PMID: 7542509Aug 1, 1994Paper

Effect of theophylline administered intratracheally as a dry powder formulation on bronchospasm and airway microvascular leakage in the anesthetized guinea-pig

Pulmonary Pharmacology
D Raeburn, V R Woodman

Abstract

The effect of theophylline (a non-selective phosphodiesterase (PDE) inhibitor), dosed intratracheally (it) as a dry powder, on histamine- and platelet activating factor (Paf)-induced bronchospasm and antigen (ovalbumin, OA)-, histamine- and Paf-induced microvascular leakage (MVL) in the airways, was studied in the anaesthetized guinea-pig. Bronchospasm was measured as the increase in pulmonary inflation pressure (PIP). MVL was assessed by fluorometric assay of fluorescein isothiocyanate dextran (FITC-dextran) content in airway tissues and tracheobronchial lavage fluid. OA (200 micrograms), histamine (60 nmol) and Paf (4 nmol), all given it, significantly increased MVL by up to 350% over levels in undosed unchallenged animals. Theophylline (50-500 micrograms it, n = 5-6) inhibited histamine-induced bronchospasm (30% inhibitory dose, ID30: 258 +/- 30 micrograms), and Paf-induced bronchospasm (ID30: 190 +/- 80 micrograms). An inhibition of 40-50% of maximal bronchospasm was the largest attained. Theophylline, at approximately the bronchospasm ID30 dose (200 micrograms it, n = 4-8), inhibited MVL induced by all agents by 30-80% in airway tissues and in lavage fluid samples. Theophylline (50-500 micrograms it, n = 3) produced plasma...Continue Reading

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