Pharmacologic modulation of antigen-induced pulmonary responses in the perfused guinea pig lung

• Published in: The American review of respiratory disease Vol. 147; no. 2; p. 262
• Main Authors: Selig, W M, Tocker, J E, Tannu, S A, Cerasoli, Jr, F, Durham, S K
• Format: Journal Article
• Language: English
• Published: United States 01.02.1993
• Subjects: Animals; Disease Models, Animal; Eicosanoids - secretion; Guinea Pigs; Histamine Release - drug effects; Immunization - methods; In Vitro Techniques; Lung - drug effects; Lung - immunology; Lung - physiopathology; Male; Organ Size - drug effects; Ovalbumin - administration & dosage; Ovalbumin - immunology; Perfusion - methods; Pulmonary Artery - drug effects; Pulmonary Artery - physiopathology; Pulmonary Edema - etiology; Pulmonary Edema - immunology; Pulmonary Edema - physiopathology; Pulmonary Wedge Pressure - drug effects; Time Factors; Vascular Resistance - drug effects
• DOI: 10.1164/ajrccm/147.2.262
• ISSN: 0003-0805

The effect of various enzyme inhibitors and receptor antagonists on antigen (ovalbumin)-induced changes in pulmonary hemodynamics (arterial pressure, capillary pressure, and arterial and venous resistance), fluid filtration, and airway reactivity were monitored for 60 min in recirculating Ringer's-perfused, actively sensitized lungs. Bolus ovalbumin (30 micrograms) injection into the pulmonary artery produced initial (3 min postovalbumin) increases in pulmonary arterial pressure of 68 +/- 9% above baseline, which were followed by secondary increases (143 +/- 45% above baseline) at 30 min postovalbumin. Ovalbumin challenge also caused initial increases in pulmonary capillary pressure, arterial resistance, and venous resistance within 3 min after administration (100 +/- 34%, 51 +/- 10%, and 221 +/- 77% above baseline, respectively), which were further elevated at the end of the 60-min experimental period (292 +/- 74%, 66 +/- 29%, and 559 +/- 61% above baseline, respectively). Ovalbumin-induced increases in intratracheal pressure (771 +/- 142% above baseline) peaked at 3 min postchallenge and gradually returned towards baseline. Ovalbumin-induced changes in lung weight increased gradually over the perfusion period (3.5 +/- 1.0 g above baseline at 60 min postovalbumin). Antigen-induced changes in pulmonary arterial pressure, intratracheal pressure, and lung weight were abolished by pretreatment with the histamine1-receptor antagonist, pyrilamine (1 microM). The cyclooxygenase inhibitor, indomethacin (1 microM), potentiated antigen-induced secondary increases in pulmonary arterial pressure, intratracheal pressure, and lung weight.