thromboxane-b2 and Pleural-Effusion

Our objective was to test the effect of inhibition of thromboxane synthase versus inhibition of cyclooxygenase (COX)-1/2 on pulmonary gas exchange and heart function during simulated pulmonary embolism (PE) in the rat. PE was induced in rats via intrajugular injection of polystyrene microspheres (25 micro m). Rats were randomized to one of three posttreatments: 1) placebo (saline), 2) thromboxane synthase inhibition (furegrelate sodium), or 3) COX-1/2 inhibition (ketorolac tromethamine). Control rats received no PE. Compared with controls, placebo rats had increased thromboxane B(2) (TxB(2)) in bronchoalveolar lavage fluid and increased urinary dinor TxB(2). Furegrelate and ketorolac treatments reduced TxB(2) and dinor TxB(2) to control levels or lower. Both treatments significantly decreased the alveolar dead space fraction, but neither treatment altered arterial oxygenation compared with placebo. Ketorolac increased in vivo mean arterial pressure and ex vivo left ventricular pressure (LVP) and right ventricular pressure (RVP). Furegrelate improved RVP but not LVP. Experimental PE increased lung and systemic production of TxB(2). Inhibition at the COX-1/2 enzyme was equally as effective as inhibition of thromboxane synthase at reducing alveolar dead space and improving heart function after PE.

Topics: Angiography; Animals; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Disease Models, Animal; Extravascular Lung Water; Hypotension; Isoenzymes; Ketorolac; Membrane Proteins; Microspheres; Pleural Effusion; Polystyrenes; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Pulmonary Circulation; Pulmonary Embolism; Rats; Rats, Sprague-Dawley; Respiratory Dead Space; Survival Rate; Thromboxane B2; Thromboxane-A Synthase

The modified Fontan procedure separates the systemic and pulmonary circulations in patients born with a functional single ventricle. Delayed recovery is frequently observed after this procedure. It was our hypothesis that complement activation or cytokine generation may contribute to the pathophysiology of this problem.. We measured activated complement C3, thromboxane B2, interleukin-6, and tumor necrosis factor-alpha levels by immunoassay in 16 patients undergoing Fontan procedure. Patient plasma samples were obtained preoperatively, on initiation of cardiopulmonary bypass, after administration of protamine, and 1, 4, 8, and 24 hours postoperatively.. There was no early or late mortality in this cohort of patients. Low cardiac output developed in 3 of 16 patients, and pleural effusions developed in 5. The median length of hospital stay was 9 days. Activated complement C3 levels increased from a baseline of 1,486 +/- 564 to 4,600 +/- 454 ng/mL after cardiopulmonary bypass and administration of protamine, and returned to baseline by 24 hours. The level of interleukin-6 increased from 42 +/- 32 to 176 +/- 22 pg/mL and at 24 hours remained elevated at 71 +/- 15 pg/mL. Neither thromboxane B2 nor tumor necrosis factor-alpha levels increased significantly.. The data demonstrate threefold to four-fold increases in activated complement C3 and interleukin-6, indicating that both humoral and cellular systems are affected. It is our conclusion that complement and cytokine activation may contribute to the delayed recovery observed after Fontan procedure.

Topics: Antibody Formation; Cardiac Output, Low; Cardiopulmonary Bypass; Child, Preschool; Cohort Studies; Complement Activation; Complement C3; Cytokines; Female; Follow-Up Studies; Fontan Procedure; Heart Defects, Congenital; Heart Ventricles; Heparin Antagonists; Humans; Immunity, Cellular; Infant; Interleukin-6; Length of Stay; Male; Pleural Effusion; Protamines; Pulmonary Circulation; Thromboxane B2; Tumor Necrosis Factor-alpha

The reactions to platelet-activating factor (PAF-acether) injected into the pleural cavity of rats were compared with the reactions in animals injected with 0.9% NaCl. PAF-acether induced a maximum exudate after 30-60 min, which then decreased and disappeared after 24 h. The number of pleural leukocytes in the exudate was clearly decreased 30 min after the injection, was slightly increased after 6 h and was unchanged at other times. The estimation of lipid mediators in the pleural exudate obtained 30 and 60 min after the injection of PAF-acether revealed an increase in type-C4 leukotriene (LTC4) and a decrease in thromboxane B2 (TxB2) and in 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha). In addition, the amount of histamine was found to be lower after 30 min. These results confirm in vivo that some biological effects of PAF-acether seem to involve the participation of other mediators.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Histamine; Kinetics; Leukocyte Count; Male; Platelet Activating Factor; Pleural Effusion; Rats; Rats, Inbred Strains; SRS-A; Thromboxane B2

Topics: Animals; Aspirin; Butylated Hydroxytoluene; Carrageenan; Disease Models, Animal; Imidazoles; Inflammation; Pleural Effusion; Pleurisy; Prostaglandin Endoperoxides; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats; Thromboxane B2; Thromboxanes