title: Characterization of an endotoxemic baboon model of metabolic and organ dysfunction.
abstract: An anesthetized endotoxemic baboon model has been developed by infusing 2.0 mg E. coli endotoxin/kg i.v. over 1 hr (n = 7). Animals were monitored for 5-7 days with analyses of: cardiovascular, metabolic, and organ dysfunction; acid base, hemostatic, and hematological alterations; as well as tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels. Pathophysiologies detected at 2 hr included transient decreases in vascular resistance and blood pressure, a 157% increase in blood lactate, and a 90% decrease in circulating neutrophils. Organ dysfunction was not observed until 24 hr and, although thrombocytopenia was prevalent (-72% at 48 hr), disseminated intravascular coagulation (DIC) was not a major pathology. Hematocrit fell 21% by 24 hr and was -41% at 5-7 days. Serum TNF peaked at 90 min (7.8 +/- 0.2 ng/mL) and was undetectable after 3 hr. IL-6 also increased early, peaked at 3 hr (3872 +/- 846 U/mL) and was still detectable at 24 hr. A low mortality primate model of gram-negative sepsis has been developed that is characterized by early cardiovascular and metabolic dysfunction (2-6 hr), late organ dysfunction (24-48 hr), sub-clinical DIC, a prolonged anemia, and a 29% mortality between 48 and 72 hr.
authors.affiliation: Miles Inc., Department of Experimental Therapeutics, Berkeley, California 94710.
authors.forename: D C
authors.initials: DC
authors.lastname: Lindsey
authors.forename: T E
authors.initials: TE
authors.lastname: Emerson
authors.forename: T E
authors.initials: TE
authors.lastname: Thompson
authors.forename: A E
authors.initials: AE
authors.lastname: John
authors.forename: M L
authors.initials: ML
authors.lastname: Duerr
authors.forename: C M
authors.initials: CM
authors.lastname: Valdez
authors.forename: H S
authors.initials: HS
authors.lastname: Kuo
authors.forename: R B
authors.initials: RB
authors.lastname: Bouffard
authors.forename: R G
authors.initials: RG
authors.lastname: Irwin
authors.forename: D
authors.initials: D
authors.lastname: Canivel
mesh_terms: D000136:Acid-Base Equilibrium; D000818:Animals; D001772:Blood Cell Count; D001831:Body Temperature; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005740:Gases / Q000097:blood; D006439:Hemodynamics; D006487:Hemostasis; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008659:Metabolic Diseases / Q000150:complications*; D010215:Papio; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D004731:Endotoxins; D005740:Gases; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides