calcimycin and Bronchial-Spasm

We examined the effect of dexamethasone on A23187-induced bronchospasm, pulmonary inflammation and airway responses to substance P. Guinea pigs, dosed orally once a day for 4 days with dexamethasone (3.0, 10.0 or 30.0 mg/kg) or saline, were exposed to an aerosol of A23187 for 12 min or until labored breathing began. Postmortem pulmonary gas trapping was used as an indicator of in vivo airway obstruction and changes in bronchial responses. Dexamethasone did not alter airway obstruction or inflammation 1 h after A23187 exposure. However, dexamethasone reduced the enhanced airway responses to substance P and bronchiolar/peribronchiolar inflammation 24 h post-A23187. It is possible that glucocorticosteroid suppression of A23187-induced pulmonary inflammation was important in reducing the increased airway responses to substance P.

Topics: Administration, Inhalation; Administration, Oral; Airway Obstruction; Airway Resistance; Animals; Bronchial Hyperreactivity; Bronchial Spasm; Calcimycin; Dexamethasone; Dyspnea; Guinea Pigs; Lung; Male; Pulmonary Gas Exchange; Substance P

Aspirin and nonsteroidal antiinflammatory drugs induce bronchospastic reactions in patients with aspirin-sensitive respiratory disease. Although the mechanism of this reaction is unknown, all drugs that induce the respiratory reaction also inhibit the cyclooxygenase enzyme. The ensuing changes in arachidonate metabolism are presumed to play a role in the pathogenesis of the reaction. We measured generation of leukotrienes and thromboxane by calcium ionophore stimulated blood monocytes. Before aspirin challenge, monocytes released significantly more thromboxane B2 in patients with aspirin sensitivity than in patients without aspirin sensitivity or in healthy control subjects (p < 0.02). During aspirin-induced bronchospasm, release of leukotriene B4 increased significantly (45.5%, p = 0.018), whereas release of thromboxane B2 decreased (-46.9%, p = 0.028). Two hours after ingestion of 60 mg aspirin, normal monocyte release of thromboxane B2 did not drop, whereas leukotriene B4 release increased. Monocytes formed only minimal amounts of leukotriene C4. We conclude that the profile of released eicosanoids from aspirin-sensitive monocytes is distinct from non-aspirin-sensitive subjects, and that these differences could contribute to the development of bronchospasm after aspirin ingestion.

Topics: Administration, Oral; Adult; Arachidonic Acid; Aspirin; Asthma; Bronchial Spasm; Calcimycin; Eicosanoids; Female; Humans; Leukotriene B4; Male; Middle Aged; Monocytes; Thromboxane B2

A brief A23187 aerosol exposure produced prolonged airway obstruction with granulocyte accumulation in conscious guinea pigs. Aminophylline, atropine, pyrilamine, salbutamol, SC-41930 (a leukotriene B4 antagonist) and WEB 2086 (a platelet activating factor antagonist) were administered intravenously (i.v.) to evaluate their ability to prevent these changes. Inhaled salbutamol was also assessed. Aminophylline, atropine, and salbutamol (i.v. and aerosol) inhibited A23187-induced gas trapping (p less than 0.01). However, pyrilamine, SC-41930 and WEB 2086 did not influence this airway obstructive effect. Only atropine, inhaled salbutamol and SC-41930 inhibited the cell influx (p less than 0.01), while pyrilamine potentiated the inflammation (p less than 0.05). We conclude that A23187 produces a sustained bronchospasm and an intense granulocyte accumulation. The treatment agents tested differ considerably in their ability to alter A23187-induced airway obstruction and inflammation.

Topics: Albuterol; Aminophylline; Animals; Atropine; Bronchial Spasm; Calcimycin; Granulocytes; Guinea Pigs; Kinetics; Lung Diseases, Obstructive; Male; Pneumonia