Development of a peritoneal sclerosis rat model using a continuous-infusion pump.
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-beta1), vascular endothelial growth factor (VEGF), and alpha-smooth muscle actin (alphaSMA). 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-beta1, VEGF, and alphaSMA were highly expressed in the peritoneum of the 10% CG group.


CONCLUSIONS
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.
Komatsu
Hirotaka
H
Department of Urology, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
Uchiyama
Koichi
K
Tsuchida
Masahiro
M
Isoyama
Naohito
N
Matsumura
Masafumi
M
Hara
Tomohiko
T
Fukuda
Masashi
M
Kanaoka
Yoshihiro
Y
Naito
Katsusuke
K
D000199:Actins / Q000378:metabolism; D000818:Animals; D002710:Chlorhexidine / Q000031:analogs & derivatives; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects; D010537:Peritoneum / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012598:Sclerosis; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000199:Actins; D002710:Chlorhexidine; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C498862:Acta2 protein, rat; C010882:chlorhexidine gluconate