Effect of leukotriene inhibitor LY-171883 on the pulmonary response to Escherichia coli endotoxemia.
The effect of the leukotriene D4 (LTD4) receptor antagonist, LY-171883, on the respiratory and cardiovascular changes in endotoxemia was studied in 20 unanesthetized sheep. In group 1 (n = 2), 4 mg/kg LY-171883 was injected iv. In group 2 (n = 12), Escherichia coli endotoxin (1 micrograms/kg) was infused iv, and in group 3 (n = 6), 4 mg/kg LY-171883 was administered 15 min before and 30 min after the same dose of endotoxin. Infusion of LY-171883 in group 1 did not alter baseline ventilatory and cardiovascular measurements. A two-phase pulmonary response was observed in group 2: an early pulmonary hypertension phase in which pulmonary artery pressure (PAP) increased from 18.7 to 51.2 mm Hg (p less than .001), with a fall in cardiac index (CI) from 171 to 114 ml/min.kg (p less than .01). The ratio of peak inspiratory/expiratory flow rate (PIF/PEF) increased from 1.08 to 1.35 (p less than .01) and the respiratory rate from 50 to 70 breath/min (p less than .005) 30 min postendotoxin. The flow rate measured at midexpiration time (V50) decreased from 81% to 25% of its peak expiration (p less than .001) and the airway resistance increased from 3.8 to 32.7 cm H2O/L.sec (p less than .001). The second permeability phase was characterized by an increase in pulmonary lymph flow (QL) from 8.5 to 35.2 ml/h (p less than .01), a decrease in PaO2 from 76 to 61 torr (p less than .01), and an increase in pulmonary shunt ratio (Qsp/Qt) from 16% to 31% (p less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)
Gross
D
D
Department of Surgery B, Hadassah University Hospital, Jerusalem, Israel.
Ben Dahan
J
J
Landau
E H
EH
Krausz
M M
MM
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000098:Acetophenones / Q000627:therapeutic use*; D000818:Animals; D012898:Autacoids / Q000037:antagonists & inhibitors*; D001393:Azoles / Q000627:therapeutic use*; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D012119:Respiration / Q000187:drug effects*; D012756:Sheep; D013777:Tetrazoles / Q000627:therapeutic use*; D013929:Thromboxane B2 / Q000097:blood
D000098:Acetophenones; D012898:Autacoids; D001393:Azoles; D013777:Tetrazoles; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C044660:LY 171883