Effect of cyclooxygenase blockade on gas exchange and hemodynamics in Pseudomonas pneumonia.
Acute bilateral Pseudomonas aeruginosa pneumonia was induced in 10 anesthetized dogs, after which five dogs received intravenous indomethacin (2 mg/kg) (indomethacin group), whereas five others were infused with saline (2 ml/kg) (control group). Plasma levels of 6-ketoprostaglandin F1 alpha(6-keto-PGF1 alpha) and thromboxane B2 (TxB2), stable metabolites of prostacyclin (PGI2) and thromboxane A2 (TxA2), respectively, were measured by radioimmunoassay. Although TxB2 levels were not different before and after inoculation in either group, 6-keto-PGF1 alpha levels increased from their base-line value in each animal as pneumonia developed (indomethacin group: less than 100 to 330 +/- 90 pg/ml; control group: less than 100 to 630 +/- 300 pg/ml). Both prostaglandins fell to less than 100 pg/ml in each dog after indomethacin infusion, whereas they remained elevated in the control group after infusion of normal saline. Perfusion of consolidated lung regions (Qp/QT), measured with radioactive microspheres and expressed as a percent of total pulmonary blood flow, was dramatically reduced after indomethacin (35 +/- 3 to 16 +/- 1%) with consequent improvement in pulmonary shunt (Qs/QT: 30 +/- 8 to 18 +/- 6%) and arterial O2 tension (PaO2: 123 +/- 25 to 274 +/- 77 Torr). These parameters remained unchanged or deteriorated further in the control group after infusion of saline. Three additional dogs with Pseudomonas pneumonia were studied in which the indomethacin-induced reduction in Qp/QT was substantially but not completely reversed by intravenous infusion of PGI2.(ABSTRACT TRUNCATED AT 250 WORDS)
Hanly
P
P
Department of Medicine and Medical Microbiology, University of Manitoba, Winnipeg, Canada.
Sienko
A
A
Light
R B
RB
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D002248:Carbon Monoxide / Q000097:blood; D004285:Dogs; D011464:Epoprostenol / Q000097:blood*; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply / Q000187:drug effects; D011014:Pneumonia / Q000097:blood* / Q000209:etiology; D011552:Pseudomonas Infections; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D013929:Thromboxane B2 / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects*
D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D002248:Carbon Monoxide; D011464:Epoprostenol; D007213:Indomethacin