The Effects of Heparin Administration in an Animal Model of Chronic Peritoneal Dialysate Exposure

Abstract

Diverse modes of heparin administration have been used in animal models of chronic peritoneal dialysate exposure to maintain catheter patency and prevent fibrinous adhesions. Heparin has biological actions independent of its well-known anticoagulant activity, including the ability to modulate extracellular matrix synthesis, cellular proliferation, angiogenesis, and inflammation. These actions may interfere with peritoneal membrane homeostasis. The present study evaluated the influence of the mode of heparin administration on technique survival and infection rate in a rat model of chronic dialysate exposure. Further, the incorporation of heparin in the peritoneal membrane was examined. A 3.86% glucose dialysate was injected twice daily into Wistar rats with a heparin-coated catheter (group A1), or with a standard catheter with heparin injections during the entire exposure time (group A2) or only during 1 week (group A3). Sham manipulations were performed in a fourth group and a fifth group was left untreated. Technique survival was 80% in group A1, 60% in group A2, and 40% in group A3. The rate of infection was highest in group A1 and lowest in group A2. Intraperitoneally administered heparin accumulated in the peritoneal membrane, whereas dextran, with a molecular weight similar to that of heparin, was not incorporated in the peritoneum. In conclusion, intraperitoneal heparin reduced the incidence of infection in an animal model of chronic dialysate exposure. The best technique survival was, however, obtained using a heparin-coated catheter. Heparin is incorporated in the peritoneal membrane, where it may exert diverse biological actions and thus bias study results. The use of a heparin-coated catheter in combination with antibiotics may be the optimal approach to obtaining peritoneal access in animal models of chronic dialysate exposure.

Experimental models in peritoneal dialysis (Review)

“…The omentum is an organ with defensive function. In a normal rat PD model, keeping the large omentum intact during the PD process can reduce the incidence of infection, however, the incidence of catheter blockage is increased ( 31 ). Goh ( 32 ) proposed that peritoneal folding is a safe and effective technique to solve the issue of catheter occlusion.…”

Loosening of the mesothelial barrier as an early therapeutic target to preserve peritoneal function in peritoneal dialysis

“…Furthermore, adenoviral BMP-7 transfection decreased peritoneal EMT and ameliorated peritoneal thickening in animal models of PD. There are other pharmacologic agents such as cyclooxygenase-2 inhibitors [65,66], renin-angiotensin blockades [67], and heparin [68] showing beneficial effects on peritoneal fibrosis and ultrafiltration in animal models of PD.…”

A New Non-Uremic Rat Model of Long-Term Peritoneal Dialysis

“…The obtained peritoneal fluid was collected for cell count. The episodes of infection, defined as a positive dialysate culture and a dialysate with white blood cell count over 1000/mm 3 , were diagnosed (De Vriese et al 2002, Mortier et al 2004.…”