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Epstein-Barr virus (EBV) reactivation may be involved in long-COVID symptoms, but reactivation of other viruses as a factor has received less attention. Here we evaluated the reactivation of parvovirus-B19 and several members of the Herpesviridae family (DNA viruses) in patients with long-COVID syndrome. We hypothesized that monovalent COVID-19 vaccines inhibit viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome, thereby reducing clinical symptoms. Clinical and laboratory data for 252 consecutive patients with PCR-verified past SARS-CoV-2 infection and long-COVID syndrome (155 vaccinated and 97 non-vaccinated) were recorded during April 2021-May 2022 (median 243 days post-COVID-19 infection). DNA virus-related IgG and IgM titers were compared between vaccinated and non-vaccinated long-COVID patients and with age- and sex-matched non-infected, unvaccinated (pan-negative for spike-antibody) controls. Vaccination with monovalent COVID-19 vaccines was associated with significantly less frequent fatigue and multiorgan symptoms (p < 0.001), significantly less cumulative DNA virus-related IgM positivity, significantly lower levels of plasma IgG subfractions 2 and 4, and significantly lower quantitative cytomegalovirus IgG and IgM and EBV IgM titers. These results indicate that anti-SARS-CoV-2 vaccination may interrupt viral cross-talk in patients with long-COVID syndrome (ClinicalTrials.gov Identifier: NCT05398952).
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(1) Background: Coronary artery stenting leads to local inflammation, disturbs vasomotion, and slows endothelialization, increasing vascular thrombus risk. We used a pig stenting coronary artery model to assess how peri-interventional triple therapy with dabigatran ameliorates these effects. (2) Methods: In a total of 28 pigs bare-metal stents were implanted. Four days before the percutaneous coronary intervention (PCI), we started 16 of the animals on dabigatran, maintained through 4 days after the procedure. As controls, the remaining 12 pigs received no therapy. In both groups, dual antiplatelet therapy (DAPT) (clopidogrel, 75 mg plus aspirin, 100 mg) was administered until animals were euthanized. Just after the PCI and on day 3 after the procedure, we performed optical coherence tomography (OCT) in eight animals in the dabigatran group and four controls and euthanized them. We followed the eight remaining animals in each group with OCT and angiography for one month before euthanizing them and performed in vitro myometry and histology on harvested coronary arteries from all animals. (3) Results: The dabigatran group showed a significantly increased vasoconstriction at 3 days after PCI (10.97 ± 3.85 mN vs. 7.32 ± 5.41 mN, p = 0.03), but we found no differences between endothelium-dependent and -independent vasodilatation. We also found no group differences in OCT, quantitative angiography, or histomorphometry findings. (4) Conclusions: Starting a short course of dabigatran just before PCI and continuing for a 3-day window along with usual post-PCI DAPT is associated with enhanced vasoconstriction after bare-metal stent implantation without reducing neointimal formation at one month.
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Objective: We evaluated the short and long-term effect of peri-interventional dabigatran therapy on vasomotion, endothelialization, and neointimal formation in a porcine coronary artery stenting model. Background: Stenting of coronary arteries induces local inflammation, impairs vasomotion and delays endothelialization. Methods: Twenty-eight animals underwent percutaneous coronary intervention (PCI) with drug eluting stents. Sixteen pigs started dabigatran therapy 4 days prior to PCI and continued for 4 days post-stenting, while 12 animals served as controls. Post-stenting dual antiplatelet therapy (75 mg clopidogrel and 100 mg aspirin) was continued in both groups until termination. Immediately post-stenting and at day 3 optical coherence tomography (OCT) was performed in all animals, followed by euthanasia of 8 dabigatran and 4 control animals. The remaining pigs (8 of each group) were followed up for 1 month, with control angiography and OCT. Tissue burden (degree of peri-strut structure-thrombus and/or fibrin) was evaluated. After euthanasia coronary arteries were harvested for in-vitro myometry and histology. Results: Thrombin generation was lower (p < 0.001) and tissue burden (0.83 ± 0.98 vs. 3.0 ± 2.45; p = 0.031) was significantly decreased in dabigatran treated animals. After 3 days post-PCI endothelium-dependent vasodilation was significantly improved (77 ± 40% vs. 41 ± 31%, p = 0.02) in dabigatran animals. Neither quantitative angiography nor histomorphometry showed differences between the groups. Endothelialization was faster in the dabigatran group as compared with controls (p = 0.045). Conclusion: Short-term peri-interventional triple therapy with dabigatran, aspirin, and clopidogrel led to an enhanced endothelium dependent vasodilation and faster endothelialization. However, neointimal formation 1-month after stent implantation was comparable between groups.
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Chronic obstructive pulmonary disease (COPD) poses a major risk for public health, yet remarkably little is known about its detailed pathophysiology. Definition of COPD as nonreversible pulmonary obstruction revealing more about spatial orientation than about mechanisms of pathology may be a major reason for this. We conducted a controlled observational study allowing for simultaneous assessment of clinical and biological development in COPD. Sixteen healthy control subjects and 104 subjects with chronic bronchitis, with or without pulmonary obstruction at baseline, were investigated. Using both the extent of and change in bronchial obstruction as main scoring criteria for the analysis of gene expression in lung tissue, we identified 410 genes significantly associated with progression of COPD. One hundred ten of these genes demonstrated a distinctive expression pattern, with their functional annotations indicating participation in the regulation of cellular coherence, membrane integrity, growth, and differentiation, as well as inflammation and fibroproliferative repair. The regulatory pattern indicates a sequentially unfolding pathology that centers on a two-step failure of surface integrity commencing with a loss of epithelial coherence as early as chronic bronchitis. Decline of regenerative repair starting in Global Initiative for Chronic Obstructive Lung Disease stage I then activates degradation of extracellular-matrix hyaluronan, causing structural failure of the bronchial wall that is only resolved by scar formation. Although they require independent confirmation, our findings provide the first tangible pathophysiological concept of COPD to be further explored.Clinical trial registered with www.clinicaltrials.gov (NCT00618137).
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Remodelación de las Vías Aéreas (Respiratorias)/genética , Bronquitis Crónica/genética , Perfilación de la Expresión Génica , Pulmón/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/genética , Regeneración/genética , Transcriptoma , Adulto , Anciano , Bronquitis Crónica/patología , Bronquitis Crónica/fisiopatología , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Humanos , Estudios Longitudinales , Pulmón/patología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Factores de Tiempo , Adulto JovenRESUMEN
Remodelling of the peripheral lung tissue and fibrotic foci are the main pathologies of idiopathic pulmonary fibrosis (IPF), a disease that is difficult to treat. TGF-ß activation of peripheral lung fibroblasts is indicated as the major cause of tissue remodelling in IPF and is resulting in fibroblast hyperplasia and deposition of extracellular matrix. Soluble guanylate cyclase (sGC) stimulators combined with cyclic AMP (cAMP) activators have been reported to reduce proliferation and matrix deposition in other conditions than IPF. Therefore, this drug combination may present a novel therapeutic concept for IPF. This study investigated the effect of BAY 41-2272 and forskolin on remodelling parameters in primary human lung fibroblasts. The study determined TGF-ß induced proliferation by direct cell counts after 3 days; and deposition of collagen type-I, type III, and fibronectin. BAY 41-2272 significantly reduced TGF-ß induced fibroblast proliferation, but did not reduce viability. This inhibitory effect was further supported by forskolin. Both BAY 41-2272 and forskolin alone reduced TGF-ß induced collagen and fibronectin de novo synthesis as well as deposition. This effect was significantly stronger when the two compounds were combined. Furthermore, the TGF-ß induced expression of fibrilar α-smooth muscle actin was reduced by BAY 41-2272 and this effect was strengthened by forskolin. In addition, BAY 41-2272 and forskolin reduced TGF-ß induced ß-catenin. All effects of BAY 41-2272 were concentration dependent. The findings suggest that BAY 41-2272 in combination with cAMP stimulation may present a novel therapeutic strategy to reduce tissue remodelling in IPF.
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Proliferación Celular/efectos de los fármacos , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Pulmón/efectos de los fármacos , Factor de Crecimiento Transformador beta/genética , Proliferación Celular/genética , Supervivencia Celular/efectos de los fármacos , Colforsina/farmacología , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , AMP Cíclico/genética , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Fibronectinas/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Guanilato Ciclasa/genética , Guanilato Ciclasa/metabolismo , Humanos , Fibrosis Pulmonar Idiopática/genética , Fibrosis Pulmonar Idiopática/patología , Pulmón/metabolismo , Pulmón/patología , Cultivo Primario de Células , Pirazoles/farmacología , Piridinas/farmacología , Transducción de Señal/efectos de los fármacos , beta Catenina/genéticaRESUMEN
Background The recent introduction of high-sensitivity cardiac troponin (hs-cTn) assays has allowed clinicians to measure hs-cTn before and after cardiac stress testing, but the hs-cTn release pattern and potential utility in identifying inducible myocardial ischemia are unclear. We thus conducted a systematic review and meta-analysis to improve our understanding of hs-cTn release associated with exercise and pharmacological stress testing. Methods and Results Studies published between January 2008 and July 2016 that reported hs-cTn change values (high-sensitivity cardiac troponin T [hs-cTnT] or high-sensitivity cardiac troponin I [hs-cTnI]) in relation to cardiac stress testing were searched and reviewed by 2 independent screeners. Primary outcomes were pooled estimates of absolute and relative hs-cTn changes after cardiac stress test, stratified by the presence of inducible myocardial ischemia. This meta-analysis included 11 studies (n=2432 patients). After exercise stress testing, hs-cTnT increased by 0.5 ng/L or 11% (6 studies, n=406) and hs-cTnI by 2.4 ng/L or 41% (4 studies, n=365) in patients with inducible myocardial ischemia versus hs-cTnT by 1.1 ng/L or 18% (8 studies, n=629; P=0.29) and hs-cTnI by 1.8 ng/L or 72% (4 studies, n=831; P=0.61) in patients who did not develop inducible myocardial ischemia. After pharmacological stress test, hs-cTnT changed by -0.1 ng/L or -0.4% (6 studies, n=251) and hs-cTnI by 2.4 ng/L or 32% (2 studies, n=108) in patients with inducible myocardial ischemia versus hs-cTnT by 0.7 ng/L or 11% (5 studies, n=443, P=0.44) and hs-cTnI by 1.7 ng/L or 38% (2 studies, n=116; P=0.62) in patients who did not develop inducible myocardial ischemia. Conclusions hs-cTn rising patterns after exercise and pharmacological stress testing appear inconsistent and comparably small, and do not appear to be correlated with inducible myocardial ischemia.
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Electrocardiografía , Isquemia Miocárdica/sangre , Troponina/sangre , Biomarcadores/sangre , Prueba de Esfuerzo , Humanos , Isquemia Miocárdica/diagnóstico , Reproducibilidad de los ResultadosRESUMEN
INTRODUCTION: Exercise (ESE) and dobutamine stress echocardiography (DSE) have high sensitivity and specificity to detect inducible myocardial ischemia in patients with significant coronary artery disease (CAD). High-sensitivity cardiac troponin (hs-cTn) assays detect troponin concentrations in the ng/L range. The aim of this study was to determine the kinetics of hs-cTnT in patients undergoing ESE and DSE and possible association of hs-cTnT with inducible myocardial ischemia. METHODS: In this prospective study adult patients undergoing ESE/DSE were enrolled. Peripheral blood samples were obtained before, and 30â¯min, 1, 2, and 4-6â¯h after completion of ESE/DSE. Hs-cTnT was measured on a Roche Diagnostics Elecsys 2010 analyzer. RESULTS: We enrolled 48 patients (33 ESE and 15 DSE); 11 patients (23%) had elevated baseline hs-cTnT concentrations >14â¯ng/L (99th percentile URL); 31/48 (65%) developed an hs-cTnT increase after ESE/DSE (peak 4-6â¯h post stress test), but only three patients (all in ESE group) had a positive stress test. Absolute and relative hs-cTnT increases were higher after DSE (median Δhs-cTnT +9.7â¯ng/L [IQR 4.5, 27.2]; +123% [IQR 49, 271]) compared to ESE (median Δhs-cTnT +2.3â¯ng/L [IQR 1, 4.9]; +37% [IQR 9.1, 221]). CONCLUSIONS: One in four patients undergoing ESE/DSE had increased hs-cTnT values prior to stress testing. Hs-cTnT increased above the upper limit of normal occurred commonly after ESE/DSE but was more pronounced after DSE. Increases in hs-cTn did not appear to be associated with inducible myocardial ischemia. These findings may have important implications for the clinical use of hs-cTnT within 6â¯h after ESE/DSE.
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Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/fisiopatología , Ecocardiografía de Estrés , Troponina T/sangre , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Anticoagulation is a cornerstone in haemodialysis (HD) therapy to avoid clotting of blood when it comes into contact with the dialysis membrane. Although heparins are usually administered as anticoagulants, they are not always sufficient to maintain adequate HD. We investigated the additional effect of acetylsalicylic acid compared with standard anticoagulation on maintaining adequate flow properties during HD in vitro. METHODS: We collected blood from 42 healthy volunteers, between 18 and 60 years of age, into bags filled with 1, 1.5 or 2 mg enoxaparin, with (treatment group) or without (control group) 100 mg of aspirin. Blood was evaluated before, during and at the end of each experiment to determine coagulation parameters, whole blood aggregation and thromboelastogram measurements. Transmembrane pressure was recorded as indirect estimate of dialysis patency. The primary endpoint was time to filter clotting. RESULTS: Addition of acetylsalicylic acid significantly prolonged the time to circuit clotting from 120 (105-150) min to >180 min (120-180) min (P = 0.047) and allowed lowering the enoxaparin concentration from 2 mg per circuit to 1 mg without an increase in clotting. Furthermore, it reduced the transmembrane pressure from 46 to 4 mmHg (P < 0.001) after 4 h of dialysis. Acetylsalicylic acid better preserved the platelet count (128 versus 116 × 10E9/L, P = 0.01) and improved platelet aggregation at the end of the dialysis procedure. CONCLUSION: Adding acetylsalicylic acid to HD circuits lowered the transmembrane pressure, better preserved platelet function and prolonged the time to circuit clotting, which in sum increases haemodialyser performance and may facilitate a more effective HD.
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Aspirina/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos , Enoxaparina/uso terapéutico , Diálisis Renal/métodos , Adolescente , Adulto , Anticoagulantes/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pronóstico , Adulto JovenRESUMEN
BACKGROUND: The objective of this investigation was to determine the etiology of perioperative acute coronary syndrome with a particular emphasis on thrombosis versus demand ischemia. METHODS: In this retrospective cohort study, adult patients were identified who underwent coronary angiography for acute coronary syndrome within 30 days of noncardiac surgery at a major tertiary hospital between January 2008 and July 2015. Angiograms were independently reviewed by two interventional cardiologists who were blinded to clinical data and outcomes. Acute coronary syndrome was classified as ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, or unstable angina; myocardial infarctions were adjudicated as type 1 (plaque rupture), type 2 (demand ischemia), or type 4b (stent thrombosis). RESULTS: Among 215,077 patients screened, 146 patients were identified who developed acute coronary syndrome: 117 were classified as non-ST-elevation myocardial infarction (80.1%); 21 (14.4%) were classified as ST-elevation myocardial infarction, and 8 (5.5%) were classified as unstable angina. After coronary angiography, most events were adjudicated as demand ischemia (type 2 myocardial infarction, n = 106, 72.6%) compared to acute coronary thrombosis (type 1 myocardial infarction, n = 37, 25.3%) and stent thrombosis (type 4B, n = 3, 2.1%). Absent or only mild, nonobstructive coronary artery disease was found in 39 patients (26.7%). In 14 patients (9.6%), acute coronary syndrome was likely due to stress-induced cardiomyopathy. Aggregate 30-day and 1-yr mortality rates were 7 and 14%, respectively. CONCLUSIONS: The dominant mechanism of perioperative acute coronary syndrome in our cohort was demand ischemia. A subset of patients had no evidence of obstructive coronary artery disease, but findings were consistent with stress-induced cardiomyopathy.
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Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/etiología , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Anciano , Estudios de Cohortes , Angiografía Coronaria/métodos , Angiografía Coronaria/tendencias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: It is unclear if cardiac troponin values are stable in patients prior to undergoing non-cardiac surgery, or if they tend to rise towards the day of surgery. METHODS: In this small pilot study (n=18) among patients with cardiac risk undergoing non-cardiac surgery, we determined if high-sensitivity cardiac troponin I (hscTnI) changes between the preoperative clinic visit and the day of surgery. HscTnI was measured on an Abbott Architect STAT (Abbott Laboratories, USA) platform. RESULTS: The mean duration between preoperative clinic visit and day of surgery was 8.7±2.8 (SD) days. Median hscTnI was 3.4ng/L [2.0-4.8, IQR] at the preoperative visit and 2.8ng/L [2.3-4.4] on the day of surgery (mean difference-0.24ng/L, 95% CI - 0.73 to 0.24ng/L, p=0.30). Only one patient had a large change (>50%) along with symptoms. DISCUSSION: Evidence from this small study suggests that cardiac troponin values are stable in most high-risk patients, absent clinical events, within 10days prior to non-cardiac surgery.
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Troponina I/análisis , Troponina I/química , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Biomarcadores/química , Estabilidad de Enzimas/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Proyectos Piloto , Factores de Riesgo , Troponina I/sangre , Troponina T/análisis , Troponina T/sangreRESUMEN
BACKGROUND: The diagnosis of myocardial infarction (MI) after noncardiac surgery has traditionally relied on using relatively insensitive contemporary cardiac troponin (cTn) assays. We hypothesized that using a recently introduced novel high-sensitivity cTnT (hscTnT) assay would increase the detection rate of perioperative MI. METHODS: In this ancillary study of the Vitamins in Nitrous Oxide trial, readjudicated incidence rates of myocardial injury (new isolated cTn elevation) and MI were compared when diagnosed by contemporary cTnI versus hscTnT. We probed various relative (eg, >50%) or absolute (eg, +5 ng/L) hscTnT change metrics. Inclusion criteria for this ancillary study were the presence of a baseline and at least 1 postoperative hscTnT value. RESULTS: Among 605 patients, 70 patients (12%) had electrocardiogram changes consistent with myocardial ischemia; 82 patients (14%) had myocardial injury diagnosed by contemporary cTnI, 31 (5.1%) of which had an adjudicated MI. After readjudication, 67 patients (11%) were diagnosed with MI when using hscTnT, a 2-fold increase. Incidence rates of postoperative myocardial injury ranged from 12% (n = 73) to 65% (n = 393) depending on the hscTnT metric used. Incidence rates of MI using various hscTnT change metrics and the presence of ischemic electrocardiogram changes, but without event adjudication, ranged from 3.6% (n = 22) to 12% (n = 74), a >3-fold difference. New postoperative hscTnT elevation, either by absolute or relative hscTnT change metric, was associated with an up to 5-fold increase in 6-month mortality. CONCLUSIONS: The use of hscTnT compared to contemporary cTnI increases the detection rate of perioperative MI by a factor of 2. Using different absolute or relative hscTnT change metrics may lead to under- or overdiagnosis of perioperative MI.
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Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Procedimientos Quirúrgicos Operativos/efectos adversos , Troponina T/sangre , Anciano , Biomarcadores/sangre , Electrocardiografía , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Missouri , Infarto del Miocardio/etiología , Infarto del Miocardio/mortalidad , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Método Simple Ciego , Procedimientos Quirúrgicos Operativos/mortalidad , Factores de Tiempo , Resultado del Tratamiento , Troponina I/sangre , Regulación hacia ArribaRESUMEN
Here we investigated how a coating of intravascular balloon with paclitaxel (drug-coated balloon; DCB, Freeway™) impacted porcine peripheral artery vascular function and remodeling. Domestic swine (n = 54) underwent percutaneous overstretch balloon dilation of femoral and iliac arteries, controlled by angiography and optical coherence tomography (OCT). Paclitaxel tissue uptake was measured at 1 h and 1, 3, and 9 days post-dilation. At these time-points and at 32 ± 2 days, vascular function of the dilated arteries was assessed using the organ chamber model. Neointimal growth and remodeling indices were determined using OCT and histology at 32 ± 2 days. Intima and media fibrosis were quantified by picrosirius red staining. Post-inflation femoral artery tissue drug levels were 460 ± 214, 136 ± 123, 14 ± 6, and 0.1 ± 0.1 ng/mg at 1 h and 1, 3, and 9 days, respectively. Compared to plain balloon, Freeway™ resulted in a significantly smaller neointimal area (P < 0.05), less tunica intima (8.0 ± 5.4 vs 14.2 ± 4.7 %) and media fibrosis (15.6 ± 7.7 vs 24.5 ± 5.4 %), and less femoral artery constrictive remodeling (remodeling index: 1.08 ± 0.08 vs 0.94 ± 0.08). The DCB was associated with significantly increased vasoconstrictor tone and endothelium-dependent vasodilation impairment shortly after post-overstretch injury. Overall, DCB dilation of peripheral arteries resulted in high drug uptake into arterial tissue. Compared with the plain balloon, the DCB was associated with decreased vessel wall fibrosis after balloon overstretch injury, and reduced degrees of constrictive remodeling and neointimal hyperplasia.
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Angioplastia de Balón/instrumentación , Arteria Femoral/patología , Arteria Ilíaca/patología , Paclitaxel/química , Túnica Íntima/patología , Túnica Media/patología , Angiografía/métodos , Animales , Materiales Biocompatibles Revestidos/química , Diseño de Equipo , Fibrosis , Hiperplasia , Ensayo de Materiales , Modelos Animales , Neointima/patología , Sus scrofa , Porcinos , Tomografía de Coherencia Óptica , Vasoconstricción , VasodilataciónRESUMEN
AIMS: To evaluate the short-, mid- and long-term safety, efficacy and vascular physiology of Axetis silicon dioxide (SiO2, abrading the micropores) inert-coated stent implantation in a randomised preclinical setting. METHODS AND RESULTS: Coronary arteries of domestic pigs were randomised to receive either Axetis or BMS (same design) stents with one-, three- and six-month follow-up (FUP), controlled by coronary angiography, optical coherence tomography (OCT), intravascular ultrasound (IVUS) and histology (n=32). The time-dependent vasomotor reaction of coronary arteries to stenting was measured using modified myography (n=12). Complete endothelialisation of the Axetis stent was confirmed by OCT, IVUS and histology at one-month FUP. Histopathology revealed continuous healing of the vessel wall with a gradual reduction of inflammation and fibrin score during the six-month FUP in both stent types. Significantly smaller neointimal area and %area stenosis were measured in Axetis stents compared with BMS at each FUP time point. Vascular reactivity measurements showed significantly better endothelium-dependent vasodilation of stented arteries with Axetis implantation. CONCLUSIONS: Implantation of the Axetis SiO2-coated stent resulted in a significantly better safety, efficacy and vessel physiology profile compared with BMS of the same design with a continuous decrease in vessel inflammation during the six-month FUP.
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Materiales Biocompatibles Revestidos , Vasos Coronarios , Metales , Intervención Coronaria Percutánea/instrumentación , Dióxido de Silicio , Stents , Animales , Angiografía Coronaria , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Vasos Coronarios/fisiopatología , Estudios de Factibilidad , Femenino , Masculino , Ensayo de Materiales , Modelos Animales , Neointima , Intervención Coronaria Percutánea/efectos adversos , Diseño de Prótesis , Sus scrofa , Factores de Tiempo , Tomografía de Coherencia Óptica , Ultrasonografía Intervencional , VasodilataciónRESUMEN
After reaching adulthood, orderly repair is probably one of the most important mechanisms throughout lifetime. Regular wound healing after an injury consists of a well-ordered sequence of overlapping phases of repair and essentially repeats the complex process of organ development. Organ failure in the ageing organism frequently represents the lost capacity to achieve an orderly reactivation of organ development, yet in varying and complex pathologic settings. One of the most aggressive manifestations of age-dependent and dysbalanced wound healing is a disease called idiopathic pulmonary fibrosis. Essentially, the disease replaces functional lung tissue with spreading scar tissue over a period of just 5 years. By a systematic comparison of wound healing conditions, the large-scale collaborative FP7-EU project RESOLVE has addressed these difficulties in a successful way. Background and outlining of the project are discussed.
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Envejecimiento , Fibrosis Pulmonar Idiopática/fisiopatología , Pulmón/fisiopatología , Proyectos de Investigación , Cicatrización de Heridas , Factores de Edad , Envejecimiento/metabolismo , Envejecimiento/patología , Animales , Humanos , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/patología , Pulmón/metabolismo , Pulmón/patologíaRESUMEN
OBJECTIVES: This study sought to determine the time dependency of the endothelium-dependent and -independent vascular responses after percutaneous coronary intervention (PCI) with drug-eluting (DEB) or plain balloons, bare-metal (BMS), and drug-eluting (DES) stents, or controls. BACKGROUND: Long-term endothelial dysfunction after DES implantation is associated with delayed healing and late thrombosis. METHODS: Domestic pigs underwent PCI using DEB or plain balloon, BMS, or DES. The dilated and stented segments, and the proximal reference segments of stents and control arteries were explanted at 5-h, 24-h, 1-week, and 1-month follow-up (FUP). Endothelin-induced vasoconstriction and endothelium-dependent and -independent vasodilation of the arterial segments were determined in vitro and were related to histological results. RESULTS: DES- and BMS-treated arteries showed proneness to vasoconstriction 5 h post-PCI. The endothelium-dependent vasodilation was profoundly (p < 0.05) impaired early after PCI (9.8 ± 3.7%, 13.4 ± 9.2%, 5.7 ± 5.3%, and 7.6 ± 4.7% using plain balloon, DEB, BMS, and DES, respectively), as compared with controls (49.6 ± 9.5%), with slow recovery. In contrast to DES, the endothelium-related vasodilation of vessels treated with plain balloon, DEB, and BMS was increased at 1 month, suggesting enhanced endogenous nitric oxide production of the neointima. The endothelium-independent (vascular smooth muscle-related) vasodilation decreased significantly at 1 day, with slow normalization during FUP. All PCI-treated vessels exhibited imbalance between vasoconstriction-vasodilation, which was more pronounced in DES- and BMS-treated vessels. No correlation between histological parameters and vasomotor function was found, indicating complex interactions between the healing neoendothelium and smooth muscle post-PCI. CONCLUSIONS: Coronary arteries treated with plain balloon, DEB, BMS, and DES showed time-dependent loss of endothelial-dependent and -independent vasomotor function, with imbalanced contraction/dilation capacity.
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Angioplastia Coronaria con Balón , Enfermedad de la Arteria Coronaria/terapia , Vasoespasmo Coronario/patología , Stents Liberadores de Fármacos , Endotelio Vascular/patología , Análisis de Varianza , Animales , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Modelos Animales de Enfermedad , Porcinos , Factores de TiempoRESUMEN
BACKGROUND: Measurement of glycated hemoglobin A1c (HbA1c) to diagnose diabetes mellitus (DM-2) is recommended by several expert groups. DM-2 occurs very frequently among patients with coronary artery disease (CAD). Therefore, we aimed to investigate the diagnostic strengths of HbA1c and oral glucose tolerance test (OGTT) in detecting latent glucometabolic disturbances among patients with CAD. MATERIALS AND METHODS: One hundred ninety-nine consecutive patients admitted with CAD were included in this observational study. Fasting plasma glucose as well as HbA1c measurement was performed in all study participants and those without preexisting DM-2 underwent an OGTT. RESULTS: Patients were subdivided according to their medical history into those with previous DM-2 (n = 37). The remaining 162 patients underwent OGTT, which revealed 39 patients with diabetes (DM-(OGTT)), 35 with impaired glucose tolerance (IGT), 20 with impaired fasting glucose (IFG) and 68 with normal glucose tolerance (NGT). Using HbA1c resulted in 6.8% DM and 45.6% at risk (HbA1c 5.7-6.4%) diagnosis. OGTT identified 24.1% DM (p = 0.002 compared with HbA1c) and 21.6% IGT patients. Among those with intermediate HbA1c (5.7-6.4%) 26.5% patients were NGT and only 30.9% displayed DM-2 by use of OGTT. Among patients with HbA1c of <5.7%, 44% (n = 31) of patients had disturbed glucose metabolism. Using receiver-operating curve HbA1c cutoff with the highest sensitivity and specificity was found to be 5.8%. DISCUSSION: There is a large discordance between OGTT and HbA1c in terms of detecting latent DM-2 in patients with CAD. Measurement of HbA1c could result in lower propensity of DM-2 diagnosis.