Experimental modelling of chronic obstructive pulmonary disease.

A method for experimental reproduction of stages of chronic obstructive pulmonary disease formation (from acute inflammation to bronchopulmonary tissue restructuring characteristic of this disease) is presented. Lung injury and inflammation were induced by nitrogen dioxide. Hyperplasia and hypersecretion of goblet cells, squamous cell metaplasia of the ciliary epithelium, emphysema, and focal fibrosis served as the morphological substrate for the formation of bronchial obstruction. The adequacy of the model is confirmed by signs characteristic of chronic obstructive pulmonary disease: hyperexpression of CD3 lymphocytes in the bronchial wall and parenchyma, manifold increased production of TNFα and TGFß, high concentrations of circulating pathogenic immune complexes. Persistence of the structural and functional shifts throughout 6 months after exposure to nitrogen dioxide indicated a chronic course of the resultant pathological process.

[Broncholytic effect of prednisolon in the rats inhaled with nitrogen dioxide].

In the rat model of chronic obstructive pulmonary disease, the dilatation effect of prednisolon was most obvious after 15 days of nitrogen dioxide inhalation. In a longer inhalation, the dilatation effect decreases, and on the 90th day of the inhalation prednisolon enhances contraction of the trachea and bronchi. Prednisolon seems to act upon the respiratory tract via interaction with endings of afferent C-fibres. In prolonged inhalation of nitrogen dioxide, resistance against corticosteroids develops as the result of the C-fibre ending inactivation.

[Alteration of trachea and bronchi smooth muscles constriction under long inhalation of dioxide nitrogen by rats].

On insulated preparation of trachea and bronchi, change of the smooth muscles constriction was studied in rats inhaling dioxide nitrogen during 15, 30 and 60 days. The inhalation enhanced 1.5-fold and bronchi 2.5-fold responses of tracheal smooth muscles to stimulation of preganglionic nerve. The delay of the response in both events increased 1.3-fold. Long repeated stimulation caused a further increase of the constriction of tracheas and bronchi (1.32-fold). Blocking receptor with Novocain (1.0 mcg/ml) reduced the amplitude of the constriction and enhanced the response delay. After 30 days of inhalation, repeated nerve stimulations enhanced the amplitude of the constriction up to 120%, but after 60 days it reduced the amplitude of the constriction to 71 and 77% in preparations of tracheas and bronchi, respectively. In our opinion, long inhalation of dioxide nitrogen broke functioning of local lung nervous system controlling activity of the smooth muscles. The research results indicate important role of neuron functional module in pathology of the respiratory ways caused inhalation of dioxide nitrogen.

[Functional disturbances in the nervous structures of the respiratory tract in rats following nitrogen dioxide inhalation].

The functional state of rat's airway smooth muscle was not changed after nitrogen dioxide inhalation for 30 days. The smooth muscle contraction increased only at second stimulation of preganglionic nervous fibers. Removal of mucosa or Novocain blockade of receptors decreased control smooth contraction at nerve and muscle fiber stimulation but the repeated stimulation of nerve increased the muscle contraction. The processing of trachea and bronchus preparations by prednisolon (1-10 microg/ml) decreased muscle reactions to 12% only at nerve stimulation. Prednisolon didn't change reactions of preparations with removed or blockaded receptors induced by nerve stimulation, but prednisolon (10 microg/ml) increased contraction at muscle stimulation. The relax effect of prednisolon on airway smooth muscle realizes via tracheobronchial receptors. High doses of prednisolon may direct effect on muscle increasing its contraction.

[Effect of prednisolon on trachea smooth muscle of normal rats and rats with fibrosing alveolitis].

Effect of prednisolone on isolated preparations of trachea of normal rats and rats with fibrosing alveolitis was studied. Prednisolone at a concentration of 0.4 microg/l decreased responses of smooth muscle on stimulation of preganglionar nerve fibers at trachea areas with intramural ganglia in rats with acute alveolitis by 48%, while in normal rats--by 19% of control. In trachea preparations without ganglia, prednisolone at a dose of 10 microg/l decreased responses of muscle to the nerve fiber stimulation by 21.3%. The higher prednisolone doses were less efficient: 0.1-10 microg/l glucocorticoid practically did not affect the smooth muscle responses produced by stimulation of muscle cells. In rats with fibrosing alveolitis, 10 microg/l prednisolone restored the smooth muscle responses to control values in preparations of trachea with intramural ganglia. After the prednisolone treatment, amplitude of the rat trachea muscle contraction in response to the nerve fiber electric stimulation did not differ statistically significantly from control and 0.1-10 microg/l prednisolone did not change the response value. The conclusion is made that prednisolone affected the diseased rats more efficiently than the healthy animals. The character of the glucocorticoid effect depends on the presence of intramural ganglia in the trachea wall.

[Effect of peptides, isolated from the tracheal mucosa, on alveolar macrophages and the nature of the course of fibrosing alveolitis in the rat]. / Vliianie peptidov, vydelennykh iz slizistoi trakhei, na al'veoliarnye makrofagi i kharakter techeniia fibroziruiushchego al'veolita u krys.

Rats with bleomycin-induced pulmonary fibrosis were treated with a complex of low-molecular weight peptides isolated from the tracheal mucosa (PTM). Cytological examinations of bronchoalveolar lavage fluid from the animals receiving PTM revealed increases in the number of alveolar macrophages (AM) as compared to that in saline-treated rats. The AM obtained from PTM-treated animals also showed an enhanced phagocytic activity, as well as increased superoxide anion production when stimulated with the opsonized zymosan. However, basal superoxide production after PTM administration was reduced to normal values. These PTM effects of the AM paralleled the reduction of pulmonary fibrotic changes and myocardial hypertrophy. The findings suggest that the AM functional activity is mediated by PTM.

[Content of trace elements and steroid hormones in blood and tissues of internal organs of rats during an inflammatory process in the bronchi]. / Soderzhanie mikroélementov i steroidnykh gormonov v krovi i tkaniakh vnutrennikh organov krys pri vospalitel'nom protsesse v bronkhakh.

Prolonged interrupted inhalation of nitrogen dioxide in a dose of 36.0 +/- 2.2 mg/m3 was attended by definite morphological signs of inflammation in the lungs of rats (hyperplasia of goblet cells, thickening of the basilar membrane, differentiation of ciliated epithelium, etc.), reduction of the zinc content in all studied tissues and testosterone levels in blood. Intramuscular injection of 1% testosterone propionate normalized the blood level of the hormone and influenced the synthetic processes in the cells of the bronchial epithelium and the rate of its regeneration. To raise the efficacy of the correction of the pathological process in the lungs it is suggested that hormonal therapy should be combined with correction of zinc deficiency in the organism.

[Content of trace elements and steroid hormones in blood and tissues of internal organs in experimental pulmonary fibrosis induced by intratracheal administration of bleomycetin]. / Soderzhanie mikroélementov i steroidnykh gormonov v krovi i tkaniakh vnutrennikh organov pri ékperimental'nom fibroze legkikh, vyzvannom vnutritrakheal'nym vvedeniem bleomitsetina.

Pulmonary fibrosis was produced in rats by intratracheal administration of bleomycetin. The development of the fibrous process in the lungs was attended by marked reduction of the zinc content in the tissues of the viscera, plasma, and formed elements of the blood, as well as of corticosterone and testosterone in blood plasma. Respiratory insufficiency is a probable cause of the developing zinc-deficiency which leads to disturbed synthesis of steroid hormones. Injection of exogenous testosterone normalizes partly the level of steroid hormones in the blood, improves the general condition of the animals, and facilitates an increase of body weight.

[The structural changes in the lungs and the phospholipids of the pulmonary surfactant in experimental bleomycin-induced pneumosclerosis in rats]. / Strukturnye izmeneniia legkikh i fosfolipidov legochnogo surfaktanta pri éksperimental'nom bleomitsinovom pnevmoskleroze u krys.

Light microscopy was used to study rat lungs. Some morphological and biochemical characteristics after single bleomycin intratracheal administration in a dose of 10 mg/kg were studied. Some metabolic changes in the alveolar epithelium and vascular endothelium were estimated quantitatively. The peculiar picture of acute toxic alveolitis in the early stage of the injury and the features of fibrotic alveolitis by the 30-60th day were observed. The LDH and succinate dehydrogenase activities in the alveolar epithelium increased by the 3-7th day and returned to normal by the 30th day. At the same time the PL content increased 2-fold by the 30-60th day. The lysolecithin, sphingomyelin and phosphatidylserine concentration increased on the 3-7th day and returned to normal level on the 14th day. The phosphatidylglicerol content decreased significantly by the 60th day.

[Changes in the functional state of the adrenal glands in experimental bronchospasm in dogs]. / Izmeneniia funktsional'nogo sostoianiia nadpochechnikov pri éksperimental'nom bronkhospazme u sobak.

Changes in the adrenal functional state were revealed during the development of bronchoconstriction induced by allergen inhalation in 7 dogs sensitized with ovalbumin. The decrease in V1 (expiratory flow-volume) on an average by 58% was noted after inhalation of 1000 microG of ovalbumin. The significant decrease in II-hydroxycorticosteroids (II-OCS), adrenaline, noradrenaline, dopamine, and a tendency to the increase in histamine content were observed in the venous blood plasma. The decrease in the adrenaline content in plasma apparently contribute to the development of early bronchoconstrictor response, and the decrease in II-OCS maintain the development and the progress of late bronchoconstrictor response.

[Role of the rise of pressure in the pulmonary artery in the distribution of perfusion and gas exchange in bronchial obstruction]. / Rol' povysheniia davleniia v legochnoi arterii v raspredelenii perfuzii i gazoobmene pri bronkhial'noi obstruktsii.

The experiments on the dogs revealed that the damage of lobar bronchus conduction resulted in the decrease of O2 tension in pulmonary venous blood of this lobe. The decrease in the ventilation and blood flow was found in the zone of obstruction by using tracers 133Xe and 99mTc. The pressure rise in the pulmonary artery caused by the spread of bronchial obstruction is one of the factors promoting the redistribution of perfusion into the reserve zones of lungs. The decrease of pressure by the ganglio-blocking preparation results in the increase of arterial hypoxemia.

[Characteristics of circulation, ventilation and gas exchange in intact and anesthetized dogs]. / Kharakteristika krovoobrashcheniia, ventiliatsii i gazoobmena u intaktnykh i narkotizirovannykh sobak.

Light hexenal anesthesia was found not to affect the mean values of hemodynamics and O2 tension in the blood but increased the CO2 tension in arterial blood and decreased the oxyhemoglobin content and pH of the blood in dogs.

[Changes in systemic and pulmonary hemodynamics during an increase in lung volume]. / Izmeneniia sistemnoi i legochnoi gemodinamiki pri uvelichenii ob"mena legkikh.

15 anesthetized dogs were subjected to a gradual increase of the lungs volume by means of administration of the 50% gas mixture of oxygen and air. The exceeding of the lungs volume by 600 ml increased pressure in the caudal vein, reduced blood flow and systolic pressure in the heart ventricles. After administration of 800 ml of the gas, the systolic pressure started to raise in the right ventricle and achieved 36.8 mm Hg at the moment of intrathoracic pressure of 21.5 mm H2O and cessation of the minor circulation. Then the right ventricle augmented its mechanic activity inducing tachycardia, raise of the pressure up to 45.2 mm Hg and restoration of the lung circulation.