Microvascular obstruction in the right ventricle in reperfused anterior myocardial infarction: macroscopic and pathologic evidence in a swine model

Intracoronary Infusion of Thioflavin-S to Study Microvascular Obstruction in a Model of Myocardial Infarction

Abstract Introduction and objectives Microvascular obstruction exerts deleterious effects after myocardial infarction. To elucidate the role of ischemia-reperfusion injury on the occurrence and dynamics of microvascular obstruction, we performed a preliminary methodological study to accurately define this process in an in vivo model. Methods Myocardial infarction was induced in swine by means of 90-min of occlusion of the mid left anterior descending coronary artery using angioplasty balloons . Intracoronary infusion of thioflavin-S was applied and compared with traditional intra-aortic or intraventricular instillation. The left anterior descending coronary artery perfused area and microvas…

Programmed death-1 (PD-1): A novel mechanism for understanding the acute immune deregulation in ST-segment elevation myocardial infarction

The Sum of ST-Segment Elevation Is the Best Predictor of Microvascular Obstruction in Patients Treated Successfully by Primary Percutaneous Coronary Intervention. Cardiovascular Magnetic Resonance Study

Introduction and objectives The usefulness of ST-segment elevation resolution (STR) for predicting epicardial reperfusion is well established. However, it is still not clear how ST-segment changes are related to microvascular obstruction (MVO) observed by cardiovascular magnetic resonance (CMR) after primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI). Methods The study involved 85 consecutive patients admitted for a first STEMI and treated by pPCI who had a patent infarct-related artery. An ECG was recorded on admission and 90 min and 6, 24, 48 and 96 h after pPCI. Thereafter, STR and the sum of ST-segment elevation (sumSTE) in all leads…

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…

The DD genotype of the angiotensin converting enzyme gene independently associates with CMR-derived abnormal microvascular perfusion in patients with a first anterior ST-segment elevation myocardial infarction treated with thrombolytic agents

Abstract Introduction The role of the angiotensin converting enzyme (ACE) gene on the result of thrombolysis at the microvascular level has not been addressed so far. We analyzed the implications of the insertion/deletion (I/D) polymorphism of the ACE gene on the presence of abnormal cardiovascular magnetic resonance (CMR)-derived microvascular perfusion after ST-segment elevation myocardial infarction (STEMI). Materials and Methods We studied 105 patients with a first anterior STEMI treated with thrombolytic agents and an open left anterior descending artery. Microvascular perfusion was assessed using first-pass perfusion CMR at 7 ±1 days. CMR studies were repeated 184 ± 11 days after STEM…

Predictors of cardiovascular magnetic resonance-derived microvascular obstruction on patient admission in STEMI

Early stratification of patients according to the risk for developing microvascular obstruction (MVO) after ST-segment elevation myocardial infarction (STEMI) is desirable. We aimed to identify predictors of cardiovascular magnetic resonance (CMR)-derived MVO from clinical+ECG, laboratory and angiographic parameters available on admission.Characteristics available on admission were documented in 97 STEMI patients referred for primary angioplasty. MVO was determined using contrast-enhanced CMR.MVO was present in 44 patients (45%). The C-statistic for predicting MVO was: clinical+ECG (.832), laboratory (.743), and angiographic parameters (.669). Adding laboratory to clinical+ECG information d…

Release of necrosis markers and cardiovascular magnetic resonance-derived microvascular perfusion in reperfused ST-elevation myocardial infarction

Abstract Introduction The association of the temporal evolution of cardiac necrosis marker release with cardiovascular magnetic resonance-derived microvascular perfusion after ST-elevation myocardial infarction is unknown. Methods We analyzed 163 patients with a first ST-elevation myocardial infarction and a patent infarct-related artery treated with thrombolysis (67%) or primary angioplasty (33%). Using first-pass perfusion CMR, abnormal perfusion was defined as a lack of contrast arrival into the infarct area in > 1 segment. Troponin I, creatine kinase MB and myoglobin were measured upon arrival and at 6, 12, 24, 48 and 96 hours after reperfusion. Results Abnormal perfusion was detected i…

Decrease of CD4+ T Lymphocytes after myocardial infarction is related with extensive myocardial fibrosis

Purpose: Myocardial fibrosis plays a potential role in left ventricular remodeling and patients' outcome. After myocardial infarction innate immune cells infiltrate infarcted area and replace necrotic tissue by fibrotic tissue. However the role of adaptive immunity, especially T cells, has not yet been investigated in this scenario. Methods: We studied 94 patients with a first STEMI treated with percutaneous revascularization. Leucocyte subsets and a wide variety of lymphocyte subtypes were determined in peripheral blood 24 h after reperfusion by means of flow cytometry. Infarct size and cardiac fibrosis were measured by late enhancement Cardiac Magnetic Resonance (CRM) 1 week and 6 months …

Effect of ischemic postconditioning on microvascular obstruction in reperfused myocardial infarction. Results of a randomized study in patients and of an experimental model in swine.

Background: Ischemic postconditioning (PCON) appears as a potentially beneficial tool in ST-segment elevation myocardial infarction (STEMI). We evaluated the effect of PCON on microvascular obstruction (MVO) in STEMI patients and in an experimental swine model. Methods: A prospective randomized study in patients and an experimental study in swine were carried out in two university hospitals in Spain. 101 consecutive STEMI patients were randomized to undergo primary angio-plasty followed by PCON or primary angioplasty alone (non-PCON). Using late gadolinium enhancement cardiovascular magnetic resonance, infarct size and MVO were quantified (% of left ventricular mass). In swine, using an ang…

Inhomogeneity of collagen organization within the fibrotic scar after myocardial infarction: results in a swine model and in human samples.

We aimed to characterize the organization of collagen within a fibrotic scar in swine and human samples from patients with chronic infarctions. Swine were subjected to occlusion of the left anterior descending artery followed by reperfusion 1 week (acute myocardial infarction group) or 1 month (chronic myocardial infarction group) after infarction. The organization of the collagen fibers (Fast Fourier Transform of samples after picrosirius staining; higher values indicate more disorganization) was studied in 100 swine and 95 human samples. No differences in collagen organization were found between the acute and chronic groups in the core area of the scar in the experimental model. In the ch…

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…

La suma de la elevación del segmento ST predice mejor la obstrucción microvascular en pacientes tratados con éxito con una intervención coronaria percutánea primaria. Un estudio de resonancia magnética cardiovascular

Introduccion y objetivos La utilidad de la resolucion del segmento ST (RST) para la prediccion de la reperfusion epicardica esta bien establecida. La asociacion de los cambios del segmento ST con la obstruccion microvascular (OMV) observada en la resonancia magnetica cardiovascular (RMC) tras una intervencion coronaria percutanea primaria (ICPp) en el infarto de miocardio con elevacion del ST (IMEST) no se ha aclarado todavia. Metodos Estudiamos a 85 pacientes consecutivos ingresados por un primer IMEST y tratados con una ICPp que tenian una arteria relacionada con el infarto permeable. Se registro un ECG al ingreso, tras 90 min y tras 6, 24, 48 y 96 h de la ICPp. Se calculo la RST y la sum…

Right ventricular involvement in anterior myocardial infarction: a translational approach.

Aims The aim of the present study was to evaluate the involvement of the right ventricle (RV) in reperfused anterior ST-elevation myocardial infarction (STEMI). Methods and results Left anterior descending (LAD)-perfused area (using thioflavin-S staining after selective infusion in proximal LAD artery, %), infarct size (using triphenyltetrazolium chloride staining, %), and salvaged myocardium (% of LAD-perfused area) in the right and left ventricle (LV) were quantified in a 90-min LAD occlusion 3-day reperfusion model in swine ( n = 8). Additionally, we studied, using cardiovascular magnetic resonance, 20 patients with a first STEMI due to proximal LAD occlusion treated with primary angiopl…

Dynamics of serum-induced endothelial cell apoptosis in patients with myocardial infarction

In patients with ST-segment elevation myocardial infarction (STEMI) reperfused with primary coronary intervention (PCI), the dynamics of endothelial cell (EC) viability, apoptosis and necrosis and its relationship with the structural consequences on the left ventricle have not been addressed so far.In 20 STEMI patients, we incubated human umbilical vein endothelial cells (HUVECs) with serum drawn before reperfusion and subsequently afterwards (24, 96 h, 30 days). Viability, apoptosis and necrosis percentages were evaluated by flow cytometry. Values were compared with 12 age- and sex-matched control subjects with normal coronary arteries. Cardiac magnetic resonance (CMR) was performed during…

P574Activation of the regulatory T-cell-indoleamine 2,3 dioxygenase Axis promotes vascular tolerance mechanisms and reduces atherosclerosis

Metabolomic Profile of Human Myocardial Ischemia by Nuclear Magnetic Resonance Spectroscopy of Peripheral Blood Serum

Objectives The aim of this study was to investigate the metabolomic profile of acute myocardial ischemia (MIS) using nuclear magnetic resonance spectroscopy of peripheral blood serum of swine and patients undergoing angioplasty balloon‐induced transient coronary occlusion. Background Biochemical detection of MIS is a major challenge. The validation of novel biosignatures is of utmost importance. Methods High-resolution nuclear magnetic resonance spectroscopy was used to profile 32 blood serum metabolites obtained (before and after controlled ischemia) from swine (n 9) and patients (n 20) undergoing transitory MIS in the setting of planned coronary angioplasty. Additionally, blood serum of c…

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…

Prognostic Value of a Comprehensive Cardiac Magnetic Resonance Assessment Soon After a First ST-Segment Elevation Myocardial Infarction

ObjectivesTo evaluate the prognostic value of a comprehensive cardiac magnetic resonance (CMR) assessment soon after a first ST-segment elevation myocardial infarction (STEMI).BackgroundCMR allows for a simultaneous assessment of wall motion abnormalities (WMA), WMA with low-dose dobutamine (WMA-dobutamine), microvascular obstruction, and transmural necrosis. This approach has been proven to be useful to predict late systolic recovery soon after STEMI. Its prognostic value and the relative prognostic weight of these indexes are not well-defined.MethodsWe studied 214 consecutive patients with a first STEMI treated with thrombolytic therapy or primary angioplasty discharged from hospital. In …

P674Metabolic deregulation in myocardial infarction is mediated by PGC-1 alpha pathway

Purpose: In the context of myocardial infarction (MI) the availability of metabolites is clearly restricted, therefore a fuel metabolic shifts takes place. Previous studies have indicated that peroxisome proliferator activated receptor co-activator alpha (PGC-1α) pathway is a crucial regulator of cardiac metabolism in response to cardiac stress. Here we address the role of PGC-1α in regulating metabolic changes of MI. Methods: We studied a group of 12 common swine in which anterior MI was induced by means of angioplasty balloon inflation. A series of 6 swine were sacrificed at 48h post-infarction (acute infarction group) and another series of 6 swine were sacrificed at 3 weeks (chronic infa…

P729PD-1/PD-L1 axis contributes to infarct size in ST elevation myocardial infarction

Programmed death-1 (PD-1) and Programmed death-1 ligand (PD-L1) regulate immune response. Previous studies associate an immune deregulation in ST-elevation myocardial infarction STEMI. We recruited 100 patients with a first STEMI treated with reperfusion. In all patients PD-1 and PD-L1 expression was studied 24 h post-reperfusion in peripheral blood mononuclear cells (PBMCs), by means of flow cytometry and molecular biology. PD-1 and PD-L1 expression was serially analyzed in the first 20 patients before reperfusion and 24h, 96h and 30 days afterwards. Results were compared with 30 age- and sex-matched controls. Cardiac Magnetic Resonance was used to quantify infarct size 1-week after infarc…

Infusión intracoronaria de tioflavina-S para el estudio de la obstrucción microvascular en un modelo de infarto de miocardio

Resumen Introduccion y objetivos La obstruccion microvascular produce efectos nocivos despues del infarto de miocardio. Con objeto de esclarecer el papel de la lesion por isquemia-reperfusion en la aparicion y la dinamica de la obstruccion microvascular, se llevo a cabo un estudio metodologico preliminar para definir con exactitud este proceso en un modelo in vivo . Metodos Se indujo un infarto de miocardio en cerdos mediante una oclusion de 90 min en la parte media de la arteria coronaria descendente anterior izquierda empleando balones de angioplastia. Se aplico una infusion intracoronaria de tioflavina-S y se comparo con la instilacion tradicional intraaortica o intraventricular. Se cuan…

Microvascular obstruction in the right ventricle in reperfused anterior myocardial infarction. Macroscopic and pathologic evidence in a swine model.

article i nfo Introduction: Data on right ventricular (RV) involvement in anterior myocardial infarction are scarce. The presence of RV microvascular obstruction (MVO) in this context has not been analyzed yet. The aim of the present study was to characterize the presence of MVO in the RV in a controlled experimental swine model of reperfused anterior myocardial infarction. Materials and Methods: Left anterior descending (LAD) artery-perfused area (thioflavin-S staining after selective infusioninLADartery),infarctsize(lackof triphenyltetrazolium-chloride staining) andMVO (lack of thioflavin-S staininginthe core oftheinfarctedarea) inthe RVwere studied.A quantitative(%of theventricularvolume…

Serum Heat Shock Protein 60 in Acute Heart Failure: A New Biomarker?

Heat shock protein 60 (HSP60) is a mitochondrial protein constitutively expressed in the majority of cells, and its expression is up-regulated by a variety of stressors. In heart failure, HSP60 is released from cardiomyocytes. The authors speculate that increased serum HSP60 (sHSP60) may be related to the severity of heart failure. This investigation sought to assess the association between sHSP60 and the composite end point of death ⁄ readmission in patients with acute heart failure (AHF). A total of 132 consecutive patients were admitted for AHF. The independent association between sHSP60 and the end point was assessed with Cox regression. During a median follow-up of 7 months (interquart…

Linfopenia post-reperfusión y obstrucción microvascular en el infarto agudo de miocardio con elevación del segmento ST

Introduccion y objetivos La obstruccion microvascular tras un infarto agudo de miocardio con elevacion del segmento ST se asocia a mal pronostico. La fisiopatologia de este fenomeno no esta totalmente definida. Analizamos las implicaciones de la linfopenia post-reperfusion en la existencia de obstruccion microvascular. Metodos Estudiamos prospectivamente a 212 pacientes que habian sufrido un primer infarto agudo de miocardio con elevacion del segmento ST reperfundido con agentes tromboliticos o con angioplastia primaria y con la arteria responsable abierta. Cuantificamos de manera seriada las cifras de linfocitos, neutrofilos y monocitos. Usamos la resonancia magnetica cardiaca para determi…

Post-Reperfusion Lymphopenia and Microvascular Obstruction in ST-Segment Elevation Acute Myocardial Infarction

The presence of microvascular obstruction after ST-segment elevation acute myocardial infarction is associated with a poor outcome. The pathophysiology of this process has not been fully defined. The aim of this study was to investigate the relationship between post-reperfusion lymphopenia and microvascular obstruction.This prospective study involved 212 patients with a first ST-segment elevation acute myocardial infarction who underwent reperfusion with thrombolytic agents or primary angioplasty and who had an open infarct-related artery. Serial measurements of lymphocyte, neutrophil and monocyte counts were taken. Cardiac magnetic resonance was used to detect microvascular obstruction dur…