title: Control of shunt pathway perfusion in diffuse granulomatous lung disease.
abstract: To assess the roles of cyclooxygenase inhibition and alveolar hypoxia in controlling the distribution of pulmonary perfusion in granulomatous lung injury, we studied 15 dogs (anesthetized and ventilated) 4 wk after intravenous injection of complete Freund's adjuvant (0.5-0.75 ml/kg). Base-line hemodynamic and blood gas observations were obtained at fractional O2 concentration (FIO2) 0.21 and 0.10. Observations at each FIO2 were repeated 30 min after infusion of meclofenemate (2 mg/kg; n = 10) or saline (n = 5). Resistance to pulmonary blood flow was assessed using the difference between pulmonary arterial diastolic and left atrial pressures (PDG). Distribution of blood flow between normal and diseased regions of the lung was evaluated with measurement of inert gas shunt flow. Before infusion, there were no significant differences between the two groups at either FIO2. At FIO2 0.10 PDG rose from 3 +/- 1 to 7 +/- 3 mmHg in the saline group and from 3 +/- 1 to 8 +/- 3 mmHg in the meclofenemate group, although the shunt flow increased from 8.7 +/- 7.7 to 12.2 +/- 9.2% and from 10.7 +/- 11.0 to 17.6 +/- 18.3 in the two groups, respectively. Saline induced no significant changes at either FIO2. After meclofenemate, PDG at FIO2 0.21 rose to 7 +/- 4 mmHg (P less than 0.015) while shunt flow fell to 5.2 +/- 6.2% (P less than 0.0125), whereas at FIO2 0.10 PDG rose to 15 +/- 5 mmHg (P less than 0.001) while shunt flow rose only to 14.3 +/- 16.4% (P = NS). We propose that perivascular inflammation enhanced perfusion of abnormal lung by elaborating vasodilator prostanoids. By inhibiting prostanoid biosynthesis, meclofenemate selectively increased resistance in diseased lung at FIO2 0.21 and lowered shunt flow. The persistent rise in shunt during hypoxia after meclofenemate suggests that factors other than prostanoids may account for the apparent attenuation of hypoxic vasoconstriction in diseased lung.
authors.affiliation: Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
authors.forename: L L
authors.initials: LL
authors.lastname: Schulman
authors.forename: J A
authors.initials: JA
authors.lastname: Wood
authors.forename: Y
authors.initials: Y
authors.lastname: Enson
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D016861:Cyclooxygenase Inhibitors; D004285:Dogs; D006099:Granuloma / Q000503:physiopathology*; D006439:Hemodynamics; D008171:Lung Diseases / Q000503:physiopathology*; D008469:Meclofenamic Acid / Q000494:pharmacology; D009929:Organ Size; D010100:Oxygen; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology*; D011652:Pulmonary Circulation; D014655:Vascular Resistance; D014692:Ventilation-Perfusion Ratio
chemical_list: D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D008469:Meclofenamic Acid; D010100:Oxygen