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1.
Artículo en Inglés | MEDLINE | ID: mdl-39095212

RESUMEN

OBJECTIVE: To determine the right ventricular (RV) systolic function echocardiographic parameter best associated with native stroke volume (SV) by thermodilution via a pulmonary artery catheter (PAC) in patients admitted to intensive care with ST elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS). DESIGN, SETTING, AND PARTICIPANTS: An observational cohort study of 43 prospectively identified patients admitted to a tertiary cardiac intensive care unit in London, United Kingdom. INTERVENTIONS: Simultaneous collection of comprehensive transthoracic echocardiographic, clinical, and PAC-derived hemodynamic data. Seven RV systolic function parameters were correlated with the PAC-derived SV. MEASUREMENTS AND MAIN RESULTS: The median patient age was 61 years (interquartile range [IQR], 52-67 years), and 36 of the 43 patients (84%) were male. The median PAC-derived SV and left ventricular ejection fraction were 57 mL (IQR, 39-70 mL) and 31% (IQR, 22%-35%), respectively. The RV outflow tract velocity time integral (RVOT VTI) and tricuspid plane systolic excursion (TAPSE) correlated significantly with the PAC-derived SV (r = 0.42 [p = 0.007] and r = 0.37 [p = 0.02], respectively). The RVOT VTI was independently associated with and predicted low PAC-derived SV (odds ratio, 1.3; p = 0.03) with a good area under the curve (AUC = 0.71; p = 0.02). An RVOT VTI <12.7 cm predicted low PAC-derived SV with a sensitivity of 66% and specificity of 72%. CONCLUSIONS: RVOT VTI is the echocardiographic RV systolic function parameter that best correlates with PAC-derived native SV in patients with STEMI complicated by CS. This parameter can help guide the hemodynamic management of this cohort.

2.
Egypt Heart J ; 76(1): 110, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39177680

RESUMEN

BACKGROUND: Transthoracic echocardiography (TTE) is the primary tool for assessing left ventricular (LV) function in cardiogenic shock (CS). However, inadequate image quality often hinders it. In this retrospective study, we investigated factors associated with LV image quality in patients admitted to the intensive care unit (ICU) with ischemic CS. RESULTS: Two critical care physicians accredited in echocardiography independently reviewed the TTEs of 100 patients admitted to our tertiary cardiac ICU with ST-elevation myocardial infarction complicated by CS between October 2016 and September 2019. Endocardial border definition (EBD) was graded for each myocardial segment of the apical 4-chamber and 2-chamber views using a conventional scoring system (1 = good, 2 = suboptimal, 3 = poor, and 4 = not possible). The biplane EBD index (EBDi) was calculated by averaging all segments from both views. An average EBDi of both observers was correlated with clinical and echocardiographic parameters. The median age was 62 years [54, 73], and 78% were males. LV ejection fraction and cardiac index (CI) medians were 29% [20, 35] and 1.93 l/min/m2 [1.40, 2.51], respectively. The median biplane EBDi was nearly suboptimal (1.833 [1.542, 2.083]). There was no correlation between EBDi and age, sex, or body mass index. However, biplane EBDi demonstrated statistically significant correlations with PaO2 (r2 = 0.066, p = 0.01), mean arterial pressure (MAP, r2 = 0.055, p = 0.03), CI (r2 = 0.105, p < 0.01), tricuspid annulus systolic velocity (RV S', r2 = 0.092, p = 0.01), and tricuspid regurge maximum velocity (TR Vmax, r2 = 0.067, p = 0.01). In a multivariate model, only CI correlated independently with EBDi (r2 = 0.105, p < 0.01). The biplane EBDi predicted CI (area under the curve (AUC) 0.70, p = 0.001) with good sensitivity (71%) and reasonable specificity (61%). CONCLUSIONS: The study suggests that in patients admitted to the ICU with ischemic CS, LV image quality by TTE deteriorates with the severity of shock, as indicated by CI.

3.
Echo Res Pract ; 11(1): 19, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39085977

RESUMEN

BACKGROUND: The pneumonitis associated with coronavirus disease 2019 (COVID-19) infection impacts the right ventricle (RV). However, the association between the disease severity and right ventricular systolic function needs elucidation. METHOD: We conducted a retrospective study of 108 patients admitted to critical care with COVID-19 pneumonitis to examine the association between tricuspid annular plane systolic excursion (TAPSE) by transthoracic echocardiography as a surrogate for RV systolic function with PaO2/FiO2 ratio as a marker of disease severity and other respiratory parameters. RESULTS: The median age was 59 years [51, 66], 33 (31%) were female, and 63 (58%) were mechanically ventilated. Echocardiography was performed at a median of 3 days [2, 12] following admission to critical care. The PaO2/FiO2 and TAPSE medians were 20.5 [14.4, 32.0] and 21 mm [18, 24]. There was a statistically significant, albeit weak, association between the increase in TAPSE and the worsening of the PaO2/FiO2 ratio (r2 = 0.041, p = 0.04). This association was more pronounced in the mechanically ventilated (r2 = 0.09, p = 0.02). TAPSE did not correlate significantly with FiO2, PaO2, PaCO2, pH, respiratory rate, or mechanical ventilation. Patients with a TAPSE ≥ 17 mm had a considerably worse PaO2/FiO2 ratio than a TAPSE < 17 mm (18.6 vs. 32.1, p = 0.005). The PaO2/FiO2 ratio predicted TAPSE (OR = 0.94, p = 0.004) with good area under the curve (0.72, p = 0.006). Moreover, a PaO2/FiO2 ratio < 26.7 (moderate pneumonitis) predicted TAPSE > 17 mm with reasonable sensitivity (67%) and specificity (68%). CONCLUSION: In patients admitted to critical care with COVID-19 pneumonitis, TAPSE increased as the disease severity worsened early in the course of the disease, especially in the mechanically ventilated. A TAPSE within the normal range is not necessarily reassuring in early COVID-19 pneumonitis.

4.
J Cardiothorac Vasc Anesth ; 38(1): 133-140, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37940458

RESUMEN

OBJECTIVE: The authors investigated if the use of ultrasound-enhancing agents (UEA) can safely improve left ventricular (LV) image quality by transthoracic echocardiography (TTE) in patients on extracorporeal membrane oxygenation (ECMO). DESIGN AND SETTING: This study was performed in a tertiary cardiothoracic and ECMO center in London, United Kingdom. PARTICIPANTS: The authors included 18 prospectively identified consecutive patients requiring TEE supported on peripherally implanted ECMO. INTERVENTION AND MEASUREMENTS: TTE was performed before and after the UEA administration. The authors assessed the LV image quality using the biplane (apical-4-chamber and apical-2-chamber views) endocardial border definition index (1 = good, 2 = suboptimal, 3 = poor, and 4 = unavailable), as well as the feasibility of LV ejection fraction (LVEF) measurement. The authors also gathered sequential clinical information for the next 24 hours. MAIN RESULTS: The patients' median age was 47 years (35, 65), and 5 (28%) were women. The biplane endocardial border definition index improved from the suboptimal to the good range (2.167 [1.812, 3.042] v 1.500 [1.417, 1.792], p = 0.0004) after the use of UEA. The feasibility of LVEF tripled from 25% (n = 5) to 83% (n = 15) (p = 0.0008) with UEA use. The UEA did not set off the bubble alarm and did not impact clinical or ECMO parameters. CONCLUSION: The use of UEA significantly improved the quality of LV biplane images by transthoracic echocardiography, transforming them from suboptimal to good in patients supported with peripherally implanted ECMO. UEA use tripled the feasibility of measuring LVEF by TTE without affecting clinical and ECMO parameters.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Humanos , Femenino , Persona de Mediana Edad , Masculino , Oxigenación por Membrana Extracorpórea/métodos , Ecocardiografía/métodos , Ultrasonografía , Función Ventricular Izquierda , Volumen Sistólico
5.
J Intensive Care Med ; 38(10): 897-902, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37287244

RESUMEN

Left ventricular outflow tract obstruction (LVOTO) is a common cardiogenic shock (CS) mimic. We present 3 cases of patients presenting with CS following myocardial infarction, exhibiting a poor response to conventional treatment with inotropy and mechanical circulatory support. This triggered echocardiographic assessment by critical care physicians using focused 2-dimensional (2D) echocardiography. This timely assessment identified anterior mitral valve leaflet entrainment into the left ventricular outflow tract (LVOT), causing LVOTO as the underlying shock mechanism. Echocardiographic findings have led to significant changes in management. The patients underwent fluid administration, weaning from inotropy, and mechanical circulatory support explantation, leading to relief of LVOTO and improved hemodynamics. Critical care basic 2D echocardiography accreditations focus on myocardial function and pericardial effusions. Relevant societies administering these accreditations should consider adding LVOT assessment to enable timely diagnosis of this life-threatening CS mimic.


Asunto(s)
Obstrucción del Flujo de Salida Ventricular Izquierda , Obstrucción del Flujo Ventricular Externo , Humanos , Choque Cardiogénico/diagnóstico por imagen , Choque Cardiogénico/terapia , Choque Cardiogénico/complicaciones , Obstrucción del Flujo Ventricular Externo/diagnóstico por imagen , Obstrucción del Flujo Ventricular Externo/etiología , Ecocardiografía , Válvula Mitral/diagnóstico por imagen
6.
J Crit Care ; 74: 154219, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36494258

RESUMEN

PURPOSE: This study investigated which commonly used right ventricular (RV) echocardiographic parameter correlates best with stroke volume (SV) estimated by Doppler echocardiography in ischemic cardiogenic shock (CS). MATERIALS AND METHODS: We retrospectively reviewed the records of 100 patients admitted to the ICU over 34 months with CS. Tricuspid annular plane systolic excursion (TAPSE), Tricuspid annulus systolic velocity (RV S'), Tricuspid regurgitation maximum velocity (TR Vmax), and RV outflow tract velocity time integral (RVOT VTI) were correlated to SV. RESULTS: Mean age was 62.6 ± 12.7 years and 78% were male. The mean SV, TAPSE, RV S', TR Vmax, and RVOT VTI were 47 ± 16 ml, 16 ± 5 mm, 11 ± 4 mm/s, 1.97 ± 0.73 m/s, and 12.7 ± 5 cm, respectively. RVOT VTI correlated best to SV (r = 0.39 p = 0.01) compared to TAPSE, RV S', and TR Vmax (r = 0.26 p = 0.01, r = 0.15 p = 0.21, r = 0.03 p = 0.78). RVOT VTI independently predicted SV. Univariate analysis demonstrated that only RVOT VTI predicted SV (OD = 1.18 p = 0.04) and had the best area under the curve (0.70, p = 0.03). CONCLUSION: RVOT VTI correlated better (albeit weakly) to and best predicted SV compared to TAPSE, RV S', and TR Vmax in patients admitted to intensive care with CS. This study suggests that RVOT VTI has the potential as a therapeutic target to optimize SV in CS.


Asunto(s)
Choque Cardiogénico , Disfunción Ventricular Derecha , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Estudios Retrospectivos , Volumen Sistólico , Choque Cardiogénico/diagnóstico por imagen , Ecocardiografía , Función Ventricular Derecha
8.
J Cardiothorac Vasc Anesth ; 36(9): 3511-3516, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35662515

RESUMEN

OBJECTIVES: Echocardiography is the main tool for cardiac assessment and helps to guide management in patients admitted to the intensive care unit (ICU) with cardiogenic shock (CS). Left ventricular ejection fraction (LVEF) is a commonly used echocardiographic surrogate for left ventricular (LV) systolic function. In this hypothesis-generating study, the authors investigated the correlation between LVEF and stroke volume (SV)/SV index (SVI) estimated by Doppler echocardiography in patients admitted to the ICU with CS and reduced LVEF. DESIGN AND SETTING: This retrospective analysis was performed in a single tertiary cardiac center in London, United Kingdom. PARTICIPANTS: Patients admitted to the ICU over a 34-month period with ST elevation myocardial infarction (STEMI) complicated by CS and LVEF <40%. INTERVENTIONS: Clinical and echocardiographic data were collected. LVEF (total, by visual estimate and by modified Simpson's method) was correlated with SV and SVI estimated by Doppler echocardiography. MEASUREMENTS AND MAIN RESULTS: One-hundred patients were included. The mean age was 62.6 ± 12.7 years and 78% were male patients. The median LVEF was 29% (20-35) and the mean SV and SVI by Doppler echocardiography were 47 mL ± 16 and 25 mL ± 9, respectively. Analysis revealed a weak yet statistically significant correlation among LVEF and Doppler SV and SVI (r = 0.44, confidence interval [CI] 0.26-0.60, p < 0.0001, r = 0.47, CI 0.28-0.62, p < 0.001, respectively). Visually estimated LVEF (n = 74) correlated weakly with Doppler SV and SVI yet better compared to LVEF by Simpson's method (n = 25) (r = 0.48, CI 0.27-0.65, p < 0.0001 and r = 0.49, CI 0.28-0.66, p < 0.0001, respectively, v r = 0.36, CI 0.05-0.67, p = 0.08 and r = 0.37, CI -0.04-0.67, p 0.07, respectively). CONCLUSIONS: There is a weak correlation between LVEF and SV or SVI estimated by Doppler echocardiography in patients admitted to the ICU with STEMI complicated by CS and reduced LVEF. Visually estimated LVEF correlated slightly better with Doppler SV compared to modified Simpson's LVEF.


Asunto(s)
Infarto del Miocardio con Elevación del ST , Función Ventricular Izquierda , Anciano , Ecocardiografía Doppler , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Infarto del Miocardio con Elevación del ST/complicaciones , Choque Cardiogénico/diagnóstico por imagen , Volumen Sistólico
9.
J Intensive Care Soc ; 23(4): 439-446, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36751361

RESUMEN

Background: Right ventricular (RV) function is increasingly being recognised as an important factor influencing outcomes in ST elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS). In this study, we investigated RV echocardiographic parameters' association with 28-day mortality in patients admitted to intensive care with STEMI complicated by CS with reduced left ventricle ejection fraction (LVEF). Method: We performed a retrospective analysis of patients admitted to intensive care unit (ICU) in a single tertiary cardiac centre over a 34-month period with STEMI complicated by CS and LVEF < 40%. Clinical and echocardiographic data were collected and correlated with 28-day mortality. Results: One-hundred patients were included with a mean age of 62.6 ±12.7 years and 78% were male. Mortality at 28 days was 37%. Respectively, 85%, 40% and 25% of patients required mechanical ventilation, mechanical circulatory support and renal replacement therapy. Tricuspid annulus peak systolic velocity (RV S') was significantly higher in survivors (12 ± 3.3 v 10 ± 3.5 cm/s, p = 0.03) and was an independent predictor of mortality (odds ratio 1.2, 95% confidence interval 1.1-1.4, p = 0.04). RV S' of 10.5 cm/s exhibited best sensitivity and specificity (64% and 65%, respectively; p = 0.02) for mortality. The Kaplan-Meier curve demonstrated 85% risk of 28-day mortality for RV S' < 10.5 cm/s v 53% for RV S' > 10.5 cm/s (p = 0.02). Conclusion: RV function is associated 28-day mortality in patients admitted to ICU with STEMI complicated by CS with reduced LVEF. RV S' predicted mortality with good sensitivity and specificity.

10.
J Cardiothorac Vasc Anesth ; 36(7): 2080-2089, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34074555

RESUMEN

Extracorporeal membrane oxygenation (ECMO) is a lifesaving intervention increasingly used to support patients with severe respiratory and cardiac dysfunction. Echocardiography is an important tool, aiding implantation and monitoring during ECMO therapy, but often its use is limited by poor acoustic windows. This limitation may be overcome by the use of echocardiography contrast agents to improve diagnostic yield and reduce the need for other imaging modalities that may require patient transfer, involve ionizing radiation and, occasionally, nephrotoxic radio-opaque contrast medium. In this article the authors review the literature addressing the use of contrast-enhanced echocardiography (CEE) in ECMO-supported patients. The authors discuss the role of CEE in guiding implantation of ECMO, cardiac assessment and diagnosis of complications during ECMO therapy, as well as the safety of ultrasound-enhancing agents in this cohort of patients.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Ecocardiografía , Oxigenación por Membrana Extracorpórea/métodos , Humanos , Respiración Artificial
12.
Echo Res Pract ; 7(3): K21-K26, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32698157

RESUMEN

Fulminant myocarditis can present with life-threatening arrhythmias and cardiogenic shock due to ventricular failure. The diagnosis of myocarditis usually requires histological and immunological information, as its aetiology may be infectious (viral or non-viral), autoimmune or drug related. The treatment of fulminant myocarditis depends on the underlying cause but usually includes high dose systemic steroids as well as physiological support. Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) can be used to support patients as a bridge to recovery by supporting biventricular function and decompressing the heart. V-A ECMO carries risks and complications of its own such as thrombus formation or bleeding. Different diagnostic modalities, such as transthoracic echocardiogram (TTE) and transoesophageal echocardiogram (TOE), are central to the monitoring of progression of disease and recovery of heart function. This case highlights the importance of early recognition and early support with V-A ECMO in fulminant myocarditis, as well as the role of repeated echocardiography when weaning from physiological support.

13.
Clin Med (Lond) ; 20(2): 227-228, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32188667

RESUMEN

We present the case of a late presenting ST-elevation myocardial infarction with a coronary dissection. After primary percutaneous coronary intervention, the patient went on to develop pericardial effusion with tamponade. Despite only a small volume of fluid, we demonstrate how it can have significant clinical consequences in the diseased heart. We also highlight the value of being able to carry out bedside echocardiography in the acutely unwell post-myocardial infarction patient.


Asunto(s)
Taponamiento Cardíaco , Infarto del Miocardio , Intervención Coronaria Percutánea , Derrame Pericárdico , Infarto del Miocardio con Elevación del ST , Taponamiento Cardíaco/diagnóstico por imagen , Taponamiento Cardíaco/etiología , Humanos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico , Derrame Pericárdico/diagnóstico por imagen , Derrame Pericárdico/etiología , Infarto del Miocardio con Elevación del ST/complicaciones , Infarto del Miocardio con Elevación del ST/diagnóstico , Resultado del Tratamiento
14.
JACC Case Rep ; 2(12): 1954-1958, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34317088

RESUMEN

We describe a 54-year-old male in whom eosinophilic myocarditis secondary to T-cell lymphoma complicated by bilateral ischemic stroke was diagnosed. The source, identified as an apical tear with thrombus formation, was revealed by transthoracic echocardiography. (Level of Difficulty: Advanced.).

15.
Clin Sci (Lond) ; 133(7): 839-851, 2019 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-30898854

RESUMEN

We have reported the existence of a distinct neutrophil phenotype in giant cell arteritis (GCA) patients arising at week 24 of steroid treatment. In the present study, we investigated whether longitudinal analysis of neutrophil phenotype in patients with polymyalgia rheumatica (PMR) could reveal a novel association with disease status and immune cell cross-talk. Thus, we monitored PMR patient neutrophil phenotype and plasma microvesicle (MV) profiles in blood aliquots collected pre-steroid, and then at weeks 1, 4, 12 and 24 post-steroid treatment.Using flow cytometric and flow chamber analyses, we identified 12-week post-steroid as a pivotal time-point for a marked degree of neutrophil activation, correlating with disease activity. Analyses of plasma MVs indicated elevated AnxA1+ neutrophil-derived vesicles which, in vitro, modulated T-cell reactivity, suggesting distinct neutrophil phenotypic and cross-talk changes at 24 weeks, but not at 12-week post-steroid.Together, these data indicate a clear distinction from GCA patient neutrophil and MV signatures, and provide an opportunity for further investigations on how to 'stratify' PMR patients and monitor their clinical responses through novel use of blood biomarkers.


Asunto(s)
Comunicación Celular/efectos de los fármacos , Glucocorticoides/uso terapéutico , Activación Neutrófila/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Polimialgia Reumática/tratamiento farmacológico , Anexina A1/sangre , Micropartículas Derivadas de Células/efectos de los fármacos , Micropartículas Derivadas de Células/inmunología , Micropartículas Derivadas de Células/metabolismo , Células Cultivadas , Técnicas de Cocultivo , Citocinas/sangre , Células Endoteliales de la Vena Umbilical Humana/inmunología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Rodamiento de Leucocito/efectos de los fármacos , Neutrófilos/inmunología , Neutrófilos/metabolismo , Fenotipo , Polimialgia Reumática/sangre , Polimialgia Reumática/diagnóstico , Polimialgia Reumática/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Factores de Tiempo , Resultado del Tratamiento
17.
Shock ; 49(4): 393-401, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-28930915

RESUMEN

RATIONALE: Microvesicles (MV) act as a nonsoluble means of intercellular communication, with effector roles in disease pathogenesis and potentially as biomarkers. Previously, we reported that neutrophil MV expressing alpha-2-macroglobulin (A2MG) are protective in experimental sepsis and associate with survival in a small cohort of patients with sepsis due to community acquired pneumonia (CAP). OBJECTIVES: To characterize MV profiles in sepsis due to CAP or fecal peritonitis (FP) and determine their relation to outcome. To investigate the effects of novel sepsis treatments (granulocyte-macrophage colony stimulating factor (GM-CSF) and interferon-υ (IFN-γ)) on MV production and functions in vitro. METHODS: Flow cytometry analysis of MV identified the cell of origin and the proportion of A2MG expression in the plasma of patients with sepsis secondary to CAP (n = 60) or FP (n = 40) and compared with healthy volunteers (HV, n = 10). The association between MV subsets and outcome was examined. The ability of GM-CSF and IFN-γ on A2MG MV production from whole blood was examined together with the assessment of their effect on neutrophil and endothelial functions. RESULTS: Circulating cell-derived and A2MG MV were higher in CAP compared with FP and HV. A2MG MV were higher in survivors of CAP, but not in FP. GM-CSF and IFN-γ enhanced A2MG MV production, with these MV eliciting pathogen clearance in vitro. CONCLUSIONS: Plasma MV profiles vary according to the source of infection. A2MG MV are associated with survival in CAP but not FP. We propose specific MV subsets as novel biomarkers in sepsis and potential effector for some of the actions of experimental therapeutic interventions.


Asunto(s)
Infecciones Comunitarias Adquiridas/inmunología , Infecciones Comunitarias Adquiridas/metabolismo , Peritonitis/inmunología , Peritonitis/metabolismo , Neumonía/inmunología , Neumonía/metabolismo , Sepsis/inmunología , Sepsis/metabolismo , Micropartículas Derivadas de Células/metabolismo , Células Endoteliales/metabolismo , Citometría de Flujo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Interferón gamma/metabolismo , Neutrófilos/metabolismo , alfa-Macroglobulinas/metabolismo
18.
EMBO Mol Med ; 6(1): 27-42, 2014 01.
Artículo en Inglés | MEDLINE | ID: mdl-24357647

RESUMEN

Incorporation of locally produced signaling molecules into cell-derived vesicles may serve as an endogenous mediator delivery system. We recently reported that levels alpha-2-macroglobulin (A2MG)-containing microparticles are elevated in plasma from patients with sepsis. Herein, we investigated the immunomodulatory actions of A2MG containing microparticles during sepsis. Administration of A2MG-enriched (A2MG-E)-microparticles to mice with microbial sepsis protected against hypothermia, reduced bacterial titers, elevated immunoresolvent lipid mediator levels in inflammatory exudates and reduced systemic inflammation. A2MG-E microparticles also enhanced survival in murine sepsis, an action lost in mice transfected with siRNA for LRP1, a putative A2MG receptor. In vitro, A2MG was functionally transferred onto endothelial cell plasma membranes from microparticles, augmenting neutrophil-endothelial adhesion. A2MG also modulated human leukocyte responses: enhanced bacterial phagocytosis, reactive oxygen species production, cathelicidin release, prevented endotoxin induced CXCR2 downregulation and preserved neutrophil chemotaxis in the presence of LPS. A significant association was also found between elevated plasma levels of A2MG-containing microparticles and survival in human sepsis patients. Taken together, these results identify A2MG enrichment in microparticles as an important host protective mechanism in sepsis.


Asunto(s)
Microesferas , Sepsis/mortalidad , Sepsis/prevención & control , alfa-Macroglobulinas/farmacología , Animales , Péptidos Catiónicos Antimicrobianos/metabolismo , Membrana Celular/metabolismo , Vesículas Citoplasmáticas/metabolismo , Vesículas Citoplasmáticas/microbiología , Escherichia coli/fisiología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Inflamación/metabolismo , Inflamación/patología , Estimación de Kaplan-Meier , Leucocitos/inmunología , Leucocitos/metabolismo , Lipopolisacáridos/toxicidad , Masculino , Ratones , Neutrófilos/citología , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Fagocitosis , Especies Reactivas de Oxígeno/metabolismo , Receptores de Interleucina-8B/metabolismo , alfa-Macroglobulinas/metabolismo , Catelicidinas
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