Detergent inhibits 70-90% of responses to intravenous endotoxin in awake sheep.
Sheep have reactive pulmonary intravascular macrophages, which are essential for the marked pulmonary vascular response to infusions of small quantities of endotoxin. In another species with reactive pulmonary intravascular macrophages, horses, our laboratory found that an intravenous biosafe detergent, tyloxapol, inhibited some systemic and pulmonary responses to endotoxin (Longworth KE, Smith BL, Staub NC, Steffey EP, and Serikov V. Am J Vet Res 57: 1063-1066, 1996). We determined whether the same detergent would inhibit endotoxin responses in awake sheep. In 10 awake, instrumented sheep with chronic lung lymph fistulas, we did a control experiment by intravenously infusing 1 microg/kg Escherichia coli endotoxin. One week later, we gave 40 micromol/kg tyloxapol intravenously 1-4 h before infusing the same dose of endotoxin. In these paired studies, we compared pulmonary hemodynamics, lung lymph dynamics, body temperature, circulating leukocyte concentrations, and circulating tumor necrosis factor for 6 h. In all 10 sheep, tyloxapol blocked 80-90% of the pulmonary responses and 70-90% of the systemic responses. Tyloxapol is safe, inexpensive, easy to use, and effective immediately. It may be a clinically useful approach to contravening many of the effects of endotoxemia, in humans as well as animals.
Staub
N C
NC
Cardiovascular Research Institute, University of California, San Francisco 94143, USA.
Longworth
K E
KE
Serikov
V
V
Jerome
E H
EH
Elsasser
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D003902:Detergents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004926:Escherichia coli; D006736:Horses; D007262:Infusions, Intravenous; D007962:Leukocytes / Q000502:physiology; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008196:Lymph / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D012756:Sheep; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014851:Wakefulness
D003902:Detergents; D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; C016811:tyloxapol