Intraperitoneal hyaluronan administration in conscious rats: Absorption, metabolism, and effects on peritoneal fluid dynamics

Background: Hyaluronan (HA) is a major component of interstitial tissue tha t participates in fluid homeostasis, response to inflammation, and wound he aling. Previous studies have shown that intraperitoneal administration of H A can affect peritoneal fluid transport during short peritoneal dialysis ex changes in anesthetized rats. We sought to investigate the effect of high m olecular weight HA on peritoneal permeability in conscious rats during dial ysis exchanges up to 8 hours in duration. In addition, we sought to investi gate the absorption of HA from the peritoneal cavity, its accumulation in p eritoneal tissues, and its metabolism in normal and uremic rats. Methods: Experiments were performed on male Wistar rats infused with 30 mt peritoneal dialysis solution (Dianeal, Baxter Healthcare; Castelbar, Irelan d) containing 10 mg/dL HA or with Dianeal alone (control). Peritoneal fluid removal (net ultrafiltration), permeability to glucose, creatinine, and to tal proteins, and tissue and blood levels of HA were determined in separate groups of rats at 1,2, 4, 6, and 8 hours after intraperitoneal infusion. H yaluronan appearance and disappearance from plasma were also studied for 24 hours in separate groups of normal and uremic rats. Results: Net ultrafiltration was significantly greater (27%) in rats infuse d with HA at 4, 6, and 8 hours (p < 0.01) compared to controls. Transperito neal equilibration of protein was reduced by 27% (p < 0.001) at 4 hours and by 30% (p < 0.01) at 8 hours. During the 8-hour exchange, peritoneal clear ance of creatinine increased by 27% (p < 0.01), whereas the clearance of to tal protein decreased by 27% (p < 0.005). After 8 hours, 25.7% +/- 3.1% of the administered HA was absorbed from the peritoneal cavity, peritoneal tis sue HA concentration was increased by 117% (p < 0.001), and plasma HA level s increased by 435% (p < 0.001). Plasma HA levels returned to normal within 24 hours after intraperitoneal administration in both healthy and uremic r ats. Conclusions: Hyaluronan added to dialysis fluid is absorbed from the perito neal cavity and accumulates in peritoneal tissues. Hyaluronan supplementati on produces changes in peritoneal permeability, leading to higher net ultra filtration and peritoneal creatinine clearance, whereas total protein clear ance decreases. The HA that is absorbed from the peritoneal cavity appears to be rapidly metabolized in both healthy and uremic rats.