DEVELOPMENT OF A PERITONEAL SCLEROSIS RAT MODEL USING A CONTINUOUS-INFUSION PUMP

• Published in: Peritoneal dialysis international Vol. 28; no. 6; pp. 641 - 647
• Main Authors: Komatsu, Hirotaka, Uchiyama, Koichi, Tsuchida, Masahiro, Isoyama, Naohito, Matsumura, Masafumi, Hara, Tomohiko, Fukuda, Masashi, Kanaoka, Yoshihiro, Naito, Katsusuke
• Format: Journal Article
• Language: English
• Published: Milton, ON Multimed 01.11.2008
• Subjects: Actins - metabolism; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Chlorhexidine - analogs & derivatives; Disease Models, Animal; Emergency and intensive care: renal failure. Dialysis management; Glomerulonephritis; Immunohistochemistry; Intensive care medicine; Male; Medical sciences; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Peritoneal Dialysis, Continuous Ambulatory - adverse effects; Peritoneum - pathology; Rats; Rats, Wistar; Sclerosis; Transforming Growth Factor beta1 - metabolism; Vascular Endothelial Growth Factor A - metabolism; Kidney disease; Urinary system disease; peritoneal sclerosis; rat model; Rat; continuous- infusion pump; Rodentia; Guanidines; Peritoneal dialysis; Extrarenal dialysis; Vertebrata; Biguanides; Mammalia; Chlorhexidine gluconate; Animal; Antiseptic; Renal failure; Chlorhexidine; Disinfecting agent
• ISSN: 0896-8608; 1718-4304
• DOI: 10.1177/089686080802800617

Department of Urology, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan Correspondence to: K. Naito, Department of Urology, Yamaguchi University School of Medicine, 1-1-1, Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan. surol{at}yamaguchi-u.ac.jp Objective: Encapsulating peritoneal sclerosis (EPS) is a serious complication of continuous ambulatory peritoneal dialysis. Previous studies have created peritoneal sclerosis rat models using daily intraperitoneal injection of chlorhexidine gluconate (CG), but this technique is cumbersome and thickening of the peritoneum makes it difficult to evaluate the injection site. We therefore aimed to make a rat model using a continuous-infusion pump. Methods: Various concentrations of CG (5%, 8%, 10%, 12%, and 14%) in ethanol were dissolved in saline within the infusion pumps, each of which was placed in the lower abdominal cavity of a male Wister rat. After a peritoneal equilibration test was performed, the rats were sacrificed and the lower anterior parietal and visceral peritoneum was removed. Each excised peritoneum was analyzed by macroscopic and microscopic examinations, including immunohistochemistry for the expression of transforming growth factor-beta 1 (TGF-β1), vascular endothelial growth factor (VEGF), and alpha-smooth muscle actin ( SMA). The results were compared with those of control rats injected with ethanol dissolved in saline within the infusion pump and with no-pump rats. Results: Two of the 5 rats in the 12% CG group and 3 of the 5 rats in the 14% CG group died of ileus within 14 days. All the rats in the 5%, 8%, and 10% CG groups survived to 28 days. Macroscopic examination in the 10% CG group showed bowel dilatation, bowel adhesion, and bloody ascites, similar to those seen in human EPS patients. All rats in each CG group showed the same extent of thickening of the submesothelial compact zone, proliferation of collagen fibers, and presence of numerous cells and neovascularization. Within same CG groups, an equal degree of thickening was observed at all sites of the peritoneum. TGF-β1, VEGF, and SMA were highly expressed in the peritoneum of the 10% CG group. Conclusion: We developed a novel method of creating a peritoneal sclerosis rat model using a continuous-infusion pump. Our technique is simple and highly reproducible, and will be useful in the study of peritoneal sclerosis mechanisms. KEY WORDS: Chlorhexidine gluconate; continuous-infusion pump; peritoneal sclerosis; rat model. Received 18 September 2007; accepted 23 April 2008.