Increased rat cardiac allograft survival by the glycosaminoglycan pentosan polysulfate.
BACKGROUND
Modulation of the inflammatory response has proven to be of benefit in salvaging cardiac allografts at risk of irreversible injury. Pentosan polysulfate (PPS), like heparin, is a negatively charged sulfated glycosaminoglycan (GAG) that possesses anti-inflammatory properties including the ability to inhibit activation of the complement system. This study was conducted to determine the potential of PPS to prolong allograft survival in an experimental model of cardiac transplantation.


METHODS
A heterotopic cardiac transplant was performed by implanting the heart from fetal Brown Norway rats into the ear pinnae of adult Lewis rats. Vehicle (saline) or PPS (30 mg/kg) was administered subcutaneously immediately after transplantation and daily thereafter (n = 6 in each group). Another GAG, heparin, was also analyzed to determine the effect of anticoagulation on transplant survival (n = 6).


RESULTS
Treatment with PPS significantly (P < 0. 05) increased allograft survival time as compared to vehicle-treated animals (8.0 +/- 0.3 days vs 5.5 +/- 0.5 days). The results noted with PPS were similar to those observed in cyclosporine (10 mg/kg; n = 6)-treated animals (8.25 +/- 0.25 days). Treatment with heparin (300 U/kg/day) did not significantly prolong cardiac graft survival time, suggesting that anticoagulation is not sufficient to prolong transplant survival. Analysis of tissue histology showed diminished transplant rejection as evidenced by decreased white blood cell infiltration and cellular necrosis.


CONCLUSIONS
The results of this study indicate that PPS possesses the ability to prolong cardiac transplant viability in a heterotopic cardiac transplant model, independent of its anticoagulant actions.
Schwartz
C F
CF
Departments of Thoracic Surgery and Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Kilgore
K S
KS
Homeister
J W
JW
Levy
B A
BA
Lucchesi
B R
BR
Bolling
S F
SF
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000925:Anticoagulants / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation; D006493:Heparin / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D010426:Pentosan Sulfuric Polyester; D006493:Heparin