Necrotic Myocardium Research Articles

Supersaturated oxygen therapy in patients with acute anterior myocardial infarction reduces infarct size

Abstract Background Myocardial final infarct size (FIS) is associated with heart failure hospitalizations and mortality in patients with ST-segment elevation myocardial infarction (STEMI). Interventional therapies beyond primary percutaneous coronary intervention (PCI) to reduce FIS are needed. Hyperoxemic supersaturated oxygen therapy (SSO2) has shown to reduce infarct size in previous clinical trials. Methods We performed routine SSO2 therapy in patients with acute anterior STEMI after successful primary PCI. Results from 22 SSO2 patients were compared with those from 22 pair-matched non-SSO2 acute anterior STEMI patients. Cardiac magnetic resonance imaging (MRI) was performed to assess left ventricular (LV) function, myocardial FIS (late gadolinium enhancement), area-at-risk (AAR, myocardial oedema), myocardial salvage index (MSI, proportion of non-necrotic inside oedematous myocardium), and microvascular obstruction (MVO, necrotic myocardium within the infarct zone). Results Both groups did not significantly differ regarding sex, age, weight, body mass index, hypertension, dyslipidaemia, smoking and diabetes status, prehospital cardiac arrest, door-to-balloon time, TIMI flow before and after PCI, numbers of stents placed, and renal function (p>0.1 each). SSO2 patients had significant lower maximum creatine kinase levels (2111 U/l) vs. non-SSO2 patients (4571 U/l, p=0.003). Cardiac MRI was performed 4 ± 2 days after PCI. LV ejection fraction (48% in SSO2 vs. 43% in non-SSO2, p=0.11) and AAR (42% of LV mass in SSO2 vs. 48% of LV mass in non-SSO2, p=0.096) did not significantly differ between the groups. SSO2 significantly reduced FIS by 38% (21% of LV mass vs. 34% of LV mass, p<0.001). MSI was significantly higher in SSO2 patients (46% vs. 18%, p<0.001). MVO occurred in 60% of SSO2 patients vs. 90% of non-SSO2 patients with a significant absolute difference (2.3% in SSO2 vs. 5.7% in non-SSO2, p=0.011). Conclusion While areas at risk were similar between both groups, SSO2 significantly reduced maximum creatine kinase levels, final infarct size and microvascular obstruction in patients with acute anterior STEMI.

New avenues in the treatment of ischemic heart disease - Stem cell therapy

Faced with the large number of patients with ischemic heart disease and high mortality rates, traditional drug treatments come with the risks of drug resistance and rebound effects after discontinuation, as well as the shortcomings of surgical treatments such as poor blood circulation and the inability to restore necrotic myocardium. This article starts from the perspective of stem cell regenerative medicine, focusing on the stem cell therapy for ischemic heart disease, and provides a comprehensive review of the types of stem cells and transplantation methods. It also includes further summaries and prospects, believing that more comprehensive and improved treatment methods will emerge in the future to benefit patients.

Experimental validation of coronary stenosis severity and development of ischemic myocardium

The current study aimed to evaluate the causal association between hemodynamically significant stenosis and the occurrence of ischemic myocardium using an experimental animal model of coronary artery stenosis. In Yorkshire swine (n = 10), coronary stenosis in the left anterior descending artery was induced using a customized vascular occluder to create varying degrees of occlusion severity (40%-99%). Serial changes in coronary pressure and flow velocity were measured in the left anterior descending artery before and after the implantation of the vascular occluder. At 1 month, 13N-ammonia positron emission tomography (PET) was performed, followed by the collection of isolated hearts for 2,3,5-Triphenyltetrazolium chloride (TTC) staining to quantify the percent area of necrotic myocardium. Three animals in the control group were evaluated using the same protocols, but without the implantation of a vascular occluder Results: The median diameter stenosis after vascular occluder implantation was 61.3% (Q1-Q3: 55.9%-72.3%). Significant differences were observed in hyperemic stenosis resistance, fractional flow reserve (FFR), stress perfusion defect and reversibility in PET, as well as in necrotic myocardium in TTC staining based on stenosis severity (control group: < 50%, 50%-70%, 70%-90%, and > 90%) (all P < .010). Animals with FFR < 0.75 at 1 month exhibited a significantly higher area of stress perfusion defect (30.7 ± 3.1% vs 6.0 ± 4.2%, P < .001), reversibility in PET (11.0 ± 4.0% vs 0.0 ± 0.0%, P = .006), and necrotic myocardium in TTC staining (15.8 ± 6.4% vs 0.0 ± 0.0%, P < .001) than those with FFR ≥ 0.75. In a porcine model, the induction of hemodynamically significant stenosis with FFR < 0.75 was associated with the development of stress perfusion defects and reversibility in PET, as well as necrotic myocardium identified by pathology.

Comprehensive review of pulmonary vein stenosis post-atrial fibrillation ablation: diagnosis, management, and prognosis.

Pulmonary vein stenosis (PVS) can occasionally occur in the follow-up after pulmonary vein isolation (PVI) for atrial fibrillation (AF). During PVI, ablation is performed at the PV ostium or distal part, leading to tissue damage. This damage can result in fibrosis of the necrotic myocardium, proliferation, and thickening of the vascular intima, as well as thrombus formation, further advancing PVS. Mild-to-moderate PVS often remains asymptomatic, but severe PVS can cause symptoms, such as dyspnea, cough, fatigue, decreased exercise tolerance, chest pain, and hemoptysis. These symptoms are due to pulmonary hypertension and pulmonary infarction. Imaging evaluations such as contrast-enhanced computed tomography are essential for diagnosing PVS. Early suspicion and detection are necessary, as underdiagnosis can lead to inappropriate treatment, disease progression, and poor outcomes. The long-term prognosis of PVS remains unclear, particularly regarding the impact of mild-to-moderate PVS over time. PVS treatment focuses on symptom management, with no established definitive solutions. For severe PVS, transcatheter PV angioplasty is performed, though the risk of restenosis remains high. Restenosis and reintervention rates have improved with stent implantation compared with balloon angioplasty. The role of subsequent antiplatelet therapy remains uncertain. Dedicated evaluation is essential for accurate diagnosis and appropriate management to avoid significant long-term impacts on patient outcomes.

Research Progress on Cardiac Tissue Construction of Mesenchymal Stem Cells for Myocardial Infarction.

Heart failure is still the main complication affecting the prognosis of acute myocardial infarction (AMI), and mesenchymal stem cells (MSCs) are an effective treatment to replace necrotic myocardium and improve cardiac functioning. However, the transplant survival rate of MSCs still presents challenges. In this review, the biological characteristics of MSCs, the progress of mechanism research in the treatment of myocardial infarction, and the advances in improving the transplant survival rate of MSCs in the replacement of necrotic myocardial infarction are systematically described. From a basic to advanced clinical research, MSC transplants have evolved from a pure injection, an exosome injection, the genetic modification of MSCs prior to injection to the cardiac tissue engineering of MSC patch grafting. This study shows that MSCs have wide clinical applications in the treatment of AMI, suggesting improved myocardial tissue creation. A broader clinical application prospect will be explored and developed to improve the survival rate of MSC transplants and myocardial vascularization.

Pulsed Field Ablation for Atrial Fibrillation: Mechanisms, Advantages, and Limitations.

Pulsed field ablation with irreversible electroporation for the treatment of atrial fibrillation involves tissue-specific and non-thermal energy-induced cell necrosis, which helps avoid complications, such as pulmonary vein stenosis, atrial collateral tissue damage, and extensive atrial structural damage, often encountered with traditional thermal ablation. In existing clinical trials, pulsed field ablation has shown excellent effects on pulmonary vein isolation in patients with paroxysmal and persistent atrial fibrillation. Pulsed field ablation is easy, simple, and quick and can reduce iatrogenic injury. Therefore, the application of pulsed field ablation technology in the treatment of atrial fibrillation has a promising future. Notably, the adjustment of parameters in pulsed field ablation with different ablation catheter systems can strongly affect the area and depth of the necrotic myocardium, which greatly affects the likelihood of atrial fibrillation recurrence and incidence of adverse complications after ablation. In this paper, we review the mechanisms, advantages, and limitations of pulsed field ablation based on the results of a series of previous studies and provide ideas and directions for future research.

Characterizing the immune response to myocardial infarction in pigs

Though myocardial infarction (MI) in pigs is a well-established translational large animal model, it has not yet been widely used for immunotherapy studies, and a comprehensive description of the immune response to MI in this species is lacking. We induced MI in Landrace pigs by balloon occlusion of the left anterior descending artery over 90 min. Within 14 days, the necrotic myocardium was progressively replaced by scar tissue with involvement of myofibroblasts. We characterized the immune response in the heart ex vivo by (immuno)histology, flow cytometry, and RNA sequencing of myocardial tissue on days 3, 7, and 14 after MI. Besides a clear predominance of myeloid cells among heart-infiltrating leukocytes, we detected activated T cells and an increasing proportion of CD4+ Foxp3+ regulatory T cells (Treg), especially in the infarct core—findings that closely mirror what has been observed in mice and humans after MI. Transcriptome data indicated inflammatory activity that was persistent but markedly changing in character over time and linked to extracellular matrix biology. Analysis of lymphocytes in heart-draining lymph nodes revealed significantly higher proliferation rates of T helper cell subsets, including Treg on day 7 after MI, compared to sham controls. Elevated frequencies of myeloid progenitors in the spleen suggest that it might be a site of emergency myelopoiesis after MI in pigs, as previously shown in mice. We thus provide a first description of the immune response to MI in pigs, and our results can aid future research using the species for preclinical immunotherapy studies.

Enhancing Prediction of Myocardial Recovery After Coronary Revascularization: Integrating Radiomics from Myocardial Contrast Echocardiography with Machine Learning.

Chronic coronary artery disease (CAD) management often relies on myocardial contrast echocardiography (MCE), yet its effectiveness is limited by subjective interpretations and difficulty in distinguishing hibernating from necrotic myocardium. This study explores the integration of machine learning (ML) with radiomics to predict functional recovery in dyskinetic myocardial segments in CAD patients undergoing revascularization, aiming to overcome these limitations. This prospective study enrolled 55 chronic CAD patients, dividing into training (39 patients, 205 segments) and testing sets (16 patients, 68 segments). Dysfunctional myocardial segments were identified by initial wall motion scores (WMS) of ≥2 (hypokinesis or higher). Functional recovery was defined as a decrease of ≥1 grade in WMS during follow-up echocardiography. Radiomics features were extracted from dyssynergic segments in end-systolic phase MCE images across five cardiac cycles post- "flash" impulse and processed through a five-step feature selection. Four ML classifiers were trained and compared using these features and MCE parameters, to identify the optimal model for myocardial recovery prediction. Functional improvement was noted in 139 out of 273 dyskinetic segments (50.9%) following revascularization. Receiver Operating Characteristic (ROC) analysis determined that myocardial blood flow (MBF) was the most precise clinical predictor of recovery, with an area under the curve (AUC) of 0.770. Approximately 1.34 million radiomics features were extracted, with nine features identified as key predictors of myocardial recovery. The random forest (RF) model, integrating MBF values and radiomics features, demonstrated superior predictive accuracy over other ML classifiers. Validation of the RF model on the testing dataset demonstrated its effectiveness, evidenced by an AUC of 0.821, along with consistent calibration and clinical utility. The integration of ML with radiomics from MCE effectively predicts myocardial recovery in CAD. The RF model, combining radiomics and MBF values, presents a non-invasive, precise approach, significantly enhancing CAD management.

Application of High Molecular Hydrogel in The Treatment of Myocardial Infarction

Myocardial infarction (MI) is the world's leading disabling and fatal disease. Currently, clinical treatment methods mainly include drug therapy, angioplasty, and coronary artery bypass grafting. These traditional treatment methods are difficult to repair damaged myocardial tissue and cannot restore normal necrotic and fibrotic myocardium. Therefore, it is imperative to improve the efficacy of traditional treatment methods and find new treatment strategies. More and more studies have found that stem cell transplantation can repair damaged myocardium, but stem cells transplanted to the affected site undergo oxidative damage, compression loss, and low cell survival and retention rates. At present, there is an urgent need to seek new methods that can effectively repair damaged myocardium and restore cardiac function. In recent years, with the development of regenerative medicine engineering and the continuous optimization of polymer technology and the development of new biomaterials, it has become a reality to create lost or functionally damaged tissues and organs through theoretical methods of biology and engineering, enabling them to have the structure and function of normal tissues and organs. This article will focus on the latest progress in methods for repairing damaged myocardium in myocardial infarction through polymer hydrogel materials.

Forensic Pathological Diagnosis of Acute and Old Myocardial Infarction Using Fourier Transform Infrared Spectroscopy.

Fourier transform infrared spectroscopy (FTIR) was used to analyze myocardial infarction tissues at different stages of pathological change to achieve the forensic pathology diagnosis of acute and old myocardial infarction. FTIR spectra data of early ischemic myocardium, necrotic myocardium, and myocardial fibrous tissue in the left ventricular anterior wall of the sudden death group of atherosclerotic heart disease and the myocardium of the normal control group were collected using hematoxylin-eosin (HE) and immunohistochemistry (IHC) staining as a reference, and the data were analyzed using multivariate statistical analysis. The mean normalized spectra of control myocardium, early ischemic myocardium and necrotic myocardium were relatively similar, but the mean second derivative spectra were significantly different. The peak intensity of secondary structure of proteins in early ischemic myocardium was significantly higher than in other types of myocardium, and the peak intensity of the α-helix in necrotic myocardium was the lowest. The peaks of amide Ⅰ and amide Ⅱ in the mean normalized spectra of myocardial fibrous tissue significantly shifted towards higher wave numbers, the peak intensities of amide Ⅱ and amide Ⅲ were higher than those of other types of myocardium, and the peak intensities at 1 338, 1 284, 1 238 and 1 204 cm-1 in the mean second derivative spectra were significantly enhanced. Principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA) showed that FTIR could distinguish different types of myocardium. FTIR technique has the potential to diagnose acute and old myocardial infarction, and provides a new basis for the analysis of the causes of sudden cardiac death.

PEG-modified nano liposomes co-deliver Apigenin and RAGE-siRNA to protect myocardial ischemia injury

Ischemic heart disease (IHD) is a cardiac disorder in which myocardial damage occurs as a result of myocardial ischemia and hypoxia. Evidence suggests that oxidative stress and inflammatory responses are critical in the development of myocardial ischemia. Therefore, the combination of antioxidant and anti-inflammatory applications is an effective strategy to combat ischemic heart disease. In this paper, polyethylene glycol (PEG)-modified cationic liposomes were used as carriers to deliver apigenin (Apn) with small interfering RNA (siRNA) targeting the receptor for glycosylation end products (RAGE) (siRAGE) into cardiomyocytes to prevent myocardial ischemic injury through antioxidant and anti-inflammatory effects. Our results showed that we successfully prepared cationic PEG liposomes loaded with Apn and siRAGE (P-CLP-A/R) with normal appearance and morphology, particle size and Zeta potential, and good encapsulation rate, drug loading and in vitro release degree. In vitro, P-CLP-A/R was able to prevent oxidative stress injury in H9C2 cells, downregulate the expression of RAGE, reduce the secretion of cellular inflammatory factors and inhibit apoptosis through the RAGE/NF-κB pathway; In vivo, P-CLP-A/R was able to prevent arrhythmia and myocardial pathological injury, and reduce apoptosis and the area of necrotic myocardium in rats. In conclusion, P-CLP-A/R has a protective effect on myocardial ischemic injury and is expected to be a potential drug for the prevention of ischemic heart disease in the future.

THE ANNEXIN-A1 MIMETIC RTP-026 PROMOTES ACUTE CARDIOPROTECTION THROUGH MODULATION OF IMMUNE CELL ACTIVATION

The cardio-protective and immuno-regulatory properties of RTP-026, a synthetic peptide that spans the Annexin-A1 (AnxA1) N-terminal region, were tested in rat acute myocardial infarction. In vitro, selective activation of formyl-peptide receptor type 2 (FPR2) by RTP-026 occurred with apparent EC50 in the 10-30nM range. With human primary cells, RTP-026 counteracted extension of neutrophil life-span and augmented phagocytosis of fluorescent E.coli by blood myeloid cells. An in vivo model of rat acute infarction was used to quantify tissue injury and phenotype immune cells in myocardium and blood. The rat left anterior descending coronary artery was occluded and then reopened for 2-hour or 24-hour reperfusion. For the 2-hour reperfusion protocol, RTP-026 (25-500µg/kg; given i.v. at the start of reperfusion) significantly reduced infarct size by ∼50 %, with maximal efficacy at 50µg/kg. Analyses of cardiac immune cells showed that RTP-026 reduced neutrophil and classical monocyte recruitment to the damaged heart. In the blood, RTP-026 (50µg/kg) attenuated activation of neutrophils and monocytes monitored through CD62L and CD54 expression. Modulation of vascular inflammation by RTP-026 was demonstrated by reduction in plasma levels of mediators like TNF-α, IL-1β, KC, PGE2 and PGF2α⊡ For the 24-hour reperfusion protocol, RTP-026 (30µg/kg given i.v. at 0, 3 and 6h reperfusion) reduced necrotic myocardium by ∼40 %. RTP-026 modulate immune cell responses and decreases infarct size of the heart in preclinical settings. Tempering over-exuberant immune cell activation by RTP-026 is a suitable approach to translate the biology of AnxA1 for therapeutic purposes.

The infarct-limiting efficacy of deltorphin-II in old rats with diet-induced metabolic syndrome

Background. The discovery of new pharmacological agents for myocardial protection during reperfusion injury is an urgent goal of modern physiology and pharmacology.The aim of the study. To identify the potential for protecting the myocardium from reperfusion injury by administering the delta-2 opioid receptor agonist deltorphin-II prior to reperfusion in old rats with diet-induced metabolic syndrome.Materials and methods. The study was performed on Wistar rats aged 60 days (young rats) and 450 days (old rats) before the onset of a study. Metabolic syndrome (MetS) was modeled for 84 days with a high-carbohydrate high-fat diet (16 % protein, 21 % fat, 46 % carbohydrate) with the replacement of drinking water with 20 % fructose solution. Myocardial infarction was performed by 45-min coronary occlusion followed by 120-min reperfusion; the size of the area of the necrotic myocardium was determined relative to the size of the hypoperfusion zone. The delta-2 opioid receptor agonist deltorphin-II was administered once intravenously 5 minutes before the end of ischemia.Results. It was found that coronary occlusion and subsequent reperfusion both in groups of young and old rats led to the formation of myocardial infarction (necrosis), the size of which was 45 % of the size of the risk zone. Administration of deltorphin-II in old rats led to a limitation of infarct size to 30 % of the size of the risk zone, i. e. 1.7-fold. The use of deltorphin-II in old rats with MetS contributed to a decrease in infarct size to 27 % of the size of the risk zone (1.5 times). The obtained results demonstrate the cardioprotective efficacy of the delta-2 opioid receptor agonist deltorphin-II in aging and metabolic syndrome in rats.Conclusions. These data may serve as a basis for conducting preclinical studies of deltorphin-II as a drug for treatment of acute myocardial infarction.

Adenosine kinase promotes post-infarction cardiac repair by epigenetically maintaining reparative macrophage phenotype

Pro-inflammatory and reparative macrophages are crucial in clearing necrotic myocardium and promoting cardiac repair after myocardial infarction (MI), respectively. Extracellular adenosine has been demonstrated to modulate macrophage polarization through adenosine receptors. However, the role of intracellular adenosine in macrophage polarization has not been explored and adenosine kinase (ADK) is a major enzyme regulating intracellular adenosine levels. Here, we aimed to elucidate the role of ADK in macrophage polarization and its subsequent impact on MI. We demonstrated that ADK was upregulated in bone marrow-derived macrophages (BMDMs) after IL-4 treatment and was highly expressed in the infarct area at day 7 post-MI, especially in macrophages. Compared with wild-type mice, myeloid-specific Adk knockout mice showed increased infarct size, limited myofibroblast differentiation, reduced collagen deposition and more severe cardiac dysfunction after MI, which was related to impaired reparative macrophage phenotype in MI tissue. We found that ADK deletion or inhibition significantly decreased the expression of reparative genes, such as Arg1, Ym1, Fizz1, and Cd206 in BMDMs after IL-4 treatment. The increased intracellular adenosine due to Adk deletion inhibited transmethylation reactions and decreased the trimethylation of H3K4 in BMDMs after IL-4 treatment. Mechanistically, we demonstrated that Adk deletion suppressed reparative macrophage phenotype through decreased IRF4 expression, which resulted from reduced levels of H3K4me3 on the Irf4 promotor. Together, our study reveals that ADK exerts a protective effect against MI by promoting reparative macrophage polarization through epigenetic mechanisms.

The cardiac wound healing response to myocardial infarction.

Myocardial infarction (MI) is defined as evidence of myocardial necrosis consistent with prolonged ischemia. In response to MI, the myocardium undergoes a series of wound healing events that initiate inflammation and shift to anti-inflammation before transitioning to tissue repair that culminates in scar formation to replace the region of the necrotic myocardium. The overall response to MI is determined by two major steps, the first of which is the secretion of proteases by infiltrating leukocytes to breakdown extracellular matrix (ECM) components, a necessary step to remove necrotic cardiomyocytes. The second step is the generation of new ECM that comprises the scar; and this step is governed by the cardiac fibroblasts as the major source of new ECM synthesis. The leukocyte component resides in the middle of the two-step process, contributing to both sides as the leukocytes transition from pro-inflammatory to anti-inflammatory and reparative cell phenotypes. The balance between the two steps determines the final quantity and quality of scar formed, which in turn contributes to chronic outcomes following MI, including the progression to heart failure. This review will summarize our current knowledge regarding the cardiac wound healing response to MI, primarily focused on experimental models of MI in mice. This article is categorized under: Cardiovascular Diseases > Molecular and Cellular Physiology Immune System Diseases > Molecular and Cellular Physiology.

Different clinical and pathological profiles of sudden cardiac death victims caused by coronary artery dissection or myocardial infarction with non-obstructed coronary arteries

Abstract Background Spontaneous coronary artery dissection (SCAD) is a potential cause of acute coronary syndrome and sudden cardiac death (SCD). Coronary fibromuscolar dysplasia (FMD) has been correlated to SCAD occurrence.The prevalence of SCAD and FMD among SCD victims are unclear. Myocardial infarction with non-obstructed coronary arteries (MINOCA) could represent a cause of SCD. Since SCAD could clinically manifest as acute myocardial infarction, expert consensus documents have often considered SCAD as a subtype of MINOCA (1,2), but studies which address direct comparison between these two conditions are lacking. Purpose To assess characteristics of decedents with SCAD and/or FMD found at autopsy, and to compare their clinical and pathological profile with MINOCA SCD victims. Methods We reviewed a database of 5325 consecutive cases of SCDs referred to our cardiac pathology center between 1994 and July 2017. Results We identified 21 (0.4%) with SCAD and 37 (0.7%) victims with MINOCA (3), whereas FMD was found only in 2 (0.04%). SCAD decedents were females in 81%, versus 38% of MINOCA (p=0.02). No signs of coronary FMD were found among SCAD and MINOCA victims. Necrotic myocardium was identified in the totality of MINOCA and only in 8 (38%) of SCAD decedents (p&amp;lt;0.001). Pre-mortem cardiac symptoms were present in 100% of SCAD and 49% of MINOCA victims (p&amp;lt;0.001); illicit drug use was reported in none of SCAD versus 46% of MINOCA decedents (p=0.001). Conclusions SCAD is a rare cause of SCD. Compared to MINOCA, SCAD victims are more frequently females, always experienced pre-mortem cardiac symptoms and have no habit of substances abuse. At autopsy coronary FMD is not present among SCAD victims. SCAD and MINOCA shows different clinical and pathological profile. SCAD should not be considered a subtype of MINOCA. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Cardiac Risk in the Young (CRY) and the Charles Wolfson Charitable Trust.

Immunohistochemical analysis of CD31 expression in myocardial tissues from autopsies of patients with ischemic heart disease

CD31, a transmembrane protein expressed on endothelial and hematopoietic cells, plays important roles in leukocyte trafficking, mechanotransduction, angiogenesis, vascular permeability, and regulation of cellular responsiveness. CD31 immunoreactivity is employed as a sensitive and specific endothelial marker in diagnostic pathology. In this study, CD31 expression in myocardial tissues from deceased patients with ischemic heart disease and a mouse model of acute myocardial infarction were examined by immunohistochemical staining. We examined 24 neutral formalin-fixed, paraffin-embedded myocardial tissue samples obtained within 48 h postmortem from the autopsies of patients who were diagnosed with ischemic heart disease. CD31 expression was observed in vascular endothelial and endocardial cells. In necrotic myocardium, diffusion of CD31 antigen was observed. Elevated CD31 expression was observed around myocardial cells undergoing remodeling, suggesting that endothelial proliferation occurred at these sites. In contrast, fibrotic myocardial foci did not show upregulated CD31 expression. The same CD31 expression characteristics as those observed in the human samples were observed in the mouse model. CD31 immunostaining as an endothelial and microvasculature marker may be a useful complement to conventional staining techniques currently used in the diagnosis of ischemic heart disease, and may allow the timing and process of myocardial remodeling to be analyzed in detail.

IL-6 inhibitors effectively reverse post-infarction cardiac injury and ischemic myocardial remodeling via the TGF-β1/Smad3 signaling pathway.

Approximately one in four myocardial infarctions occur in older patients. The majority of therapeutic advances are either not appropriate or not tested in elderly patients. The main reasons for deviating from the guidelines are justified concerns regarding the effectiveness of the recommended forms of therapy, fear of adverse drug reactions and ethical concerns. Targeting interleukin 6 (IL-6) for ventricular remodeling after cardiovascular damage is a feasible alternative to standard polypharmaceutics, but the underlying molecular mechanisms are not well understood. Continuous activation of the IL-6-associated cytokine receptor gp130 leads to cardiomyopathic hypertrophy. TGFβ1 is involved in forming fibrosis in various organs, and its overexpression can cause myocardial hypertrophy and fibrosis. Il-6 has been hypothesized to be indirectly involved in cardiac remodeling via the TGFβ1/Smad signaling transduction pathway. In the present study, a rat model of acute myocardial ischemia, IL-6 and IL-6 receptor blockers were injected directly into the necrotic myocardium. Changes in cardiac function, myocardial infarction area, myocardial collagen, necrotic myocardial fibrosis and levels of TGFβ1, IL-6 and MMP2/9 were quantified in myocardial tissue fibrosis by ELISA. The present study demonstrated that IL-6 stimulated myocardial fibrosis through the TGFβ1-Smad-MM2/9 signaling transduction pathway. Overall, this provided a solid foundation for understanding the relationship between IL-6 and ventricular remodeling.

Theranostic Contribution of Extracellular Matrix Metalloprotease Inducer-Paramagnetic Nanoparticles Against Acute Myocardial Infarction in a Pig Model of Coronary Ischemia-Reperfusion.

Background:Rapid screening and accurate diagnosis of acute myocardial infarction are critical to reduce the progression of myocardial necrosis, in which proteolytic degradation of myocardial extracellular matrix plays a major role. In previous studies, we found that targeting the extracellular matrix metalloprotease inducer (EMMPRIN) by injecting nanoparticles conjugated with the specific EMMPRIN-binding peptide AP9 significantly improved cardiac function in mice subjected to ischemia/reperfusion.Methods:In a porcine model of coronary ischemia/reperfusion, we tested the theragnostic effects of administering 0.1 mg/kg gadolinium-containing nanoparticles conjugated with AP9 (NAP9), a synthetic peptide that targets EMMPRIN or a control nanoparticle (NAPSC). Cardiac magnetic resonance assessment of the infarct progression, ventricular function, and nanoparticle distribution was performed the next 7 days. We also measured the infarcted area of the heart and cardiac remodeling at 7 or 21 days after ischemia/reperfusion.Results:After 21 days of ischemia/reperfusion, NAP9 reduced the extension of cardiac necrosis (14.1±9.7 versus 35.5±1.8) and the levels of collagenolytic activity of MMPs (matrix metalloproteases), along with a significant reduction in collagen deposition (7.5±4.5 versus 41.3±20); including the ratio of type I versus III collagen fibers in the necrotic myocardium. In terms of cardiac function, the response to NAP9 administration resulted in a significant improvement of cardiac performance overtime, as evidenced by the left ventricle ejection fraction (64.0±7.8), when compared with those present in the NAPSC group (47.3±4.7). As shown by magnetic resonance imaging, noninvasive molecular imaging of NAP9 enabled us to find a significant reduction in cardiac necrosis, myocardial edema, hemorrhage, and microvascular obstruction, suggesting that NAP9 may reduce myocardial injury and preserve left ventricular function, at least, by preventing the effect of EMMPRIN on extracellular matrix degradation.Conclusions:Our data point towards NAP9 as a promising theragnostic tool in managing acute myocardial infarction, by inhibiting EMMPRIN-induced extracellular matrix degradation and allowing noninvasive visualization of cardiac necrosis progression over time.

C41 AN UNUSUAL CASE OF “PULMONARY EMBOLISM”

Abstract Background Pulmonary vein stenosis (PVS) is a complication of catheter–based radiofrequency ablation (RFA) for atrial fibrillation (AF), caused by a vascular response which leads to replacement of necrotic myocardium with collagen. Clinical presentation can mimic pulmonary embolism (PE) and usually appears some months after procedure. Case report A 65–year–old man was hospitalized in March 2021 with a complaint of worsening dyspnoea on exertion, over the course of one month. He had a past medical history of persistent atrial fibrillation, because of which he underwent four pulmonary vein ablations (both RFA and crioablation), the last one in 2019. The previous echocardiogram showed a high systolic pulmonary arterial pressure (sPAP of 75 + 5 mmHg) with normal right ventricular function and dimensions. Despite D–dimer at admission was negative, a CT pulmonary angiography was performed and showed occlusion of left superior pulmonary vein and a severe stenosis of right superior pulmonary vein; ventilation–perfusion scintigraphy (V/Q scan) demonstrated widespread decreased perfusion of both superior lung lobes. The patient underwent angioplasty of right pulmonary vein and after the procedure sPAP greatly decreased (35 mmHg). Discussion Despite its reduction in incidence and its short–term presentation from procedure, severe symptomatic pulmonary vein stenosis must be considered among complications of ablation for atrial fibrillation. Delayed symptoms can also present years after procedure, even if in literature few similar cases are described. Ventilation–perfusion scintigraphy is a very sensible method to assess the functional significance of pulmonary vein stenosis and it also relates with symptoms’ severity. It should be performed in case of a high clinical suspicion, considering that the characteristic ventilation–perfusion mismatch of this condition can be seen in other diseases too, over all pulmonary embolism. Conclusions This case report emphasizes the importance of a thorough anamnesis and an exact interpretation of diagnostic imaging to correctly identify this AF ablation complication and optimize the patient’s therapeutic management. It must be considered that PV stenosis can develop late and with unusual symptoms, mimicking other diseases, like pulmonary embolism, which has the same scintigraphic imaging.