Decrease In Dynamic Lung Compliance Research Articles

Enhanced bronchoconstriction responses to prostaglandin F 2α following inhalation of sulfur dioxide

The effect of chronic sulfur dioxide (SO 2) inhalation was investigated in pharmacologic-induced bronchoconstruction in beagle dogs. Increase in pulmonary resistance (R L) and decrease in dynamic lung compliance (C DYN) were observed with i.v. and aerosol administration of prostaglandin F 2α (PGF 2α). After control historical data were accumulated, the animals received exposures of 500 ppm of SO 2 for two hours twice a week. After six months of chronic SO 2 exposure, a significant enhancement in the R L response to i.v. and aerosolized PGF 2α was observed as compared to pre-SO 2 data. Tracheobronchial inflammation, as observed by fiberoptic bronchoscopy, occurred as a result of the chronic inhalation of SO 2; however, only a small increase in mucous production was observed visually. In additon, hypercapnic and acidotic changes in blood gas profiles were found. Therefore, beagle dogs chronically exposed to SO 2, developed hyperactive airways as seen by increased sensitivity to PGF 2α. This model appears to reflect many of those changes observed in clinical bronchial hyperreactivity and may provide an additional insight into obstructive disease.

In vivo metabolism of dihomo-γ-linolenic acid to bronchoactive products in the canine lung

We investigated the effects of dihomo-γ-linolenic acid (DGLA), the fatty acid precursor to the monoenoic prostaglandins, on pulmonary mechanics in the intact chest, artificially ventilated dog. Under conditions of normal airway tone, intravenously administered DGLA produced a modest, dose-related increase in lung resistance and decrease in dynamic lung compliance. These responses were approximately 30–100 times less than those produced by arachidonic acid. The bronchoconstrictive responses to DGLA were abolished by prior inhibition of the cyclooxygenase with indomethacin. PGD 1 was equal in activity to PGF 1α in causing constriction of central and peripheral airways of the dog. PGE 1 was without significant airway effects in these animals under conditions of resting airway tone. We conclude that DGLA is a moderately good substrate for the cyclooxygenase pathway enzymes of the canine lung, producing products having a predominantly bronchoconstrictive effect. This bronchoconstriction is most likely due to the synthesis of PGD 1 and PGF 1α and is not due to the synthesis of lipoxygenase pathway products.

Sequential effects of acute meconium obstruction on pulmonary function.

The relationship between pulmonary function and the migration of meconium to distal airways was determined in 10 rabbits (mean weight 2.6 kg) after insufflation of a meconium-saline mixture (1--2 ml/kg). Animals were anesthetized, cannulated, intubated, and mechanically ventilated with 100% oxygen. Lung mechanical dysfunction was most severe during the early phase of meconium migration, 15 min postinsufflation. Substantial increases in inspiratory lung resistance (RI) and expiratory lung resistance (RE) suggest that the site of obstruction at 15 min was the large airways. A decrease in dynamic lung compliance with unchanged static compliance characterizes the obstruction as partial. At 15 min and throughout the migration process, RE was greater than RI, demonstrating a check-valve effect. This phenomenon was substantiated by an increased functional residual capacity (FRC) in all rabbits, presumably due to gas trapping. Secondary to these changes, marked hypoxemia, hypercapnea, and acidosis developed in spite of assisted ventilation with 100% oxygen. At 60 and 120 min postinsufflation, both RI and RE decreased as compared to 15 min. This suggests that the predominant site of obstruction shifted to medium and small airways concomitant with the migration of meconium. Widespread and uneven distribution of meconium still produced significant frequency dependence of lung compliance. Static compliance remained unchanged, indicating that meconium does not affect surface-active or tissue properties of the lung within 120 min postinsufflation. These data suggest that effective respiratory management after meconium aspiration is dependent on the degree of meconium migration, as reflected by pulmonary mechanics.

The effect of catecholamines on the in vivo and in vitro responses of the cat lung during anaphylaxis.

1. Anaphylaxis in the lung of cats actively sensitized to Ascaris antigen has been investigated in vivo and in vitro. 2. In vivo there was a 100% increase in airways resistance and a 50% decrease in dynamic lung compliance following intravenous challenge with Ascaris antigen. Prostaglandin F2alpha induced similar changes but with histamine only dynamic lung compliance was affected. (-)-Isoprenaline prevented these prostaglandin F2alpha- and histamine-induced changes and caused a delay of about 2 min in the onset of the mechanical changes following anaphylactic challenge. 3. In vitro the isolated lung strip contracted within seconds of challenge whereas there was a delay of 2 to 3 min in the onset of the tracheal anaphylactic response. (-)-Isoprenaline, (-)-adrenaline and (+/-)-noradrenaline reduced the magnitude of anaphylactic contractions of the isolated trachea but did not significantly affect those of the isolated lung strip. This indicated lack of inhibition of mediator release from the lung parenchyma. 4. Histamine was released from sensitized lung fragments following challenge with the Ascaris extract. This release constituted 6.3% of the total tissue histamine and was not inhibited by (-)-isoprenaline (1 micrometer). 5. (-)-Isoprenaline abolished 5-hydroxytryptamine (5-HT)-induced contractions of the isolated trachea but not those elicited in response to acetylcholine. The isolated lung strip responses to histamine, prostaglandin F2alpha and 5-HT were highly resistant to inhibition by (-)-isoprenaline.

Vagal reflexes in the bronchoconstriction occurring after induced intravascular platelet aggregation.

Intravascular platelet aggregation induced in cats by i.v. infusions of collagen caused a transient increase in pulmonary vascular resistance (PVR) and in non-elastic pulmonary resistance (RL), and a transient decrease in dynamic lung compliance (dyn CL). PVR,dyn CL and platelet aggregation after collagen infusions were unaffected by bilateral cervical vagotomy and atropinization, wheras these procedures reduced the post-infusion rise in RL by about 50 per cent. The administration of indomethacin inhibited platelet aggregation as well as bronchoconstriction after collagen infusion. The present investigation indicates that intravascular platelet aggregation will cause reflex bronchoconstriction mediated by vagal efferent fibres.