Relationship of increased lung serotonin levels to endotoxin-induced pulmonary hypertension in sheep. Effect of a serotonin antagonist.
A persistent pulmonary artery hypertension, increased airways resistance, increased vascular permeability to protein, and hypoxia are characteristic of sepsis-induced ARDS in humans and are present in the late phase injury response seen in sheep after endotoxin. Our purpose was to determine the role of serotonin, 5-HT, in the steady-state pulmonary hypertension and decreased arterial oxygen tension seen beginning approximately 3 h after Escherichia coli endotoxin injury (2 micrograms/kg) in the adult sheep. Plasma 5-HT levels remained constant, whereas lung lymph values increased from a baseline of 60 +/- 40 to 180 +/- 70 and 270 +/- 90 ng/ml at 1-h and at 3- to 5-h periods, respectively, after endotoxin. Platelet count decreased significantly only at the 3-h time period. Ketanserin, a 5-HT antagonist, was infused (0.15 mg/kg/h) in 7 sheep during endotoxin injury. The degree of early pulmonary hypertension and hypoxia was not affected by ketanserin. Mean values for pulmonary artery pressure and arterial oxygen tension were 40 +/- 8 mmHg and 70 +/- 8 torr for endotoxin alone and 38 +/- 7 mmHg and 72 +/- 7 torr for the ketanserin group. Steady-state, protein-rich pulmonary perfusion was also not altered, being increased 3-fold in both groups. Pulmonary hypertension and hypoxia were significantly attenuated, however, at the 3- to 5-h period with ketanserin, compared with endotoxin alone, the pulmonary artery pressure decreasing from 29 +/- 5 to 22 +/- 4 mmHg and the PaO2 increasing from 75 +/- 4 to 83 +/- 5 torr.(ABSTRACT TRUNCATED AT 250 WORDS)
Demling
R H
RH
Wong
C
C
Fox
R
R
Hechtman
H
H
Huval
W
W
D000818:Animals; D001794:Blood Pressure; D004731:Endotoxins; D004926:Escherichia coli; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology; D007650:Ketanserin; D008168:Lung / Q000032:analysis; D008196:Lymph / Q000032:analysis; D010100:Oxygen / Q000097:blood; D010880:Piperidines / Q000494:pharmacology*; D010976:Platelet Count; D011651:Pulmonary Artery / Q000503:physiopathology; D012701:Serotonin / Q000032:analysis*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D012756:Sheep
D004731:Endotoxins; D010880:Piperidines; D012702:Serotonin Antagonists; D012701:Serotonin; D007650:Ketanserin; D010100:Oxygen