RESUMEN
OBJECTIVES: The purpose of this study was to assess whether the newer stent delivery systems provide a stented lumen cross-sectional area (CSA) that is equal to the delivery balloon nominal dimensions. BACKGROUND: First generation stents were often not adequately expanded with their delivery system and frequently required higher pressure or a larger balloon after deployment. Newer stents were designed to optimize expansion with noncompliant, high-pressure balloons provided as the delivery systems. METHODS: Intravascular ultrasound (IVUS) was used to evaluate 38 stents in 32 patients after deployment at 14 to 16 atm with their delivery balloon system. Minimum stent lumen CSA and stent minimum lumen diameter (MLD) were measured by IVUS imaging. The manufacturer's expected stent diameter was defined as the balloon diameter measured by the company at the maximum pressure used. The manufacturer's expected stent area was calculated based on the manufacturer's expected stent diameter. RESULTS: The MLD (2.5 +/- 0.5 mm) and minimum stent CSA (6.0 +/- 1.7 mm(2)) by IVUS were significantly smaller than the manufacturer's expected stent diameter (3.5 +/- 0.4 mm) and area (9.5 +/- 1.9 mm(2)) (p < 0.0001, respectively). The mean MLD by IVUS was 72 +/- 8% of the expected stent diameter, and the mean minimum stent CSA by IVUS was 62 +/- 10% of the expected stent area. CONCLUSIONS: Despite moderately high-pressure inflations, the mean minimum stent CSA actually achieved was, on average, only 62% of the manufacturer's expected stent area. To optimize stent deployment, these IVUS observations should be considered during coronary artery stenting.
Asunto(s)
Vasos Coronarios/diagnóstico por imagen , Infarto del Miocardio/terapia , Stents , Ultrasonografía Intervencional , Anciano , Análisis de Varianza , Cateterismo , Angiografía Coronaria , Femenino , Humanos , Masculino , Infarto del Miocardio/diagnóstico por imagen , Resultado del TratamientoRESUMEN
Cross-sectional studies by intravascular ultrasound (IVUS) in heart transplant recipients have suggested that vascular remodeling occurs in coronary arteries years after transplant. However, no reports describe vascular remodeling in the same cohort of patients studied prospectively using morphometric analysis (10 evenly spaced images obtained from a slow pullback from the left anterior descending coronary artery). Morphometric analysis better reflects total vessel anatomy compared with previously reported site (2 to 3 images) analysis. We reviewed 20 patients studied by IVUS at 2 months, 1 year, 2 years, and 3 years after heart transplant.Over time, the coronary artery luminal area decreased from baseline level of 12.0 mm(2) to a 3-year mark of 9.7 mm(2) (p = 0.02). Vessel shrinkage was seen in 16/20 patients. After an initial rise in intimal parameters (maximal intimal thickness, intimal index, and plaque area) from baseline to 1 year, we found a significant decrease in intimal parameters between Year 1 and Year 3 after transplant. For example, plaque area decreased from 2.05 mm(2) at 1 year post-transplant to 1.48 mm(2) by 3 years post-transplant (p = 0.05). In a majority of heart transplant patients, early intimal thickening in the first year post-transplant is accompanied by constrictive remodeling. Over the subsequent 2 years, further constrictive remodeling is seen despite a decrease in intimal area.
Asunto(s)
Enfermedad Coronaria/fisiopatología , Vasos Coronarios/fisiopatología , Trasplante de Corazón/fisiología , Adulto , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/etiología , Vasos Coronarios/diagnóstico por imagen , Estudios Transversales , Femenino , Trasplante de Corazón/efectos adversos , Trasplante de Corazón/diagnóstico por imagen , Humanos , Masculino , Periodo Posoperatorio , Pronóstico , Estudios Prospectivos , Túnica Íntima/diagnóstico por imagen , Ultrasonografía IntervencionalRESUMEN
Recent studies suggest that arterial remodeling plays an important role in restenosis and that remodeling at the reference site may also occur. To assess the chronic effect of the reference site remodeling on angioplasty results, we evaluated reference site remodeling in an experimental atherosclerotic restenosis model. Histological sections of iliac stenoses and their associated proximal reference segments from 50 atherosclerotic rabbits killed 4 weeks after angioplasty were analyzed. Lumen area (LA), external elastic lamina area (EEL), and intimal plus medial areas (I+M) were measured at the lesion (L) and reference (R) sites. Angiography was performed preangioplasty, immediately postangioplasty, and 4 weeks postangioplasty. Restenosis was defined as an angiographic loss/gain ratio of greater than 50% at follow-up angiography. Twenty-three lesions were restenotic (R+) and 32 were not (R-). There was no difference in reference site diameters (RD) between these two groups at the time of angioplasty. However, RDs were significantly smaller in the R+ group than in the R- group (1.24+/-0.18 versus 1.52+/-0.28 mm, n=55, P<.01) at 4-week follow-up. Morphometric analysis also showed a smaller LA(R) in the R+ group (0.85+/-0.27 versus 1.06+/-0.37 mm2, n=55, P<.02), whereas there was no difference in I+M(R) between the two groups. EEL(R) significantly correlated with EEL(L), LA(R), and I+M(R) in both groups combined (r=.53, n=55, P<.0001; r=.62, n = 55, P < .0001; and r = .86, n = 55, P < .0001, respectively). Remodeling can favorably and unfavorably affect both the lesion and the reference sites and appears to occur in parallel and proportionately at both sites. These data suggest that angiographic measurement of late percent stenosis using reference site diameters may lead to an underestimation of the percent luminal narrowing in restenotic lesions because unfavorable remodeling occurs in both the lesion and reference sites in restenotic vessels.
Asunto(s)
Angioplastia , Arteriopatías Oclusivas/etiología , Arteriosclerosis/cirugía , Angiografía , Angioplastia/efectos adversos , Animales , Arteriosclerosis/patología , Modelos Animales de Enfermedad , Tejido Elástico/patología , Arteria Ilíaca/patología , Arteria Ilíaca/cirugía , Masculino , Conejos , Factores de Tiempo , Túnica Íntima/patologíaRESUMEN
BACKGROUND: It is recognized that restenosis is primarily due to alterations in geometric remodeling of the extracellular matrix rather than intimal hyperplasia. Prior studies have shown that angioplasty stimulates an increase in both synthesis and degradation of collagen in the atherosclerotic vessel. However, differences in collagen content and metabolism between restenotic and nonrestenotic vessels have not been examined. METHODS AND RESULTS: Four weeks after angioplasty in an atherosclerotic rabbit model, collagen content in restenotic and nonrestenotic vessels was measured both biochemically by hydroxyproline quantitation and histologically by a digital subtraction method with the use of circularly polarized images of picrosirius red-stained sections. Collagenase and gelatinase activity also were measured in the same restenotic and nonrestenotic vessels by use of a radiosubstrate assay. Collagen content was found to be significantly lower in restenotic vessels than in nonrestenotic vessels both biochemically (127.0 +/- 32.6 versus 212.6 +/- 84.3 micrograms/mg tissue; n = 11 vessels; P < .05) and histologically (67.3 +/- 7.9% versus 76.3 +/- 11.8% area fraction; n = 20 sections from 6 vessels; P = .05). There was a significant inverse correlation between biochemically determined collagen content and gelatinase activity (P = .02) and a significant correlation between histologically determined lumen are and percent collagen content (P = .0071). CONCLUSIONS: Collagen content is significantly decreased in restenotic versus nonrestenotic vessels after angioplasty in the atherosclerotic rabbit model. The increased collagen content in nonrestenotic vessels was associated with preserved lumen area and may play a role in geometric remodeling after angioplasty.
Asunto(s)
Angioplastia de Balón , Arteriosclerosis/metabolismo , Arteriosclerosis/terapia , Colágeno/metabolismo , Arteria Ilíaca/metabolismo , Músculo Liso Vascular/metabolismo , Animales , Biomarcadores , Colagenasas/metabolismo , Gelatinasas/metabolismo , Hidroxiprolina/análisis , Arteria Ilíaca/patología , Masculino , Metaloproteinasa 1 de la Matriz , Metaloproteinasa 2 de la Matriz , Metaloendopeptidasas/metabolismo , Músculo Liso Vascular/patología , Conejos , Recurrencia , Análisis de RegresiónRESUMEN
Animal studies have been instrumental in elucidating the process of remodelling and its contribution to restenosis relative to neointimal formation following angioplasty. The majority of studies have utilized rabbit, porcine and nonhuman primate models of vascular injury. Despite the use of different experimental models, different forms of vascular injury, different methods of analysis and different definitions of arterial remodelling, all animal studies, with rare exceptions, have demonstrated the importance of remodelling in the maintenance of vascular patency in both atherogenesis and in restenosis following angioplasty. The finding that remodelling in the non-human primate is most comparable to that that occurs in man suggests that there may be a genetic predisposition to the balance of neointimal formation and arterial remodelling following vascular injury.
Asunto(s)
Arterias/patología , Arteriosclerosis/patología , Adaptación Fisiológica , Angioplastia de Balón , Animales , Arterias/fisiopatología , Arteriosclerosis/fisiopatología , Arteriosclerosis/terapia , RecurrenciaRESUMEN
BACKGROUND: Patients with diabetes mellitus are at increased risk of cardiovascular disease. To date, the baseline status and subsequent outcomes of diabetic coronary angioplasty (percutaneous transluminal coronary angioplasty, or PTCA) patients with advanced atherosclerotic disease and with procedures performed across North America have not been well characterized. METHODS AND RESULTS: Data on baseline clinical and angiographic characteristics and short- and long-term outcomes of 281 diabetic and 1833 nondiabetic PTCA patients in the multicenter National Heart, Lung, and Blood Institute 1985-1986 PTCA Registry were analyzed. Diabetic patients were older, were more likely to be female, and had more comorbid baseline conditions, triplevessel disease, and atherosclerotic lesions. Angiographic success and completeness of revascularization did not differ significantly, yet diabetic patients experienced more in-hospital death (women) and nonfatal myocardial infarction. Nine-year mortality was twice as high in diabetic patients (35.9% versus 17.9%). Similarly, 9-year rates of nonfatal myocardial infarction (29.0% versus 18.5%), bypass surgery (36.7% versus 27.4%), and repeat PTCA (43.7% versus 36.5%) were higher in diabetics than in nondiabetics. In multivariate analysis, diabetes remained a significant predictor of decreased 9-year survival and other untoward events. CONCLUSIONS: Compared with nondiabetic PTCA patients, diabetic patients have more extensive and diffuse atherosclerotic disease. Despite similar probability of angiographic success, diabetic patients are more likely to suffer in-hospital death(women) and nonfatal myocardial infarction. Long-term survival and freedom from myocardial infarction and coronary revascularization is also reduced in diabetic PTCA patients. Whether PTCA or coronary bypass surgery is more suitable for these patients is currently under investigation.
Asunto(s)
Angioplastia Coronaria con Balón , Enfermedad Coronaria/terapia , Angiopatías Diabéticas/terapia , National Institutes of Health (U.S.) , Anciano , Angiografía Coronaria , Puente de Arteria Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/fisiopatología , Angiopatías Diabéticas/diagnóstico por imagen , Angiopatías Diabéticas/fisiopatología , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Mortalidad , Infarto del Miocardio/complicaciones , Sistema de Registros , Reoperación , Análisis de Supervivencia , Resultado del Tratamiento , Estados UnidosRESUMEN
Angioplasty has been reported to increase collagen content and to alter vascular collagen alpha 1(I), alpha 2(I), and alpha 1(III) mRNA levels. Collagen synthesis is tightly regulated by complex translational and post-translational mechanisms such that mRNA levels may not necessarily reflect biosynthesis. To test whether collagen subtype I and III protein levels are altered by angioplasty, we quantitatively analysed collagen I/III protein ratios at 4 weeks after balloon angioplasty. Twenty New Zealand White rabbits underwent iliac artery balloon de-endothelialization and then were placed on a 0.5% cholesterol/6% peanut oil diet for 7 weeks at which time angioplasty was performed on arteries with > or = 50% stenosis. Arteries with < 50% stenosis were not dilated and served as controls. Animals were killed 4 weeks later and hydroxyproline (OH-pro) content and subtype I/III ratios were analysed in 5-mm mid-iliac sections. OH-pro was measured by a colorimetric assay. Subtype ratios were determined by a highly quantitative two-dimensional cyanogen bromide peptide mapping method. The degree of stenosis was measured as the minimal vessel lumen diameter and calculated as a percentage stenosis compared to a proximal reference segment. Calculated collagen content (micrograms/mg tissue) was significantly higher 4 weeks following angioplasty compared to the non-dilated group (220.4 +/- 70.8 v 308.2 +/- 26.9, P = 0.04; n = 12), despite similar percentage stenosis in the primary and restenotic lesions. The ratio of collagen I/III subtype protein distribution was not significantly different in the non-dilated and angioplastied groups (4.88 +/- 1.00 v 4.70 +/- 0.82, respectively). These studies are the first to provide data on collagen I/III subtypes following angioplasty and suggest that collagen accumulation may be more important in restenosis than alteration of collagen protein subtypes.
Asunto(s)
Angioplastia de Balón , Arteriosclerosis/metabolismo , Colágeno/metabolismo , Arteria Ilíaca/metabolismo , Animales , Bromuro de Cianógeno , Masculino , Mapeo Peptídico/métodos , ConejosRESUMEN
Smooth muscle cell proliferation is a major component of restenosis following angioplasty. Hematoporphyrin derivative and other photosensitive compounds inhibit proliferation by causing cellular necrosis upon light activation (photodynamic therapy). Other photosensitive compounds, such as benzoporphyrin derivative, have been suggested as having non-cytotoxic antiproliferative effects without photodynamic therapy, although other studies using benzoporphyrin derivative were negative. Inhibition of smooth muscle cell proliferation was examined in an in vivo rabbit model of vascular injury using a novel synthetic chlorin derivative, tin ethyl etiopurpurin, and benzoporphyrin derivative without photodynamic therapy. Tin ethyl etiopurpurin and benzoporphyrin derivative inhibited smooth muscle cell proliferation by 50-90% of control (p < or = 0.05) without toxic side effects. These results suggest that tin ethyl etiopurpurin and benzoporphyrin derivative without photodynamic therapy may provide a novel and potent antiproliferative therapy that might be useful in the treatment of restenosis.
Asunto(s)
Músculo Liso Vascular/efectos de los fármacos , Fármacos Sensibilizantes a Radiaciones/farmacología , Animales , Bromodesoxiuridina/metabolismo , División Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Masculino , Porfirinas/farmacología , ConejosRESUMEN
Restenosis after percutaneous coronary balloon angioplasty remains a significant problem. Despite success with a variety of agents in animal models, no agent has proved clearly successful in reducing restenosis in humans. There are many potential reasons for this, but one possibility is that because of our incomplete understanding of the restenotic process, therapy has been directed at the wrong target. Arterial remodeling (changes in total vessel area or changes in area circumscribed by the internal elastic lamina) is well described in de novo atherosclerosis, and there is increasing evidence that this process occurs after angioplasty. Thus, restenosis can be thought of not merely as neointimal formation in response to balloon injury, but as arterial remodeling in response to balloon injury and neointimal formation. Arterial remodeling may consist of actual constriction of the artery, as has been described in some animal models and in preliminary fashion in humans, or of compensatory enlargement as has been described in de novo atherosclerosis and in the hypercholesterolemic rabbit iliac artery model. Arterial constriction can result in restenosis with minimal neointimal formation. Compensatory enlargement accommodates significant amounts of neointimal formation, with preservation of lumen area despite an increase in neointimal area adequate to cause restenosis in a noncompensated artery. This expanded paradigm of arterial remodeling and intimal formation may in part account for the lack of success in clinical trials to date, and therapy directed at arterial remodeling as well as intimal formation may be required to reduce restenosis after coronary interventions.
Asunto(s)
Angioplastia Coronaria con Balón , Enfermedad Coronaria/prevención & control , Animales , Enfermedad de la Arteria Coronaria/patología , Enfermedad Coronaria/terapia , Vasos Coronarios/patología , Vasos Coronarios/fisiopatología , Humanos , Hiperplasia/patología , Recurrencia , Túnica Íntima/patologíaRESUMEN
Significant improvements in the success of angioplasty combined with a major reduction in complications have led to widespread use of the technique in the treatment of symptomatic patients with coronary disease. Restenosis, however, remains the most significant limitation of angioplasty, occurring in 20-50% of patients following a successful procedure. Over the past 10 years, more than 40 large randomized pharmacological trials have attempted to address this problem. Currently no single agent has clearly been shown to reduce restenosis. As a consequence of intensive research, improved understanding of the pathophysiology of restenosis as well as the design of clinical studies necessary to study the process has resulted. Recent experimental studies suggest that vascular remodeling may be as important as intimal hyperplasia, and future trials will need to address this aspect of the restenosis process. Current approaches to preventing restenosis include the use of combined drug therapy to attack several pathophysiological processes, local delivery of drug at the site of the injury to maximize drug effect, and the use of highly specific drugs including local gene therapy.
Asunto(s)
Angioplastia Coronaria con Balón/efectos adversos , Arteriopatías Oclusivas/etiología , Plaquetas/efectos de los fármacos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Arteriopatías Oclusivas/cirugía , Calcio/antagonistas & inhibidores , Colchicina/uso terapéutico , Aceites de Pescado/uso terapéutico , Humanos , Lovastatina/uso terapéutico , Molsidomina/uso terapéutico , Oligopéptidos/uso terapéutico , Péptidos Cíclicos , Recurrencia , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Esteroides/uso terapéutico , Trombosis/etiologíaAsunto(s)
Angioplastia Coronaria con Balón/efectos adversos , Enfermedad Coronaria/terapia , Vasos Coronarios/lesiones , Anciano , Angioplastia Coronaria con Balón/instrumentación , Distribución de Chi-Cuadrado , Constricción Patológica/etiología , Constricción Patológica/terapia , Enfermedad Coronaria/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
BACKGROUND: In de novo human atherosclerosis, compensatory vessel enlargement limits the effect of intimal plaque formation on lumen narrowing. We hypothesized that arterial remodeling may also play an important role in determining the chronic lumen size after angioplasty and tested this hypothesis using the hypercholesterolemic rabbit iliac artery angioplasty model. METHODS AND RESULTS: Morphometric analysis of histological cross-sectional areas of vessels from animals killed immediately after angioplasty (acute group, n = 11) were compared with the same areas from animals killed 4 weeks after the procedure (chronic group, n = 37), when restenosis occurs in this model. The area circumscribed by the internal elastic lamina (IEL) increased by 20% from acute to 4 week follow-up after angioplasty (acute group, 2.36 +/- 0.45 mm2, chronic group, 2.84 +/- 0.89 mm2). Over the same time period, intimal area increased by 0.82 mm2. Despite this increase in intimal area, lumen area decreased by only 0.34 mm2 because of the compensatory enlargement of the IEL area. In the chronic group, polynomial regression analysis revealed a quadratic relation between intimal area and lumen area (R2 = .35, P < .001). A lumen area of 0.45 mm2 (the nadir of the quadratic relation) was used to divide the chronic group into two subgroups: restenotic (n = 21; lumen area, < 0.45 mm2) and nonrestenotic (n = 16; lumen area, > 0.45 mm2). By definition, there was a significant difference in lumen area between the two subgroups (0.15 +/- 0.15 mm2 for restenotic; 0.73 +/- 0.18 mm2 for nonrestenotic). Surprisingly, the intimal areas in the two subgroups were virtually identical (2.41 +/- 0.92 mm2 for restenotic, 2.49 +/- 0.69 mm2 for nonrestenotic, P = NS). The difference in the lumen area between restenotic and nonrestenotic vessels was a result of the significantly greater IEL area in the nonrestenotic subgroup (3.22 +/- 0.83 mm2 for nonrestenotic, 2.56 +/- 0.84 mm2 for restenotic, P < .05). In both restenotic and nonrestenotic vessels, the IEL area increased with increases in intimal area. In the restenotic arteries, the slope of this correlation was < 1, showing inadequate compensatory enlargement for the intimal plaque. In the nonrestenotic vessels, the slope was > 1, limiting the effect of intimal plaque on luminal narrowing. CONCLUSIONS: These data indicate that the iliac artery in an atherosclerotic rabbit model compensates for intimal formation after angioplasty by vessel enlargement. Furthermore, the degree of vessel enlargement is more important than intimal area in determining the chronic lumen size.
Asunto(s)
Angioplastia de Balón/efectos adversos , Hipercolesterolemia/patología , Arteria Ilíaca/patología , Músculo Liso Vascular/patología , Animales , Arteriosclerosis/patología , Arteria Ilíaca/diagnóstico por imagen , Masculino , Conejos , RadiografíaRESUMEN
OBJECTIVES: The purpose of this study was to determine the effectiveness of microwave balloon angioplasty in sealing arterial dissections and to characterize the histologic features associated with this intervention. BACKGROUND: Coronary dissection accompanying balloon dilation is frequently associated with abrupt closure and acute ischemic complications. Effective management of this complication remains an active area of investigation. Because thermal energy is effective in welding separated atherosclerotic plaques, a microwave-based catheter system that provides controlled local heating was utilized in vessels with angioplasty-induced dissections. METHODS: Iliac artery dissections were induced in ahypercholesterolemic rabbit model. Vessels were randomly assigned to treatment with standard balloon angioplasty (control vessels) or microwave balloon angioplasty using an average temperature of 80 degrees C. The response of the artery was assessed angiographically and histologically. RESULTS: Angiographic success, defined as a reduction of dissection length by > 50% or the resolution of lumen haziness, was achieved in 63% of microwave-treated vessels and in 16% of control vessels (p < 0.005). Dissection length (mean +/- SD) was reduced 8.0 +/- 4.8 mm in microwave-treated vessels compared with 0.1 +/- 7.9 mm in vessels receiving standard balloon inflations (p < 0.005). Cellular necrosis was more commonly observed in microwave-treated vessels than in control vessels (73% vs. 17%, p < 0.05), but less intraluminal thrombus was seen in vessels exposed to microwave energy (p < 0.05). CONCLUSIONS: Microwave balloon angioplasty is more effective than routine balloon inflations in sealing arterial dissections in this model and appears to be less thrombogenic in these markedly disrupted vessels.
Asunto(s)
Angioplastia de Balón/métodos , Arteriosclerosis/terapia , Microondas/uso terapéutico , Angiografía , Angioplastia de Balón/efectos adversos , Angioplastia Coronaria con Balón/métodos , Angioplastia por Láser , Animales , Arteriosclerosis/diagnóstico por imagen , Arteriosclerosis/patología , Modelos Animales de Enfermedad , Arteria Ilíaca , Masculino , ConejosRESUMEN
The primary success rate for angioplasty of total occlusions is significantly worse than for subtotal lesions. Pharmacologic recanalization of total occlusions before angioplasty has the potential to improve the primary success rate. To determine the ability of recombinant tissue-type plasminogen activator (rt-PA) to recanalize occlusive thrombi before elective percutaneous transluminal coronary angioplasty, 12 patients with total occlusions, 100% obstruction and Thrombolysis in Myocardial Infarction (TIMI) grade 0 flow, and 5 with functional total occlusions, severe stenoses and TIMI grade 1 flow received an intracoronary infusion of rt-PA. The first 10 patients received 0.2 mg/min for 90 minutes, and the next 7 patients received 0.4 mg/min for 60 minutes. Flow improved by greater than or equal to 1 TIMI grade in 11 patients. Mean TIMI flow improved from 0.3 +/- 0.5 to 1.5 +/- 1.2 (p less than 0.0001). There was a significant improvement in severity of stenosis after rt-PA infusion by both digital caliper (99 +/- 2 vs 84 +/- 16%; p less than 0.0001) and quantitative videodensitometric area assessment (99 +/- 3 vs 94 +/- 6%; p less than 0.004). Angioplasty was successful in 16 of 17 patients (94%). There were 2 out-of-laboratory abrupt closures at 4 days; both were medically treated and 1 had a small myocardial infarction. Only 1 patient had a bleeding complication significant enough to need a transfusion. It is concluded that low-dose intracoronary rt-PA is effective at lysing thrombi less than 3 weeks old. This approach warrants further investigation since it may significantly improve the primary success rate of percutaneous transluminal coronary angioplasty in patients with occlusive thrombus.
Asunto(s)
Angioplastia Coronaria con Balón , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/terapia , Premedicación , Terapia Trombolítica , Activador de Tejido Plasminógeno/uso terapéutico , Adulto , Anciano , Constricción Patológica/tratamiento farmacológico , Constricción Patológica/terapia , Angiografía Coronaria , Trombosis Coronaria/tratamiento farmacológico , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Infarto del Miocardio/tratamiento farmacológico , Proteínas Recombinantes , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/efectos adversos , Activador de Tejido Plasminógeno/sangreRESUMEN
Smooth muscle cell proliferation is central to the process of restenosis. Attempts to inhibit the events leading to this proliferation have met with little success. In addition to its known antithrombotic effects, heparin also has inhibitory effects on smooth muscle cell proliferation. These effects appear to be unrelated to its anticoagulant properties and are retained in low molecular weight heparin derivatives. Although the use of heparin for as long as 18 to 24 h after coronary angioplasty in humans has not prevented restenosis, longer treatment periods have not been assessed. This study examines the effect of treatment with a low molecular weight heparin (enoxaparin) in a hypercholesterolemic rabbit iliac artery model. Control rabbits had a mean iliac artery diameter of 0.70 +/- 0.06 mm, which increased to 1.73 +/- 0.09 mm after balloon angioplasty. At follow-up angiography 4 weeks later, the mean vessel diameter was 0.56 +/- 0.12 mm. Animals treated with low dose enoxaparin (1 mg/kg per day) for 4 weeks and high dose enoxaparin (10 mg/kg per day) for either 2 or 4 weeks had similar mean luminal diameters before and immediately after angioplasty. At follow-up angiography, the mean luminal diameter was 0.82 +/- 0.17 mm for low dose enoxaparin, 1.04 +/- 0.20 mm for 2 week high dose enoxaparin (p = 0.03 versus control) and 1.19 +/- 0.09 mm for 4 week high dose enoxaparin (p = 0.001 versus control). When defined as loss of 50% of the initial gain achieved with angioplasty, restenosis was found in all control vessels.(ABSTRACT TRUNCATED AT 250 WORDS)