Protection from endotoxemia: a rat model of plasmapheresis and specific adsorption with polymyxin B.
Polymyxin B (PB), a cyclic polypeptide antibiotic, has potent antiendotoxin properties but is associated with significant toxicity when given parenterally. As an alternative, PB was immobilized on a solid phase (Sepharose 4B; Pharmacia, Uppsala, Sweden), and a system of plasmapheresis was developed in the conscious rat, with specific on-line plasma adsorption of endotoxin by a PB-Sepharose column. PB-Sepharose columns removed 94% of a challenge dose of 5 micrograms of endotoxin in vitro. Rats were pretreated with lead acetate so that they were sensitized to endotoxin and then given 10 micrograms of endotoxin/kg intraarterially. After 15 min plasmapheresis was begun and continued for 90 min. Animals whose plasma was perfused over PB-Sepharose were protected from endotoxin-induced leukopenia (P less than .01), thrombocytopenia (P less than .001), and death (four of four survivors compared with none of four controls). Thus plasmapheresis with on-line removal of endotoxin is a safe and highly effective means of protecting animals from the effects of endotoxemia.
D000818:Animals; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D007970:Leukopenia / Q000209:etiology / Q000628:therapy; D010956:Plasmapheresis; D011112:Polymyxin B / Q000627:therapeutic use*; D011113:Polymyxins / Q000627:therapeutic use*; D051381:Rats; D012772:Shock, Septic / Q000628:therapy*; D013921:Thrombocytopenia / Q000209:etiology / Q000628:therapy
D004731:Endotoxins; D011113:Polymyxins; D011112:Polymyxin B