Prosthetic dialysis access
thrombosis and/or
stenosis is the most common cause of graft impairment or loss and is primarily attributed to venous outflow
stenosis due to intimal
hyperplasia. Intimal
hyperplasia is thought to result from interactions between areas of exposed subendothelial
collagen in an injured vessel and platelets, resulting in platelet adhesion.
Saratin, an inhibitor of the vWF-dependent binding of platelet to
collagen interaction, has been shown in vitro to reduce the adhesion of platelets to
collagen. In the current study, the authors investigated the effects of topical
saratin administration in a canine dialysis access model in regard to intimal
hyperplasia development at the venous anastomosis. Fourteen female mongrel dogs underwent placement of a femoral
polytetrafluoroethylene (
PTFE) dialysis access graft and were placed into 1 of 2 groups: 1) control or 2) experimental with topical
saratin application. The experimental group had 600 microg of
saratin (1 microg/microL) applied for 5 minutes directly onto the venous anastomosis before restoration of blood flow;control groups received vehicle control. At 4 weeks postoperative, a portion of the graft was removed along with a segment of the outflow vein. Veins were subsequently processed, sectioned, and analyzed along the length of the excised segment and divided into blocks that included the area of the graft toe, midanastomotic region and heel, and blocks A-E. Intimal
hyperplasia was assessed by a computer-assisted morphometric analysis. Platelet counts and bleeding times were also measured. Vein segments in the control group (n=7) showed pronounced intimal
hyperplasia in blocks B, C, and D as compared to the
saratin group (n=6). Distribution of intimal
hyperplasia by blocks between control and
saratin groups were as follows: block [A] 8.6 +/- 1.9 vs 9.7 +/- 3.0% (p=NS), [B] 32.7 +/- 6.3 vs 10.7 +/- 3.5% (p=0.01), [C] 44.8 +/- 6.2% vs 10.3 +/- 1.5% (p=0.0004), [D] 40.8 +/- 11.0 vs 9.1 +/- 4.2% (p=0.02), [E] 7.5 +/- 5.5 vs 2.7 +/- 0.4% (p=NS). Intimal
hyperplasia normalized to vein wall thickness also showed a significant reduction with
saratin application. Bleeding times and platelet counts obtained at different time points during the experiment showed no difference between control and
saratin groups. In a canine dialysis access model using
PTFE grafts, topical application of
saratin at the venous anastomosis decreased intimal
hyperplasia development by as much as 77% when compared with control animals.
Saratin provides for a method of substantially reducing intimal
hyperplasia by direct local application without systemic side effects.