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Peritoneal Changes after Exposure to Sterile Solutions by Catheter

Michael F. Flessner^*, Kimberly Credit^*, Karla Henderson^*, Heather M. Vanpelt^*, Rebecca Potter^*, Zhi He, Jeffrey Henegar and Barry Robert

Departments of ^* Medicine and Pathology, University of Mississippi Medical Center, Jackson, Mississippi; and Pennington Biomedical Research Center, Baton Rouge, Louisiana

Correspondence: Dr. Michael F. Flessner, Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505. Phone: 601-984-5670; Fax: 601-984-5765; E-mail: mflessner{at}umsmed.edu

Received for publication December 30, 2006. Accepted for publication April 15, 2007.

Most current animal models that are used to study effects of long-term peritoneal exposure to dialysis solutions use an indwelling catheter for daily injections. It was hypothesized that the presence of a foreign body in the peritoneal cavity (PC) might alter the inflammatory response to the solutions and that the response would depend on exposure duration. For addressing these, long-term injections were carried out for 2 to 8 wk in 90 Sprague-Dawley rats: 40 via a subcutaneous port connected to a silicone catheter tunneled to the PC, 40 via direct needle injection, and 10 noninjected, age-control rats. Daily volumes were 30 to 40 ml of filter-sterilized, bicarbonate-buffered solutions that contained 4% dextrose. After 2, 4, 6, and 8 wk, anesthetized rats underwent transport experiments with a chamber affixed to the abdominal wall to determine mass transfer coefficients of mannitol (MTC_mannitol) and albumin (MTC_BSA), osmotic filtration flux (J_osm), and hydrostatic pressure–driven flux. After the rats were killed, tissues were collected for measurement of peritoneal thickness, vascular density, and immunohistochemical staining. ANOVA demonstrated significant (P < 0.01) differences in thickness, vessel density, MTC_mannitol, and MTC_BSA among the groups at the various time intervals and in overall means. Differences among the groups were less pronounced for hydrostatic pressure–driven flux and J_osm. Vessel density, MTC_mannitol, MTC_BSA, and J_osm were dependent on injection duration (P < 0.01). There were marked differences between the needle injection and catheter injection groups at various intervals in the expression of three cytokines. It is concluded that the histologic and functional response depends on the duration of injection with animals that are exposed for as little as 2 wk demonstrating alterations. These findings confirm the hypothesis that the presence of a PC catheter increases inflammatory response to sterile solutions as evidenced by the structural and functional changes in the peritoneal barrier.

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673