No abstract

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.

Hemoperfusion and on-line removal of superantigens merits further study as a possible treatment strategy for streptococcal shock syndromes. The mechanism by which the fibers are operating requires further investigation.

No abstract

1. We have studied kidney structure and func tion in female Sprague-Dawley rats with chronic obstructive jaundice after bile-duct ligation and section and in age-matched sham-operated control animals.2. High bile-duct ligation and section resulted in immediate hyperbilirubinaemia and progressive hepatomegaly with histological evidence of bileduct proliferation and periportal inflammation and flbrosis.3. Only 20% of the jaundiced animals developed ascites, but 42% became hypotensive and died during preparation for micropuncture.4. In the surviving rats there was no significant change in blood pressure, whole-kidney glomerular filtration rate, single-nephron glomerular filtration rate or calculated glomerular capillary hydrostatic pressure from control animals. However, renal plasma flow was increased so that whole-kidney filtration fraction was low. These changes were largely reversed by choledochoduodenostomy.5. Proximal tubular reabsorption in the jaun diced group was not different from control rats, although the inulin (urine/plasma) ratio was sig nificantly reduced, indicating diminished reab sorption distal to the proximal convoluted tubule. Proximal intratubular hydrostatic pressure was sig nificantly increased in some nephrons.6. Electron microscopy of the glomeruli from the jaundiced animals revealed evidence of marked increase in activity of both epithelial and endothelial cells.7. Rats who survive chronic obstructive jaun dice for 3-4 weeks have changes in renal function and also structural changes suggestive of diminished glomerular permeability.