(Circulation. 1995;92:1383-1386.)
© 1995 American Heart Association, Inc.
Articles |
Intracoronary Radiation Before Stent Implantation Inhibits Neointima Formation in Stented Porcine Coronary Arteries
From the Andreas Gruentzig Cardiovascular Center, Division of Cardiology, Department of Medicine (R.W., K.A.R., S.J.P., G.D.C., S.B.K.), Department of Radiation Oncology (I.R.C.), and Department of Pathology (M.B.G.), Emory University School of Medicine, and the Health Physics Program, Georgia Institute of Technology (C.W.), Atlanta, Ga.
Correspondence to Spencer B. King III, MD, Andreas Gruentzig Cardiovascular Center, F606 Emory University Hospital, 1364 Clifton Rd NE, Atlanta, GA 30322.
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Abstract |
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Background Stent implantation has been shown to reduce restenosis by establishing a larger lumen but not by reducing neointima formation. We have previously shown that ionizing radiation reduced neointima formation after balloon injury in a swine model of restenosis. The purpose of this study was to determine whether endovascular irradiation of the coronary artery before stent implantation would affect neointima formation.
Methods and Results Nine normolipemic pigs underwent coronary angiography, and segments of the left anterior descending and left circumflex arteries were chosen as targets for stenting. A high-activity 192Ir source was used to deliver 14 Gy by random assignment to one of the vessels. After this, 3.5-mm tantalum stents were implanted in both arteries. Three additional pigs were treated with a 90Sr/Y source (a pure ß-emitter) delivering 14 Gy to five segments of coronary vessels that were stented immediately after irradiation. Stent-to-artery ratio was similar in the radiated and the control arteries. Animals received aspirin 325 mg daily and were killed at 28 days. The intimal area was significantly reduced in the irradiated stented arteries compared with control arteries treated with stent only (1.98 mm2 with 192Ir and 2.53 mm2 with 90Sr/Y versus 3.82 mm2 in the control stented arteries, P<.005).
Conclusions Endovascular radiation before coronary stenting reduces neointima formation and may further reduce the restenosis rate after stent implantation.
Key Words: stents • restenosis
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Intracoronary metallic stents are being used with increasing frequency for prevention of restenosis.1 2 3 4 The presumed mechanism by which stents reduce restenosis is the achievement of a larger initial lumen size and reduction of both the acute and chronic recoil phenomena after balloon dilatation.5 Clinical and experimental data suggest that restenosis results partly from recoil and remodeling but also from migration, proliferation, and matrix deposition by smooth muscle cells after vascular injury.6 7 The only modest effect of stenting on restenosis rate is due to the more pronounced neointimal formation with stents compared with that found in balloon angioplasty. This has been demonstrated in animal models8 and more recently in a clinical study using intravascular ultrasound.9 A potent antiproliferative therapy in conjunction with stenting might therefore provide a means for effective reduction of restenosis.
We have previously demonstrated the efficacy of endovascular
low-dose 
irradiation with 192Ir to inhibit
neointima formation in response to balloon overstretch
injury in pig coronary arteries.10 This work has
been corroborated by two additional
studies.11 12 13 Similar
results were obtained in the same model using a 90Sr/Y
source.14 The only clinical study of radiation after
balloon dilatation, in which restenotic stented lesions
were ballooned and treated with 192Ir, was carried out in
peripheral arteries with a very low restenosis
rate reported at 5 years of follow-up.15 Recently,
low-dose/low-rate radioactive endovascular stents with either
ß or emission energy have been implanted in rabbit iliac arteries
and shown to significantly reduce neointimal
hyperplasia.16 17
The purpose of this study was to investigate whether delivering endovascular radiation (192Ir or 90Sr/Y) to the coronary artery before stent implantation would affect neointima formation.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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All experiments and animal care conformed to National Institutes of Health and American Heart Association guidelines for the care and use of animals and were approved by the Emory University Institutional Animal Care and Use Committee.
Experimental Protocol
Nine normolipemic pigs
(Sus scrofa, 21.2 to 30.1 kg)
were given aspirin (325 mg) 1 day before and the day of the procedure,
sedated, and anesthetized as previously
described.10 After placement of an 8F introducer sheath in
the right femoral artery by surgical cutdown, each animal received a
single dose of heparin (200 U/kg) and bretylium tosylate (2.5 mg/kg).
Under fluoroscopic guidance, an 8F hockey-stick guiding catheter
was positioned in the left coronary ostium. After the
intracoronary administration of
nitroglycerin (200 µg), coronary angiography
was performed, and segments of the left anterior descending or the left
circumflex arteries were chosen as targets for stent implantation. One
artery was then randomly assigned to receive radiation treatment. Over
a flexible 0.014-in. wire, a 4F perfusion delivery catheter (USCI Corp)
was introduced to the chosen site of the assigned artery, the guide
wire was withdrawn, and a 3-cm ribbon of 192Ir was
positioned at the assigned segments of the left anterior descending or
left circumflex arteries by use of cinefluoroscopic visualization. The
isotope was left in place within the delivery catheter for a period
sufficient to deliver 14 Gy to a depth of 2 mm (28 to 38 minutes,
depending on source activity). Then 3.5-mm tantalum stents (Cordis
Corp) were implanted and apposed well to the artery wall by use of
high-pressure (14-atm) balloon inflation at the irradiated site and
in the control, nonirradiated artery. After the completion of stent
implantation, additional nitroglycerin (200 µg) was
administered to limit coronary spasm. Repeat angiography was
then performed to assess vessel patency.
Three additional pigs received radiation treatment with 90Sr/Y (16 mCi) to a total of five coronary arteries with a 4.5F delivery catheter (Novoste Corp). The catheter was positioned over a flexible 0.014-in. guide wire, the wire was removed, and a train 2.5 cm long with five seeds of 90Sr/Y was positioned at the targeted site within the delivery catheter. It was left in place for a period sufficient to deliver the assigned dose (14 Gy) to a depth of 2 mm (196 seconds). After irradiation, the delivery catheter was removed, and 3.5-mm tantalum stents (Cordis Corp) were implanted in the same manner as for the nine pigs treated with 192Ir. At the end of all procedures, the femoral cutdown was repaired, nitroglycerin ointment (1 in.) was administered topically, and the animals were returned to routine care. They received aspirin 325 mg daily until specimen harvest at 28 days.
Radiation Details
For 192Ir, the treatment time
was determined in
standard fashion by entering the activity of the 3-cm 192Ir
ribbon, as supplied by the manufacturer (Medi-Physics Inc), into a
commercial radiation treatment planning system (CMS Modulex). The dose
distribution and the dose rate at the prescription point were then
calculated by the system by use of standard brachytherapy dose
algorithms. The dose distribution and dose rate around the 2.5-cm
90Sr/Y line source was calculated by the Monte Carlo
electron transport code ITS.18 The ß-energy spectrum
of 90Sr/Y was obtained from Cross et al.19 The
activity of each seed and of the total source train was determined by
the manufacturer with an NIST-traceable standard. The dose rate at the
prescription point of the 192Ir source was calculated with
both ITS and the CMS Modulex planning system. These were found to agree
within 5%. There was no mechanism for centering of the catheter within
the arterial lumen, nor was any attempt made to account for
curvature of the artery with either source.
Tissue Analysis
Four weeks after the stent implantation, the
animals were
heparinized, a lethal dose of barbiturate was given, the chest was
opened, and the heart was rapidly excised. The coronary system
was perfusion-fixed at 100 to 110 mm Hg driving pressure with 10%
formaldehyde for 15 minutes, and the heart was stored overnight in the
same fixative. The stented arteries were embedded in methyl
methacrylate and sectioned with the stents in place with a
low-speed saw. Serial sections spanning the injury site were glued
to acrylic slides, ground to 50 µm thick, and stained with toluidine
blue. Each segment (three to five per stent, one from the midportion
and at least one each in the proximal and distal regions) was
analyzed by histopathological and morphometric techniques. The
histological features were measured with a computerized
IBM-based system (Bioscan 2, Thomas Optical Measurement System,
Inc). Sections were magnified at x26, digitized, and stored in a
frame-grabber board. The maximal intimal thickness was determined
in each section by a radial line drawn from the lumen border to the
internal lamina at the point of greatest tissue growth, just adjacent
to the stent wire. Area measurements were obtained by tracing the lumen
perimeter (luminal area, mm2), neointima
perimeter (intimal area, mm2, defined by the borders
of the internal elastic lamina, lumen, media, and external elastic
lamina or stent wires), and vessel perimeter (to determine vessel area,
mm2). Sections were also evaluated for the presence of
intraluminal thrombus and inflammatory cell infiltrate.
Statistical Analysis
Data are presented as mean±SD.
Data were
analyzed by the two-tailed paired Student's t
test to compare group means for 192Ir-treated versus
control stented arteries in the same animal. Arteries treated with
90Sr/Y were compared with the same controls by unpaired
t tests. Significance was established at the 95% confidence
level (P<.05).
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Group Characteristics
Twelve animals underwent interventions on 23 coronary arteries. There were no significant differences in body weight between groups at the time of balloon injury. Angiographic arterial diameter was similar between groups (2.67±0.15 mm), and stent artery ratio was similar in the irradiated arteries (1.52±0.55) and controls (1.50±.033). The distribution of left anterior descending and left circumflex arteries was similar among the treated and the control stented arteries. In two animals, the distal RCA was irradiated and stented with the 90Sr/Y source (Table 1
).
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Histological and Morphometric
Analysis
All arterial stented segments were examined. In both
control and irradiated arteries, the stents were well embedded into the
vascular wall, resulting in thinning of the media. There was overall
similarity between groups in the degree of injury to the media,
including occasional instances of medial fracture and stent penetration
into the adventitia. Occasionally there was evidence of
hemorrhage into the perivascular space. Control stented
arteries showed substantial neointima, consisting of either
round, stellate, or spindle-shaped cells in a loose extracellular
matrix (Fig 1). Many segments showed inflammatory
infiltrates surrounding the stent wire. The inflammatory reaction in
the treated arteries was minimal compared with the control arteries.
These rarely included foreign-body giant cells (histiocytes) in the
neointima. Irradiated stented arteries exhibited modest
neointima formation compared with controls (Fig 2), although
there was some variability in thickness
within the treatment group (Fig 3). A certain degree of
eccentricity in the neointimal proliferation was noted. In
all samples, there appeared to be complete coverage of the luminal
surface by a monolayer of endothelial cell–like
cells.
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The luminal area was significantly increased and the intimal
area was
significantly reduced in both radiation treatment groups compared with
control, whereas the vessel perimeter and the vessel area were
unchanged by the radiation treatment. There were no significant
morphological or morphometric differences between arteries treated with
the ß- or -emitting isotopes (Table 2).
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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Restenosis after stent implantation in patients with coronary artery disease is caused primarily by an intimal hyperplastic response. Stenting induces comparatively more neointimal thickening than balloon angioplasty.9 This study demonstrates the first successful use of intracoronary low-dose radiation treatment as an adjunct to stent implantation and shows the efficacy of this approach in reducing neointimal hyperplasia.
The histological and histomorphometric results in this
study using 90Sr/Y were comparable to those for
192Ir. However, pure ß-emitters like
90Sr/Y have a distinct advantage over the use of energetic
-emitters like 192Ir in that ß-particles have
a limited penetration in tissue and deliver significantly less dose
beyond the prescription point than do
-emitters.19 20 This is important in limiting
the
whole-body exposure to the patient and the operator. In addition,
the treatment with 90Sr/Y took only 190 seconds compared
with 32 minutes with 192Ir, thus reducing the length of
time of intracoronary catheterization.
The use of radioactive stents, or a stent coated with a radioactive isotope, has been proposed by two separate groups.16 17 Impregnating the stent with a ß-emitting isotope would seem to be the more desirable approach of the two, but concerns regarding (1) potential leaching of the radioactive material from the metallic stent, (2) possible thrombosis on the stent wire due to delayed reendothelialization of the stent struts, and (3) continued delivery of dose by a permanently implanted stent beyond the period of time required to inhibit restenosis need to be addressed.
Although radioactive stents have the potential advantage of application of the radioisotope close to the proliferating tissue, the practical issues of active shelf life and the logistical problem of having available the necessary activity of a rapidly decaying source may be problematic. The ease and safety of a catheter-based delivery system with an isotope whose half-life is 28 years make the 90Sr/Y source used in this study an attractive alternative.
The high stent-to-artery ratio (1.5:1) used in this study induced a profound intimal response and provided a rigorous model in which to test our hypothesis. Unlike the balloon response, which appears to be primarily proliferative, the stent tissue has a more heterogeneous origin, including substantial thrombosis and inflammation as well as cellular replication. Despite this, localized irradiation produced marked diminution of neointima formation and inflammatory response. The mechanism by which radiation inhibits the development of neointima is unknown but may be the arrest of mitosis and therefore inhibition of smooth muscle cell growth.
Conclusions
Endovascular low-dose ionizing radiation before
stent
implantation significantly reduced the development of intimal
hyperplasia after stent implantation. The beneficial effect was seen 30
days after stent implantation and was not associated with any adverse
reaction to the stented segment or to the adjacent segments.
Histological and histomorphometric results are similar
between (192Ir) and ß (90Sr/Y)
-irradiated stented arteries.
Received May 8, 1995; revision received July 12, 1995; accepted July 20, 1995.
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References |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
1. Sigwart U, Puel J, Mirkowitch V, Joffre F, Kappenberger L. Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty. N Engl J Med. 1987;316:701-706. [Abstract]
2.
Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP,
Penn I, Detre K, Veltri L, Ricci D, Nobuyoshi M, Cleman M, Heuser R,
Almond D, Treistein PS, Fish D, Colombo A, Brinker J, Moses J,
Shaknovich A, Hirshfeld J, Bailey S, Ellis SG, Rake R, Goldberg S, for
the Stent Restenosis Study Investigators. A
randomized comparison of coronary stent placement and balloon
angioplasty in the treatment of coronary artery
disease. N Engl J Med. 1994;331:496-401.
3.
Serruys PW, De Jaegere P, Kiemeneij F, Macaya C,
Rutsch W, Heyndricks G, Emanuelsson H, Marco J, Legrand V, Materne P,
Belardi J, Sigwart U, Colombo A, Goy JJ, van den Heuvel P, Delcan J,
Morel MA, for the BENESTENT Study Group. A comparison of
balloon-expandable-stent implantation with balloon angioplasty
in patients with coronary artery disease. N
Engl J Med. 1994;331:489-495.
4. Santoian EC, King SB III. Intravascular stents, intimal proliferation and restenosis. J Am Coll Cardiol. 1992;19:877-879. Editorial. [Medline] [Order article via Infotrieve]
5. Haude M, Erbel R, Hassan I, Meyer J. Quantitative analysis of elastic recoil after balloon angioplasty and after intracoronary implantation of balloon-expandable Palmaz-Schatz stents. J Am Coll Cardiol. 1993;21:26-34. [Abstract]
6. Forrester JS, Fishbein M, Helfant R, Fagin J. A paradigm for restenosis based on cell biology: clues for the development of new preventive therapies. J Am Coll Cardiol. 1991;17:758-769. [Abstract]
7.
Liu MW, Roubin GS, King SB III.
Restenosis after coronary angioplasty:
potential biologic determinants and role of intimal
hyperplasia. Circulation. 1989;79:1374-1387.
8. Karas SP, Gravanis MB, Santoian EC, Robinson KA, Anderberg K, King SB III. Coronary intimal proliferation after balloon injury and stenting in swine: an animal model of restenosis. J Am Coll Cardiol. 1992;20:467-474. [Abstract]
9. Mintz GS, Pichard AD, Kent K, Satler LF, Popma JJ, Wong SC, Painter JA, Deforty D, Leon MB. Endovascular stents reduce restenosis by eliminating geometric arterial remodeling: a serial intravascular ultrasound study. J Am Coll Cardiol. 1995;35A:701-705. Abstract.
10. Waksman R, Robinson KA, Crocker IR, Gravanis MB, Cipolla GD, King SB III. Endovascular low dose irradiation inhibits neointima formation after coronary artery balloon injury in swine: a possible role for radiation therapy in restenosis prevention. Circulation. 1995;91:1553-1539.
11. Verin V, Popowski Y, Urban P, Belneger J, Redard M, Costa M, Widmer CM, Schwager M, Kurtz J, Rutishouser W. Intraarterial beta irradiation prevents neointimal hyperplasia in hypercholesterolemic rabbit restenosis model. J Am Coll Cardiol. 1995;2A:407-6. Abstract.
12. Wiedermann JG, Marboe C, Schwartz A, Amols H, Weinberger J. Intracoronary irradiation reduces restenosis after balloon angioplasty in a porcine model. J Am Coll Cardiol. 1994;23:1491-1498. [Abstract]
13. Mazur W, Ali MN, Dabaghi SF, Cristead C, Abukhalil J, Parasdise P, DeFelice CA, Schulz D, Berner BM, Fajardo LF, French BA, Raizner AE. High dose rate intracoronary radiation suppresses neointimal proliferation in the stented and ballooned model of porcine restenosis. Circulation. 1994;90(suppl I):I-652. Abstract.
14. Waksman R, Robinson KA, Crocker IR, Wang C, Gravanis MB, Cipolla GD, Hillstead RA, King SB III. Intracoronary low dose beta irradiation inhibits neointima formation after coronary artery balloon injury in the swine restenosis model. In press.
15. Liermann DD, Boettcher HD, Kollatch J, Schopol B, Strassman G, Strecker EP, Breddin KH. Prophylactic endovascular radiotherapy to prevent intimal hyperplasia after stent implantation in femoro-popliteal arteries. Cardiovasc Intervent Radiol. 1994;17:12-16. [Medline] [Order article via Infotrieve]
16. Hehrlein C, Zimmerman M, Metz J, Fehsenfeld P, von Hodenberg E. Radioactive stent implantation inhibits neointimal proliferation in non-atherosclerotic rabbits. Circulation. 1993;88(suppl I):I-65. Abstract.
17. Laird JR, Carter AJ, Kufs WM, Hoopes TG, Farb A, Nott S, Fischell RE, Fischell DR, Vitami R, Fischell TA. Inhibition of neointimal proliferation with a beta particle emitting stent. J Am Coll Cardiol. 1995;287A:773-3. Abstract.
18. Halbleib JA, Mehlhorn TA. ITS: the integrated TIGER series of coupled electron/photon Monte Carlo transport codes. CCC-467 Radiation Information Shielding Center, Oak Ridge National Laboratory, Oak Ridge, Tenn.
19. Cross WG, Ing H, Freedman N. A short atlas of beta-ray spectra. Phys Med Biol. 1983;28:1251-1260.
20. Hall EJ. Cell-survival curves 29-43, and The cell cycle 91-105. In: Radiobiology for the Radiologist. 4th ed. Philadelphia, Pa: Lippincott; 1994.
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|
|
D. Brieger and E. Topol Local drug delivery systems and prevention of restenosis Cardiovasc Res, September 1, 1997; 35(3): 405 - 413. [Full Text] [PDF]
|
|
|
|
 |
|
 P. S. Teirstein, V. Massullo, S. Jani, J. J. Popma, G. S. Mintz, R. J. Russo, R. A. Schatz, E. M. Guarneri, S. Steuterman, N. B. Morris, et al. Catheter-Based Radiotherapy to Inhibit Restenosis after Coronary Stenting N. Engl. J. Med., June 12, 1997; 336(24): 1697 - 1703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Holmes Preventing Coronary Restenosis and Complications N. Engl. J. Med., June 12, 1997; 336(24): 1747 - 1749. [Full Text]
|
|
|
|
|
|
M. Kearney, A. Pieczek, L. Haley, D. W. Losordo, V. Andres, R. Schainfeld, K. Rosenfield, and J. M. Isner Histopathology of In-Stent Restenosis in Patients With Peripheral Artery Disease Circulation, April 15, 1997; 95(8): 1998 - 2002. [Abstract] [Full Text]
|
|
|
|
|
|
E. Van Belle, F. O. Tio, T. Couffinhal, L. Maillard, J. Passeri, and J. M. Isner Stent Endothelialization: Time Course, Impact of Local Catheter Delivery, Feasibility of Recombinant Protein Administration, and Response to Cytokine Expedition Circulation, January 21, 1997; 95(2): 438 - 448. [Abstract] [Full Text]
|
|
|
|
|
|
W. J. van der Giessen and P. W. Serruys ß-Particle–Emitting Stents Radiate Enthusiasm in the Search for Effective Prevention of Restenosis Circulation, November 15, 1996; 94(10): 2358 - 2360. [Full Text]
|
|
|
|
|
|
A. J. Carter, J. R. Laird, L. R. Bailey, T. G. Hoopes, A. Farb, D. R. Fischell, R. E. Fischell, T. A. Fischell, and R. Virmani Effects of Endovascular Radiation From a ß-Particle–Emitting Stent in a Porcine Coronary Restenosis Model: A Dose-Response Study Circulation, November 15, 1996; 94(10): 2364 - 2368. [Abstract] [Full Text]
|
|
|
|
|
|
P. N. Ruygrok and P. W. Serruys Intracoronary Stenting: From Concept to Custom Circulation, September 1, 1996; 94(5): 882 - 890. [Full Text]
|
|
|
|
 |
|
 Radioactive Stents in Animal Models Journal Watch Cardiology, December 1, 1995; 1995(1201): 10 - 10. [Full Text]
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