Brachytherapy for the Prevention of Stenosis in a Canine Hemodialysis Graft Model: Preliminary Observations
Abstract
PURPOSE: To determine whether gamma brachytherapy can prevent in-stent stenosis in hemodialysis grafts.
MATERIALS AND METHODS: Six-millimeter polytetrafluoroethylene arteriovenous grafts were created bilaterally in six dogs. After 1 month, Wallstents spanning the venous anastomosis were placed to accelerate restenosis. Gamma irradiation (12 Gy) was delivered endoluminally to one of the two grafts by using aniridium 192 source; thus, each animal served as its own control. Fistulography was performed monthly for 10 months or until graft thrombosis, with measurement of stenosis at each time point. At the conclusion of the study period, the treated area was examined histologically, and a computer model was used to calculate the volume of intimal hyperplasia.
RESULTS: Delayed stent migration resulted in exclusion of one dog. In the remaining five dogs, maximum stenosis across all time intervals was less for the treated side (P < .04), and the volume of intimal hyperplasia was less for the treated side (P < .045). In one animal studied at 1 year, this trend reversed in terms of percentage stenosis but not total neointimal volume.
CONCLUSION: Brachytherapy with 192Ir (gamma) delivered at the time of stent placement reduces restenosis in this hemodialysis graft model, but, depending on the parameter evaluated (stenosis vs total volume of neointima), the benefit may wane or even reverse with time.
References
- 1 Swedberg S, Brown B, Sigley R, Wight T, Gordon D, Nicholls S. Intimal fibromuscular hyperplasia at the venous anastomosis of PTFE grafts in hemodialysis patients: clinical, immunocytochemical, light and electron microscopic assessment. Circulation 1989; 80:1726-1736. Crossref, Medline, Google Scholar
- 2 Diskin CJ, Stakes TJ, Pennell AT. Pharmacologic intervention to prevent intimal hyperplasia. In: Ferguson RM, Henry ML, eds. Vascular access for hemodialysis III. Chicago, Ill: Precept Press, 1993; 41-73. Google Scholar
- 3 Beathard GA. Percutaneous transvenous angioplasty in the treatment of vascular access stenosis. Kidney Int 1992; 42:1390-1397. Crossref, Medline, Google Scholar
- 4 Glanz S, Gordon D, Butt K, Hong J, Lipkowitz G. The role of percutaneous angioplasty in the management of chronic hemodialysis fistulas. Ann Surg 1987; 206:777-781. Crossref, Medline, Google Scholar
- 5 Kanterman RY, Vesely TM, Pilgram TK, Guy BW, Windus DW, Picus D. Dialysis access grafts: anatomic location of venous stenosis and results of angioplasty. Radiology 1995; 195:135-139. Link, Google Scholar
- 6 Safa AA, Valji K, Roberts AC, Ziegler TW, Hye RJ, Oglevie SB. Detection and treatment of dysfunctional hemodialysis access grafts: effect of a surveillance program on graft patency and the incidence of thrombosis. Radiology 1996; 199:653-657. Link, Google Scholar
- 7 Schwab S, Raymond J, Saeed M, Newman G, Dennis P, Bollinger R. Prevention of hemodialysis fistula thrombosis: early detection of venous stenoses. Kidney Int 1989; 36:707-711. Crossref, Medline, Google Scholar
- 8 Besarab A, Sullivan KL, Ross RP, Moritz MJ. Utility of intra-access pressure monitoring in detecting and correcting venous outlet stenoses prior to thrombosis. Kidney Int 1995; 47:1364-1373. Crossref, Medline, Google Scholar
- 9 Turmel-Rodrigues L, Pengloan J, Blanchier D, et al. Insufficient dialysis shunts: improved long-term patency rates with close hemodynamic monitoring, repeated percutaneous balloon angioplasty, and stent placement. Radiology 1993; 187:273-278. Link, Google Scholar
- 10 Beathard GA. Gianturco self-expanding stent in the treatment of stenosis in dialysis access grafts. Kidney Int 1993; 43:872-877. Crossref, Medline, Google Scholar
- 11 Quinn SF, Schuman ES, Demlow TA, et al. Percutaneous transluminal angioplasty versus endovascular stent placement in the treatment of patients undergoing hemodialysis: intermediate results. JVIR 1995; 6:851-855. Crossref, Google Scholar
- 12 Hoffer EK, Sultan S, Herskowitz MM, Daniels ID, Sclafani S. Prospective randomized trial of a metallic intravascular stent in hemodialysis graft maintenance. JVIR 1997; 8:965-973. Crossref, Google Scholar
- 13 Teirstein PS, Massullo V, Jani S. Catheter-based radiotherapy to inhibit restenosis after coronary stenting. N Engl J Med 1997; 336:1697-1703. Crossref, Medline, Google Scholar
- 14 Verin V, Popowski Y, Urban P, et al. Intra-arterial beta irradiation prevents neointimal hyperplasia in a hypercholesterolemic rabbit restenosis model. Circulation 1995; 92:2284-2290. Crossref, Medline, Google Scholar
- 15 Sarac TP, Riggs PN, Williams JP, et al. The effects of low-dose radiation on neointimal hyperplasia. J Vasc Surg 1995; 22:17-24. Crossref, Medline, Google Scholar
- 16 Wiedermann JG, Marboe C, Amols H, Schwartz A, Weinberger J. Intracoronary irradiation markedly reduces restenosis after balloon angioplasty in a porcine model. J Am Coll Cardiol 1994; 23:1491-1498. Crossref, Medline, Google Scholar
- 17 Waksman R, Robinson KA, Crocker IR, Gravanis MB, Cipolla GD, King SB. Endovascular low-dose irradiation inhibits neointima formation after coronary artery balloon injury in swine. Circulation 1995; 91:1533-1539. Crossref, Medline, Google Scholar
- 18 Waksman R, Robinson KA, Crocker IR, et al. Intracoronary low-dose β-irradiation inhibits neointima formation after coronary artery balloon injury in the swine restenosis model. Circulation 1995; 92:3025-3031. Crossref, Medline, Google Scholar
- 19 Waksman R, Robinson KA, Crocker IR, et al. Intracoronary radiation before stent implantation inhibits neointima formation in stented porcine coronary arteries. Circulation 1995; 92:1383-1386. Crossref, Medline, Google Scholar
- 20 Bottcher HD, Schopohl B, Liermann D, Kollath J, Adamietz IA. Endovascular irradiation: a new method to avoid recurrent stenosis after stent implantation in peripheral arteries—technique and preliminary results. Int J Radiat Oncol Biol Phys 1994; 29:183-186. Crossref, Medline, Google Scholar
- 21 Liermann D, Bottcher HD, Kollath J, et al. Prophylactic endovascular radiotherapy to prevent intimal hyperplasia after stent implantation in femoropopliteal arteries. Cardiovasc Intervent Radiol 1994; 17:12-16. Crossref, Medline, Google Scholar
- 22 Smith , IIIEF, Pipes D, Konijnenberg M, Ferguson MS, Kirkman T. Efficacy of a Re-186 filled PTCA balloon system to prevent restenosis of peripheral vessels in swine and AV grafts in sheep. ; Presented at Advances in Cardiovascular Radiation Therapy, Washington, DC, 1997. Google Scholar
- 23 Waksman R, Crocker IR, Lumsden AB, MacDonald JM, Kikeri D, Martin LG. Long term results of endovascular radiation therapy for prevention of restenosis in the peripheral vascular system (abstr). Circulation 1996; 94:I-300. Google Scholar
- 24 Fillinger MF,, Kerns DB, Bruch D, Reinitz ER, Schwartz RA. Does the end-to-end venous anastomosis offer a functional advantage over the end-to-side venous anastomosis in high-output arteriovenous grafts?. J Vasc Surg 1990; 12:676-690. Crossref, Medline, Google Scholar
- 25 Fillinger MF, Reinitz ER, Schwartz RA, et al. Beneficial effects of banding on venous intimal-medial hyperplasia in arteriovenous loop grafts. Am J Surg 1989; 158:87-94. Crossref, Medline, Google Scholar
- 26 Fillinger MF, Reinitz ER, Schwartz RA, et al. Graft geometry and venous intimal-medial hyperplasia in arteriovenous loop grafts. J Vasc Surg 1990; 11:556-566. Crossref, Medline, Google Scholar
- 27 Sottiurai VS. Biogenesis and etiology in distal anastomotic intimal hyperplasia. Int Angiol 1990; 9:59-69. Medline, Google Scholar
- 28 Trerotola SO, Fair JH, Davidson D, Samphilipo MA, Magee CA. Comparison of Gianturco Z stents and Wallstents in a hemodialysis graft animal model. JVIR 1995; 6:387-396. Crossref, Google Scholar
- 29 Hehrlein C, Gollan C, Donges K, et al. Low-dose radioactive endovascular stents prevent smooth muscle cell proliferation and neointimal hyperplasia in rabbits. Circulation 1995; 92:1570-1575. Crossref, Medline, Google Scholar
- 30 Laird JR, Carter AJ, Kufs WM, et al. Inhibition of neointimal proliferation with low-dose irradiation from a β-particle-emitting stent. Circulation 1996; 93:529-536. Crossref, Medline, Google Scholar
- 31 Fischell TA, Kharma BK, Fishchell DR, et al. Low-dose, β-particle emission from “stent” wire results in complete, localized inhibition of smooth muscle cell proliferation. Circulation 1994; 90:2956-2963. Crossref, Medline, Google Scholar
- 32 Nori D, Parikh S, Moni J. Management of peripheral vascular disease: innovative approaches using radiation therapy. Int J Radiat Oncol Biol Phys 1996; 36:847-856. Crossref, Medline, Google Scholar
- 33 Sreedhara R, Himmelfarb J, Lazarus JM, Hakim RM. Anti-platelet therapy in graft thrombosis: results of a prospective, randomized, double-blind study. Kidney Int 1994; 45:1477-1483. Crossref, Medline, Google Scholar
- 34 Schwartz RS, Koval TM, Edwards WK, et al. Effect of external beam irradiation on neointimal hyperplasia after experimental coronary artery injury. J Am Coll Cardiol 1992; 19:1106-1112. Crossref, Medline, Google Scholar
- 35 Shimotakahara S, Mayberg MR. Gamma irradiation inhibits neointimal hyperplasia in rats after arterial injury. Stroke 1994; 25:424-428. Crossref, Medline, Google Scholar
- 36 Diamond DA, Vesely TM. The role of radiation therapy in the management of vascular restenosis. II. Radiation techniques and results. JVIR 1998; 9:389-400. Google Scholar
- 37 Schurmann K, Vorwerk D, Uppenkamp R, Klosterhalfen B, Bucker A, Gunther RW. Determination of stent stenosis: an in vivo experimental comparison of intravascular ultrasound and angiography with histology. Cardiovasc Intervent Radiol 1998; 21:189-198. Crossref, Medline, Google Scholar







