comparison of the thrombogenicity of stainless steel and tantalum coronary stents

May 1995 Scott et al. American Heart Journal

16. Kempczinsski RF, Ramalanjoana GR, Douville C, Silberstein EB. Thrombogenicity of a fibronectin-coated, experimental polytetrafluo- roethylene graft. Surgery 1987;101:439-44.

17. Ellis SG, Roubin GS, King SBI, Douglas JSJ, Weintraub WS, Thomas RG, Cox WR. Angiographic and clinical predictors of acute closure after native vessel coronary angiop!asty. Circulation 1988;77:372-9.

18, Ades EW, Candal FJ, Swerlick RA, George VG, Summers S, Bosse DC, Lawley TJ. HMEC-I: establishment of an immortalized human mi- crovascular endothelial cell line. J Invest Dermatol 1992;99:683-90.

Comparison of the thrombogenicity of stainless steel and tantalum coronary stents

This study was designed to compare the thrombogenicity of stainless steel and tantalum coronary stents of the same design. Stainless steel and tantalum coronary stents are being evaluated for their utility in treating acute closure and restenosis. A major disadvantage of stainless steel stents is radiolucency. To determine whether radioopaque tantalum stents may be safely substituted for stainless steel stents, we compared the relative thrombogenicity of these materials in stents of identical design. Total platelet and fibrin deposition on the stents were determined from measurements of indium 111-labeled platelet and iodine 125-labeled fibrinogen accumulation after deployment into exteriorized chronic arteriovenous shunts in seven untreated baboons. In another series of experiments, 1111n-plateiet deposition was compared 2 hours after stent implantation in coronary arteries of pigs. In baboons, platelet tbrombus formation on stainless steel and tantalum stents was equivalent and plateaued at approximately 2.5 × 109 platelets after 1 hour (p > 0,05). Fibrin deposition averaged approximately 1 mg/stent and did not differ between the stainless steel and tantalum stents (p > 0.05), in the porcine coronary model there was no significant difference in 111In-labeled platelet deposition between the stainless steel and tantalum stents (p > 0.05). This result was confirmed by scanning electron microscopic analysis of the coronary stents. Based on these two models, w e conclude that there is no significant difference in the thrombogenicity of stainless steel and tantalum wire coil stents. (AM HEART J 1995;129:866-72.)

Neal A. Scott, MD, PhD, a Keith A. Robinson, PhD, a Gilberto L. Nunes, MD, a

Clifford N. Thomas, MBBS, a Kevin Viel, BS, a Spencer B. King III, MD, a Laurence A. Harker, MD, b Steven M. Rowland, PhD, e Ike Juman, PhD, e

Gustavo D. Cipolla, DVM, a and Stephen R. Hanson, PhD b Atlanta, Ga., and Miami, Fla.

Intracoronary stenting has proved to be an effective therapy for treating dissections and acute occlusions

From the aAndreas Gruentzig Cardiovascular Center, Emory University Hospital, and the bDivision of Hematology and Oncology, Emory University School of Medicine, Atlanta, and the CCordis Corporation, Miami.

Dr. Scott is a fellow of the Robert Wood Johnson Foundation for Minority Faculty Development. This work was supported by research grants HL41619 and HL31469 from the National Institutes of Health and part by National Institutes of Health grant RR-00165, awarded to the Yerkes Regional Pri- mate Center, which is fully accredited by the American Association for Ac- creditation of Laboratory Animal Care.

Received for publication Nov. 17, 1993; accepted Aug. 15, 1994.

Reprint requests: Neal A. Scott, MD, PhD, Andreas Gruentzig Cardiovas- cular Center, Emory University Hospital, Suite F-606, 1364 Clifton Rd., Atlanta, GA 30322.

Copyright © 1995 by Mosby-Year Book, Inc. 0002-8703/95/$3.00 + 0 4/1/61641

that occur during percutaneous transluminal coronary angioplasty. 1-3 In selected cases, coronary stenting may also decrease the incidence of restenosis. 4, 5 However, thrombotic occlusion of stented vessels has significantly limited the use of this device. Thus, de- spite the concomitant use of heparin, warfarin, aspirin, and dipyridamole, the incidence of thrombotic occlusion is 2 % to 25 % .1, 6-10 Not surprisingly, hem- orrhagic complications related to the anticoagulation regimen also are frequently seen. 2, 7 Issues relating to stent thrombogenicity are therefore of considerable interest.

Most stents currently under investigation are composed of stainless steel. 11-14 However, platelets and fibrinogen adhere to stainless steel on contact with

866

Volume 129, Number 5 American Heart Journal Scot]; et al. 867

blood in vitro. 15 In vivo, ba l loon-expandable and se l f -expanding stainless steel s tents have been shown to accumula te significant and equivalent amoun t s of t h r o m b u s in arterial-f low condit ions in pr imates . 16 The rad ioopac i ty of t a n t a l u m 17 is a significant advan tage over stainless steel because exact p lacement of a s ten t is of ten necessary. Al though initial evalu- a t ions suggested t h a t t a n t a l u m was less th rombogenic t h a n stainless steel, 18, 19 th rombo t i c occlusion has been d o c u m e n t e d in pa t i en t s with t a n t a l u m coronary stents. 1°' 20,21 However , there have been no control led an imal exper imenta l studies for direct ly assessing the poten t ia l advan tage of s ten t meta l composi t ion on thrombogenic i ty . This s tudy was pe r fo rmed to compare in two an imal models and in identical expe r imen ta l condit ions the th rombogenic - i ty of stainless steel and t a n t a l u m coronary s tents of the same design.

METHODS Baboon experiments. Seven normal male baboons (Pa-

pio anubis) were used in these experiments. The animals weighed 10 to 12 kg and had been quarantined and observed to be disease-free for 3 months before use. All animals had a chronic arteriovenous shunt surgically im- planted between the femoral artery and vein. Ketamine hydrochloride, 10 mg/kg intramuscularly was given as a preanesthetic agent, and the operation was performed after the animals had been given 1% hal0thane general anesthesia. All procedures were approved by the Emory Uni- versity Institutional Animal Care and Use Committee in accordance with federal guidelines. 22 The permanent shunt system consisted of two 2.5 cm lengths of polydimethyl si- loxane (Silastic, Dow Coming, Midland, Mich.) tubing, 3.0 mm inside diameter (i.d.) Blood flow was established by connecting the two Silastic shunt segments with a 2 cm length of polytetrafluorethylene (Teflon) tubing (2.8 mm i.d.). As described in detail previously, the permanent Te- flon-Silastic shunts do not detectably shorten platelet sur- vival or produce measurable platelet activation. 23

Platelet count and hematocrit determinations were performed on whole blood collected in Na2-ethylenediamine tetraacetic acid at 2 mg/ml by using a whole-blood analyzer (System 9000, Serono-Baker Diagnostics, Allentown, Pa.). Whole-blood platelet counts averaged 402,000 _+ 40,000 platelets/ml, and hematocrits averaged 37.0% +_ 1.3%. Mean blood flow rates through vascular graft segments incorporated into the arteriovenous shunt system were mea- sured continuously by using an ultrasonic flowmeter (model 2101, Transonics, Ithaca, N. Y.) with a transducer probe around the Silastic tubing constituting the shunt. In all studies blood flow rates were maintained at 100 ml/min (wall shear rate 265 sec -1, a flow rate typical of medium- sized arteries. Stents were initially placed and imaged after the injection of autologous indium 111-labeled platelets (see below). The stents were imaged for 2 hours and then removed.

Autologous baboon blood platelets were labeled with 111In-oxine as previously described. 24 In brief, 100 ml whole blood was collected directly into two conical tubes each containing 10 ml of acid-citrate-dextrose anticoagulant (formula A, National Institutes of Health). The blood was centrifuged at 300g for 10 min. The supernatant platelet- rich plasma (PRP) was transferred to a second conical tube and the pH was adjusted to 6.5 by the addition of 0.15 mol/L citric acid (0.1 ml per 10 ml PRP). The erythrocyte fraction was returned to the donor animal. The platelets were formed into a pellet by centrifugation of the PRP at 1300g for 15 minutes. The supernatant platelet-poor plasma was completely decanted and discarded. To remove resid- ual plasma proteins, the platelet pellet was carefully washed once by overlaying with 30 ml of Ringer's citrate dextrose (pH 6.5), which was decanted and discarded. The

, pellet was then gently resuspended in 5.0 ml of RCD and incubated for 10 min with 800 to 1000 mCi (1 Ci = 37 GBq) of 111In-oxine (Amersham, Arlington Heights, Ill.). Con- taminating erythrocytes were removed by a final slow centrifugation at 200g for 5 minutes. Labeling efficiencies averaged >90%. Previous studies with this method have shown that the labeled platelet population is functionally normal as demonstrated by equivalent reductions in circulating platelet count and circulating platelet radioactivity in response to infused collagen suspensions or blood exposure to vascular grafts. 24

Images of the stents, including proximal and distal Silastic segments, were acquired with a gamma camera (400T MaxiCamera, General Electric, Milwaukee, Wis.) and stored on and analyzed by a computer (Medical Data Systems A 3 Medtronic, Ann Arbor, Mich.), interfaced with the camera. Immediately before imaging the vascular grafts, images also were acquired of 4.0 mm-i.d. Silastic tubing filled with autologous blood and having the same luminal volume as the graft segment (blood standard). The activities of the standard and 2 cm stent segments were measuredinthesame3 x 6cm(10 x 20pixels)regionofinter- est as defined by image analysis software routines. Images of the lower energy l~lIn peak were acquired at 5-minute intervals in 128 x 128 word mode as previously described. 16 Deposited 111In-platelet activity, calculated by subtracting the blood standard activity from all dynamic study images, increased monotonically over the exposure period. The total number of platelets deposited at each time point (labeled and unlabeled cells) was calculated by dividing the deposited platelet activity by the blood standard platelet activity and multiplying by the volume of the blood standard and the circulating platelet count (platelets per milliliter)24

Eleven untreated Teflon grafts (4.0 mm i.d.) served as controls. Stainless steel and tantalum wire coil balloon-expandable coronary stents of the same design (4.0 mm i.d., Cordis, Miami Lakes, Fla.) (Fig. 1) were inserted into 10 cm segments of Teflon grafts. Silicone rubber tubing, 10 cm x 4.0 mm i.d., was connected to both ends of the graft segment with Silastic medical adhesive (type A). This procedure produced impervious grafts rigidly constrained to a linear geometry and having a precise i.d. (4.0 mm). The re- sulting flow channel was smooth in its transition from the

May 1995

868 Scott et al. American Heart Journal

Fig. 1. Cordis stainless steel (A) and tantalum (B) balloon-expandable stents. Stents are fully expanded.

4.0

3 ,5

3.0

? o 2.5

It W

2.0

~ 1,5

1.0

0.5

0.0

CORONARY STENTS (CORDIS)

v STAINLESS STEEL (n-7) • TANTALUM (n-7)

I 0 ] ~ 810 I I 0 2 ¢0 SO 1 O0 120

TIME (rain)

111In-labeled platelet deposition on tantalum and Fig. 2. stainless steel stents in baboon arteriovenous shunt. Stents were deployed in 10 cm segment of ePTFE vascular graft. Graft segment containing stent was then interposed into shunt.

Silastic to the graft as a result of the coupling procedure. The avoidance of a hemodynamic "step" at the graft junc- tions has been found to be essential to ensure reproducible and uniform platelet deposition after blood exposure. 24 The 4.0 mm-i.d. Silastic tubing segments proximal and distal to the Teflon graft were subsequently connected to the 3.0 mm-i.d. Silastic tubing comprising the chronic arteriovenous shunt with 2 cm-long tapered Teflon connec- tors (Small Parts, Miami Lakes, Fla.).

Iodine 125-Fibrinogen. To quantify fibrin deposition on the stents, homologous iodine 125-fibrinogen (approximately 5 mCi) was injected approximately 15 minutes before the stents were incorporated into the arteriovenous shunts. Homologous fibrinogen was purified by b-alanine precipitation and labeled with 125I by using the iodine monochloride method. 25 In vivo, this preparation was >95% clottable and was functionally equivalent to unlabeled fibrinogen. At the time of stent exposure, blood was collected for the determination of both 125I-fibrinogen activity and fibrinogen concentration. Specific activity of 125I-fibrinogen was then calculated. After exposure to flowing blood for 2 hours, the Teflon segments containing the stent were removed, placed in a 2% glutaraldehyde fixative, and stored at 4 ° C. After 30 days was allowed for the 111In activity to decay (half-life 2.8 days), the 125I ac- t iv i ty in each segment was counted. Deposited fibrin (milligrams) was calculated by dividing the 125I-activity segment (counts per minute) by the clottable plasma 125I ac- t iv i ty (counts per minute per milliliter) and multiplying by the plasma fibrinogen level (milligrams per milliliter). Re- sults were expressed as total fibrin (milligrams) contained in the thrombus associated with each segment.

Pig exper iments . Five pigs were used in this study. Platelet labeling was accomplished with methods identical to those described above. Animals were tranquilized with an intramuscular injection of ketamine (20 mg/kg), ace- promazine maleate (1 mg/kg), and atropine (0.04 mg/kg). Intravenous access was established in an ear vein with an 18-gauge Angiocath (Becton-Dickinson Vascular Access, Sandy, Utah). Endotracheal intubation was performed with a 7F endotracheal tube, and general anesthesia was maintained with 1% to 2 % isofluorane. A cut-down on the right femoral artery was then performed. An 8F sheath (United States Catheters and Instruments, Billerica, Mass.) was inserted into the artery by direct vision. An 8F guide catheter (SciMed, Minneapolis, Minn.) with a hockey-stick curve was advanced to the ostium of the left coronary artery with fluoroscopic guidance. After administration of intracoronary nitroglycerin, 0.66 tLg/kg, coronary angiogra- phy was performed in orthogonal views. Coronary stents (3.5 mm i.d.) were then placed in the proximal segments of the left anterior descending and circumflex arteries. Each animal received one stainless steel and one tantalum stent. Two hours after stent deployment, a blood sample was taken for determination of platelet count and specific activity.

The animal was then killed with an overdose of intravenous barbiturate. The heart was rapidly removed and the left coronary perfused with heparinized lactated Ringer's solution at 110 mmHg to clear the artery of blood. The vasculature was then fixed by perfusion with 2.5 % glutaraldehyde in 0.1 mol/L cacodylate, pH 7.4, at 110 mm Hg

Volume 129, Number 5

American Heart Journal Scott et al. 869

Fig. 3. Fluoroscopic image of pig heart with tantalum stent (arrow) in left anterior descending artery (A) and stainless steel stent (arrow) in first obtuse marginal artery (B). Tantalum stent is radioopaque; stainless steel stent is radiolucent.

and 37 ° C for 5 to 10 minutes. Both solutions were bubbled with 95 % oxygen-5 % carbon dioxide for at least 20 minutes before use. After at least 15 minutes of primary fixa- tion, the stented epicardial arterial segments were carefully dissected free from the heart, immersed in the same fixative, and analyzed in a scintillation counter for determination of il iIn radioactivity. The number of platelets deposited was calculated as described earlier in this article.

Scanning electron microscopy. The coronary arterial segments containing the stents were kept in fixative at 4 ° C for 24 to 48 h. Each sample was carefully cut with scis- sors and razor into four longitudinal hemisections about 1 cm in length while immersed in 0.1 mol/L cacodylate. They were postfixed for I hour in 1% osmium tetroxide in 0.1 mol/L cacodylate and rinsed with distilled water. After de- hydration in graded ethanol, the stents were critical point-dried from liquid carbon dioxide with use of ther- moregulation and flow monitoring. The stents were then attached to aluminum supports with silver paste and sput- ter-coated with 15 to 30 nm 60%-40% gold-palladium al- loy. The stents were imaged with a scanning electron mi- croscope equipped with a high-brightness lanthanum hexaborate emitter operated at 10 to 15 kV accelerating volt- age in the conventional secondary electron imaging mode.

One low-magnification image of at least two representative hemisections from each artery was recorded. These were graded (by artery) for overall extent of thrombosis by an experienced microscopist blinded to treatment group (stainless steel vs tantalum). A numerical grading scheme was applied as follows: 0, no thrombus; 1, coverage of luminal surface including stent by thrombus < 30 %; 2, coverage of surface by thrombus 30% to 70%; 3, coverage of surface by thrombus >70%; 4, total coverage of surface by thrombus; and 5, total occlusion of arterial lumen by thrombus. Higher magnification images were also recorded to characterize blood elements deposited on the stent material and on the damaged arterial luminal surface.

Statistics. All data are presented as mean + standard

error of the mean. Comparisons between two groups were made with the Student's t test (two-tailed) for paired and unpaired sample groups. All data analyses were performed on 386-processor personal computer with statistical analysis software (SigmaStat, San Rafael, Calif.).

RESULTS Baboon experiments. In this group of seven awake

un t r ea t ed baboons, the pla te le t deposi t ion on control e P T F E grafts was de tec ted and reached a p la teau value by 60 minutes of approx ima te ly 0.87 x 10 9 -- 0 . 1 5 X 109 pla te le ts /cm. Images showed uni- fo rm dis t r ibut ion of radioact iv i ty over the entire length of the graft. In contrast , a b u n d a n t pla te le t deposi t ion occurred on bo th stents. P la te le t deposi- t ion for the stainless steel s tents reached a p la teau value of approx ima te ly 2.3 X 109 -2_ 0.3 x 109 versus 2.5 X 109 +_ 0.4 x 109 platelets in the t a n t a l u m stents at 60 minutes . The re was no significant difference in the amoun t of p la te le t deposi t ion between the stainless steel and t an t a lum s tents (p > 0.05) (Fig. 2). Fi- br in deposi t ion on the s tents was not significantly different be tween the stainless steel and t an t a lum stents (1.08 _+ 0.26 mg on the stainless steel vs 1.03 _+ 0.21 mg on the t an ta lum; p > 0.05).

Pig experiments. The p la te le t counts in the five anesthet ized, un t rea ted pigs averaged 295,000 _+ 75,000 plate le ts /ml . The mean hematocr i t was 21.0% _+ 2.0%. Both s tents were easily deployed in the ta rge t coronary arteries. Unlike the stainless steel stents, the t an t a lum s tents were easily visualized by fluoroscopy (Fig. 3). P la te le t deposi t ion on the stainless steel s tents averaged 3.2 × 10 s _+ 2.2 x 10Splate - lets whereas the t a n t a l u m stents conta ined 2.3 x 10 s _+ 1.3 X 10 s plate le ts (p > 0.5).

May 1995 870 Scott et al. American Heart Journal

Fig. 4. Scanning electron micrographs of swine coronary arteries fixed 2 hours after placement of endovascular stents. A, Low-magnification survey of representative longitudinal hemisection of stainless steel stent. Stent wires are partially covered by thrombus. B, Low magnification survey of representative longitudinal hemisection of tantalum stent. Amount of thrombus shown on this stent is slightly less than that observed on stainless steel stent. C, Higher magnification of area from A, showing platelets, fibrin, and leukocytes attached to stent wire. C and D, Higher magnification of tantalum stent shown in B, partially covered with platelets, leukocytes, and fibrin.

Scanning electron microscopy. When the coronary stents were assessed with scanning electron microscopy, there was no significant difference in thrombus formation between the tantalum and stainless steel stents (1.38 ± 0.52 vs 1.30 ± 0.48, respectively; p > 0.5) (Fig. 4). There was also no consistent difference between the composition of thrombus associated with tantalum compared to that observed on stainless steel, as determined by representative higher magnification micrographs (Fig. 4). The thrombi were composed primarily of platelets and leukocytes. Fibrin was also present in all stents, particularly in the specimens with more extensive thrombosis. Erythrocytes were absent except in two instances in which the stents were grossly oversized (one stainless steel and one tantalum), where large arterial dissections with perivascular hemorrhage occurred, and occlusive luminal thrombi were formed. These sam- ples were not included in the statistical analysis.

DISCUSSION

This study demonstrated that platelet and fibrin deposition was substantial on both stainless steel and

tantalum intracoronary stents placed within non- thrombogenic Teflon grafts in arterial-flow condi- tions in nonhuman primates. In addition, after intracoronary deployment in pigs, there was no difference in platelet deposition between the two types of metal stents, when total platelet thrombus formation was evaluated by measurements of 111In-labeled platelet deposition, or when explanted stents were graded semiquantitatively by scanning electron microscopy.

Stents shaped into the same coil design were used to eliminate any obvious difference in thrombogenicity that could be related specifically to the stent structure or area of metallic surface. Of interest, the absolute number of platelets deposited on the stents was similar to the results obtained with stainless steel stents that had markedly different design features: the slotted tube (Johnson & Johnson Interventional Systems, Warren, N.J.) and self-expanding mesh (Wallstent, Schneider (USA), Plymouth, Minn.) that have been studied previously in this baboon model. 16

This model also has been shown to provide reproducible thrombus formation on various prosthetic

Volume 129, Number 5 American Heart Journal Sco t t e t al. 871

materials and is suitable for assessing the effects of antithrombotic agents. 23, 26, 27 Graft material, chem- ical properties, and topographic characteristics are major factors influencing platelet deposition on vascular prostheses. In this regard, Teflon, in contrast to knitted Dacron, produces little platelet deposition. 2s By constraining grafts to their intended cylindrical shape, with smooth transitions between tubing and graft material, stents were evaluated in a manner free of confounding hemodynamic variables. Teflon grafts rather than rigid tubes were used to allow better conformation of the stent to the conduit wall, as would normally occur. The rather robust thrombus formation seen with this method may result from ex- clusion of modulating factors normally associated with or released by the vessel wall. Thus in this system, thrombosis is mediated primarily by the stent properties alone. Another contributing factor for the abundant thrombotic response could be that all experiments in this study were performed in untreated animals. Although treatment with heparin in this species does not prevent clinical or experimental stent thrombosis, 1~ systemic heparin in large doses has been shown to inhibit platelet deposition on stents. 29 The combination of several antithrombotic agents (e.g., aspirin, persantine, dextran, and hepa- tin) that are commonly used clinically to prevent stent thrombosis has not yet been examined in experimental models.

Because the stents in the baboon shunt experiments were deployed onto an artifical surface, in vivo coronary implantation was performed to obtain more relevant data on the thrombogenicity of the different stents. In contrast to the studies in primates, the porcine model of stent thrombosis offered an in vivo model of coronary structure that is almost identical to the human with respect to vessel diameters and flow characteristics. There was no significant difference in platelet deposition betwen the two stents when they were placed in the coronary system of the same pig. A potential limitation of this study is that the coronary arteries used were angiographically normal, and hence platelet deposition was relatively modest as compared to the studies in baboons. Clin- ically, these devices are commonly deployed in se- verely atherosclerotic coronary arteries after a significant dissection or an acute occlusion, when a significant amount of the arterial media or ruptured plaque is exposed to circulating blood. Significant flow disturbances caused by arterial dissections also may be present at the time of clinical stent placement.

Another variable that could have influenced our

results was the time chosen to examine the stent after implantation. A period of 2 hours was selected because prior studies performed in a similar manner demonstrated abundant platelet deposition on coil stents within a relatively short period of time. 3° Ex- amination of the stents at earlier or later times may have yielded different results; the possible impor- tance of these factors cannot be inferred from the present study. Nonetheless, in the models used, which demonstrated brisk thrombosis in the absence of vessel wall modulating factors (baboons) and moderate platelet accumulation on stents placed in normal vessels (pigs), equivalent stent reactivity was a consistent finding. This study is consistent with clinical observations: examination of clinical stent thrombosis rates reveals no essential difference between stainless steel and tantalum stents. 1, G-so, 20, 21

Because there appears to be no significant difference in acute thrombogenicity between tantalum and stainless steel stents, the radioopacity of tantalum is a significant advantage. The stent can be seen clearly by fluoroscopy and therefore can be placed accu- rately. Longer-term studies are therefore warranted to determine whether tantalum compares favorably with respect to later thrombotic events and restenosis.

We t h a n k Andrew B. Kelly, DVM, Deborah Whi te , and N o r m a n Tarazona, DVM, for thei r excel lent technical assist- flllce.

REFERENCES

1. Roubin GS, Cannon AD, Agrawal SK, Macander PJ, Dean LS, Baxley WA, Breland J. Intracoronary stenting for acute and threatened acute closure complicating percutaneous transluminal coronary angioplasty. Circulation 1992;83:916-27.

2. Sigwart U, Urban P, Golf S, Kauffman V, Imbertt C, Fischer A, Kap- penberger S. Emergency stenting for acute occlusion after coronary balloon angioplasty. Circulation 1988;78:1121-7.

3. Schatz RA, Baim DS, Leon M, Ellis SG, Goldberg S, Hirshfeld JW, Cleman MW, Cabin HS, Walker C, Stagg J, Buchbinder M, Teirstein PS, Topol E J, Savage M, Perez JA, Curry RC, Whitworth H, Sousa JE, Tio F, Almagor Y, Ponder R, Penn IM, Leonard B, Levine SL, Fish RD, Palmaz JC. Clinical experience with the Palmaz-Schatz coronary stent: initial results of a multicenter study. Circulation 1991;83:148-61.

4. Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyn- drickx G, Emanuelsson H, Marco J, Legrand V, Materne P. A comparison of balloon-expandable stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. N Engl J Med 1994;331:489-95.

5. Fischman DL, Leon MB, Bairn DS, Schatz RA, Savage MP, Penn I, De- tre K, Veltri L, Ricci D, Nobuyoshi M. A randomized comparison of coronary stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenesis Study Investigators. N Engl J Med 1994;331:496-501.

6. Goy JJ, Sigwart U, Vogt P, Stauffer JC, Kanfmann U, Urban P, Kap- penberger L. Long-term follow-up of the first 56 patients treated with intracoronary self-expanding stents (the Lausanne experience). Am J Cardiol 1991;67:569-72.

7. Hearn JA, King SB III, Douglas JS Jr, Carlin SF, Lembo NJ, Ghazzal ZMB. Clinical and angiographic outcomes after coronary artery stent-

May 1995 872 Scott et al. American Heart Journal

ing for acute closure following percutaneous transluminal coronary angioplasty: initial results with a balloon-expandable, stainless steel design. Circulation 1993;88:2086-96.

8. Kiemeneij F, Laarman G, Suwarganda J, van der Wieken R; Emergency coronary stenting after failed coronary angioplasty: immediate and mean term results with the Palmaz-Schatz stent [Abstract]. J Am Coll Cardiol 1992;19:47A.

9. De Feyter PJ, DeScheerder I, van den Brand M, Laarman GJ, Surypra- nata H, Serruys PW. Emergency stenting for refractory acute coronary artery occlusion during coronary angioplasty. Am J Cardiol 1990; 66:1147-50.

10. de Jaegere PP, Serruys PW, Bertrand M, Wiegand V, Kober G, Mar- quis JF, Valeix B, Uebis R, Piessens J. Wiktor stent implantation in patients with restenosis following balloon angioplasty of a native coronary artery. Am J Cardiol 1992;69:598-602.

11. Dotter CT. Transinminally-placed coilspring endarterial tube grafts. Invest Radiol 1969;4:329-32.

12. Duprat G, Wright KC, Wallace S, Gianturco C. Flexible balloon- expanded stent for small vessels. Radiology 1987;162:276-8.

13. Sigwart U, Puel J, Mirkovitch V, Joffre F, Kappenberger L. Intravas- cular stents to prevent occlusion and restenosis after transluminal angioplasty. N Engl J Med 1987;316:701-6.

14. Schatz RA, Palmaz JC, Tio FO, Garcia F, Garcia O, Reuter SR. Balloon-expandable intracoronary stents in the adult dog. Circulation 1987;76:450-7.

15. Baier RE. Initial events in interactions of blood with a foreign surface. J Biomed Mater Res 1969;3:191-206.

16. Krupski WC, Bass A, Kelly AB, Marzec UM, Hanson SR, Harker LA. Heparin-resistant thrombus formation by endovascular stents in baboons: interruption with a synthetic antithrombin. Circulation 1990; 81:570-7.

17. Nadel JA, Wolfe WG, Graf PD. Powdered tantalum as a medium for bronchography in canine and human lungs. Invest Radio11968;3:229-38.

18. van der Giessen WJ, van Woerkens LJ, Beatt KJ, Serruys PW, Verdouw

PD. Coronary stenting with a radiopaque, athrombogenic, balloon-expandable stent [Abstract]. Circulation 1989;80:II-173.

19. Hearn JA, Robinson KA, Roubin GS. In-vitro thrombus formation of stent wires: role of metallic composition and heparin coating [Abstract]. J Am CoU Cardiol 1991;17:302A.

20. White CJ, Ramee SR, Collins TJ. Elective placement of the Wiktor stent after coronary angioplasty. Am J Cardiel 1994;74:274-6.

21. Laird JR, Carter AJ, Kufs WM, Farb A, Prewitt KC, Wortham DC. Placement and angiographic patency of the Strecker coronary stent. Cathet Cardiovasc Diagn 1994;31:322-9.

22. Committee on the Care and Use of Laboratory Animals. Guide for the care and use of laboratory animals. Publication 86-23. Bethesda, Md.: National Institutes of Health, 1985:1-57.

23. Hanson SR, Harker LA. Effects of platelet-modifying drugs on arterial thromboembolism in baboons. J Clin Invest 1985;75:1591-9.

24. Hanson SR, Kotze HF, Savage B, Harker LA. Ptatelet interactions with Dacron vascular grafts: a model of acute thrombosis in baboons. Arte- riosclerosis 1985;5:595-603.

25. Cadroy Y, Horbett TA, Hanson SR. Discrimination between platelet- mediated and coagulation-mediated mechanisms in a model of complex thrombus formation in vivo. J Lab Clin Med 1989;113:436-48.

26. Hanson SR, Harker LA. Vascular graft thrombus formation. Ann N Y Acad Sci 1987;516:653-61.

27. Hanson SR, Harker LA. Interruption of acute platelet-dependent thrombosis by the synthetic antithrombin D-phenylalanyl-L-prolyl-L- arginyl chloromethyl ketone. Proc Natl Acad Sci U S A 1988;85:3184-8.

28. Schneider PA, Kotze HF, Heyns AD, Hanson SR. Thromboembolic potential of synthetic vascular grafts. J Vasc Surg 1989;10:75-82.

29. Breckwoldt WL, Belkin M, Gould K, Allen M, Connolly RJ, Termin P. Modification of the thrombogenicity of a self-expanding vascular stent. J Invest Surg 1991;4:269-78.

30. Robinson KA, Hunter RL, Stack JE, Hearn JA, Apkarian RP, Roubin GS. Inhibition of coronary arterial thrombosis in swine by poloxamer 188. Journal of Invasive Cardiology 1990;2:9-20.

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comparison of the thrombogenicity of stainless steel and tantalum coronary stents

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