(Circulation. 1995;91:2857-2861.)
© 1995 American Heart Association, Inc.
Articles |
Meeting Highlights
From the Texas Heart Institute, St Luke's Episcopal Hospital, Baylor College of Medicine, the University of Texas Health Science Center at Houston.
 |
Introduction |
|---|
 Top Introduction Intracoronary Irradiation Postmenopausal...EPIC Substudies High-Dose Heparin for Acute...Transesophageal
Echocardiography...The Scandinavian Simvastatin...Anticoagulation for Stents Drug Delivery |
|---|
The following studies were presented at the 67th Scientific Sessions of the American Heart Association, Dallas, Tex, November 14-17, 1994.
|
Intracoronary Irradiation |
|---|
|
TopIntroductionIntracoronary Irradiation Postmenopausal...EPIC Substudies High-Dose Heparin for Acute...Transesophageal
Echocardiography...The Scandinavian Simvastatin...Anticoagulation for Stents Drug Delivery |
|---|
Dr Joseph Wiederman from Columbia University in New York, NY, presented data from a dose-ranging study of radiation therapy after balloon injury in pigs. A total of 30 animals (10 per group) were pretreated with either 2000, 1500, or 1000 cGy of radiation from a 192Ir wire at the site of balloon overstretch injury and were compared with a control group of 10 animals who did not receive any radiation before balloon injury. All animals were treated with aspirin and killed at 30 days. A stimulatory effect on neointimal area was noted in the 1000-cGy group, whereas the 1500- and 2000-cGy groups had significantly lower neointimal area and percent area stenosis. The authors concluded that the effect of radiation appears to be dose dependent; the minimal therapeutic dose of radiation was 1500 cGy.
Dr Wiederman also presented data from a controlled long-term follow-up study in which pigs undergoing balloon injury of a proximal coronary segment were pretreated with a 2-cm ribbon of 192Ir positioned at the treatment site to deliver 2000 cGy of radiation before balloon injury. All animals received daily oral aspirin and were killed at 180±8 days. The irradiated group (n=11) showed a significant decrease of percent area stenosis (12.7±10.5% versus 37.9±12.4%) and maximal neointimal area (0.42±0.39 versus 1.59±0.78 mm2) in comparison with control animals (n=9). Dr Wiederman concluded that intracoronary irradiation significantly reduces restenosis after balloon injury, and that this benefit persists at 6-month follow-up without untoward late radiation sequellae.
Dr Wojcieh Mazur from Baylor College of Medicine in Houston, Tex, presented a similar study in minipigs using a number of different doses of radiation. With a 1-Ci 192Ir source wire, four groups were treated at the time of balloon overstretch injury and oversized stent injury: the control (n=8), 1000-cGy (n=8), 1500-cGy (n=9), and 2500-cGy (n=9) groups. Animals were killed 28 days after treatment. Both percent area stenosis and maximal intimal thickness were decreased in the two higher-dose irradiated groups. Histologically, irradiated vessels had more adventitial hemorrhage, leukocyte infiltration, and fibrosis. Dr Mazur concluded that radiation therapy is successful in inhibiting neointimal proliferation after arterial injury in this swine model.
Dr Ron Waksman from Emory University School of Medicine in Atlanta, Ga, also examined the dose-response relation to ionizing radiation in a pig model. A high-energy 192Ir source was used to deliver 300, 700, and 1400 cGy immediately after balloon injury and 700 cGy 48 hours after injury in pigs. Animals were killed 2 weeks later, and the maximal intimal thickness, intimal area, and intimal area corrected for degree of injury (IA/FL) were assessed. There appeared to be a linear dose-response relation (r=.75) between IA/FL and radiation dose. Delaying treatment until 48 hours after injury was more effective in reducing restenosis than treatment immediately after injury. Dr Waksman concluded that radiation significantly reduces neointimal proliferation in a dose-dependent manner and that delaying the administration of radiation by 48 hours may provide additional benefit in this model.
|
Postmenopausal Estrogen/Progestin Intervention Study |
|---|
|
TopIntroductionIntracoronary Irradiation Postmenopausal...EPIC Substudies High-Dose Heparin for Acute...Transesophageal
Echocardiography...The Scandinavian Simvastatin...Anticoagulation for Stents Drug Delivery |
|---|
Dr Trudy Bush from Johns Hopkins University in Baltimore, Maryland and Dr Elizabeth Barrett-Connor from the University of California in San Diego presented the results of the Postmenopausal Estrogen/Progestin Interventional Trial (PEPI). This major multicenter trial was designed to look at the effects of estrogen replacement therapy on risk factors (HDL cholesterol, systolic blood pressure, fibrinogen, and 2-hour glucose tolerance) rather than at hard clinical end points. A total of 875 women from seven clinical centers were randomized to one of five regimens: placebo, unopposed estrogen, estrogen plus low-dose continuous progestin, estrogen plus higher-dose cyclic progestin, and estrogen plus cyclic micronized progesterone. The mean age of the study subjects was 56 years (range, 45 to 64 years); 68% of the women had an intact uterus. Treatment was continued for a period of 36 months. Analyses were done on an intention-to-treat basis.
One third of women with a uterus were removed from the unopposed estrogen arm, usually because of endometrial hyperplasia. In the hysterectomy group, the placebo-treated patients were more likely to cross over to active regimes. HDL levels were highest in the unopposed estrogen group; all active treatment groups had HDL and triglyceride levels higher than placebo and LDL levels lower than placebo. Systolic and diastolic blood pressures tended to rise with age in all groups, with no differences among treatment arms. Fibrinogen levels were lowest in the unopposed estrogen group and highest in the placebo group. Two-hour postchallenge insulin levels were not different among groups. Women in all five treatment arms tended to gain weight, although women on estrogen alone gained significantly less weight than those in the other treatment arms. The investigators concluded that from the standpoint of effect on risk factors for cardiovascular disease, the best estrogen replacement regimen for women with a uterus was estrogen plus micronized progesterone, and for women without a uterus, unopposed estrogen.
|
EPIC Substudies |
|---|
|
TopIntroductionIntracoronary Irradiation Postmenopausal...EPIC Substudies High-Dose Heparin for Acute...Transesophageal
Echocardiography...The Scandinavian Simvastatin...Anticoagulation for Stents Drug Delivery |
|---|
A number of additional substudy analyses of the EPIC study (Evaluation of 7E3 for the Prevention of Ischemic Complications) were presented. This study of the GP IIb/IIIa antibody c7E3 compared placebo, bolus c7E3, and bolus plus infusion c7E3 in patients undergoing high-risk coronary interventions (percutaneous transluminal coronary angioplasty [PTCA] or directional coronary atherectomy [DCA]).
Dr Michael Lincoff from the Cleveland Clinic Foundation in Cleveland, Ohio, presented a substudy analysis focusing on 470 EPIC patients with unstable angina. In contrast to the overall cohort, in which a c7E3 bolus plus infusion was associated with a 35% reduction (from 12.8% to 8.3%) in the 30-day composite end point of death, myocardial infarction (MI), or urgent intervention, in the unstable angina population treated with a c7E3 bolus and infusion, the 30-day event rate was decreased by 70.6% (from 13% to 3.8%). By the 6-month follow-up end point, there was an even more dramatic effect of a c7E3 bolus plus infusion on the incidence of death (0.7% versus 6.7%) and MI (1.3% versus 11.3%). There was no effect of c7E3 on the incidence of repeat PTCA or coronary artery bypass graft surgery (CABG) by 6 months in this unstable angina population. Dr Lincoff concluded that in unstable angina patients c7E3 treatment is associated with a dramatic decrease in both short- and long-term risks of death and MI, with no effect on the need for revascularization in this population.
Dr Jeffrey Lefkovits, also from the Cleveland Clinic, presented the results of an EPIC substudy analysis in 64 patients who underwent PTCA within 12 hours of the onset of a MI (43 direct PTCA, 22 rescue PTCA). Treatment with bolus plus infusion c7E3 was associated with significant decrease in 6-month composite end points (4.5% versus 47.8% in the placebo group; P=.002) and a trend toward lower 30-day end points (4.5% versus 26.1%; P=.058) and higher major bleeding events (18.2% versus 13%; P=NS). Dr Lefkovits concluded that the use of potent platelet antagonists such as c7E3 may significantly improve the clinical outcome of patients undergoing PTCA within 12 hours of MI.
Dr Lefkovits also presented the results of a subanalysis of 199 patients in the EPIC trial who underwent DCA. As in prior studies, placebo-treated DCA patients had an incidence of non–Q-wave MI that was approximately twice that found in the PTCA population (15.2% versus 5.5%). In contrast, the incidence of non–Q-wave MI in c7E3-treated (bolus plus infusion) DCA patients showed no such increase over that in c7E3-treated (bolus plus infusion) PTCA patients (4.5% versus 4.2%). As with PTCA patients, the incidence of major bleeding was significantly higher in c7E3-treated DCA patients (10.4% versus 1.5%). Dr Lefkovits concluded that sustained platelet glycoprotein IIb/IIIa receptor blockade eliminates the increased risk for non–Q-wave MI that is present with directional atherectomy.
|
High-Dose Heparin for Acute MI |
|---|
|
TopIntroductionIntracoronary Irradiation Postmenopausal...EPIC Substudies High-Dose Heparin for Acute...Transesophageal
Echocardiography...The Scandinavian Simvastatin...Anticoagulation for Stents Drug Delivery |
|---|
Dr Freek Verheugt from the Free University Hospital in Amsterdam, Netherlands, and Dr Randall Marsh from North Colorado Medical Center presented the results of the Heparin Early Patency (HEAP) pilot study. A total of 26 patients with symptoms of acute MI who presented within 6 hours of pain onset were treated with a single 300-U/kg bolus of heparin (doses ranged from 17 000 to 32 000 U) and aspirin, with no thrombolytic agents administered. At 90-minute angiography, 15 of 26 patients (58%) had TIMI grade 2 (n=2) or grade 3 (n=13, 50% of the total) flow. At 90 minutes, the activated partial thromboplastin time (aPTT) exceeded 120 seconds in all patients; there were no bleeding events. Patients were subsequently treated with intravenous heparin, titrated to an aPTT of 2 to 2.5 times control. Ten of the thirteen patients with TIMI 3 flow at 90 minutes had TIMI 3 flow at predischarge angiography. Dr Verheught concluded that high-dose heparin may be a simple and inexpensive alternative to thrombolytic therapy in patients with acute MI; these results will need to be confirmed in larger prospective randomized trials.
|
Transesophageal Echocardiography in the Evaluation of Atrial Fibrillation and Unexplained Embolic Events |
|---|
|
TopIntroductionIntracoronary Irradiation Postmenopausal...EPIC Substudies High-Dose Heparin for Acute...Transesophageal
Echocardiography...The Scandinavian Simvastatin...Anticoagulation for Stents Drug Delivery |
|---|
Two presentations specifically examined the role that transesophageal echocardiography (TEE) may play in the evaluation of patients with atrial fibrillation before cardioversion.
Dr Warren Manning from Beth Israel Hospital in Boston, Mass, presented their experience with a TEE-guided approach over a 4-year period. All patients presenting with new atrial fibrillation over a 54-month period were screened; of 270 patients who qualified for inclusion, 233 agreed to participate. The mean age of the patients was 73±13 years; the average prior duration of atrial fibrillation was 3.4±6.0 weeks. Most patients (91%) had received oral anticoagulation before evaluation by TEE and for 1 to 30 days after cardioversion.
Atrial thrombi were noted in 34 patients (15.5%), usually in the left atrium (n=34) and sometimes in the right atrium (n=6). Seventeen of the patients with atrial thrombi underwent successful cardioversion after a period of prolonged oral anticoagulation, 14 remained in atrial fibrillation, and 3 died. In the remaining 196 patients without atrial thrombi, 186 (95%) were successfully cardioverted during the index admission without additional prolonged anticoagulation. None of these 186 patients had clinical evidence for thromboembolism during a subsequent follow-up period of 1 month. Dr Manning concluded that this TEE-guided approach to patients with atrial fibrillation is safe and has an efficacy similar to that of conventional therapy.
Dr Allan Klein from the Cleveland Clinic presented the results of the ACUTE pilot study, which randomized 123 patients to either conventional anticoagulant therapy (n=63; 7 weeks of oral therapy) or TEE-guided therapy (n=60; TEE to screen for the presence of thrombi, anticoagulation at the time of cardioversion, prolonged anticoagulation only if thrombus identified on TEE, and 4 weeks of oral anticoagulation after cardioversion). Patients in the TEE arm tended to have fewer embolic events (0% versus 2%), fewer episodes of clinical instability (2% versus 8%), early detection of thrombi, and earlier cardioversion (77% of the TEE patients underwent cardioversion, compared with 57% of the conventionally treated patients; 17% of the conventionally treated patients converted spontaneously in the prolonged anticoagulation period, as opposed to 7% of the TEE arm patients). Dr Klein concluded that a TEE-guided strategy with a brief period of anticoagulation is feasible and safe and may decrease the embolic risks usually associated with cardioversion by detecting thrombi. A large multicenter randomized study (ACUTE) is currently under way to extend this investigation to a much larger group of patients.
Dr Arthur Labovitz from St. Louis University presented the current status of the STEPS trial, a multicenter study evaluating the significance of TEE findings in identifying potential cardiac sources of otherwise unexplained embolic events. A total of 805 patients from 16 participating centers were enrolled over a 1-year period (January through December 1992); the mean age of the patients was 59 years (range, 18 to 95 years). Patients were subdivided into those in normal sinus rhythm (NSR; n=623) and those in atrial fibrillation (AFib; n=182). Positive TEE findings included left atrial thrombus (5% in NSR, 18% in AFib), spontaneous echo contrast (10% in NSR, 50% in AFib), patent foramen ovale (22% in NSR, 12% in AFib), atrial septal aneurysm (10% in NSR, 3% in AFib), and complex atherosclerotic aortic debris (3% in NSR, 2% in AFib). Totally negative studies were found in only 15% of the patients in atrial fibrillation and only 50% of the patients in normal sinus rhythm. Dr Labovitz concluded that the yield of abnormal TEE findings in patients with otherwise unexplained embolic events appears to be substantial; however, the effect of specific therapies on these abnormalities remains to be tested.
|
The Scandinavian Simvastatin Survival Study |
|---|
|
TopIntroductionIntracoronary Irradiation Postmenopausal...EPIC Substudies High-Dose Heparin for Acute...Transesophageal
Echocardiography...The Scandinavian Simvastatin...Anticoagulation for Stents Drug Delivery |
|---|
Dr Terje Pedersen from Oslo, Norway, presented the results of the Scandinavian Simvastatin Survival Study (SSSS). This large, prospective, randomized study was first initiated in 1988 and sought to determine whether lipid-lowering therapy can reduce the incidence of cardiac events in patients with documented coronary artery disease. A total of 4444 patients with coronary artery disease and no evidence of heart failure were randomized to placebo (n=2221) or Simvastatin (20 mg/D, could be increased to 40 mg/D if the total cholesterol remained >200; n=2223) and were followed for a period of at least 5 years. Seventy-nine percent of the patients in the study qualified for inclusion on the basis of a documented prior MI. The primary end point of the study was all-cause mortality; secondary end points included the incidence of MI, sudden death, repeat hospitalization, and revascularization. By 5 years, in the placebo group, 11.5% of the patients had died, compared with 8.2% in the Simvastatin group. The incidence of nonfatal MI was also significantly higher in the placebo group (22.6% versus 15.9% in the Simvastatin group); there was a 37% relative decrease in the need for CABG or PTCA in the Simvastatin group. The authors concluded that in this population of patients with coronary artery disease, lipid-lowering therapy with Simvastatin was safe and significantly improved survival, significantly reduced the incidence of cardiac events, and significantly reduced the need for revascularization.
|
Anticoagulation for Stents |
|---|
|
TopIntroductionIntracoronary Irradiation Postmenopausal...EPIC Substudies High-Dose Heparin for Acute...Transesophageal
Echocardiography...The Scandinavian Simvastatin...Anticoagulation for Stents Drug Delivery |
|---|
A lot of attention has recently been focused on new anticoagulation regimens for stents. One session on Monday afternoon was devoted solely to this topic and included presentations from a number of institutions.
Drs Antonio Colombo and Patrick Hall from Columbus Hospital in Milan, Italy, presented their extensive experience with a variety of different stent devices, using only oral antiplatelet therapy with either aspirin alone or aspirin plus ticlopidine. Their experience with Palmaz-Schatz, Wiktor, and Gianturco-Roubin stents with antiplatelet therapy alone suggests that antiplatelet agents are effective in preventing stent thrombosis when stents are optimally expanded at the time of implantation (under intravascular ultrasound guidance).
A subsequent presentation by Dr Simonetta Blengino from the same group compared aspirin alone and ticlopidine plus short-term aspirin in a cohort of patients with a variety of different types of stents. There was no difference in the angiographic outcome or clinical events between either antiplatelet regimen in this preliminary series.
Dr Joseph Elias from the Centre Hospitalier Mulhouse in France presented their experience with Wiktor stents, treated with 48 hours of postprocedure heparin, and subsequent low-molecular-weight heparin, aspirin, and ticlopidine for 1 month. Again, in this uncontrolled series of patients, there was a low incidence of untoward clinical events in these patients treated without coumarin.
Dr Henrique Carvalho and Christian Jordan from the Clinique Pasteur in Toulouse, France, presented their experience with Palmaz-Schatz and Gianturco-Roubin stents. They compared their early experience with standard anticoagulation (with coumarin) and their later experience (with no coumarin) and found a much lower clinical event rate (and fewer bleeding complications) in the patients treated with the new anticoagulation protocol, regardless of the type of stent used.
Dr Pierre Aubry from the Hospital Bichat in Paris and Dr Marie-Claude Morice from the Centre Cardiologique du Nord in Saint-Denis, France, presented the combined stent experience of more than 20 institutions in France. Dr Aubry reported the results of 80 patients stented in a bailout situation, defined as an occlusive dissection with ischemia during or after PTCA. These patients were all treated with ticlopidine (250 mg/D), aspirin (100 mg/D), and low-molecular-weight heparin (0.1 mL/10 kg BID for 2 to 4 weeks); no patients received coumarin. At 1 month, the subacute thrombosis rate was 2.5%, and event-free survival was 93.75%. Dr Aubry concluded that even with an anticoagulation regimen that does not include coumarin, stenting is an effective alternative to emergent surgery for the treatment of occlusive dissection after coronary angioplasty.
Dr Morice presented the group's experience with a shortened (2-week) period of anticoagulation with low-molecular-weight heparin in Palmaz-Schatz, Gianturco-Roubin, and Wiktor stents (elective use 38.5%, 22% de novo, 16.4% restenosis) for a variety of indications, including 29.7% nonocclusive dissections, 18.9% suboptimal PTCA, and 12.8% bailout. This shortened regimen had low event rates similar to their prior published experience with a 4-week period of low-molecular-weight heparin treatment.
Their overall incidence of subacute thrombosis was 1.5%, with in-hospital complication rates of 1% for death, 0.25% for MI, 1% emergency surgery, and a 3.5% incidence of transfusion/surgical groin repair. Dr Morice concluded that shortening the duration of low-molecular-weight heparin does not adversely affect clinical outcome; the key for poststent treatment appears to be aggressive antiplatelet therapy.
Dr S. Chiu Wong from Washington Hospital Center in Washington, DC,
presented the results of the Reduced Anticoagulation in Saphenous
Vein Graft Stent (RAVES) trial. Twenty-eight consecutive patients (35
lesions) undergoing stent placement underwent a treatment strategy
incorporating intravascular ultrasound–guided stent deployment,
adjunctive high-pressure (
15-atm) balloon inflations, and reduced
anticoagulation (aspirin and ticlopidine only). There were no
in-hospital or early posthospital clinical events (death/MI/CABG), no
subacute thromboses, and no vascular or bleeding complications. Dr
Wong concluded that an intravascular ultrasound–guided
reduced-anticoagulation regimen appears feasible for stents in
saphenous vein grafts.
|
Drug Delivery |
|---|
|
TopIntroductionIntracoronary Irradiation Postmenopausal...EPIC Substudies High-Dose Heparin for Acute...Transesophageal
Echocardiography...The Scandinavian Simvastatin...Anticoagulation for Stents Drug Delivery |
|---|
Another area of considerable interest at the meeting was local drug delivery by a variety of creative approaches.
Dr Satoshi Takeshita and coworkers from St Elizabeth's Medical Center and Tufts University School of Medicine in Boston, Mass, developed a new gene delivery system that involves deployment of a thin biodegradable photopolymerized hydrogel coating onto the endoluminal surface of the vessel. As the endoluminal hydrogel dissolves, DNA is released into the tissue. This appears to be an alternative approach to vascular gene transfer that has the potential for more protracted depot effects.
Dr Keith Robinson and coworkers from Emory University School of Medicine used an alternative approach of delivering a microparticulate suspension rather than an aqueous solution to avoid the inflammatory reactions often seen with biodegradable microspheres. They examined the reaction of porcine coronary arteries to the local delivery of colloidal gold suspension through a porous balloon at periods of up to 2 weeks after balloon injury. In all specimens, colloidal gold was found at the site of the medial defect created by balloon injury, covering the external lamina and exposed medial edges and extending into the adventitia. At first the deposition was mostly extracellular, but at 14 days, colloidal gold was found in lysosomes of both macrophages and synthetic smooth muscle cells. There was no evidence of any foreign-body response. Deposition of radiolabelled protein adsorbed to colloidal goal was 6-fold higher than protein alone acutely, and remained 50% higher at 7 days; this suggests improvement in both acute transfer and chronic retention using colloidal gold as a vector.
Dr Laurent Feldman from St Elizabeth's Medical Center reported the use of a channeled angioplasty balloon catheter manufactured by Boston Scientific Corp. This catheter incorporates a conventional angioplasty balloon covered by a layer of porous channels that are perfused via an independent lumen. This system was used successfully by Dr Feldman and coworkers as a means for delivering gene therapy to the arterial wall via an adenoviral vector. They also noted that transgene expression was significantly reduced when the exposure time was decreased from 30 minutes to 15 minutes.
Dr Marvin Slepian from University Heart Center and the University of Arizona in Tucson evaluated the ability of endoluminally delivered biodegradable polymer films to provide sustained in vivo local drug delivery of heparin to the vessel wall. At days 1 and 7 after treatment, heparin was detected across the arterial wall, with the highest levels in the subintima and nearer portion of the media. By 7 days, more than 40% of the heparin remained in explanted polymer films. Dr Slepian concluded that this technique may turn out to be a versatile method for local, long-term, high-dose controlled release of pharmacological agents after PTCA.
Dr J.F. Mitchell from Hartford Hospital and the University of Connecticut in Hartford compared the efficacy of four different systemic and local administration techniques for vessel wall delivery of 123I-labeled urokinase after balloon angioplasty in swine. The four techniques included a systemic venous bolus (0.0007% actually delivered to the wall), a 30-minute infusion through a guiding catheter (0.004% delivered), local delivery with a channeled angioplasty balloon catheter (0.1% delivered), and local delivery via a hydrogel-coated balloon (1% delivered). Dr Mitchell concluded that local delivery techniques are much more efficient in conveying material to the vessel wall than conventional techniques but that further refinements will be necessary to improve the still relatively low overall efficiency of drug delivery.
Dr Mitchell also reported that group's results with an iontophoretic catheter. This novel device uses an applied electric field to selectively deliver charged drug molecules to the vessel wall. The investigators found that iontophoretic delivery of [3H]heparin in rats was approximately 13 times more effective than passive delivery and could be further enhanced by increasing the concentration of delivered drug. Furthermore, additional experiments in pigs showed that local iontophoretic delivery of heparin was capable of decreasing platelet deposition by approximately 90%, paving the way for future work with this approach.
Dr John Baker and coworkers from the Medical College of Wisconsin in Milwaukee presented an ingenious technique for using fibrin glue to reattach endothelial cells to areas of injury in New Zealand White rabbits. This technique allowed them to achieve circumferential reattachment of the glue/endothelial cell matrix to 70% to 90% of the denuded arterial wall in comparison to a control reattachment rate of 5% to 8% for seeding with endothelial cells alone.
Dr Campbell Rogers and coworkers from Brigham and Women's Hospital in Boston compared drug delivery via endovascular stents and perivascular polymer implants. They found that after perivascular delivery vascular drug-deposition was dependent on arterial circumference and was 1000 times higher than circulating levels. It also depended on the state of the artery (denuded and/or stented) and the type of material being delivered. After endovascular delivery, deposition of drug was dependent on wall thickness and also varied with the compound delivered. Dr Rogers concluded that deposition of drug after local delivery is dependent on properties of the drug, the state of the artery, the mode of delivery, and the degree of exposure to arterial flow.
Dr James Sanderson and coworkers from the NeoRx Corp in Seattle, Wash, and the Southern Research Institute in Birmingham, Ala, examined the utility of monoclonal antibody–coated microspheres for drug delivery. The antibody chosen binds to vascular smooth muscle cell membranes but not endothelial cells, myocardial cells, or fibrovascular stroma. They used flow cytometry to assess the degree of uptake of fluorescent microspheres by cultured vascular smooth muscle cells; the uptake was increased sevenfold when microspheres were coated with antibody. Electron microscopy showed that internalized microspheres were accumulated free in the cytoplasm, without evidence of vesicular membranes.
Dr Luis Guzman from the Cleveland Clinic used biodegradable nanoparticles as an alternative means to prolong drug delivery. A biodegradable poly-lactic glycolic acid polymer was used to construct nanoparticles, which were then infused into balloon-injured rat carotid arteries (with a 60-second infusion at 2 atm). Nanoparticles could be identified in the whole thickness of the media at 24 hours and 3 days after treatment; fewer were seen at 7 days, and none were identified at 14 days. There was no evidence that nanoparticle treatment increased the amount of intimal area. Dr Guzman concluded that biodegradable nanoparticles can be successfully delivered into the vessel wall with a brief infusion, can persist for up to at least 7 days, and do not engender an intimal hyperplastic reaction.
|
Footnotes |
|---|
Reprint requests to James J. Ferguson, MD, Cardiology Research, MC 1-191, Texas Heart Institute, PO Box 20345, Houston, TX 77225.
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||