RESUMEN
BACKGROUND AND AIM: Systems of care to treat acute ST-elevation myocardial infarction (STEMI) have been developed world wide in the past decade. Their effectiveness can only be proven by including and analyzing outcome data of consecutive patients in registries, which is not the case in the majority of STEMI networks. This study investigates 1-year mortality in STEMI patients in Vienna included over a 14 months time interval. The Vienna STEMI network is organized by a specific rotational system and offers both, primary percutaneous intervention (PPCI) and thrombolytic therapy (TT) as reperfusion strategies according to the recent guidelines. METHODS: At the time of investigation, the Vienna STEMI network consisted of the Viennese Ambulance Systems and five high-volume interventional cardiology departments. This network has been organized in order to increase the number of STEMI patients admitted for PPCI and to offer the fastest available reperfusion strategy, in the majority PPCI but in selected patients also TT (STEMI of short duration, mainly anterior wall MI and mainly patients younger than 75 years), followed by rescue PCI in non-responders and elective angiography with/without PCI in responders to TT during the index hospital stay. RESULTS: One-year all-cause mortality rates in the Vienna STEMI network by use of the fastest available reperfusion strategy were 13.4% in patients who received reperfusion therapy after 2 h of symptom onset and 7.4% in patients treated within 2 h; (p = 0.017). Whereas PPCI and TT demonstrated a nonsignificant difference in 1-year mortality rates when initiated within 2 h of symptom onset (10.0% vs 5.7%; p = 0.59), PPCI was more effective in acute STEMI of > 2 h duration as compared to TT but this difference did not reach statistical significance (12.1% vs 18.2%; p = 0.07). CONCLUSIONS: The reassuring long-term results of the Viennese STEMI network are another example of a specific regional system of care to offer timely diagnosis, transfer and reperfusion in patients with STEMI. In contrast to other metropolitan areas where TT has almost completely abandoned, we still use pharmacological reperfusion as a backup in case of expected and unacceptable time delays for PPCI in order to reduce myocardial damage especially in patients with larger infarctions of short duration with a low risk of bleeding complications.
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Infarto del Miocardio/mortalidad , Infarto del Miocardio/terapia , Intervención Coronaria Percutánea/mortalidad , Hemorragia Posoperatoria/mortalidad , Sistema de Registros , Terapia Trombolítica/mortalidad , Anciano , Austria/epidemiología , Terapia Combinada/mortalidad , Terapia Combinada/estadística & datos numéricos , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/estadística & datos numéricos , Prevalencia , Factores de Riesgo , Tasa de Supervivencia , Terapia Trombolítica/estadística & datos numéricos , Resultado del TratamientoRESUMEN
BACKGROUND: The purpose of this study was to determine whether implementation of recent guidelines improves in-hospital mortality from acute ST-elevation myocardial infarction (STEMI) in a metropolitan area. METHODS AND RESULTS: We organized a network that consisted of the Viennese Ambulance Systems, which is responsible for diagnosis and triage of patients with acute STEMI, and 5 high-volume interventional cardiology departments to expand the performance of primary percutaneous catheter intervention (PPCI) and to use the fastest available reperfusion strategy in STEMI of short duration (2 to 3 hours from onset of symptoms), either PPCI or thrombolytic therapy (TT; prehospital or in-hospital), respectively. Implementation of guidelines resulted in increased numbers of patients receiving 1 of the 2 reperfusion strategies (from 66% to 86.6%). Accordingly, the proportion of patients not receiving reperfusion therapy dropped from 34% to 13.4%, respectively. PPCI usage increased from 16% to almost 60%, whereas the use of TT decreased from 50.5% to 26.7% in the participating centers. As a consequence, in-hospital mortality decreased from 16% before establishment of the network to 9.5%, including patients not receiving reperfusion therapy. Whereas PPCI and TT demonstrated comparable in-hospital mortality rates when initiated within 2 to 3 hours from onset of symptoms, PPCI was more effective in acute STEMI of >3 but <12 hours' duration. CONCLUSIONS: Implementation of recent guidelines for the treatment of acute STEMI by the organization of a cooperating network within a large metropolitan area was associated with a significant improvement in clinical outcomes.
Asunto(s)
Angioplastia Coronaria con Balón/normas , Infarto del Miocardio/terapia , Reperfusión Miocárdica/normas , Anciano , Austria/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/cirugía , Garantía de la Calidad de Atención de Salud , Sistema de Registros , Estudios Retrospectivos , Choque Cardiogénico/epidemiología , Factores de TiempoRESUMEN
OBJECTIVES: We sought to demonstrate the safety and performance of the actinomycin D-coated Multilink-Tetra stent(Guidant Corp., Santa Clara, California) in the treatment of patients with single de novo native coronary lesions. BACKGROUND: Drug-eluting stents (DES) releasing sirolimus or paclitaxel dramatically reduce restenosis. The anti-proliferative drug, actinomycin D, which is highly effective in reducing neointimal proliferation in preclinical studies, was selected for clinical evaluation. METHODS: The multi-center, single-blind, three-arm ACTinomycin-eluting stent Improves Outcomes by reducing Neointimal hyperplasia (ACTION) trial randomized 360 patients to receive a DES (2.5 or 10 microg/cm(2) of actinomycin D) or metallic stent (MS). The primary end points were major adverse cardiac events (MACE) at 30 days, diameter stenosis by angiography, tissue effects, and neointimal volume by intravascular ultrasound (IVUS) at six months. When early monitoring revealed an increased rate of repeat revascularization, the protocol was amended to allow for additional follow-up for DES patients. Angiographic control of MS patients was no longer mandatory. RESULTS: The biased selection of DES patients undergoing IVUS follow-up invalidated the interpretation of the IVUS findings. The in-stent late lumen loss and that at the proximal and distal edges were higher in both DES groups than in the MS group and resulted in higher six-month and one-year MACE (34.8% and 43.1% vs. 13.5%), driven exclusively by target vessel revascularization without excess death or myocardial infarction. CONCLUSIONS: The results of the ACTION trial indicate that all anti-proliferative drugs will not uniformly show a drug class effect in the prevention of restenosis.
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Enfermedad de la Arteria Coronaria/terapia , Reestenosis Coronaria/prevención & control , Vasos Coronarios/efectos de los fármacos , Dactinomicina/uso terapéutico , Revascularización Miocárdica/métodos , Stents , Anciano , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Reestenosis Coronaria/complicaciones , Reestenosis Coronaria/diagnóstico por imagen , Reestenosis Coronaria/patología , Dactinomicina/administración & dosificación , Dactinomicina/farmacología , Muerte Súbita Cardíaca/prevención & control , Esquema de Medicación , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/prevención & control , Estudios Prospectivos , Sesgo de Selección , Método Simple Ciego , Stents/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Túnica Íntima/efectos de los fármacos , Ultrasonografía IntervencionalRESUMEN
OBJECTIVES: We sought to demonstrate the safety and formance of the actinomycin D-coated Multilink-Tetra stent(Guidant Corp., Santa Clara,California) in the treatment of patients with single de novo native coronary lesions. BACKGROUND: Drug-eluting stents (DES) releasing sirolimus or paclitaxel dramatically reduce restenosis. The anti-proliferative drug, actinomycin D, which is highly effective in reducing neointimal proliferation in preclinical studies, was selected for clinical evaluation. METHODS: The multi-center, single-blind,three-arm ACTinomycin-eluting stent Improves Outcomes by reducing Neointimal hyperplasia (ACTION) trial randomized 360 patients to receive a DES (2.5 or 10 microg/cm(2) of actinomycin D) or metallic stent (MS). The primary end points were major adverse cardiac events (MACE) at 30days, diameter stenosis by angiography, tissue effects, and neointimal volume by intravascular ultrasound (IVUS) at six months. When early monitoring revealed an increased rate of repeat revascularization, the protocol was amended to allow for additional follow-up for DES patients. Angiographic control of MS patients was no longer mandatory. RESULTS: The biased selection of DES patients undergoing IVUS follow-up invalidated the interpretation of the IVUS findings. The in-stent late lumen loss and that at the proximal and distal edges were higher in both DES groups than in the MS group and resulted in higher six-month and one-year MACE (34.8% and 43.1% vs. 13.5%), driven exclusively by target vessel revascularization without excess death or myocardial infarction...
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Masculino , Femenino , Adulto , Persona de Mediana Edad , Animales , Humanos , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Método Doble Ciego , Reestenosis Coronaria , Revascularización Miocárdica , Túnica Íntima , Vasos CoronariosRESUMEN
OBJECTIVES: We sought to assess the efficacy of vascular brachytherapy (VBT) combined with stenting for the primary prevention of restenosis. BACKGROUND: Intravascular brachytherapy after stent implantation for de novo lesions has been abandoned for the present. We revisited this procedure by optimizing all procedural steps-the use of glycoprotein IIb/IIa blockers, direct stenting, adequate radiation coverage, avoidance of edge damage, source centering, intravascular ultrasound-guided dosimetry, and continuation of a dual anti-platelet regimen for one year. METHODS: The Beta-Radiation Investigation with Direct stenting and Galileo in Europe (BRIDGE) study is a multicenter, randomized controlled trial evaluating the long-term efficacy of VBT with P-32 (20 Gy at 1 mm in the coronary wall) after direct stenting. The primary end point was angiographic intra-stent late loss; secondary end points were six months binary restenosis and neo-intimal hyperplasia. Patients (n = 112) with de novo lesions (2.5 to 4.0 mm in diameter up to 15 mm long) were randomized to either VBT or no-VBT. RESULTS: At six months, intra-stent loss was 0.43 and 0.84 mm (p < 0.001) in the irradiated and control groups, respectively. Intra-stent neo-intimal volume was reduced from 36 mm3 to 10 mm3. However, in the irradiated group there were six late occlusions as well as eight restenoses outside the stented and peri-stented area at the fall-off dose edges of the irradiated area. Accordingly, the target vessel revascularization and major adverse cardiac and cerebrovascular events rates at one year in the VBT group (20.4% and 25.9%, respectively) were higher than in the control group (12.1% and 17.2%, respectively). CONCLUSIONS: Despite the optimization of pre-, peri-, and post-procedural factors and despite the relative efficacy of the brachytherapy for the prevention of the intra-stent neo-intimal hyperplasia, the clinical outcome of the irradiated group was less favorable than that of the control group.
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Braquiterapia/métodos , Reestenosis Coronaria/prevención & control , Radioisótopos de Fósforo/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Stents , Ticlopidina/análogos & derivados , Ultrasonografía Intervencional , Anciano , Aspirina/uso terapéutico , Clopidogrel , Angiografía Coronaria , Reestenosis Coronaria/complicaciones , Reestenosis Coronaria/diagnóstico por imagen , Europa (Continente) , Femenino , Humanos , Hiperplasia/prevención & control , Masculino , Persona de Mediana Edad , Prevención Primaria/métodos , Dosis de Radiación , Ticlopidina/uso terapéutico , Túnica Íntima/patologíaRESUMEN
PPARgamma, a nuclear transcription factor, is expressed in various cells within the vasculature and in cardiomyocytes. It has been suggested that PPARgamma is involved in atherogenesis and in cardiac hypertrophy. Therefore, we sought to quantify PPARgamma mRNA in coronary arteries, the aorta and left ventricular specimens from patients with ischaemic (CHD) and dilated cardiomyopathy (CMP). Using real-time PCR, we were able to demonstrate the expression of PPARgamma in all of the human specimens. The lowest expression of PPARgamma was detected in the aorta specimens of both groups (this was set to one). In comparison, the expression in coronary arteries was 2.32-fold in CHD- and 3.78-fold in CMP specimens and in the left ventricle specimens, 2.12-fold in CHD- and 3.51-fold in CMP. Samples from CHD patients showed a higher expression of PPARgamma in all of the samples compared to those from CMP patients (aorta: 1.99-fold; coronary arteries: 1.35; left ventricles: 1.23). PPARgamma levels were not significantly correlated to CD 36 expression values in any group, suggesting that higher levels of PPARgamma are not principally due to increased PPARgamma expression in macrophages. This was confirmed by immunohistochemical analysis, which showed that PPARgamma is also located in the smooth muscle layer and in cardiomyocytes. In conclusion, our observations of increased PPAR mRNA expression in the coronary arteries and left ventricles from CHD and CMP patients suggest an important function of this nuclear receptor in the pathogenesis of heart disease.
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Cardiomiopatía Dilatada/metabolismo , Isquemia Miocárdica/metabolismo , Receptores Citoplasmáticos y Nucleares/análisis , Factores de Transcripción/análisis , Adulto , Anciano , Aorta/metabolismo , Antígenos CD36/metabolismo , Cardiomiopatía Dilatada/etiología , Vasos Coronarios/metabolismo , Proteínas de Unión al ADN/análisis , Proteínas de Unión al ADN/genética , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/etiología , Miocardio/metabolismo , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Factores de Transcripción/genéticaRESUMEN
Prostaglandin E1 (PGE-1) treatment has proved to stimulate angiogenesis in vital non-infarcted myocardium of patients with ischemic cardiomyopathy (ICMP). We investigated infarcted myocardial tissue for a possible angiogenic response to PGE-1. Neovascularization was investigated in infarcted areas of 12 hearts explanted from patients with ICMP who had been treated with PGE-1 before heart transplantation (HTX). In transmural sections containing myocardial scar tissue, CD34 and VEGF were immunohistochemically quantified to estimate capillary density and the extent of angiogenesis. To investigate a possible effect of PGE-1 on collagen turnover, the collagen content was determined in myocardial scar tissue by assessing the intensity of the area positively stained with sirius red. PGE-1-treated patients had significantly more CD34- and VEGF-positive cells in infarcted areas, and showed a significant reduction in collagen content as compared with the non-PGE-1 group (CD34: 120.3 +/- 6.1 vs. 47.7 +/- 6.1 capillary profiles/mm2; VEGF: 52.8 +/- 5.6 vs. 24.0 +/- 4.8 capillary profiles/mm2, and collagen content: 2.18 +/- 0.4 eU vs. 3.59 +/- 0.38 eU). Our data demonstrate that PGE-1 stimulates angiogenesis by upregulating VEGF expression, and reduces fibrosis in cardiac scar tissue of ischemic origin. The induction of therapeutic angiogenesis in vital and at sites of putative dead myocardial scar tissue, along with the hemodynamic improvement in patients with severe ICMP, might explain the favorable clinical outcome in PGE-1-treated patients before HTX.
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Alprostadil/uso terapéutico , Corazón/efectos de los fármacos , Isquemia Miocárdica/tratamiento farmacológico , Revascularización Miocárdica , Miocardio/patología , Antígenos CD34/metabolismo , Cicatriz , Colágeno/análisis , Femenino , Fibrosis/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Miocardio/química , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
New evidence suggests that Prostaglandin E1 (PGE-1) stimulates myocardial angiogenesis in human chronic ischemic myocardium. We sought to investigate whether PGE-1 may participate in the process of neoangiogenesis within the myocardial infarct scar. Neovascularization was investigated in 14 explanted hearts from patients with ischemic cardiomyopathy, who had been bridged to heart transplantation (HTX) with PGE-1 and compared with 14 hearts from patients who did not receive PGE-1 prior to HTX. In transmural sections obtained from the left ventricular wall and containing myocardial scar tissue, CD34 and vascular endothelial growth factor (VEGF) were quantified immunohistochemically to estimate capillary density and amount of angiogenesis. Additionally, to assess the hypoxic state of myocardium of the infarct border zone, hypoxia inducible factor 1-alpha (HIF-1alpha) was determined by immunohistochemistry and quantified by means of planimetric analysis. PGE-1-treated patients had significantly more CD34-and VEGF-positive cells in infarct areas as compared to nonPGE-1 group, respectively (CD34: 116.7 +/- 5.9 vs. 45.1 +/- 5.2 capillary profiles/mm(2), P < 0.001, and VEGF: 48.3 +/- 4.9 vs. 22.9 +/- 4.7 capillary profiles/mm(2)). HIF-1alpha enrichment (in %) as well as staining intensity (in estimated units (eU)) was significantly decreased in PGE-1-treated as compared to non-treated controls (enrichment: 11.3 +/- 2.5% vs. 19.4 +/- 4.36%; staining intensity: 0.95 +/- 0.3 vs. 1.97 +/- 0.44 eU). Our data demonstrate that PGE-1 stimulates neoangiogenesis in infarct areas adjacent to viable myocardium, via upregulation of VEGF expression. The induction of therapeutic angiogenesis along with the improved hypoxic state of chronic ischemic myocardial tissue might explain the favorable clinical outcome in PGE-1 treated patients.
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Alprostadil/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Isquemia Miocárdica/tratamiento farmacológico , Neovascularización Fisiológica/efectos de los fármacos , Vasodilatadores/uso terapéutico , Antígenos CD34/metabolismo , Biomarcadores , Presión Sanguínea/fisiología , Capilares/patología , Femenino , Trasplante de Corazón , Humanos , Hipoxia/metabolismo , Hipoxia/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Infarto del Miocardio/patología , Isquemia Miocárdica/patología , Arteria Pulmonar/fisiología , Presión Esfenoidal Pulmonar/fisiología , Estimulación Química , Factores de Transcripción/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
We showed that the melatonin receptor subtype, MT1, is expressed in healthy and diseased human coronary arteries. As studies in experimental animals suggest that the MT2 melatonin receptor subtype is also present in the vasculature, we investigated whether the MT2 is expressed in human aorta and coronary arteries. Additionally, MT2 expression in human ventricular specimens was analysed, as melatonin was shown to affect myocyte function. Expression of the MT2-receptor was studied in sections of isolated coronary arteries, aorta and left ventricular specimens from healthy heart donors (control) and patients with dilated or ischemic cardiomyopathy. MT2 expression was found by reverse transcriptase (RT)-nested-polymerase chain reaction (PCR) in all of the specimens (aorta, left ventricle and coronary arteries) derived from controls. Also, visible evidence for receptor expression was found in 12 of 15 samples from cardiomyopathy patients and 10 of 15 of coronary heart disease patients. Additionally, the expression of MT2-receptor between aorta, left ventricle and coronary arteries varied among the individuals, some of them showing highest expression in the aorta while in others principal expression sites were coronary arteries or left ventricles. In conclusion, the MT2-receptor subtype is present in human arteries and left ventricles and it is suggested that in coronary heart disease MT2-receptor expression is altered. Furthermore, there is evidence for heterogeneous MT2 expression patterns in individual patients.
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Aorta/metabolismo , Vasos Coronarios/metabolismo , Ventrículos Cardíacos/metabolismo , Receptor de Melatonina MT2/metabolismo , Humanos , ARN Mensajero/metabolismo , Receptor de Melatonina MT2/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: The role of stents, especially of heparin-coated stents for the treatment of stenoses in small coronary arteries, is still unclear. Therefore, we performed this prospective, randomized trial to evaluate the angiographic and clinical outcome after treatment of stenoses in small coronary arteries (2.0 to 2.6 mm) of symptomatic patients. METHODS AND RESULTS: We randomly assigned 588 patients to angioplasty (n=195), bare stenting (n=196), or heparin-coated stenting (n=197). The primary end point was minimal lumen diameter (MLD) at 6 months. With comparable baseline parameters, the two stent arms showed a larger postinterventional MLD, larger acute gain, and smaller residual percent diameter stenosis, although a residual stenosis of 12+/-16% was achieved in the angioplasty arm, including a 27% crossover rate to stenting. Eighty percent of patients had follow-up angiography, which documented a borderline significantly larger MLD and smaller percent diameter stenosis for the two stent groups (1.34+/-0.48 mm and 42+/-20% after angioplasty, 1.47+/-0.48 mm and 36+/-20% after bare stenting, and 1.45+/-0.54 mm and 38+/-23% after heparin-coated stenting; P=0.049 and P=0.038, respectively), but restenosis rates were not different (32%, 25%, and 30%). Thrombotic events occurred in 1.0% after angioplasty and 0.5% after bare or heparin-coated stenting. Survival without myocardial infarction or target vessel revascularization at 250 days was 84.6% (angioplasty), 88.3% (bare stenting), and 88.3% (heparin-coated stenting; log-rank P=0.39). CONCLUSION: Compared with angioplasty with provisional stenting, bare and heparin-coated stenting confer superior angiographic results and a nonsignificant 24% reduction in clinical events, with no difference between bare and heparin-coated stenting in the treatment of stenoses in small coronary arteries.
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Estenosis Coronaria/tratamiento farmacológico , Estenosis Coronaria/cirugía , Vasos Coronarios/cirugía , Fibrinolíticos/uso terapéutico , Heparina/uso terapéutico , Stents , Angioplastia Coronaria con Balón , Terapia Combinada , Angiografía Coronaria , Reestenosis Coronaria/prevención & control , Estenosis Coronaria/diagnóstico , Vasos Coronarios/anatomía & histología , Supervivencia sin Enfermedad , Femenino , Fibrinolíticos/administración & dosificación , Heparina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Stents/efectos adversos , Resultado del TratamientoRESUMEN
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand activated transcription factor which regulates gene expression in various tissues. PPARgamma was primarily found to be associated with lipid and glucose metabolism. Recent experimental studies provided evidence that PPARgamma is also expressed in the arterial wall and in cardiomyocytes and described PPARgamma as a transducer of antihypertropic signaling in the heart. This comparative study sought to investigate whether PPARgamma is differently expressed in the aorta, coronary arteries and left ventricle specimens derived from healthy heart donors (n = 5). By using quantitative PCR, we found that PPARgamma is expressed in all of the human specimens with the by far highest expression (5.01-fold) in the left ventricles compared to aorta, whereas no significant difference was detected between coronary arteries (0.93-fold) vs. aorta. Furthermore, especially great interindividual variations were observed in PPARgamma expression in aorta, and to a lesser extent, in coronary arteries and left ventricle specimens. In conclusion, our data argue for the prominent role of PPARgamma in the human heart, particularly in the normal left ventricle.
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Miocardio/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Factores de Transcripción/metabolismo , Adulto , Análisis de Varianza , Aorta/metabolismo , Vasos Coronarios/metabolismo , Femenino , Ventrículos Cardíacos/metabolismo , Humanos , Masculino , Especificidad de Órganos , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Factores de Transcripción/genéticaRESUMEN
The objective of this study was to investigate the expression of the arylhydrocarbon receptor (AhR) and its partner AhR-nuclear translocator (ARNT) in left ventricle specimens from explanted hearts from patients with cardiomyopathy (CMP). Explanted hearts from 16 patients with ischemic (n=9, age 63+/-12 years) and dilative (n=7, age 54+/-12 years) CMP, undergoing heart transplantation were examined. Healthy donor hearts from five accident victims served as controls. As these donors were of younger age (32+/-11 years), additionally, donor hearts from three older accident victims (age 48+/-15 years) without clinical symptoms but with signs of ventricular hyperthrophy (n=1) or atherosclerotic lesions (n=2) were included ("pathological controls"). Expression of AhR and ARNT was analyzed using semi-quantitative immunohistochemistry, and in selected samples, Western blot- and reverse-transcription polymerase chain reaction analysis were performed to confirm AhR and ARNT expression. Immunohistological analysis revealed weak to intermediate staining of anti-AhR in control, but weak to intense staining in CMP- and "pathologic control" specimens, indicating significantly increased AhR levels in the diseased heart. Moreover, in CMP specimens, the percentage of AhR-positive cells was strongly increased. Higher anti-AhR staining was also seen in two atherosclerotic "pathologic control" specimens. In all groups, the intensity of anti-ARNT staining was more pronounced than AhR staining, but significant differences or any age-related alterations were not observed. In conclusion, the increased cellular content of AhR in left ventricular specimens from CMP patients suggests a role for AhR in heart disease.
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Cardiomiopatías/metabolismo , Proteínas de Unión al ADN , Receptores de Hidrocarburo de Aril/metabolismo , Factores de Transcripción/metabolismo , Adulto , Translocador Nuclear del Receptor de Aril Hidrocarburo , Western Blotting , Cardiomiopatías/patología , Recuento de Células , Cartilla de ADN/química , Femenino , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/patología , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismo , Receptores de Hidrocarburo de Aril/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción/genéticaRESUMEN
OBJECTIVE: Prostaglandin E1 (PGE-1) is a potent vasodilative agent which has been used to bridge patients with chronic heart failure listed for heart transplantation (HTX). In various experimental settings PGE-1 appears to stimulate angiogenesis by inducing vascular endothelial growth factor expression. This observational clinical study sought to investigate the angiogenic effects of PGE-1 in the failing human heart. METHODS: Neovascularization was investigated in 14 explanted hearts from patients with ischemic cardiomyopathy (ICMP) who had been bridged to HTX with PGE-1 (8+/-1 mg/kg/min, 97+/-75.6 days) and compared with 14 hearts who did not receive PGE-1 prior to HTX. In three sectional areas obtained from the left ventricular wall CD34, von Willebrand factor (vWf), nuclear Ki67 (MIB-1), and VEGF were quantified by immunohistochemistry to estimate capillary density and endothelial cell proliferation. Additionally, to investigate a possible angiogenic effect of PGE-1 in vitro, cultured human coronary artery smooth muscle cells (HCASMCs) were treated with PGE-1. RESULTS: PGE-1-treated patients had significantly more CD34- and vWf-positive cells in the subepicardium (both P<0.01), myocardium (both P<0.0001) and subendocardium (P<0.01 and P<0.001) as compared to the nonPGE-1 group. Proliferative endothelial activity expressed by the presence of MIB-1- and VEGF-positive cells (both P<0.0001 in all layers) was increased more than twofold. Addition of PGE-1 to HCASMCs in cell culture resulted in a significant increase in VEGF production (164.0+/-19.7 pg/10(5) cells/24 h, P<0.005) as compared to the control cell line (66.6+/-8.7 pg/10(5) cells/24 h, P<0.005). CONCLUSIONS: Our data demonstrate that PGE-1 is a potent stimulator of angiogenesis via upregulation of VEGF expression. The induction of therapeutic angiogenesis in patients with severe ICMP might explain the favorable clinical outcome in PGE-1 treated patients until HTX.