title: Cyclooxygenase inhibition aggravates pulmonary hypertension and deteriorates gas exchange in canine pulmonary embolism.
abstract: We examined the effects of cyclooxygenase inhibitors on pulmonary hemodynamics and gas exchange after experimental acute pulmonary embolism in 12 intact anesthetized dogs. Pulmonary hemodynamics were evaluated by pulmonary arterial pressure (Ppa)/cardiac output (Q) plots before and 60 min after autologous blood clot embolization and again 30 min after cyclooxygenase inhibition, either by acetylsalicylic acid (ASA, n = 6) or by indomethacin (INDO, n = 6). Gas exchange was assessed using the multiple inert gas elimination technique, at a constant intermediate Q, under each of these experimental conditions. Embolization increased Ppa at all levels of Q studied (p less than 0.001), increased true shunt (p less than 0.05), and shifted perfusion (Q) and ventilation (VA) distributions to lower and higher VA/Q (p less than 0.05), respectively. ASA and INDO further shifted Ppa/Q plots toward higher pressures (p less than 0.05). Concomitantly, the physiologic dead space increased after INDO (p less than 0.001), and the proportion of lung units with a high VA/Q increased and the inert gas dead space decreased after both ASA (p less than 0.05) and INDO (p less than 0.05). We conclude that, in experimental pulmonary embolism, structurally different cyclooxygenase inhibitors aggravate pulmonary hypertension and deteriorate gas exchange by an altered distribution of VA/Q essentially to lung units with a higher than normal VA/Q. These findings may be explained by changes in the distributions of both VA and of Q as a consequence of cyclooxygenase inhibition-associated increases in both bronchial and vascular tone in embolized lung regions.
authors.affiliation: Laboratory of Cardiovascular and Respiratory Physiology, Erasme University Hospital, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Delcroix
authors.forename: C
authors.initials: C
authors.lastname: Melot
authors.forename: P
authors.initials: P
authors.lastname: Lejeune
authors.forename: M
authors.initials: M
authors.lastname: Leeman
authors.forename: R
authors.initials: R
authors.lastname: Naeije
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004285:Dogs; D006976:Hypertension, Pulmonary / Q000139:chemically induced*; D007213:Indomethacin / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D011655:Pulmonary Embolism / Q000503:physiopathology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects*
chemical_list: D016861:Cyclooxygenase Inhibitors; D001241:Aspirin; D007213:Indomethacin