may be related to vascular or exocrine gland function rather than to bronchial smooth muscle control. In the tracheal mucosa, many VIP-positive perivascular nerve fibres, likely to be of local parasympathetic origin, were present, whereas very few or no such fibres were found in the bronchial mucosa or in the pulmonary vascular bed. A dense innervation of the tracheobronchial and pulmonary vasculature by NPY/DBH-containing perivascular fibres suggested that the sympathetic control of these vascular beds may not only involve NA as transmitter. 2. Mainly sensory axon reflex mechanisms occurred upon systemic capsaicin injection in the pig after pretreatment with a combination of autonomic blocking agents, as revealed by plasma elevations of CGRP- and NKA-LI but not NPY-LI or catecholamines. Repeated capsaicin injections, in the presence of autonomic blocking agents, caused a marked reduction in the elevation of plasma CGRP- and NKA-LI with a clear-cut fall in the bronchial vascular response, suggesting development of tachyphylaxis for local sensory mechanisms. 3. Vasodilatory vagal mechanisms involved different neurotransmitters in the lower airway vasculature of the pig. Thus, local blood flow in the laryngo-tracheal circulation was regulated by cholinergic and non-cholinergic parasympathetic mechanisms and a small capsaicin-sensitive sensory component, while the vagal control of the bronchial circulation seemed to mainly involve capsaicin-sensitive sensory nerves. VIP and ACh were more potent as vasodilators in the laryngo-tracheal compared to the bronchial circulation. Exogenous SP was the most potent vasodilator peptide in the lower airway mucosa. SP and CGRP mimicked capsaicin-induced vasodilatation in the laryngo-tracheal and bronchial circulations. In the pulmonary circulation, vagal activation evoked atropine-sensitive vasoconstriction, probably due to sympathetic reflexes, but not vasodilatation. 4. Both NA and NPY had potent vasoconstrictor effects in the airway mucosa.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1991

[Maximal ventilatory pressure through the mouth in adults: normal values and explanatory variables].

Mouth pressure measured during maximal inspiratory or expiratory efforts depends on the force exerted by ventilatory muscles. Normal values and anthropometric factors accounting for maximal inspiratory and expiratory pressures (MIP, MEP) are not fully agreed upon to date. We measured MIP and MEP in 253 normal subjects (135 females and 118 males, age 15-59 years) using a digital transducer (163 Sibelmed). All subjects had normal forced vital capacity (FVC) and one second forced expiratory volume (FEV1). Sex, age, height and weight were recorded for all subjects and were entered as independent variables in computation of linear multiple regressions with MEP or MIP the dependent variables. MEP and MIP were greater in males than in females (p less than 0.01) with MIP lower than MEP in both sexes (p less than 0.01). In both males and females, FVC and FEV1 depend on age and height (p less than 0.01). In the entire group, we found a correlation of MIP in females and MEP in males with age (p less than 0.01) and of both MIP and MEP in females with weight (p less than 0.01). However, in subjects aged 20-59 years, there was no significant dependence of MIP and MEP on age, and when the weight of subjects was normal (n = 170), MIP and MEP were independent of weight. We conclude that in adults aged 20-59 years and with normal weight, maximal ventilatory pressures depend solely on sex. In this subgroup mean (+/- SD) values of MEP and MIP were 111 +/- 25 cmH2O and 79 +/- 19 cmH2O respectively in females and 192 +/- 42 cmH2O and 117 +/- 25 cmH2O in males.

Adolescent↗
PubMed1991

[Nervous control of bronchial circulation in pigs: application to the airway stimulation].

Vascular responses in airways were studied in an anesthetized pig model. Nervous control of bronchial mucosa blood flow was found to involve mainly the non-adrenergic, non-cholinergic (NANC) system (activation of afferent C-fibers) and the sympathetic system. Nervous control of tracheal and laryngeal vascularization involved the cholinergic and non-cholinergic parasympathetic system and the sympathetic system. Exposure of airways to irritants was followed by vasodilatation in the tracheobronchial mucosa, partly as a result of activation of afferent C-fibers. In sensitized animals, respiratory challenge with the specific allergen produced activation of the NANC system with antidromic vasodilatation in the mucosa. This response can be likened to the "axon reflex" seen in skin. Activation of airway autonomic nerves thus was found to be a central step in the genesis of inflammatory reactions in the lungs.

Animals↗
PubMed1990

Occurrence, specific binding sites and functional effects of endothelin in human cardiopulmonary tissue.

Endothelin (ET)-like immunoreactivity (-LI) was detected in the human cardiopulmonary system, with the highest levels being found in the left anterior descending coronary artery, followed by the lung, right atrium, pulmonary artery, bronchus, pulmonary vein and left ventricle. Chromatographic characterization showed that the ET-LI in the lung and left ventricle corresponded to synthetic ET-1. Specific, high-affinity binding sites for ET-1, with an extremely slow dissociation rate, were found in the lung, right atrium and left ventricle. Displacement studies revealed a rank order of potency of ET-1 greater than ET-2 and sarafotoxin 6b greater than ET-3 and big ET-1. Scatchard analysis indicated a single receptor population in the lung (KD 1.53 x 10(-10) M) and left ventricle (KD 3.0 x 10(-11) M). In functional experiments, ET-1 evoked concentration-dependent, long-lasting vasoconstriction of a higher potency than that evoked by ET-2 and ET-3 in epicardial coronary arteries as well as in pulmonary arteries. ET-1 and ET-2 also showed bronchoconstrictor activity at considerably lower concentrations (threshold 10(-11) M) of ET-1 than those needed to cause vasoconstriction (10(-9) M). ET-LI, mainly consisting of ET-1, occurs in human cardiopulmonary tissue. Specific, high-affinity sites with irreversible binding for ET-1 are found in both the heart and lung. ET-1 is more potent than ET-2 or ET-3 in displacing ET-1 binding and in causing vasoconstriction and bronchoconstriction. Thus, in the human heart and lung, ET-1 seems to be the most abundant and biologically active of the endothelin peptides.

Adult↗
PubMed1990

Endothelin-1 increases airway mucosa blood flow in the pig.

The vascular effects of bolus intravenous injections (4.5, 45 and 450 pmol.kg-1) of porcine endothelin-1 on the bronchial and nasal circulations were investigated in ten anesthetized pigs. Endothelin-1 produced a dose-dependent and long-lasting increase in bronchial blood flow with a concomitant rise in systemic arterial pressure suggesting vasodilatation. The highest doses of endothelin-1 also caused a slight decrease in the nasal vascular resistance. Furthermore, the vascular responses to endothelin-1 were not modified in systemically capsaicin pretreated animals or after pretreatment with a cyclocoxygenase inhibitor, diclofenac. Our results suggest that endothelin-1 has a potent and regional vasodiator effect of the bronchial circulation.

Animals↗
PubMed1990

Innervation of lower airways and neuropeptide effects on bronchial and vascular tone in the pig.

The occurrence and distribution of peptide-containing nerve fibres [substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), neuropeptide Y (NPY)] and noradrenergic nerve fibres [tyrosine hydroxylase (TH)- and dopamine beta hydroxylase (DBH)-positive] in the airways of the pig were studied by means of immunohistochemistry. SP- and CGRP-immunoreactive (-IR) nerve fibres were present close to and within the lining respiratory epithelium, around blood vessels, within the tracheobronchial smooth muscle layer and around local tracheobronchial ganglion cells. The content of CGRP- and neurokinin A (NKA)-like immunoreactivity (-LI) measured by radioimmunoassay (RIA) was twice as high in the trachea compared to that in the peripheral bronchi. SP was a more potent constrictor agent than NKA on pig bronchi in vitro. CGRP had a relaxant effect on precontracted pig bronchi. On blood vessels CGRP exerted a relaxant effect that was more pronounced on pulmonary arteries than on bronchial arteries. VIP/PHI-IR fibres were seen in association with exocrine glands and in the tracheobronchial smooth muscle layer. VIP-positive nerve fibres were abundant around blood vessels in the trachea but sparse or absent around blood vessels in the peripheral bronchi. This histological finding was supported by RIA; it was shown that the content of peptides displaying VIP-like immunoreactivity (-LI) was 18 times higher in the trachea compared to peripheral bronchi. VIP was equally potent as CGRP in relaxing precontracted pig bronchi in vitro. Both bronchial and pulmonary arteries were relaxed by VIP. NPY was colocalized with VIP in tracheal periglandular nerve fibres and in nerve fibres within the tracheobronchial smooth muscle layer. NPY was also present in noradrenergic (DBH-positive) vascular nerve fibres. The content of NPY was much higher (15-fold) in the trachea compared to small bronchi. NPY caused a contraction of both pulmonary and bronchial arteries. The bronchial smooth muscle contraction to field stimulation in vitro was purely cholinergic. A noncholinergic relaxatory effect following field stimulation was observed after bronchial precontraction. Capsaicin had no effect on pig bronchi in vitro.

Animals↗