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Biomedical subjects

N Eigler

Publications and source records attributed to N Eigler.

At least 19 recordsLinked to original sources
PubMed2002

A porcine coronary stent model of increased neointima formation in the left anterior descending coronary artery.

BACKGROUND: Clinical trials suggest an increased frequency of restenosis after coronary intervention in left anterior descending (LAD) compared to the left circumflex or right coronary arteries. Experimental studies correlate stent-induced arterial injury and the extent of neointima formation. This study investigates whether the coronary artery affects the relationship between arterial injury and neointima hyperplasia in the porcine stent model. METHODS: Non-lipemic farm pigs underwent stent placement in the LAD (n = 26) and the right coronary artery (RCA; n = 30). Quantitative coronary angiography (QCA) was performed before and after stent placement, and at follow-up; quantitative histomorphometry and injury score were analyzed at 30-day follow-up. RESULTS: Initial procedure balloon/artery ratios (LAD 1.17 +/- 0.11 vs RCA 1.17 +/- 0.09, P = NS), and minimal stent lumen diameters (MLD; LAD 2.91 +/- 0.31 vs RCA: 2.93 +/- 0.28 mm, P = NS) were similar suggesting no difference in deployment technique. At follow-up there was more restenosis in the LAD (diameter stenosis: 55.0 +/- 26.4% vs 37.3 +/- 18.1%, and MLD: 1.24 +/- 0.78 mm vs. 1.71 +/- 0.57 mm, P < 0.05 for both comparisons). No differences were seen for injury score (1.09 +/- 0.51 vs 1.01 +/- 0.57; LAD vs RCA) or stent area (6.13 +/- 0.99 vs 6.55 +/- 1.42 mm2). Histomorphometry demonstrated smaller lumen area (2.15 +/- 0.94 vs 2.96 +/- 1.29 mm2) and thicker neointima (0.63 +/- 0.25 vs 0.51 +/- 0.17 mm; all P < 0.05) in the LAD. Multiple linear regression analysis identified the LAD as an independent predictive factor for increased neointima formation. CONCLUSIONS: These observations establish an animal model that is consistent with clinical experience showing that restenosis after stenting is more common in the LAD. The findings may be useful for understanding and developing systemic and local antirestenotic strategies.

Angioplasty, Balloon, Coronary↗
PubMed2001

Usefulness of intracoronary brachytherapy for in-stent restenosis with a 188Re liquid-filled balloon.

The objective of this randomized pilot trial with 21 patients was to evaluate the effectiveness of a rhenium-188 liquid-filled balloon system to prevent recurrent restenosis after percutaneous transluminal coronary angioplasty for in-stent restenosis. A significant benefit from brachytherapy was seen at 6-month repeat angiography, as well as during the clinical follow-up of 12 months.

Aged↗
PubMed2001

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.

Journal Article↗
PubMed2000

Elevated troponin I level on admission is associated with adverse outcome of primary angioplasty in acute myocardial infarction.

BACKGROUND: In patients with acute myocardial infarction (AMI) undergoing thrombolytic therapy, an elevated troponin level on admission is associated with a lower reperfusion rate and a complicated clinical course. Whether an elevated troponin level on admission similarly predicts an adverse outcome in patients undergoing primary angioplasty is currently unknown and was investigated in the present study. METHODS AND RESULTS: Cardiac troponin I (cTnI) was determined on admission in 110 consecutive patients with AMI associated with ST-segment elevation or left bundle branch block who underwent primary angioplasty. Fifty-four patients (49%) had an elevated cTnI (>/=0.4 ng/mL) on admission. In patients with elevated cTnI, primary angioplasty was less likely to achieve TIMI 3 flow (as classified by the Thrombolysis in Myocardial Infarction trial) in univariate (76% versus 96%, P:=0.03) or in multivariate (odds ratio 0.1, 95% CI 0.02 to 0.54) analysis. Patients with elevated cTnI were more likely to develop congestive heart failure (23% versus 9%, P:<0.05) and death, heart failure, or shock (30% versus 9%, P:=0.006). Elevated cTnI remained a significant predictor of the composite end point after controlling for other clinical data that were available early in the course, including time to presentation and angiographic results (relative risk 5.2, 95% CI 1.03 to 26.3). During a follow-up of 426+/-50 days, elevated admission cTnI was a predictor of cardiac mortality (11% versus 0%, P:=0.012), adverse cardiac events (cardiac mortality or nonfatal reinfarction; 19% versus 5.4%, P:=0.04), and adverse cardiac events plus target vessel revascularization (32% versus 14%, P:=0.054). CONCLUSIONS: In patients with ST-segment elevation AMI, an elevated cTnI on admission is associated with an increased risk of primary angioplasty failure and a more complicated clinical course.

Acute Disease↗
PubMed1999

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.

Animals↗
PubMed1999

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.

Abciximab↗
PubMed1998

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.

Animals↗
PubMed1997

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.

Aged↗
PubMed1997

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.

Alloys↗
PubMed1997

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.

Angioplasty, Balloon, Coronary↗
PubMed1996

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.

Acute Disease↗
PubMed1996

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.

Journal Article↗
PubMed1995

Kinetics of drug delivery to the arterial wall via polyurethane-coated removable nitinol stent: comparative study of two drugs.

Polymer-coated removable stents were used to deliver 14C-labeled etretinate and 3H-labeled forskolin to the vessel wall in 31 New Zealand White rabbits to study their kinetics. Stents loaded with etretinate (n = 8) and forskolin (n = 14) were implanted in the rabbit carotid arteries, and the animals were euthanized at different time intervals. Drug levels were measured in the media and adventitia of the stented segment, in distant tissues, and in blood. In four rabbits, forskolin-loaded stents were percutaneously retrieved 2 hr after implantation in the carotid artery, and the tissue and blood levels were determined 2 and 24 hr after retrieval. In seven rabbits etretinate-loaded stents were retrieved 72 hr after implantation in abdominal aorta, and drug levels were measured in the tissues and blood immediately after and at 1 and 4 days after retrieval. Levels of etretinate in the vessel wall peaked at 24 hr (250 ng/mg) and remained high up to 72 hr (185 ng/mg) after stent placement. Levels of forskolin peaked within 2 hr of stent placement (135 ng/mg) and rapidly declined to 4.9 ng/mg at 24 hr with the stent in situ. About 50% (1.4 mg) of the original etretinate remained in the stent at 72 hr compared to about 5% (0.08 mg) of forskolin at 24 hr. Ratio of peak drug levels in the vessel wall to those in the blood was 6,000 for etretinate and 780 for forskolin. (ABSTRACT TRUNCATED AT 250 WORDS)

Alloys↗
PubMed1995

Effect of intracoronary ultrasound imaging on clinical decision making.

The aim of this study was to determine the effect of intravascular ultrasound (IVUS) imaging on decision making in the performance of coronary interventions. One hundred lesions were assessed in 87 patients undergoing balloon or laser angioplasty, atherectomy, stent placement, and additional diagnostic examination. Angiographically acceptable results were deemed inadequate by IVUS in 29% of angioplasties and 30% of stent deployments, and planned procedures subsequently were altered. Abnormalities commonly identified by IVUS and not by angiography were 13 coronary dissections after the procedure and 14 significant stenoses in apparently normal angiograms and significant stenoses were excluded in 7 patients with ambiguous angiograms. The apparent contribution of coronary IVUS imaging led to its significantly increased use over a 1-year period, as coronary interventional decisions on the basis of IVUS findings increased from 4 (17%) of 19 to 60 (74%) of 81. These data suggest that IVUS is a useful adjunct to angiography in selected patients for (1) identification or exclusion of dissection, (2) assessment of the adequacy of balloon angioplasty, (3) identification or exclusion of thrombus, (4) measurement of the depth of tissue removal, (5) determination of stent size and the result of stent deployment, and (6) assessment of the severity of stenoses, especially at ostial sites.

Adult↗
PubMed1995

Six month outcome and determinants of adverse clinical events after successful excimer laser coronary angioplasty. ELCA A.I.S. Multicenter Registry.

OBJECTIVE: To describe the six month outcome and predictors of adverse clinical events following successful excimer laser coronary angioplasty (ELCA). DESIGN: Retrospective analysis of comprehensive data collected at time of initial procedure and during planned follow-up intervals. SETTING: There were 35 participating institutions throughout the United States. PATIENTS: The study population was comprised of 3,069 patients who had successful ELCA and completed follow-up at 6 months, representing 91% of eligible cases. Forty percent had prior balloon angioplasty and 34% had prior bypass surgery. MEASUREMENTS: Patient symptomatology was assessed by Canadian Cardiovascular Society functional (CCSF) class. Interim adverse clinical events [death, Q wave myocardial infarction (QMI), repeat intervention, bypass surgery, and a composite end-point] were tracked. Twenty-six pre-ELCA clinical, angiographic and procedural variables were evaluated to assess their ability to predict outcome. RESULTS: At 6 months, there was 2.8% mortality, 2.5% incidence of QMI, and 28.7% required either repeat intervention or bypass surgery. Overall, 69.2% of patients had no adverse event. In this cohort, the pre-ELCA CCSF class grade was 2.7 +/- 1.2, but at 6 months, it was 0.7 +/- 1.1 (p < 0.001). The multivariate predictors of the composite end point were gender, stenosis location, and rest and unstable angina. CONCLUSIONS: There is an excellent 6 month outcome after successful ELCA in this selected population with complex coronary artery disease. The majority of patients without interim events enjoy significant alleviation of symptoms. The predictors of adverse events are clinical rather than angiographic.

Angioplasty, Balloon, Laser-Assisted↗