Pulmonary transvascular fluid and protein exchange after thrombin-induced microembolism. Differential effects of cyclooxygenase inhibitors.
We studied the effects of cyclooxygenase inhibitors (indomethacin, meclofenamate, and ibuprofen) on the increases in pulmonary transvascular fluid and protein fluxes that occur after thrombin-induced intravascular coagulation. Each drug-pretreated group was compared with a control group receiving the same amount of alpha-thrombin (alpha-T), the native enzyme used to induce intravascular coagulation. Studies were made in the following groups of anesthetized sheep prepared with lung lymph fistulas: low dose-indomethacin (bolus injection of 5 mg/kg and infusion of 3 mg/kg/h, high-dose indomethacin (bolus injection of 20 mg/kg and infusion of 12 mg/kg/h), meclofenamate (bolus injection of 5 mg/kg and infusion of 3 mg/kg/h), low-dose ibuprofen (bolus of 6.2 mg/kg and infusion of 3.1 mg/kg/h), and high-dose ibuprofen (bolus of 25 mg/kg and infusion of 12.5 mg/kg/h). The concentrations of the arachidonic acid metabolites, thromboxane B2 and 6-keto-prostaglandin F1 alpha, did not increase in the treated groups. Infusion of alpha-T increased the mean pulmonary arterial pressure and pulmonary vascular resistance in the control and treated groups, but to higher levels in the indomethacin and meclofenamate groups. In the control group, alpha-T increased pulmonary lymph flow (Qlym) and lymph protein clearance (Qlym X lymph/plasma protein concentration ratio), a measure of lung vascular permeability. In the indomethacin, meclofenamate, and low-dose ibuprofen groups, alpha-T resulted in delayed increases in Qlym and lymph protein clearance, but these lymph parameters attained the same levels as the control groups. However, the high-dose of ibuprofen significantly attenuated the increases in Qlym and lymph protein clearance after alpha-T.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000097:blood; D005110:Extracellular Space / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000098:blood supply* / Q000378:metabolism; D008196:Lymph / Q000378:metabolism; D008469:Meclofenamic Acid / Q000494:pharmacology; D011655:Pulmonary Embolism / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D012756:Sheep; D013917:Thrombin / Q000008:administration & dosage*; D013929:Thromboxane B2 / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects
D001798:Blood Proteins; D016861:Cyclooxygenase Inhibitors; D008469:Meclofenamic Acid; D013929:Thromboxane B2; D011464:Epoprostenol; D013917:Thrombin; D007052:Ibuprofen; D007213:Indomethacin