EpCAM and microvascular obstruction in patients with STEMI: a cardiac magnetic resonance study
Abstract Introduction and objectives Microvascular obstruction (MVO) is negatively associated with cardiac structure and worse prognosis after ST-segment elevation myocardial infarction (STEMI). Epithelial cell adhesion molecule (EpCAM), involved in epithelium adhesion, is an understudied area in the MVO setting. We aimed to determine whether EpCAM is associated with the appearance of cardiac magnetic resonance (CMR)-derived MVO and long-term systolic function in reperfused STEMI. Methods We prospectively included 106 patients with a first STEMI treated with percutaneous coronary intervention, quantifying serum levels of EpCAM 24 hours postreperfusion. All patients underwent CMR imaging 1 w…
El suero de seno coronario tras un infarto de miocardio induce angiogénesis y reparación de la obstrucción microvascular. Implicación del factor inducible por hipoxia-1A
Resumen Introduccion y objetivos El objetivo es estudiar la angiogenesis coronaria inducida por el suero coronario y la implicacion del factor inducible por hipoxia-1A (FIH-1A) en la reparacion de la obstruccion microvascular (OMV) tras un infarto agudo de miocardio (IAM). Metodos Se indujo un IAM en cerdos mediante oclusion coronaria durante 90 min. Se dividio a los animales entre 1 grupo de control y 4 grupos con IAM: sin reperfusion y 1 min, 1 semana y 1 mes tras la reperfusion. Se cuantificaron la OMV y la densidad microvascular. Se determino la capacidad angiogenica del suero coronario mediante una prueba de tubulogenesis in vitro. Se determinaron las concentraciones circulantes del FI…
ST2 and left ventricular remodeling after ST-segment elevation myocardial infarction: A cardiac magnetic resonance study.
Background: The association of soluble interleukin-1 receptor-like 1 (ST2) with left ventricular (LV) remodeling is unclear in patients with a first ST-segment elevation myocardial infarction (STEMI). The objective of this work was to assess the relationship between ST2, a marker of inflammation, and cardiac magnetic resonance (CMR) imaging-derived LV remodeling after a first STEMI. Methods: We prospectively evaluated 109 patients with a first STEMI treated with primary percutaneous coronary intervention who had ST2 assessed 24 h post-reperfusion. All patients underwent CMR imaging 1 week and 6 months after STEMI. The independent associations between ST2, LV diastolic and systolic volume in…
EpCAM y obstrucción microvascular en pacientes con un IAMCEST: estudio con resonancia magnética cardiaca
Resumen Introduccion y objetivos La obstruccion microvascular (OMV) se asocia negativamente con la estructura cardiaca y el pronostico de los pacientes tras un infarto agudo de miocardio con elevacion del segmento ST (IAMCEST). El factor epithelial cell adhesion molecule (EpCAM), implicado en la cohesion de las celulas epiteliales, esta poco estudiado en el contexto de la OMV. Por ello, el objetivo de este estudio es evaluar en una cohorte de pacientes con IAMCEST la asociacion entre la concentracion de EpCAM circulante con la extension de la OMV, determinada por resonancia magnetica cardiaca (RMC), y la funcion sistolica en fases cronicas. Metodos Se incluyo prospectivamente a 106 paciente…
Efavirenz induces interactions between leucocytes and endothelium through the activation of Mac-1 and gp150,95
The potential cardiovascular (CV) toxicity associated with combined antiretroviral therapy (cART) has been attributed mainly to the nucleoside reverse transcriptase inhibitors abacavir and didanosine. However, the other two components of cART--non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)--may also be implicated, either directly or by influencing the action of the other drugs. This study evaluates the acute direct effects of the NNRTIs efavirenz and nevirapine and one of the most widely employed PIs, lopinavir, on leucocyte-endothelium interactions, a hallmark of CV disease.Drugs were analysed in vitro in human cells (interactions of peripheral blood…
Sequential cardiovascular magnetic resonance assessment of left ventricular ejection fraction for prediction of subsequent events in a large multicenter STEMI registry
Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” Background. Cardiovascular magnetic resonance (CMR) is the best tool for left ventricular ejection fraction (LVEF) quantification, but as yet the prognostic value of sequential LVEF assessment for major adverse cardiac event (MACE) prediction after ST-segment elevation myocardial infarction (STEMI) is uncertain. Purpose. We explored the prognostic impact of sequential assessment of CMR-derived LVEF after STEMI to predict subsequent MACE. Methods. We recruited 1036 STEMI p…
Magnetic Resonance Assessment of Left Ventricular Ejection Fraction at Any Time Post-Infarction for Prediction of Subsequent Events in a Large Multicenter STEMI Registry
Background Magnetic resonance imaging (MRI) is the most accurate imaging technique for left ventricular ejection fraction (LVEF) quantification, but as yet the prognostic value of LVEF assessment at any time after ST-segment elevation myocardial infarction (STEMI) for subsequent major adverse cardiac event (MACE) prediction is uncertain. Purpose To explore the prognostic impact of MRI-derived LVEF at any time post-STEMI to predict subsequent MACE (cardiovascular death or re-admission for acute heart failure). Study Type Prospective. Population One thousand thirteen STEMI patients were included in a multicenter registry. Field Strength/Sequence 1.5-T. Balanced steady-state free precession (c…
Coronary Serum Obtained After Myocardial Infarction Induces Angiogenesis and Microvascular Obstruction Repair. Role of Hypoxia-inducible Factor-1A.
Microvascular obstruction (MVO) exerts deleterious effects following acute myocardial infarction (AMI). We investigated coronary angiogenesis induced by coronary serum and the role of hypoxia-inducible factor-1A (HIF-1A) in MVO repair.Myocardial infarction was induced in swine by transitory 90-minute coronary occlusion. The pigs were divided into a control group and 4 AMI groups: no reperfusion, 1minute, 1 week and 1 month after reperfusion. Microvascular obstruction and microvessel density were quantified. The proangiogenic effect of coronary serum drawn from coronary sinus on endothelial cells was evaluated using an in vitro tubulogenesis assay. Circulating and myocardial HIF-1A levels an…
Role of antiangiogenic VEGF-A165b in angiogenesis and systolic function after reperfused myocardial infarction
Abstract Introduction and objectives Angiogenesis helps to reestablish microcirculation after myocardial infarction (MI). In this study, we aimed to further understand the role of the antiangiogenic isoform vascular endothelial growth factor (VEGF)-A165b after MI and to explore its potential as a coadjuvant therapy to coronary reperfusion. Methods Two mice MI models were formed: a) permanent coronary ligation (nonreperfused MI); b) transient 45-minute coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. We determined serum and myocardial VEGF-A165b levels. In both experimental MI models…
Coronary Revascularization and Long-Term Survivorship in Chronic Coronary Syndrome
Ischemic heart disease (IHD) persists as the leading cause of death in the Western world. In recent decades, great headway has been made in reducing mortality due to IHD, based around secondary prevention. The advent of coronary revascularization techniques, first coronary artery bypass grafting (CABG) surgery in the 1960s and then percutaneous coronary intervention (PCI) in the 1970s, has represented one of the major breakthroughs in medicine during the last century. The benefit provided by these techniques, especially PCI, has been crucial in lowering mortality rates in acute coronary syndrome (ACS). However, in the setting where IHD is most prevalent, namely chronic coronary syndrome (CC…
Overexpression of genes involved in lymphocyte activation and regulation are associated with reduced CRM-derived cardiac remodelling after STEMI
Abstract Aims Lymphopenia after ST-segment elevation myocardial infarction (STEMI) correlates with deleterious cardiac consequences and worse prognosis. An in-depth examination of genes implicated in lymphocyte proliferation, activation and regulation and their association with short- and long-term cardiac structure and function is therefore of great interest. Methods Peripheral blood mononuclear cells were isolated from 10 control subjects and 64 patients with a first STEMI treated with primary percutaneous coronary intervention and submitted to cardiac magnetic resonance after 1 week and 6 months. mRNA expression of genes implicated in lymphocyte activation (CD25 and CD69) and regulation …
Sex differences in mortality in stable patients undergoing vasodilator stress cardiovascular magnetic resonance
Abstract Introduction The prognostic value and therapeutic implications of ischemia as derived from vasodilator stress cardiovascular magnetic resonance (CMR) could differ in men and women, but it has not been stablished. Purpose We assessed the influence of the ischemic burden as derived from CMR on the risk of death and the effect of revascularization across sex. Methods We evaluated 6,237 consecutive patients with known or suspected chronic coronary syndrome (CCS). Extensive ischemia was defined as >5 segments with perfusion deficit. Multivariate Cox proportional hazard regression models were used. Results A total of 2,371 (38.0%) patients were women and 583 (9.3%) underwent CMR-r…
Combined assessment of stress cardiovascular magnetic resonance and angiography to predict the effect of revascularization in chronic coronary syndrome patients
Abstract Aims The role of revascularization in chronic coronary syndrome (CCS) and the value of ischaemia vs. anatomy to guide decision-making are in constant debate. We explored the potential of a combined assessment of ischaemic burden by vasodilator stress cardiovascular magnetic resonance (CMR) and presence of multivessel disease by angiography to predict the effect of revascularization on all-cause mortality in CCS. Methods and results The study group comprised 1066 CCS patients submitted to vasodilator stress CMR pre-cardiac catheterization (mean age 66 ± 11 years, 69% male). Stress CMR-derived ischaemic burden (extensive if >5 ischaemic segments) and presence of multivessel di…
Unraveling the thread of uncontrolled immune response in COVID-19 and STEMI: an emerging need for knowledge sharing
The outbreak of severe acute respiratory syndrome coronavirus 2 that first emerged in Wuhan in December 2019 has resulted in the devastating pandemic of coronavirus disease 2019, creating an emerging need for knowledge sharing. Meanwhile, myocardial infarction is and will probably remain the foremost cause of death in the Western world throughout the coming decades. Severe deregulation of the immune system can unnecessarily expand the inflammatory response and participate in target and multiple organ failure, in infection but also in critical illness. Indeed, the course and fate of inflammatory cells observed in severe ST-elevation myocardial infarction (neutrophilia, monocytosis, and lymp…
Ejection Fraction by Echocardiography for a Selective Use of Magnetic Resonance After Infarction
[EN] Background Cardiac magnetic resonance (CMR) permits robust risk stratification of discharged ST-segment-elevation myocardial infarction patients, but its indiscriminate use in all cases is not feasible. We evaluated the utility of left ventricular ejection fraction (LVEF) by echocardiography for a selective use of CMR after ST-segment-elevation myocardial infarction. Methods Echocardiography and CMR were performed in 1119 patients discharged for ST-segment-elevation myocardial infarction included in a multicenter registry. The prognostic power of CMR beyond echocardiography-LVEF was assessed using adjusted C statistic, net reclassification improvement index, and integrated discriminati…
Euphorbia honey and garlic: Biological activity and burn wound recovery
Currently, chronic wounds and microbial resistance to antibiotics have led to search new healing agents. Combinations of natural products are widely practiced in traditional medicine and exhibited synergistic activity with increased efficacy in treating several pathologies. This study assays the antioxidant, synergistic antimicrobial and burn wound healing activities of Euphorbia honey and Allium sativum (garlic). The minimal inhibitory concentration (MIC) of each natural product was determined against microorganisms commonly found in wound infections. The synergistic antimicrobial effect was assessed by mixing different concentrations of honey and garlic extract below their relative MICs. …
Implicación de la isoforma antiangiogénica VEGF-A165b en la angiogénesis y la función sistólica tras un infarto de miocardio reperfundido
Resumen Introduccion y objetivos La angiogenesis participa en la restauracion de la microcirculacion despues de un infarto agudo de miocardio (IAM). El objetivo de este estudio es explorar el papel que juega la isoforma anti-angiogenica del factor de crecimiento endotelial vascular (VEGF)-A165b y explorar su potencial como terapia coadyuvante a la reperfusion coronaria. Metodos Se realizaron dos modelos murinos de IAM: a) ligadura permanente de la arteria coronaria (IAM no reperfundido) y b) oclusion transitoria durante 45 minutos de la arteria coronaria seguida de reperfusion (IAM reperfundido); en ambos modelos, se realizo a los animales una ecocardiografia previa a la eutanasia el dia 21…
Sex differences on new-onset heart failure in patients with known or suspected coronary artery disease
Abstract Aims The impact of sex in patients with CAD has been widely reported, but little is known about the influence of sex on the risk of new-onset HF in patients with known or suspected CAD. We aimed to examine sex-related differences and new-onset heart failure (HF) risk in patients with known or suspected coronary artery disease (CAD) undergoing vasodilator stress cardiac magnetic resonance (CMR). Methods and results We prospectively evaluated 5899 consecutive HF-free patients submitted to stress CMR for known or suspected CAD. Ischaemic burden (number of segments with stress-induced perfusion deficit) and left ventricular ejection fraction (LVEF) were assessed by CMR. The association…
EpCAM and microvascular obstruction in patients with STEMI: a cardiac magnetic resonance study
Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” Bachground. Microvascular obstruction (MVO) is negatively associated with cardiac structure and worse prognosis after ST-segment elevation myocardial infarction (STEMI). Epithelial cell adhesion molecule (EpCAM), involved in endothelium adhesion, is an understudied area in the MVO setting. Purpose. We aimed to evaluate whether EpCAM is associated with the appearance of cardiac magnetic resonance (CMR)-derived MVO and long-term systolic function in reperfused STEMI. Methods.…
Metformin modulates human leukocyte/endothelial cell interactions and proinflammatory cytokines in polycystic ovary syndrome patients
Abstract Objective We aim to assess the effect of metformin treatment on metabolic parameters, endothelial function and inflammatory markers in polycystic ovary syndrome (PCOS) subjects. Methods The study population consisted of 40 reproductive-age women with PCOS, who underwent treatment with metformin during a 12-week period, and their corresponding matched controls (n = 44). We evaluated endocrinological parameters, adhesion molecules (vascular cell adhesion molecule 1 (VCAM-1), intercellular cell adhesion molecule 1 (ICAM-1) and E-selectin) and proinflammatory cytokines (interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα)) in serum. In addition, interactions between human umbili…
Similar Clinical Course and Significance of Circulating Innate and Adaptive Immune Cell Counts in STEMI and COVID-19
This study aimed to assess the time course of circulating neutrophil and lymphocyte counts and their ratio (NLR) in ST-segment elevation myocardial infarction (STEMI) and coronavirus disease (COVID)-19 and explore their associations with clinical events and structural damage. Circulating neutrophil, lymphocyte and NLR were sequentially measured in 659 patients admitted for STEMI and in 103 COVID-19 patients. The dynamics detected in STEMI (within a few hours) were replicated in COVID-19 (within a few days). In both entities patients with events and with severe structural damage displayed higher neutrophil and lower lymphocyte counts. In both scenarios, higher maximum neutrophil and lower mi…
Risk score for early risk prediction by cardiac magnetic resonance after acute myocardial infarction.
BACKGROUND: Cardiac magnetic resonance (CMR) performed early after ST-segment elevation myocardial infarction (STEMI) can improve major adverse cardiac event (MACE) risk prediction. We aimed to create a simple clinical-CMR risk score for early MACE risk stratification in STEMI patients.; METHODS: We performed a multicenter prospective registry of reperfused STEMI patients (n=1118) in whom early (1-week) CMR-derived left ventricular ejection fraction (LVEF), infarct size and microvascular obstruction (MVO) were quantified. MACE was defined as a combined clinical endpoint of cardiovascular (CV) death, non-fatal myocardial infarction (NF-MI) or re-admission for acute decompensated heart failur…
Insulin Resistance in PCOS Patients Enhances Oxidative Stress and Leukocyte Adhesion: Role of Myeloperoxidase
Cardiovascular diseases and oxidative stress are related to polycystic ovary syndrome (PCOS) and insulin resistance (IR). We have evaluated the relationship between myeloperoxidase (MPO) and leukocyte activation in PCOS patients according to homeostatic model assessment of IR (HOMA-IR), and have explored a possible correlation between these factors and endocrine and inflammatory parameters. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 101 PCOS subjects and 105 control subjects. We divided PCOS subjects into PCOS non-IR (HOMA-IR2.5). Metabolic and anthropometric parameters, total and mitochondrial reactive oxygen species (…
Long-term prognostic implications of revascularization in patients with known or suspected chronic coronary syndromes without ischemia in vasodilator stress cardiovascular magnetic resonance
In this study, we evaluated the association between symptoms-guided revascularization occurred within three months following a negative vasodilator stress cardiovascular magnetic resonance (negative stress-CMR) and long-term adverse events in patients with known or suspected chronic coronary syndrome (CCS).We retrospectively evaluated 3517 patients in which the stress first-pass perfusion imaging revealed no ischemia. The primary endpoint was the composite of death, spontaneous myocardial infarction, heart failure (HF), or stroke. The association between symptoms-guided revascularization after a negative stress-CMR and the endpoint was assessed using the multivariable Cox proportional hazar…
Hypoxic burden and angiogenic factors in patients with myocardial infarction and obstructive sleep apnea
Introduction: The amount and severity of hypoxia have been related to risk of cardiovascular events. Aim: To determine the relationship between nocturnal hypoxic burden and pro- angiogenic factors in patients with obstructive sleep apnea (OSA) and myocardial infarction (MI). Method: A prospective, observational study in patients with a first acute MI. Eligible patients underwent a polysomnography within 30 days after MI, and a serum blood sample was drawn in order to measure a panel of angiogenic factors by Luminex technology. A hypoxic burden index (HBI) was calculated as the integral area under the desaturation curve (obtained by calculating the integral of the oxygen saturation reduction…
Resonancia magnética cardiaca de estrés para predecir mortalidad y toma de decisiones: registro de 2.496 pacientes mayores con síndrome coronario crónico
Resumen Introduccion y objetivos El tratamiento del paciente mayor con sindrome coronario cronico (SCC) es un reto. Se exploro el valor pronostico y la utilidad para la toma de decisiones de la carga isquemica determinada mediante resonancia magnetica cardiaca (RMC) de estres con vasodilatador en pacientes mayores con SCC. Metodos Se incluyo a 2.496 pacientes mayores de 70 anos estudiados con una RMC de estres con vasodilatador por SCC conocido o sospechado. La carga isquemica (numero de segmentos con deficit de perfusion inducido por el estres) se calculo siguiendo el modelo de 17 segmentos. Posteriormente se analizo de manera retrospectiva su asociacion con la mortalidad por cualquier cau…
Abacavir induces platelet-endothelium interactions by interfering with purinergic signalling: A step from inflammation to thrombosis.
The controversy connecting Abacavir (ABC) with cardiovascular disease has been fuelled by the lack of a credible mechanism of action. ABC shares structural similarities with endogenous purines, signalling molecules capable of triggering prothrombotic/proinflammatory programmes. Platelets are leading actors in the process of thrombosis. Our study addresses the effects of ABC on interactions between platelets and other vascular cells, while exploring the adhesion molecules implicated and the potential interference with the purinergic signalling pathway. The effects of ABC on platelet aggregation and platelet-endothelium interactions were evaluated, respectively, with an aggregometer and a flo…
Anatomy, immunohistochemistry, and numerical distribution of human splenic microvessels.
Abstract The microvascular architecture of the spleen plays an important role in the immunological function of this organ. The different types of vessels are related to different reticular cells each with their own immunomodulatory functions. The present study describes an immunohistochemical and morphometric analysis of the various types of vessels in 21 human autopsy non-pathological splenic samples. On an area of 785,656.37 μm2 for each sample, we classified and quantified the type and number of vascular structures, each according to their morphology and immunohistochemical profile, and obtained the ratios between them. The distribution of trabecular vessels and the characteristics of th…
Prognostic Value of Strain by Tissue Tracking Cardiac Magnetic Resonance After ST-Segment Elevation Myocardial Infarction
The aim of this study was to evaluate the prognostic value of strain as assessed by tissue tracking (TT) cardiac magnetic resonance (CMR) soon after ST-segment elevation myocardial infarction (STEMI).The prognostic value of myocardial strain as assessed post-STEMI by TT-CMR is unknown.The authors studied the prognostic value of TT-CMR in 323 patients who underwent CMR 1 week post-STEMI. Global (average of peak segmental values [%]) and segmental (number of altered segments) longitudinal (LS), circumferential, and radial strain were assessed using TT-CMR. Global and segmental strain cutoff values were derived from 32 control patients. CMR-derived left ventricular ejection fraction, microvasc…
Vasodilator Stress CMR and All-Cause Mortality in Stable Ischemic Heart Disease
Abstract Objectives This study explored the association of ischemic burden, as measured by vasodilator stress cardiovascular magnetic resonance (CMR), with all-cause mortality and the effect of revascularization on all-cause mortality in patients with stable ischemic heart disease (SIHD). Background In patients with SIHD, the association of ischemic burden, derived from vasodilator stress CMR, with all-cause mortality and its role for decision-making is unclear. Methods The registry consisted of 6,389 consecutive patients (mean age: 65 ± 12 years; 38% women) who underwent vasodilator stress CMR for known or suspected SIHD. The ischemic burden (at stress first-pass perfusion imaging) was com…
Stress cardiac magnetic resonance for mortality prediction and decision-making: registry of 2496 elderly patients with chronic coronary syndrome
Abstract Introduction and objectives The management of elderly patients with chronic coronary syndrome (CCS) is challenging. We explored the prognostic value and usefulness for decision-making of ischemic burden determined by vasodilator stress cardiac magnetic resonance (CMR) imaging in elderly patients with known or suspected CCS. Methods The study group comprised 2496 patients older than 70 years who underwent vasodilator stress CMR for known or suspected CCS. The ischemic burden (number of segments with stress-induced perfusion deficit) was calculated following the 17-segment model. Subsequently, we retrospectively analyzed its association with all-cause mortality and the effect of CMR-…
Role of PCSK9 in the course of ejection fraction change after ST-segment elevation myocardial infarction: a pilot study
Altres ajuts: Conselleria d'Educació, Investigació, Cultura i Esport GV/2018/116 Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for reducing plasma low-density lipoprotein cholesterol. Beyond lipid control, recent findings suggest a deleterious effect of this protein in the pathogenesis of postmyocardial infarction left ventricle remodelling and heart failure-related complications. The aim of this study was to assess the relationship between circulating PCSK9 and 6 month cardiac magnetic resonance imaging-derived left ventricular ejection fraction (LVEF) after a first ST-segment elevation myocardial infarction (STEMI). We prospectively evaluated 40…
Implication of anti-angiogenic VEGF-A165b in angiogenesis and systolic function after reperfused myocardial infarction
Abstract Background Angiogenesis participates in re-establishing microcirculation after myocardial infarction (MI). Purpose In this study, we aim to further understand the role of the anti-angiogenic isoform vascular endothelial growth factor (VEGF)-A165b after MI and explore its potential as a co-adjuvant therapy to coronary reperfusion. Methods Two mice MI models were formed: 1) permanent coronary ligation (non-reperfused MI), 2) transient 45-min coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. Serum and myocardial VEGF-A165b levels were determined. In both experimental MI models,…
Exercise ECG Testing and Stress Cardiac Magnetic Resonance for Risk Prediction in Patients With Chronic Coronary Syndrome
Vasodilator stress cardiac magnetic resonance (VS-CMR) has become crucial in the workup of patients with known or suspected chronic coronary syndrome (CCS). Whether traditional exercise ECG testing (ExECG) contributes prognostic information beyond VS-CMR is unclear.We retrospectively included 288 patients with known or suspected CCS who had undergone ExECG and subsequent VS-CMR in our institution. Clinical, ExECG, and VS-CMR variables were recorded. We defined the serious adverse events (SAE) as a combined endpoint of acute coronary syndrome, admission for heart failure, or all-cause death.During a mean follow-up of 4.2 ± 2.15 yr, we registered 27 SAE (15 admissions for acute coronary syndr…
Differential effects of anti-TNF-α and anti-IL-12/23 agents on human leukocyte–endothelial cell interactions
AbstractEnhanced leukocyte recruitment is an inflammatory process that occurs during early phases of the vascular dysfunction that characterises atherosclerosis. We evaluated the impact of anti-TNF-α (adalimumab, infliximab and etanercept) and anti-IL-12/23 (ustekinumab) on interactions between human leukocytes and endothelial cells in a flow chamber that reproduced in vivo conditions. Clinical concentrations of anti-TNF-α were evaluated on the leukocyte recruitment induced by a variety of endothelial (TNF-α, interleukin-1β, lymphotoxin-α and angiotensin-II) and leukocyte (PAF, IL-12 and IL-23) stimuli related to inflammation and atherosclerosis. Treatment with anti-TNF-α, even before or af…
Ischemia-reperfusion injury to coronary arteries: Comprehensive microscopic study after reperfused myocardial infarction.
Abstract Background Coronary arteries supply oxygen and nutrients to the heart. We evaluated the dynamics of microscopic damage throughout the ischemia-reperfusion process in the wall of coronary arteries following myocardial infarction (MI). Methods In a swine model of reperfused MI, animals were divided into one control and four MI groups: 90-min ischemia without reperfusion, or followed by one minute, one week or one month reperfusion. Left anterior descending (LAD; infarct-related artery) and control right coronary arteries (RCA) were isolated. Taking the balloon inflation region as a reference, we isolated the proximal and distal LAD areas, performing histological staining and immunohi…
Changes in the spatial distribution of the Purkinje network after acute myocardial infarction in the pig
Purkinje cells (PCs) are more resistant to ischemia than myocardial cells, and are suspected to participate in ventricular arrhythmias following myocardial infarction (MI). Histological studies afford little evidence on the behavior and adaptation of PCs in the different stages of MI, especially in the chronic stage, and no quantitative data have been reported to date beyond subjective qualitative depictions. The present study uses a porcine model to present the first quantitative analysis of the distal cardiac conduction system and the first reported change in the spatial distribution of PCs in three representative stages of MI: an acute model both with and without reperfusion; a subacute …
Apoptosis and Mobilization of Lymphocytes to Cardiac Tissue Is Associated with Myocardial Infarction in a Reperfused Porcine Model and Infarct Size in Post-PCI Patients
ST-segment elevation myocardial infarction (STEMI) is the most severe outcome of coronary artery disease. Despite rapid reperfusion of the artery, acute irrigation of the cardiac tissue is associated with increased inflammation. While innate immune response in STEMI is well described, an in-depth characterization of adaptive immune cell dynamics and their potential role remains elusive. We performed a translational study using a controlled porcine reperfusion model of STEMI and the analysis of lymphocyte subsets in 116 STEMI patients undergoing percutaneous coronary intervention (PCI). In the animal model, a sharp drop in circulating T lymphocytes occurred within the first hours after reper…
Microvascular Obstruction in ST-Segment Elevation Myocardial Infarction: Looking Back to Move Forward. Focus on CMR
After a myocardial infarction (MI), despite the resolution of the coronary occlusion, the deterioration of myocardial perfusion persists in a considerable number of patients. This phenomenon is known as microvascular obstruction (MVO). Initially, the focus was placed on re-establishing blood flow in the epicardial artery. Then, the observation that MVO has profound negative structural and prognostic repercussions revived interest in microcirculation. In the near future, the availability of co-adjuvant therapies (beyond timely coronary reperfusion) aimed at preventing, minimizing, and repairing MVOs and finding convincing answers to questions regarding what, when, how, and where to administe…
Early reductive stress and late onset overexpression of antioxidant enzymes in experimental myocardial infarction.
Reductive stress is defined as a pathophysiological situation in which the cell becomes more reduced than in the normal, resting state. It represents a disturbance in the redox state that is harmful to biological systems. Our aim was to study the occurrence of reductive stress in the early phases of experimental myocardial infarction and to determine the mechanisms leading to such stress using a swine model. During the ischemic period, we found a decrease in the oxidized to reduced glutathione ratio (GSSG/GSH) (0.7-0.3), in the lactate to pyruvate ratio (42.7-132.4), in protein glutathionylation (111.8-96.1), and in p38 phosphorylation (0.9-0.4). This was accompanied by a significant increa…
Characterization and implications of the dynamics of eosinophils in blood and in the infarcted myocardium after coronary reperfusion.
Objective We characterized the dynamics of eosinophils in blood and in the infarcted myocardium in patients and in a swine model of reperfused myocardial infarction (MI). The association of eosinophil dynamics with various outcomes was assessed. Methods Serial eosinophil count and pre-discharge cardiac magnetic resonance were carried out in a prospective series of 620 patients with a first ST-elevation MI. In a swine model of reperfused MI, the dynamics of circulating eosinophils and their presence in the infarcted myocardium were determined. In autopsies from chronic MI patients, eosinophils were quantified. Results Patient eosinophil count sharply decreased 12h post-reperfusion compared t…
Stress cardiovascular magnetic resonance and mortality in a registry of 2496 elderly patients with chronic coronary syndrome. Prognosis and decision-making
Abstract Funding Acknowledgements Type of funding sources: None. Background. In recent guidelines, non-invasive imaging techniques play a pivotal role in the management of chronic coronary syndrome (CCS). The elderly represent a large percentage of our routine CCS population and risk stratification in this scenario is challenging. The potential of vasodilator stress cardiovascular magnetic resonance (CMR) for this purpose is unknown. Purpose. We explore the prognostic value and the usefulness for decision-making of the ischemic burden determined by vasodilator stress CMR imaging in a large cohort of elderly patients with known or suspected CCS. Methods. The study group was made up of 2496 p…