PMID- 19164250
OWN - NLM
STAT- MEDLINE
DCOM- 20090428
LR  - 20200109
IS  - 0896-8608 (Print)
IS  - 0896-8608 (Linking)
VI  - 29
IP  - 1
DP  - 2009 Jan-Feb
TI  - Long-term intervention with heparins in a rat model of peritoneal dialysis.
PG  - 26-35
AB  - BACKGROUND: Peritoneal dialysis (PD) is associated with functional and structural 
      alterations of the peritoneal membrane, particularly new vessel formation and 
      fibrosis. In addition to anticoagulant effects, heparin displays 
      anti-inflammatory and angiostatic properties. Therefore, the effects of 
      administration of heparins on function and morphology of the peritoneal membrane 
      were studied in a rat PD model. METHODS: Rats received 10 mL conventional PD 
      fluid (PDF) daily, with or without the addition of unfractionated heparin (UFH) 
      or low molecular weight heparin (LMWH) in the PDF (1 mg/10 mL intraperitoneally) 
      via a mini access port. Untreated rats served as controls. After 5 weeks, a 
      90-minute functional peritoneal transport test was performed and tissues and 
      peritoneal leukocytes were taken. RESULTS: PD treatment induced loss of 
      ultrafiltration (p<0.01), a twofold increase in glucose absorption (p<0.03), 
      increased urea transport (p<0.02), and loss of sodium sieving (p<0.03), which 
      were also found in the PDF+heparin groups. Increased peritoneal cell influx and 
      hyaluronan production (p<0.02) as well as an exchange of mast cells and 
      eosinophils for neutrophils after PD treatment were observed in PD rats; addition 
      of heparin did not affect those changes. Mesothelial regeneration, submesothelial 
      blood vessel and matrix formation, and accumulation of tissue macrophages were 
      seen in PD animals. Spindle-shaped vimentin-positive and cytokeratin-negative 
      cells indicated either partial injury and denudation of mesothelial cells or 
      epithelial-to-mesenchymal transition. Neither UFH nor LMWH affected any of these 
      morphological changes. CONCLUSION: Within 5 weeks, PD treatment induces a chronic 
      inflammatory condition in the peritoneum, evidenced by high transport, leukocyte 
      recruitment, tissue remodeling, and induction of spindle-shaped cells in the 
      mesothelium. Addition of LMWH or UFH to the PDF did not prevent these adverse 
      PDF-induced peritoneal changes.
FAU - Schilte, Margot N
AU  - Schilte MN
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical 
      Center, Amsterdam, The Netherlands. m.schilte@vumc.nl
FAU - Loureiro, Jesus
AU  - Loureiro J
FAU - Keuning, Eelco D
AU  - Keuning ED
FAU - ter Wee, Piet M
AU  - ter Wee PM
FAU - Celie, Johanna W A M
AU  - Celie JW
FAU - Beelen, Robert H J
AU  - Beelen RH
FAU - van den Born, Jacob
AU  - van den Born J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Perit Dial Int
JT  - Peritoneal dialysis international : journal of the International Society for 
      Peritoneal Dialysis
JID - 8904033
RN  - 0 (Anticoagulants)
RN  - 9005-49-6 (Heparin)
SB  - IM
CIN - Perit Dial Int. 2009 Jan-Feb;29(1):16-9. PMID: 19164247
MH  - Animals
MH  - Anticoagulants/*administration & dosage/pharmacokinetics
MH  - Biological Transport/physiology
MH  - Disease Models, Animal
MH  - Fibrosis/etiology/pathology/prevention & control
MH  - Follow-Up Studies
MH  - Heparin/*administration & dosage/pharmacokinetics
MH  - Kidney Failure, Chronic/metabolism/therapy
MH  - Male
MH  - Mesentery/drug effects/metabolism/pathology
MH  - Neovascularization, Pathologic/pathology/prevention & control
MH  - Omentum/drug effects/metabolism/pathology
MH  - Peritoneal Dialysis/adverse effects/*methods
MH  - Peritoneum/drug effects/*metabolism/pathology
MH  - Rats
MH  - Rats, Wistar
MH  - Time Factors
EDAT- 2009/01/24 09:00
MHDA- 2009/04/29 09:00
CRDT- 2009/01/24 09:00
PHST- 2009/01/24 09:00 [entrez]
PHST- 2009/01/24 09:00 [pubmed]
PHST- 2009/04/29 09:00 [medline]
AID - 29/1/26 [pii]
PST - ppublish
SO  - Perit Dial Int. 2009 Jan-Feb;29(1):26-35.