Leakage of a liquid 188Re-filled balloon system during intracoronary brachytherapy. A case report.

We are reporting the first case of an accidental radioactive 188Re leakage of a liquid-filled balloon system. Different analytical methods estimated that approximately 4 mCi 188Re were released. The radiation burden was reduced considerably by the combined therapy with perchlorate and forced volume diuresis. Estimated exposures to all organs were very low with 1.8 rad. A total body nuclear scintigraphy demonstrated uniform 188Re distribution, without specific organ concentration.

Effects of beta(-)-emitting (188)Re balloon in stented porcine coronary arteries: an angiographic, intravascular ultrasound, and histomorphometric study.

BACKGROUND: Restenosis within stents may be prevented by ionizing radiation from an intravascular source. METHODS AND RESULTS: A liquid beta(-) radiation ((188)Re) balloon was evaluated in a randomized and blinded porcine coronary model of stent restenosis. Group A pigs (n=17) received 0,16, 22, or 29 Gy at 0.5-mm depth, followed by stenting. Restenosis was quantified by angiography, ultrasound, and histomorphometry at 30 days. Group B (n=7) was stented first and then treated with 0 or 29 Gy with follow-up at 60 days. There was a measurable effect at 16 Gy, which improved with increasing doses. At 29 Gy, the histological stenotic area was reduced by 67% (22% versus 66% in controls, P<0.001). Radiation after stenting was equally effective; the stenotic area was reduced (21% versus 65%, P<0.001). At 16 Gy, the vessel just distal to the stent was significantly smaller than control vessels because of intimal thickening (P=0.003). Radiated vessels had distinctive histology consisting of neointimal fibrin and reduced smooth muscle cells and matrix (P<0.0001). CONCLUSIONS: (188)Re balloon brachytherapy in porcine coronary arteries results in dose-dependent and injury-independent inhibition of stent restenosis for up to 60 days. Restenosis at the borders of the irradiated zone is a potential limitation and may be related to underdosing. Brachytherapy with the (188)Re balloon appears to be safe and feasible for clinical studies.

Leakage of a liquid 188Re-filled balloon system during intracoronary brachytherapy. A case report.

We are reporting the first case of an accidental radioactive 188Re leakage of a liquid-filled balloon system. Different analytical methods estimated that approximately 4 mCi 188Re were released. The radiation burden was reduced considerably by the combined therapy with perchlorate and forced volume diuresis. Estimated exposures to all organs were very low with 1.8 rad. A total body nuclear scintigraphy demonstrated uniform 188Re distribution, without specific organ concentration.

Effect of glycoprotein IIb/IIIa inhibition without thrombolytic therapy on reperfusion in acute myocardial infarction: results of ReoMI pilot study.

The efficacy of abciximab and moderate dose heparin in attaining reperfusion in acute MI was tested in a multicenter pilot study. Patients with acute MI of less than 6-hr onset triaged to primary PTCA received intravenous abciximab bolus and infusion and heparin (70 u/kg) in the emergency room. Mean time to angiography from administration of abciximab was 34 +/- 23 min. TIMI flow rates were: grade 0-62%, grade I-20%, grade II-9%, and grade III-9%. Primary PTCA was performed with 100% success rate. Access site bleeding occurred in 10% of patients with no incidence of intracranial bleeding. TIMI II/III flow rates were 50% in a patient subset where angiography was delayed by 45 min. While not an alternative to thrombolytics in AMI, abciximab administration in the emergency room in patients triaged to PTCA may be beneficial in situation where door to needle time is delayed as TIMI II/III flows may be attained in some patients. Cathet. Cardiovasc. Intervent. 48:430-434, 1999.

Chimeric DNA-RNA hammerhead ribozyme to proliferating cell nuclear antigen reduces stent-induced stenosis in a porcine coronary model.

BACKGROUND: Stent-induced coronary restenosis is a major clinical and public health problem. Proliferating cell nuclear antigen (PCNA) is an important regulator of cell division, and blocking of its expression after angioplasty may limit intimal proliferation. METHODS AND RESULTS: We cloned the porcine PCNA gene and constructed a chimeric hammerhead ribozyme to a segment of the gene with human homology. In vitro studies with both cultured porcine and human vascular smooth muscle cells demonstrated uptake of ribozyme within the nucleus and significant inhibition of cellular proliferation. The ribozyme was then delivered locally into pig coronaries in a stent model. At 30 days, histomorphometric analysis showed neointimal thickness of 0.51+/-0.20 mm in the ribozyme group versus 0.71+/-0.27 and 0.66+/-0.25 mm in stent controls and scrambled ribozyme control, respectively (P=0.002, P=0.03). Quantitative angiographic analysis showed late loss of 1.4+/-0.5 mm for ribozyme versus 1.9+/-0.4 and 2.0+/-0.4 mm for the controls (P=0.05 and P=0. 02). CONCLUSIONS: Chimeric hammerhead ribozyme to PCNA inhibits smooth muscle cell proliferation in vitro and reduces both histomorphometric and angiographic restenosis in the porcine coronary stent model when delivered locally.

Effects of a positron-emitting vanadium-48 nitinol stent on experimental restenosis in porcine coronary arteries: an injury-response study.

BACKGROUND: The major limitation of coronary stenting is restenosis due to exaggerated neointimal thickening. We evaluated a positron-emitting V48 nitinol stent in a porcine coronary model of restenosis. METHODS AND RESULTS: Pigs (n = 16) received a control nonradioactive and a V48 stent (1.5 or 10.6 muCi) randomized to the left anterior descending artery (LAD) and right coronary artery (RCA). Histology, morphometric variables, and strut injury scores were evaluated after 32 days. Peristrut fibrinoid deposits were greater in the high-dose group (p < 0.0001). Control stent area stenosis (AS) and mean neointimal thickness (NIT) correlated with injury (r = 0.81 and 0.79, respectively). Higher-dose stents reduced AS by 20% (0.57 +/- 0.13 vs. 0.71 +/- 0.16; p = 0.029) and mean NIT by 35% (0.44 +/- 0.16 vs. 0.71 +/- 0.24mm; p = 0.001) compared with controls. Lower-dose 1.5-muCi stents did not differ from controls. NIT over individual struts was reduced in the high-dose group compared with controls by 0.18 mm for grade 1 injury, 0.31 mm for grade 2, and 0.38 mm for grade 3 (p < 0.02 for all comparisons). CONCLUSIONS: 1.5-muCi V48 nitinol stents did not influence vessel histology or restenotic parameters in pig coronary arteries. In contrast, 10.6-muCi stents created a distinctive histological picture consisting of increased fibrinoid deposits on the neointimal-facing side of the struts without cellular organization. Higher dose radioactive stents significantly reduced AS and mean NIT. The reduction in neointimal thickening was greatest when the depth of strut penetration into the vascular wall was most severe.

Effects of clopidogrel, aspirin and combined therapy in a porcine ex vivo model of high-shear induced stent thrombosis.

AIMS: Use of ticlopidine in coronary stenting is limited by delayed onset of action. We studied the effects of clopidogrel, a rapidly acting analog of ticlopidine alone, and in combination with aspirin, in inhibiting stent thrombosis. METHODS: Unpolished nitinol stents were deployed in a porcine ex vivo arteriovenous shunt and exposed to flowing arterial blood at a shear rate of approximately 1500. s-1. Stent thrombus, platelet aggregation and bleeding times were measured at baseline and after treatment. RESULTS: Intravenous clopidogrel produced a rapid (within 30 min) and dose-dependent inhibition of stent thrombosis, with 87% reduction at a dose of 10 mg.kg-1 (P < 0.001). Aspirin alone (10 mg.kg-1) was minimally effective (20% inhibition P > 0.05) in inhibiting stent thrombosis. Combined treatment with clopidogrel and aspirin produced 95-98% inhibition of stent thrombosis, even at low doses of clopidogrel (2.5-5.0 mg.kg-1) (P < 0.0001). At effective doses both clopidogrel and combined therapy produced significant prolongation of bleeding time (P < 0.05) and inhibition of platelet aggregation (P < 0.05). CONCLUSION: Clopidogrel, either alone or combined with aspirin, may have a potential role in preventing stent thrombosis in high-risk clinical situations.

Biocompatibility of polyurethane-coated stents: tissue and vascular aspects.

To assess the arterial injury triggered by polyurethane-coated vs. uncoated stents, six polyurethane-coated and six bare nitinol stents were implanted in rabbit carotid arteries. All animals were sacrificed 4 wk after stent placement. Sections were evaluated by histology and morphometric analysis. At 4 wk, both the coated and uncoated stent struts were entirely endothelialized. The spaces between the struts showed a relatively mild proliferative response, with a few sections demonstrating neovascularization around the struts. Polyurethane coating was associated with an inflammatory tissue response consisting of lymphocytic infiltration and foreign-body reaction, with the appearance of multinucleated giant cells. Lumen, intimal, and medial cross-sectional areas varied little between coated and uncoated stented vessels (2.45+/-0.19 vs. 2.47+/-0.47 mm2, 1.17+/-0.52 vs. 0.78+/-0.30 mm2, and 0.66+/-0.18 vs. 0.58+/-0.27 mm2, respectively). In the rabbit carotid artery model, polyurethane coating does not affect the degree of neointimal proliferation after endovascular stenting compared with the conventional stenting approach. However, the inflammatory tissue response may indicate a low intrinsic biocompatibility of this stable polymer, so that it may not be an ideal material for coating intravascular devices.

Laser wire for crossing chronic total occlusions: "learning phase" results from the U.S. TOTAL trial. Total Occlusion Trial With Angioplasty by Using a Laser Wire.

The Prima laser guidewire system (Spectranectics Corp., Colorado Springs, CO) consists of an 0.018" hypotube containing a bundle of 45-microm optical fibers coupled to a pulsed excimer laser operating at a tip fluence of 60 ml/mm2 and a repetition rate ranging from 25-40 Hz. This laser guidewire was specifically designed to cross total occlusions refractory to passage with conventional wires. The Prima wire was evaluated in a feasibility study at 15 U.S. centers. Following failure to cross a total occlusion with approved guidewires, the Prima wire was utilized in 179 patients. Average age of subjects was 61 yr. Lesion locations included left anterior descending (36%), right (45%), and circumflex (19%) coronary arteries. Mean angiographic age of total occlusions was 70 wk (range, 2-1,020 wk, median, 14 wk). The use of the Prima wire either solely or in combination with conventional guidewires resulted in successful crossing in 61% of these previously impenetrable occlusions. Failure of the device was commonly related to length of the occlusion and tortuosity along the occluded pathway. Major complications included myocardial infarction in 7 patients (3.9%), tamponade in 3 (1.7%), and death in 2 (1.1%). This "learning phase" pilot study confirmed the feasibility of a laser guidewire in chronic total occlusions that are resistant to passage of conventional guidewires. An extended registry at these investigative sites is planned.

Characterization of a positron emitting V48 nitinol stent for intracoronary brachytherapy.

Percutaneous transluminal coronary angioplasty (PTCA) is currently one of the most common treatments for obstructive coronary artery disease. The long term success of the treatment, however, is severely limited by restenosis. Recently, different investigators have begun to study the possibility of radiation therapy in restenosis prevention and have shown promising results. However, an optimal radiation delivery device for delivering a highly localized radiation dose to the arterial medial layer while preserving the viability of the artery has yet to be established. In this article, we discuss the development of a unique mixed gamma/beta brachytherapy source capable of delivering high radiation dose to a 0.5 mm thick vessel wall by proton-beam activating an existing nickel titanium stent to produce vanadium-48. The dose distribution of the activated stent is determined by computer simulation using MCNP Monte Carlo code and is verified by radiochromic film measurement.

Excimer laser coronary angioplasty: the New Approaches to Coronary Intervention (NACI) experience.

In the New Approaches to Coronary Intervention (NACI) registry, 887 patients were electively treated with excimer laser coronary angioplasty (ELCA) for coronary artery disease. The Advanced Interventional System (AIS) system was used in 487 cases; the Spectranetics system, in 400. The mean age was 63.4 years. Most patients had unstable angina (60.3%); 43.7% had a prior myocardial infarction; and 18.6% were high risk or inoperable patients. Mean ejection fraction was 55.4%. A total of 1,000 lesions were treated in the 887 patients. Of the 1,000 lesions treated with ELCA in the 887 patients, 36% were in the right coronary artery; 33%, left anterior descending; 13%, circumflex; 3%, left main; and 16.6%, vein graft. By angiographic core laboratory analysis available for 752 (85%) patients with 839 lesions, lesions were 12.76 mm long. The minimum lumen diameter increased to 1.29 mm after the laser and finally to 1.95 mm after adjunctive percutaneous transluminal coronary angioplasty (PTCA) (which was performed in 93% of all lesions), with a final residual stenosis of 32.1% and Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in 95%. Dissections of grades B, C, or D were seen after 22.0% of initial laser attempts, and postlaser perforations were noted in 2.6%. Additional such dissections accumulated after adjunctive PTCA but the perforation rate remained low. Procedural success was achieved in 84% of patients, but 1.2% died, 0.7% experienced Q-wave myocardial infarction (MI), and 2.7% required emergency bypass surgery. Multiple logistic regression analysis could not identify any independent predictors of these in-hospital complications. One-year mortality was 5.7% and the cumulative incidence of Q-wave MI was 1.5%. Coronary artery bypass graft (CABG) surgery was performed in 15.0% of patients whereas 25.5% required repeat percutaneous intervention with a target lesion revascularization rate of 31%. Independent predictors of death, Q-wave MI, or target lesion revascularization (which, combined, occurred in 35.6% of patients) were the absence of prior MI, ELCA in the circumflex, perforation after the procedure, and small (<2 mm) final minimal lumen diameter. Considering the large number of patients with high-risk lesions, laser angioplasty was performed with excellent procedural success rates and a reasonable incidence of major complications.

Influence of gender on in-hospital clinical and angiographic outcomes and on one-year follow-up in the New Approaches to Coronary Intervention (NACI) registry.

Higher complication rates and lower success rates for treatment of women compared with men have been reported in prior studies of coronary angioplasty and in most early reports of outcome with new coronary interventional devices. In multivariate analysis this has been attributed largely to older age and other unfavorable clinical characteristics. These results are reflected in the current guidelines for coronary angioplasty. Women in prior studies have also had different distributions of vessel and lesion characteristics, but the influence of these differences on the outcome of new-device interventions have not been adequately evaluated. This article evaluates the influence of gender on clinical and angiographic characteristics, interventional procedure and complications, angiographic success, and clinical outcomes at hospital discharge and 1-year follow-up, as observed in the New Approaches to Coronary Intervention (NACI) registry. The NACI registry methodology has been reported in detail elsewhere in this supplement. This study focuses on the 90% of patients-975 women and 1,880 men-who had planned procedures with a single new device and also had angiographic core laboratory readings. Women compared with men were older, had more recent onset of coronary ischemic pain that was more severe and unstable, and had more frequent histories of other adverse clinical conditions. The distributions of several but not all angiographic characteristics before intervention were considered more favorable to angioplasty outcome in women. Differences were observed in device use and procedure staging. Angiographically determined average gain in lumen diameter after new-device intervention, with or without balloon angioplasty, was significantly less in women (1.38 mm) than in men (1.53 mm; p < 0.001); this 0.15 mm difference is consistent with the 0.16-mm smaller reference vessel lumen diameter of women. However, final percent diameter stenoses and TIMI flow and lesion compliance characteristics were similar. Among procedural complications, only treatment for hypotension, blood transfusion, and vascular repair occurred more often in women. More women than men were clinically unstable (2.1% vs 1.1%) or went directly to emergent coronary artery bypass graft surgery (CABG; 1.2% vs 0.6%) on leaving the interventional laboratory. However, in-hospital death (1.4% vs 1.1%), Q-wave myocardial infarction (MI) (0.9% vs 1.1%), and emergent CABG (1.5% vs 1.0%, for women and men, respectively) were not significantly different. Nonemergent CABG was more frequent in women (1.8% vs 0.9%; p < 0.05) and length of hospital stay after device intervention was longer (4.4 days vs 3.8 days in men; p < 0.01). In both univariate and multivariate analyses gender did not emerge as a significant variable in relation to the combined endpoint, death, Q-wave MI, or emergent CABG at hospital discharge. At 1-year follow-up more women than men reported improvement in angina (70% vs 62%) and fewer women than men had had repeat revascularization (32% vs 36%). Similar proportions were alive and free of angina, Q-wave MI and repeat revascularization (46% of women vs 45% of men). Although several procedure-related complications were more frequent in women than men after coronary interventions with new devices, no important disadvantages were observed for women in the rates of major clinical events at hospital discharge and at 1-year clinical follow-up. Additional studies are needed to evaluate the complex interplay of clinical, vessel, and lesion characteristics on success and complications of specific interventional techniques and to determine whether gender, per se, is a risk factor and whether gender specific interventional strategies may be beneficial.

Long-term follow-up of a high risk cohort after stent implantation in saphenous vein grafts.

OBJECTIVES: We sought to provide short- and long-term clinical outcomes of a high risk cohort treated with stents in saphenous vein grafts (SVGs). BACKGROUND: Data on the long-term outcome of SVG stenting in high risk patients are limited. METHODS: Johnson & Johnson stents were implanted in the SVGs of 186 patients (302 stents, 244 lesions). Ninety percent of patients presented with myocardial infarction (MI) or unstable angina (mean +/- SD ejection fraction [EF] 44 +/- 11%, patient age 71 +/- 9 years, graft age 9.4 +/- 5 years). Using a risk score classification, 155 patients (83%) were defined as high risk for repeat surgical repair or angioplasty. RESULTS: The procedural success rate was 97.3%, with 2.7% major complications (death, Q wave MI, coronary artery bypass graft surgery [CABG]). Clinical follow-up was obtained in 177 patients (mean 19.1 +/- 13.5 months, range 7 to 59). Event rates were 10% for death; 9% for MI; 11% for repeat CABG; and 15% for repeat angioplasty (total events 45%). Kaplan-Meier estimated survival and event-free survival at 4 years were 0.79 +/- 0.06 and 0.29 +/- 0.07, respectively. Predictors of death were congestive heart failure (p < 0.01) and EF <44% (p < 0.05). Predictors of combined events of death, MI and CABG were low EF (p < 0.01) and high SVG age (>10 years, p < 0.01). There were 66 revascularization procedures (35% of patients), 24% of which were in nontarget lesions. Fifty-three percent of the cardiac events occurred during the first year of follow-up. Of the 160 survivors, 36% were free of angina, 49% were in Canadian Cardiovascular Society functional class I or II, and 15% were in class III or IV. Sixty-nine percent of patients were in class I or II according to the Specific Activity Scale, and 31% of patients were in class III or IV. CONCLUSIONS: Balloon-expandable stent implantation in the SVGs of high risk patients is associated with a low early complication rate. Expected survival rates are good, as are the anginal and functional classifications, but there is a high rate of recurrent events and need for repeat revascularization. Vein graft stenting is an acceptable palliative option in many high risk patients.

Sustained local drug delivery to the arterial wall via biodegradable microspheres.

This study was designed to evaluate the feasibility of applying locally delivered polylactic acid microspheres for drug delivery to the arterial wall. To study drug persistence, rhodamine-loaded microspheres were infused into one carotid artery of 14 rabbits and plain rhodamine solution into the other by using a porous balloon. To study tissue response, plain microspheres and dexamethasone-loaded microspheres were infused into the carotid arteries of another group of rabbits. To study the antiproliferative effects of locally delivered drug, 20 rabbits were subjected to overstretch balloon injury to both carotid arteries and divided into 4 groups: injury alone, plain microspheres, dexamethasone-loaded microspheres, and microspheres containing colchicine and dexamethasone. Fluorescent microspheres persisted in the vessel wall for 4 wk, whereas rhodamine without microspheres disappeared at 72 h. Histopathologic studies in arteries infused with unloaded microspheres showed inflammatory cell infiltrate with polymorphonuclear cells at 1 wk and macrophages and giant cells at 4 wk. Arteries infused with dexamethasone-loaded microspheres did not show any inflammatory cell infiltrate. Local delivery of dexamethasone or dexamethasone plus colchicine did not result in significant change in the intima-to-media ratio or in residual lumen following balloon injury. Polylactic acid microspheres may be used for prolonged delivery of drugs or other bioactive agents locally to the arterial wall. They induce an inflammatory reaction that is suppressable by dexamethasone in the microspheres. Dexamethasone or dexamethasone and colchicine delivered via this system, however, failed to reduce the degree of intimal hyperplasia after overstretch balloon injury to the rabbit carotid arteries.

Temporary arterial stenting: comparison to permanent stenting and conventional balloon injury in a rabbit carotid artery model.

The objective was to assess the arterial wall response to temporary stenting with a removable nitinol stent in comparison with permanent stenting and balloon injury at 28 days in the rabbit carotid artery. Restenosis remains an important limiting factor after the implantation of permanent metallic stents and balloon angioplasty. We have developed a temporary nitinol stent that uses a bolus injection of warmed saline to collapse the stent for percutaneous removal. Vascular changes related to the thermal saline bolus injection required to remove a nitinol implanted stent were assessed in 12 rabbit carotid arteries at 7 and 28 days postinjection. Nitinol stents, inflated to 3.0 mm diameter, were implanted for 3 days (n = 6) and histology and quantitative histomorphometry examined at 28 days. Results were compared with permanently implanted stents (n = 5) and balloon injury (n = 9). Dual bolus injection of 10 ml at 70 degrees C created an acute necrotizing injury and chronic neointimal proliferation, whereas injections of 5 ml at 63 degrees C were minimally injurious. Temporary stenting resulted in the least neointimal proliferation measured by the intima to media ratio (0.22 +/- 0.10 vs. 1.59 +/- 0.31 for permanent stenting and; 0.49 +/- 0.14 for balloon injury; P < 0.001). Temporary stenting maintained a significantly larger lumen than balloon (1.53 +/- 0.72 mm2 vs. 0.64 +/- 0.14 mm2; P < 0.001), which could not be explained by absolute changes in intimal cross sectional area (0.14 +/- 0.07 mm2 vs. 0.21 +/- 0.06 mm2 respectively; P = 0.33). Temporary stenting resulted in a relatively larger vessel area within the external elastic lamina than with balloon (2.28 +/- 1.06 mm2 vs. 1.30 +/- 0.18 mm2; P = 0.007). The thermal stent recovery process can create necrotizing vascular injury and neointimal proliferation at higher temperatures and injectate volumes. Stent removal after 3 days using 63 degrees C saline bolus injection results in less neointimal proliferation than with permanent stents or balloon injury. In comparison to balloon injury, temporary stenting also may have a long-lasting beneficial effect on vessel recoil and remodeling, resulting in larger lumen size after stent removal.

Effects of GP IIb/IIIa receptor monoclonal antibody (7E3), heparin, and aspirin in an ex vivo canine arteriovenous shunt model of stent thrombosis.

BACKGROUND: Thrombosis is an important limitation of metallic coronary stents, especially in smaller vessels in which shear rates are high. Monoclonal antibody to platelet glycoprotein IIb/IIIa receptor (7E3) has been shown to inhibit shear-induced platelet aggregation. In this study, we compared the effects of 7E3, heparin, and aspirin on stent thrombosis in an ex vivo arteriovenous shunt model of high-shear blood flow. METHODS AND RESULTS: An ex vivo arteriovenous shunt was created in 10 anesthetized dogs. Control rough-surface slotted-tube nitinol stents (n = 72) expanded to 2 mm in diameter in a tubular perfusion chamber were interposed in the shunt and exposed to flowing arterial blood at a shear rate of 2100s-1 for 20 minutes. The animals were treated with intravenous murine 7E3 (Fab')2 (0.2, 0.4, and 0.8 mg/kg), heparin (100 U/kg), or aspirin (10 mg/kg). Effects of the test agents on thrombus weight, platelet aggregation, platelet P-selectin expression, bleeding time, and activated clotting time (ACT) were quantified. 7E3 reduced stent thrombosis by 95% (20 +/- 1 to 1 +/- 1 mg, P < .001) and platelet aggregation by 94% (14 +/- 2 to 1 +/- 1 omega, P < .001) at the highest dose (0.8 mg/kg). 7E3 significantly prolonged bleeding time but had no effect on ACT and platelet P-selectin expression. Heparin prolonged ACT but had no significant effect on stent thrombosis or platelet aggregation. Aspirin, although it inhibited platelet aggregation by 65%, had no effect on stent thrombosis (19 +/- 2 versus 20 +/- 1 mg in controls). CONCLUSIONS: 7E3 produced a dose-dependent inhibition of acute stent thrombosis under high-shear flow conditions. Stent thrombosis was resistant to heparin and aspirin. Thus, 7E3 may be an effective agent for preventing stent thrombosis.

Inhibition of acute stent thrombosis under high-shear flow conditions by a nitric oxide donor, DMHD/NO. An ex vivo porcine arteriovenous shunt study.

BACKGROUND: Coronary stenting is limited by subacute thrombosis, especially in smaller-diameter vessels, in which shear rates are high. The objective of the present study was to determine whether local delivery of a new type of NO donor, the NO adduct of N,N'-dimethylhexanediamine (DMHD/NO), inhibits acute stent thrombosis (ST) at high-shear flow. METHODS AND RESULTS: Effects of local infusion of DMHD/NO; intravenous aspirin, and heparin on ST were evaluated in an ex vivo porcine AV shunt model. Nitinol stents (2 mum in diameter, n = 120) were placed in a tubular chamber and perfused with blood from pigs (n = 13) at a shear rate of 2100s-1 for 20 minutes. ST was quantified by measurement of dry thrombus weight(TW). Effects on platelet aggregation (PA), blood pressure, bleeding time, and activated clotting time (ACT) were also examined. There was a dose-dependent inhibition of ST and PA by DMHD/NO. TW was reduced by 95% (1 +/- 2 versus 16 +/- 4 mg control, mean +/- SD, P < .001), and PA was reduced by 75% (4 +/- 3 versus 14 +/- 9 omega/min control, P < .05) at the highest dose of 10 mumol/L. DMHD/NO had no effects on bleeding time, ACT, or blood pressure. In contrast, aspirin (10 mg/kg), despite inhibiting PA, had no effects on TW (12 +/- 5 versus 16 +/- 8 mg control, P = .3). Heparin (200 U/kg) reduced TW by 33% (14 +/- 4 versus 21 +/- 3 mg control, P < .05) and prolonged ACT. CONCLUSIONS: Local delivery of DMHD/NO produced a 15-fold inhibition of acute ST at high-shear flow without producing adverse systemic hemostatic or hemodynamic effects. Thus, treatment with DMHD/NO may be an effective strategy for prevention of stent thrombosis.

Subacute thrombosis and vascular injury resulting from slotted-tube nitinol and stainless steel stents in a rabbit carotid artery model.

BACKGROUND: Our objectives were to quantify the thrombogenicity and extent of vascular injury created by slotted-tube geometry stainless steel and nitinol coronary stents in a rabbit carotid artery model. METHODS AND RESULTS: Stents were implanted in rabbit right carotid arteries without antiplatelet therapy. Stainless steel stents were implanted for 4 days while nitinol stents were placed for 4 and 14 days (n = 8, 8, and 6, respectively). Stent thrombosis was assessed by thrombus weight, grading thrombus encroachment of the lumen, and by blood flow in the stented and contralateral arteries. Stainless steel stents at 4 days contained more thrombus than 4- and 14-day nitinol stents (20.0 +/- 5.9 versus 2.5 +/- 0.6 and 2.7 +/- 0.3 mg, respectively; P < .000001). Stainless steel stents were more often occluded by thrombus (6 of 8) or contained more subocclusive thrombus (2 of 8) than nitinol stents (0 of 14, P < .002). Resting blood flow was reduced in arteries with stainless steel stents compared with 4- and 14-day nitinol stents (1.5 +/- 2.8 versus 24.0 +/- 2.0 and 25.5 +/- 1.9 mL/min, respectively, P < .000001). Stainless steel stents were less uniformly expanded, had deeper strut penetration into the vascular wall, and were associated with more extensive medial smooth muscle cell necrosis. There were strong correlations (r = .77 to .95) between variables of thrombosis extent (thrombus weight and grade) and histologically determined vascular injury (strut penetration and medial necrosis). CONCLUSIONS: Slotted-tube stainless steel stents were more thrombogenic and created more extensive vascular injury than nitinol stents in a rabbit carotid artery model. The mechanisms underlying these differences probably are related to metallurgic and design geometry properties of the two stent types.

Prevention of Restenosis by Local Drug Delivery.

Local drug therapy for preventing restenosis after angioplasty has been investigated for over a decade. Biologically active agents ranging from drugs to genes can be delivered locally using a wide variety of catheters. Microspheres, liposomes, and polymers have been used to enhance drug retention at the delivery site. More recently stents have been investigated as devices to attain local drug delivery, either by coating with polymers, seeding with genetically modified cells or by using them as a source of local radiation. Though the best method of delivering agents locally remains undefined, this approach is likely to emerge as an essential mode of therapy in the near future.

Usefulness of a prototype directional catheter for excimer laser coronary angioplasty in narrowings unfavorable for conventional excimer or balloon angioplasty.

We report clinical and angiographic results in 53 patients with 57 significant coronary or saphenous vein graft narrowings treated with directional excimer laser angioplasty. The target vessels were the left main (1%), anterior descending (32%), circumflex (19%), right coronary artery (39%), and vein grafts (9%). Lesions were morphologic class B1 (18%), B2 (79%), or C (3%), with 40 de novo and 17 restenotic lesions. Adjunctive balloon angioplasty was used in 53 lesions (93%). Mean pre- and postprocedural minimal lumen diameters were 0.6 +/- 0.3 and 1.9 +/- 0.7 mm (p < 0.001), corresponding to a mean diameter stenosis of 72 +/- 20% and 27 +/- 16%. Procedural success rate was 91%. Cumulative risk of death, Q-wave myocardial infarction, or emergency bypass operation was 9% (5 patients). Of patients who had a successful laser procedure, 28 (60%) with 30 lesions underwent angiographic follow-up at 6 +/- 3 months after the procedure. Restenosis rates (> 50% diameter restenosis or acute gain loss) were 37% and 23%, respectively. Four patients underwent bypass, 3 angioplasty, and 1 patient died from cancer. This study demonstrates the feasibility of directional application of laser energy to selected unfavorable narrowings for conventional excimer laser or balloon angioplasty. Further evaluation of this device using the now standard saline infusion technique is necessary to establish its ultimate role as a primary interventional device.