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BACKGROUND: Left bundle branch area pacing (LBBAP) has been performed exclusively using lumen-less pacing leads (LLL) with fixed helix design. This registry study explores the safety and feasibility of LBBAP using stylet-driven leads (SDL) with extendable helix design in a multicenter patient population. METHODS: This study prospectively enrolled consecutive patients who underwent LBBAP for bradycardia pacing or heart failure indications at eight Belgian hospitals. LBBAP was attempted using SDL (Solia S60; Biotronik) delivered through dedicated delivery sheath (Selectra3D). Implant success, complications, procedural, and pacing characteristics were recorded at implant and follow-up. RESULTS: The study enrolled 353 patients (mean age 76 ± 39 years, 43% female). The mean number of implants per center was 25 (range: 5-162). Overall, LBBAP with SDL was successful in 334/353 (94%), varying from 93% to 100% among centers. Pacing response was labeled as left bundle branch pacing in 73%, whereas 27% were labeled as myocardial capture. Mean paced QRS duration and stimulus to left ventricular activation time measured 126 ± 21 ms and 74 ± 17. SDL-LBBAP resulted in low pacing thresholds (0.6 ± 0.4 V at 0.4 ms), which remained stable at 12 months follow-up (0.7 ± 0.3, p = .291). Lead revisions for SDL-LBBAP occurred in 5 (1.4%) patients occurred during a mean follow up of 9 ± 5 months. Five (1.4%) septal coronary artery fistulas and 8 (2%) septal perforations occurred, none of them causing persistent ventricular septal defects. CONCLUSION: The use of SDL to achieve LBBAP is safe and feasible, characterized by high implant success in low and high volume centers, low complication rates, and stable low pacing thresholds.
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Marcapaso Artificial , Tabique Interventricular , Adulto , Anciano , Anciano de 80 o más Años , Fascículo Atrioventricular , Estimulación Cardíaca Artificial/efectos adversos , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
INTRODUCTION: Management of subcutaneous implantable cardioverter defibrillator (S-ICD) patients with newly acquired pacing needs remains problematic. His bundle pacing (HBP) allows for cardiac pacing without significant changes in the QRS morphology. We hypothesized that HBP does not alter S-ICD sensing and functions. METHODS: Twenty consecutive patients were implanted with a HB pacemaker. Among them, 17 demonstrated successful His recruitment and were prospectively screened with the automated screening tool (AST). Results of screenings performed immediately after implant and during follow-up, during intrinsic rhythm and while pacing from all available pacing configurations, were compared using the AST score. Positive-screening tests were defined by greater than or equal to 1 positive vector. RESULTS: Among the 17 patients successfully implanted (male: 41%; mean age: 73), 13 presented an indication of ventricular pacing and four of cardiac resynchronization. Absolute AST scores during both HBP (all configurations) and intrinsic rhythm were similar (p: NS). Due to left bundle branch block correction, HBP resulted in higher number of positive vectors (AST ≥ 100). AST scores were higher during HBP when compared with right ventricular pacing (RVP) (primary vector: 272 [16; 648] vs 4.6 [0.8; 16.2]; P = .003; secondary vector: 569 [183; 1186] vs 1.5 [0.7; 8.3]; P < .0001; alternate vector: 44 [2;125] vs 4.8 [0.9; 9.3]; P = .02) and resulted in a much higher number of positive vectors. Up to 90% of the patients had a positive-screening test during HBP. This passing rate was higher when compared RVP (17%; P < .0001). CONCLUSION: HBP restores normal intrinsic conduction and minimally modifies the surface electrocardiograph and subcutaneous electrograms. When ventricular pacing is needed, HBP might represent an ideal pacing option for patients implanted with a S-ICD.
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Terapia de Resincronización Cardíaca , Desfibriladores Implantables , Anciano , Fascículo Atrioventricular , Estimulación Cardíaca Artificial/efectos adversos , Electrocardiografía , Estudios de Factibilidad , Humanos , Masculino , Resultado del TratamientoRESUMEN
INTRODUCTION: We investigated whether pacing-induced electrical dyssynchrony at the time of cardiac resynchronization therapy (CRT) device implantation was associated with chronic CRT response. METHODS AND RESULTS: We included a total of 69 consecutive heart failure patients who received a CRT device. Left (LVp-RVs) and right (RVp-LVs) pacing-induced interlead delays were measured intraoperatively and used to determine if there was paced left ventricular (LV) dyssynchrony, defined as present when LVp-RVs is larger than RVp-LVs. CRT response was defined as a reduction in LV end-systolic volume ≥15%, 6 months after implantation. Paced left ventricular dyssynchrony (PLVD) was associated with ischemic cardiomyopathy (ICM) (χ2 : 8; P = .005) but not with QRS morphology nor with pacing lead positions. In a univariate analysis, PLVD (odds ratio [OR], 6.53; 95% confidence interval [CI], 2.2-18.9; P = .001), atypical left bundle branch block (LBBB) (OR, 3.3; 95% CI, 1.2-9.4; P = .022), and ICM (OR, 5.2; 95% CI, 1.6-17; P = .006) were associated with nonresponse. In a multivariate analysis, both PLVD (OR, 9.74; 95% CI, 2.8-33.9; P < .0001) and atypical LBBB (OR, 5.6; 95% CI, 1.5-20.3; P = .009) were independently associated with nonresponse. Adding PLVD to a model based on QRS morphology provided a significant and meaningful incremental value to predict LV reverse remodeling after CRT (χ2 to enter: 8; P < .005). Computer simulations corroborate these findings by showing that, while intrinsic electrical dyssynchrony is a prerequisite, the level of pacing-induced dyssynchrony modulates acute CRT response. CONCLUSION: In addition to the intrinsic electrical substrate, PLVD is strongly associated with less LV reverse remodeling, demonstrating that measuring the electrical substrate during pacing has additional value for prediction of CRT response in an already well-selected patient population.
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Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca/terapia , Disfunción Ventricular Izquierda/terapia , Función Ventricular Izquierda , Remodelación Ventricular , Adulto , Anciano , Anciano de 80 o más Años , Simulación por Computador , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Modelos Cardiovasculares , Estudios Prospectivos , Recuperación de la Función , Factores de Tiempo , Resultado del Tratamiento , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
Recent studies suggest the use of topical nitroglycerin (NTG) application in systemic sclerosis (SSc)-associated Raynaud phenomenon (RP). With the current study, we aimed to characterize for the first time the microvascular response to a NTG patch (Trinipatch® 5 mg/24 h) applied to the hand dorsum in patients with SSc using Laser Doppler imaging (LDI) at baseline and following a cold challenge. The study included 21 patients with SSc and 13 controls. Blood flow was evaluated by LDI at the level of the fingertips and metacarpus. Microvascular morphology was evaluated by nailfold capillaroscopy (NC). LDI revealed decreased fingertip baseline perfusion and a stronger vasoconstrictor response to a cold challenge in patients with SSc versus control. Metacarpal application of a NTG patch led to an increase in blood flow and hand temperature in patients with SSc. Furthermore, NTG administration led to a faster reperfusion after cold challenge. Correlation analyses revealed that the magnitude of the vasodilatory response was inversely related to baseline fingertip perfusion and hand temperature, but unrelated to the number of capillaries/mm assessed using NC. In conclusion, we provide evidence of a vasodilatory reaction following NTG patch application in patients with SSc using LDI and a protective effect against cold challenge. The magnitude of the response to NTG was related to functional, but not structural features. Our results support a further evaluation of the NTG patch as a possible therapeutic agent in SSc-associated RP.
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Mano/irrigación sanguínea , Flujometría por Láser-Doppler , Microcirculación/efectos de los fármacos , Nitroglicerina/administración & dosificación , Imagen de Perfusión , Esclerodermia Sistémica/diagnóstico por imagen , Esclerodermia Sistémica/tratamiento farmacológico , Vasodilatación/efectos de los fármacos , Vasodilatadores/administración & dosificación , Administración Cutánea , Velocidad del Flujo Sanguíneo , Estudios de Casos y Controles , Frío , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Flujo Sanguíneo Regional , Esclerodermia Sistémica/fisiopatología , Factores de Tiempo , Parche Transdérmico , Resultado del TratamientoRESUMEN
BACKGROUND: Left Ventricular Assist Device (LVAD) is a promising therapy for patients with advanced heart failure (HF), but bleeding complications remain an important issue. Previous series show that acquired von Willebrand syndrome was present in up to 100 % of first generation LVAD recipients. We report the effects of new generation LVADs on vW factor (vWF) metabolism and activity in our center. METHODS: Fifteen LVAD recipients (HeartWare®, Framingham, MA, USA) were compared to 12 HF patients, matched for age and body mass index. vWF antigen and activity, as well as D-dimers, were measured on hemostasis analyzers. A vWF LVAD-induced alteration was evocated when the [vWF activity]/[vWF antigen] ratio was <0.6. ADAMTS13 and high molecular weight multimers of vWF were also assessed. RESULTS: LVAD recipients had similar levels of endothelial vWF production than the HF subjects (137 ± 14.5 vs. 147 ± 11.7 %; respectively, p = 0.611) but a decreased vWF activity (90 ± 11 vs. 132.6 ± 13 %; respectively, p = 0.017). [vWF activity]/[vWF antigen] ratio was 0.65 ± 0.02 in the LVAD recipients and 0.92 ± 0.06 in the subjects with HF (p = 0.001). ADAMTS13 activity was 80.3 ± 4.7 % in LVAD recipients and 96.2 ± 3.5 % in the HF patients (p = 0.016). LVAD patients disclosed markedly elevated D-dimers (3217.7 ± 735 vs. 680.6 ± 223.2 ng/mL FEU in the HF patients, p = 0.006). The LVAD patients experienced one major hemorrhagic event and one systemic thrombotic event during the median follow-up of 345 days. CONCLUSIONS: LVAD recipients achieved a new hemostatic equilibrium characterized by infrequent major hemorrhagic and thrombotic events, despite a mildly impaired vWF function and a markedly enhanced thrombin formation. TRIAL REGISTRATION: ISRCTN39517567.
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Centros Médicos Académicos , Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Función Ventricular Izquierda , Factor de von Willebrand/metabolismo , Proteína ADAMTS13/sangre , Adulto , Bélgica , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Corazón Auxiliar/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Factores de Riesgo , Trombina/metabolismo , Trombosis/sangre , Trombosis/etiología , Factores de Tiempo , Resultado del Tratamiento , Enfermedades de von Willebrand/sangre , Enfermedades de von Willebrand/etiologíaRESUMEN
Air pollution has recently been associated with the development of acute decompensated heart failure, but the underlying biological mechanisms remain unclear. A pulmonary vasoconstrictor effect of air pollution, combined with its systemic effects, may precipitate decompensated heart failure. The aim of the present study was to investigate the effects of acute exposure to diesel exhaust (DE) on pulmonary vascular resistance (PVR) under resting and stress conditions but also to determine whether air pollution may potentiate acquired pulmonary hypertension. Eighteen healthy male volunteers were exposed to ambient air (AA) or dilute DE with a particulate matter of <2.5 µm concentration of 300 µg/m(3) for 2 h in a randomized, crossover study design. The effects of DE on PVR, on the coefficient of distensibilty of pulmonary vessels (α), and on right and left ventricular function were evaluated at rest (n = 18), during dobutamine stress echocardiography (n = 10), and during exercise stress echocardiography performed in hypoxia (n = 8). Serum endothelin-1 and fractional exhaled nitric oxide were also measured. At rest, exposure to DE did not affect PVR. During dobutamine stress, the slope of the mean pulmonary artery pressure-cardiac output relationship increased from 2.8 ± 0.5 mmHg · min · l (-1) in AA to 3.9 ± 0.5 mmHg · min · l (-1) in DE (P < 0.05) and the α coefficient decreased from 0.96 ± 0.15 to 0.64 ± 0.12%/mmHg (P < 0.01). DE did not further enhance the hypoxia-related upper shift of the mean pulmonary artery pressure-cardiac output relationship. Exposure to DE did not affect serum endothelin-1 concentration or fractional exhaled nitric oxide. In conclusion, acute exposure to DE increased pulmonary vasomotor tone by decreasing the distensibility of pulmonary resistive vessels at high cardiac output.
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Contaminantes Atmosféricos/toxicidad , Gasto Cardíaco Elevado/fisiopatología , Circulación Pulmonar/efectos de los fármacos , Resistencia Vascular/efectos de los fármacos , Emisiones de Vehículos/toxicidad , Estudios Cruzados , Ecocardiografía de Estrés , Endotelina-1/sangre , Humanos , Hipoxia/fisiopatología , Masculino , Músculo Liso Vascular/efectos de los fármacos , Óxido Nítrico/metabolismo , Material Particulado/efectos adversos , Material Particulado/análisis , Descanso , Vasoconstricción/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacos , Adulto JovenRESUMEN
The role of atrial metabolism alterations for initiation and atrial fibrillation (AF) persistence remains poorly understood. Therefore, we evaluated left atrial glucose metabolism by nicotinic acid derivative stimulated 18-fluorodeoxyglucose positron emission tomography in 36 patients with persistent AF undergoing catheter ablation before and 3 months after return to sinus rhythm and compared values against healthy controls. Under identical hemodynamics and metabolic conditions, and although left ventricular FDG uptake remained unchanged, patients in persistent AF presented significantly higher total left atrial and left atrial appendage uptake, which decreased significantly after return to sinus rhythm, despite improvement of passive and active atrial contractile function. These findings support a role of altered glucose metabolism and metabolic wasting underlying the pathophysiology of persistent AF.
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BACKGROUND: Decreased endothelial Nitric oxide (NO) bioavailability is one of the earliest events of endothelial dysfunction. Assessment of microvascular blood flow using a Laser Doppler Imager during local noninvasive administration of L-N-Arginine-Methyl-Ester (L-NAME) by skin iontophoresis may help discriminate the relative contributions of NO and non-NO pathways during a skin thermal hyperemic test. METHODS: In healthy nonsmokers, the effects of thermal vasodilation and sodium nitroprusside-mediated vasodilation were tested on skin pretreated with 0.9% saline solution, 2% L-NAME iontophoresis (n = 12), or intradermal injection of 25 nmol L-NAME (n = 10). The effects of L-NAME iontophoresis were also measured in a group of smokers (n = 10). RESULTS: L-NAME iontophoresis and intradermal injection of L-NAME decreased the skin response to local heating to a similar degree (-41% ± 4% vs. -44% ± 6%). L-NAME iontophoresis site-to-site and day-to-day coefficients of correlation were 0.83 and 0.76, respectively (P < 0.01). The site-to-site and day-to-day coefficients of correlation of L-NAME injection were lower than those of iontophoresis at 0.66 (P < 0.05) and 0.12, respectively (P = not significant). Sodium nitroprusside-induced skin hyperemia was not affected by L-NAME administration. L-NAME iontophoresis-mediated inhibition of skin thermal hyperemia was greater in smokers than in nonsmokers (P < 0.05). CONCLUSIONS: Laser Doppler Imager assessment of skin thermal hyperemia after L-NAME iontophoresis provides a reproducible and selective bedside method of qualitatively analyzing the contribution of the NO pathway to microvascular vasomotor function.
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Inhibidores Enzimáticos/administración & dosificación , Hiperemia/fisiopatología , Hipertermia Inducida , Iontoforesis , NG-Nitroarginina Metil Éster/administración & dosificación , Piel/irrigación sanguínea , Vasodilatación/fisiología , Adulto , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiología , Estudios de Factibilidad , Humanos , Inyecciones Intradérmicas , Flujometría por Láser-Doppler , Masculino , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/metabolismo , Donantes de Óxido Nítrico/administración & dosificación , Nitroprusiato/administración & dosificación , Reproducibilidad de los Resultados , Transducción de Señal , Fumar/efectos adversos , Fumar/fisiopatología , Vasodilatación/efectos de los fármacos , Adulto JovenRESUMEN
BACKGROUND: Cardiac implantable electronic device (CIED)-related infections are associated with severe morbidity and mortality. Few cases have previously documented both lead endocarditis and lead rupture simultaneously. CASE SUMMARY: We describe the case of a 73-year-old man with a dual-chamber pacemaker presenting with subacute endocarditis and recurrent cholangitis. A few months prior, the patient was diagnosed with localized colon cancer and Streptococcus sanguinis lead endocarditis based on nuclear imaging. He was given prolonged antibiotic therapy and lead explantation was to be performed after sigmoidectomy. During the following weeks, his condition worsened and he was readmitted for biliary sepsis. A chest X-ray revealed, incidentally, a complete ventricular lead rupture. Pacemaker electrogram showed ventricular undersensing, loss of ventricular capture, and high impedance. As his health declined, removal of the pacemaker was deemed unreasonable and the patient died of biliary sepsis in the next few weeks. DISCUSSION: We describe the case of an asymptomatic intracardiac lead fracture in the setting of colon cancer and a medically managed Streptococcus lead infection. As this complication occurred during lead infection, bacterial damage may have weakened the lead over time. As illustrated by the patient's outcomes, long-term antibiotic therapy should only be used in cases unsuitable for device removal. Complete hardware removal remains the first-line therapy in patients with CIED-related infections.
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Non-bacterial thrombotic endocarditis (NBTE) is a rare condition related to a state of hypercoagulability in advanced neoplastic disease. Most of the time, arterial thromboembolic event precedes the diagnosis of NBTE. We report here a case of NBTE responsible for multiple ischaemic strokes, which leads to the diagnosis of metastatic pancreatic adenocarcinoma. Aortic and mitral valvular regurgitations secondary to NBTE appeared within 6 weeks despite therapeutic anticoagulation with direct oral anticoagulant (DOAC) in stroke prevention of paroxysmal atrial fibrillation. Bivalvular regurgitations resolved 8 weeks after therapeutic switch to low-molecular-weight heparin (LMWH) and chemotherapy. DOACs are a possible alternative to LMWH for the prevention of venous thromboembolism in patients with active neoplasia. There is a lack of evidence for a clinical efficiency for the prevention of arterial thromboembolism in NBTE. We propose here a short review of the efficacy of anticoagulant therapy for the prevention of arterial thromboembolism in NBTE.
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Adenocarcinoma , Endocarditis no Infecciosa , Neoplasias Pancreáticas , Adenocarcinoma/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Endocarditis no Infecciosa/diagnóstico , Endocarditis no Infecciosa/tratamiento farmacológico , Endocarditis no Infecciosa/etiología , Heparina , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/tratamiento farmacológicoRESUMEN
Left bundle branch area pacing (LBBAP) has emerged as a novel pacing modality which aims to capture the left bundle branch area and avoids the detrimental effects of right ventricular pacing. Current approaches for LBBAP have been developed using lumen-less pacing leads (LLL). Expanding the tools and leads for LBBAP might contribute to a wider adoption of this technique. Standard stylet-driven pacing leads (SDL) differ from current LLL as they are characterized by a wider lead body diameter, are stylet-supported and often have a non-isodiametric extendable helix design. Although LBBAP can be performed safely with SDL, the implant technique of LBBAP differs compared to LLL. In the current overview we describe in detail how different types of SDL can be used to target a deep septal position and provide a practical guide on how to achieve LBBAP using SDL.
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Background: Non-invasive evaluation of left atrial structural and functional remodeling should be considered in all patients with persistent atrial fibrillation (AF) to optimal management. Speckle tracking echocardiography (STE) has been shown to predict AF recurrence after catheter ablation; however in most studies, patients had paroxysmal AF, and STE was performed while patients were in sinus rhythm. Aim: The aim of this study was to evaluate the ability of STE parameters acquired during persistent AF to assess atrial fibrosis measured by low voltage area, and to predict maintenance of sinus rhythm of catheter ablation. Methods: A total of 94 patients (69 men, 65 ± 9 years) with persistent AF prospectively underwent measurement of Global Peak Atrial Longitudinal Strain (GPALS), indexed LA Volume (LAVI), E/e' ratio, and LA stiffness index (the ratio of E/e' to GPALS) by STE prior to catheter ablation, while in AF. Low-voltage area (LVA) was assessed by electro-anatomical mapping and categorized into absent, moderate (>0 to <15%), and high (≥15%) atrial extent. AF recurrence was evaluated after 3 months of blanking. Results: Multivariable regression showed that LAVI, GPALS, and LA stiffness independently predicted LVA extent after correcting for age, glomerular filtration rate, and CHA2DS2-VASc score. Of all the parameters, LA stiffness index had the highest diagnostic accuracy (AUC 0.85), allowing using a cut-off value ≥0.7 to predict moderate or high LVA with 88% sensitivity and 47% specificity, respectively. In multivariable Cox analysis, both GPALS and LA stiffness were able to significantly improve the c statistic to predict AF recurrence (n = 40 over 9 months FU) over CHARGE-AF (p < 0.001 for GPALS and p = 0.01 for LA stiffness) or CHA2DS2-VASc score (p < 0.001 for GPALS and p = 0.02 for LA stiffness). GPALS and LA stiffness also improved the net reclassification index (NRI) over the CHARGE-AF index (NRI 0.67, 95% CI [0.33-1.13] for GPALS and NRI 0.73, 95% CI [0.12-0.91] for LA stiffness, respectively), and over the CHA2DS2-VASc score (NRI 0.43, 95% CI [-0.14 to 0.69] for GPALS and NRI 0.52, 95% CI [0.10-0.84], respectively) for LA stiffness to predict AF recurrence at 9 months. Conclusion: STE parameters acquired during AF allow prediction of LVA extent and AF recurrence in patients with persistent AF undergoing catheter ablation. Therefore, STE could be a valuable approach to select candidates for catheter ablation.
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Exposure to diesel exhaust is an important cardiovascular risk factor and may promote atherothrombotic events. Some data suggest that polluted air exposure could affect haemostasis through platelet activation. The aim of the study was to investigate the effects of acute exposure to diesel exhaust on platelet activation and platelet function. We tested the hypothesis in a randomised, crossover study in 25 healthy men exposed to ambient and polluted air; 11 of the subjects also performed exercise during exposure sessions. Platelet activation was evaluated by surface expression of CD62P (P-selectin) and CD63 (dense granule glycoprotein) using flow cytometry of labelled platelets. Platelet function was measured using the PFA-100 platelet function analyser and by Multiplate whole blood impedance platelet aggregometry. Acute diesel exhaust exposure had no effect on platelet activation at rest, but exercise in polluted air increased the collagen-induced expression of CD62P and CD63 (both p< 0.05). The increase in the expression of CD62P and CD63 was related to the total amount of PM2.5 inhaled during the exercise sessions (r=+0.58 and +0.60, respectively, both p< 0.05). Platelet aggregation was not impaired after polluted air exposure at rest or during exercise. In conclusion, in healthy subjects, diesel exhaust exposure induces platelet activation as illustrated by a dose-response increase in the release of CD62P and CD63. This platelet priming effect could be a contributor to the triggering of atherothrombotic events related to air pollution exposure.
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Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Plaquetas/efectos de los fármacos , Ejercicio Físico , Selectina-P/sangre , Material Particulado/efectos adversos , Activación Plaquetaria/efectos de los fármacos , Tetraspanina 30/sangre , Emisiones de Vehículos , Bélgica , Biomarcadores/sangre , Plaquetas/metabolismo , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Exposición a Riesgos Ambientales/efectos adversos , Citometría de Flujo , Voluntarios Sanos , Humanos , Masculino , Pruebas de Función Plaquetaria , Factores de Riesgo , Factores de Tiempo , Regulación hacia Arriba , Adulto JovenRESUMEN
Exposure to diesel exhaust was recently identified as an important cardiovascular risk factor, but whether it impairs nitric oxide (NO)-mediated endothelial function and increases production of reactive oxygen species (ROS) in endothelial cells is not known. We tested these hypotheses in a randomized, controlled, crossover study in healthy male volunteers exposed to ambient and polluted air (n=12). The effects of skin microvascular hyperemic provocative tests, including local heating and iontophoresis of acetylcholine and sodium nitroprusside, were assessed using a laser Doppler imager. Before local heating, skin was pretreated by iontophoresis of either a specific NO-synthase inhibitor (L-N-arginine-methyl-ester) or a saline solution (Control). ROS production was measured by chemiluminescence using the lucigenin technique in human umbilical vein endothelial cells preincubated with serum from 5 of the subjects. Exposure to diesel exhaust reduced acetylcholine-induced vasodilation (P<0.01) but did not affect vasodilation with sodium nitroprusside. Moreover, the acetylcholine/sodium nitroprusside vasodilation ratio decreased from 1.51 ± 0.1 to 1.06 ± 0.07 (P<0.01) and was correlated to inhaled particulate matter 2.5 (r=-0.55; P<0.01). NO-mediated skin thermal vasodilatation decreased from 466 ± 264% to 29 ± 123% (P<0.05). ROS production was increased after polluted air exposure (P<0.01) and was correlated with the total amount of inhaled particulate matter <2.5 µm (PM2.5). In healthy subjects, acute experimental exposure to diesel exhaust impaired NO-mediated endothelial vasomotor function and promoted ROS generation in endothelial cells. Increased PM2.5 inhalation enhances microvascular dysfunction and ROS production.