Site Of Myocardial Infarction Research Articles

Risk factors for left ventricular remodeling after myocardial infarction: A meta-analysis.

This study aimed to assess potential risk factors for left ventricular remodeling (LVR) after acute myocardial infarction (MI). We systematically searched PubMed, the Cochrane Library, MEDLINE, Embase, Web of Science databases CNKI Scholar, VIP, and WanFang databases for all relevant epidemiological studies published up to August 1, 2023. Fixed-effects model or random-effects model was employed to pool the study-specific effect sizes and 95% confidence intervals (CIs). Fifteen studies with a total of 3,093,792 participants were included according to inclusion criteria. Major modifiable risk factors associated with LVR after MI were diabetes (odds ratio [OR] = 2.053, 95% CI: 1.504-2.803), MI site (OR = 2.423, 95% CI: 1.584-3.708), cystatin C (OR = 6.204, 95% CI: 1.830-21.036), B-type natriuretic peptide (OR = 2.280, 95% CI: 1.466-3.546), as well as creatine kinase-myocardial band (OR = 1.013, 95% CI: 0.985-1.042). The current study provides evidence indicating that diabetes, the site of MI, cystatin C, B-type natriuretic peptide, and creatine kinase-myocardial band are the primary risk factors for LVR after MI. Recognizing and addressing these modifiable risk factors is crucial for the development of effective preventive and treatment strategies.

Peroxynitrite-Free Nitric Oxide-Embedded Nanoparticles Maintain Nitric Oxide Homeostasis for Effective Revascularization of Myocardial Infarcts.

Revascularization is crucial for treating myocardial infarction (MI). Nitric oxide (NO), at an appropriate concentration, is recognized as an ideal and potent pro-angiogenic factor. However, the application of NO in the treatment of MI is limited. Improper NO supplementation is harmful to revascularization because NO is converted into harmful peroxynitrite (ONOO-) in MI tissues with high reactive oxygen species (ROS) levels. We overcome these obstacles by embedding biliverdin and NO into Prussian blue (PB) nanolattices to obtain an ONOO--free NO-embedded nanomedicine (OFEN). Unlike previous NO donors, OFEN provides NO stably and spontaneously for a longer time (>7 days), which makes it possible to maintain a stable concentration of NO, suitable for angiogenesis, through dose optimization. More importantly, based on the synergy between PB and biliverdin, OFEN converts ROS into beneficial O2 and inhibits the production of ONOO- from the source. OFEN specifically targets MI tissues and achieves sustained and stable NO delivery at the MI site. OFEN effectively promotes revascularization in the MI tissue, significantly reduces myocardial death and fibrosis, and ultimately promotes the complete recovery of cardiac function. Our strategy provides a promising approach for the treatment of myocardial and other ischemic diseases.

Myocardial infarction in rats was alleviated by MSCs derived from the maternal segment of the human umbilical cord.

Mesenchymal stem cells (MSCs) are safe and effective in treating myocardial infarction (MI) and have broad application prospects. However, the heterogeneity of MSCs may affect their therapeutic effect on the disease. We recently found that MSCs derived from different segments of the same umbilical cord (UC) showed significant difference in the expression of genes that are related to heart development and injury repair. We therefore hypothesized that those MSCs with high expression of above genes are more effective to treat MI and tested it in this study. MSCs were isolated from 3cm-long segments of the maternal, middle and fetal segments of the UC (maternal-MSCs, middle-MSCs and fetal-MSCs, respectively). RNA-seq was used to analyze and compare the transcriptomes. We verified the effects of MSCs on oxygen-glucose deprivation (OGD)-induced cardiomyocyte apoptosis in vitro. In vivo, a rat MI model was established by ligating the left anterior descending coronary artery, and MSCs were injected into the myocardium surrounding the MI site. The therapeutic effects of MSCs derived from different segments of the UC were evaluated by examining cardiac function, histopathology, cardiomyocyte apoptosis, and angiogenesis. Compared to fetal-MSCs and middle-MSCs, maternal-MSCs exhibited significantly higher expression of genes that are associated with heart development, such as GATA-binding protein 4 (GATA4), and myocardin (MYOCD). Coculture with maternal-MSCs reduced OGD-induced cardiomyocyte apoptosis. In rats with MI, maternal-MSCs significantly restored cardiac contractile function and reduced the infarct size. Mechanistic experiments revealed that maternal-MSCs exerted cardioprotective effects by decreasing cardiomyocyte apoptosis, and promoting angiogenesis. Our data demonstrated that maternal segment-derived MSCs were a superior cell source for regenerative repair after MI. Segmental localization of the entire UC when isolating hUCMSCs was necessary to improve the effectiveness of clinical applications.

Clinical profile and risk factors of patients presenting with acute myocardial infarction at RIMS, Imphal

Background: Cardiovascular diseases are the leading cause of mortality in India. Ischemic heart disease is a result of an inadequate supply of blood to a portion of the myocardium caused by atherosclerotic disease of an epicardial coronary artery. The increasing incidence of myocardial infarction (MI) and associated mortality is a concern. Aims and Objectives: The aims and objectives of the study were to evaluate the clinical profile and determine the association of risk factors in patients presenting with acute MI. The study highlights the trend of occurrence of acute MI so as appropriate measures can be taken to mitigate the incidence of coronary artery disease (CAD). Materials and Methods: A cross-sectional study was conducted among 100 patients with acute MI admitted to the intensive coronary care unit and medicine wards of a tertiary center in North-East India. The study was carried out for a period of 2 years from September 2019 to August 2021. Results: The mean age of the study population was 63.13±10.47 years, with an age range from 41 to 90 years. The study population had 75% males and 25% females. The most common presenting symptom was chest pain in 96% of patients. Hypertension in 75% of patients was the most common risk factor studied. About 97% of patients had at least one cardinal risk factor for MI. Inferior wall MI in 47% of patients was the most common site of MI. The highest mortality was seen in those who presented with Killip Class IV. Conclusions: Increasing age and male gender predisposed to MI. The association of risk factors such as hypertension, diabetes, obesity, and family history was higher in females. To bring about a reduction in the risk of CAD, emphasis should be laid on the adoption of a healthy lifestyle particularly for those at risk of CAD.

Engineered nanovesicles mediated cardiomyocyte survival and neovascularization for the therapy of myocardial infarction

Myocardial infarction (MI) leads to substantial cellular necrosis as a consequence of reduced blood flow and oxygen deprivation. Stimulating cardiomyocyte proliferation and angiogenesis can promote functional recovery after cardiac events. In this study, we explored a novel therapeutic strategy for MI by synthesizing a biomimetic nanovesicle (NV). This biomimetic NVs are composed of exosomes sourced from umbilical cord mesenchymal stem cells, which have been loaded with placental growth factors (PLGF) and surface-engineered with a cardiac-targeting peptide (CHP) through covalent bonding, termed Exo-P-C NVs. With the help of the myocardial targeting effect of homing peptides, NVs can be enriched in the MI site, thus improve cardiac regeneration, reduce fibrosis, stimulate cardiomyocyte proliferation, and promote angiogenesis, ultimately resulted in improved cardiac functional recovery. It was demonstrated that Exo-P-C NVs have the potential to offer novel therapeutic strategies for the improvement of cardiac function and management of myocardial infarction.

A Whole-Course-Repair System Based on Stimulus-Responsive Multifunctional Hydrogels for Myocardial Tissue Regeneration.

Myocardial infarction (MI) has emerged as the predominant cause of cardiovascular morbidity globally. The pathogenesis of MI unfolds as a progressive process encompassing three pivotal phases: inflammation, proliferation, and remodeling. Smart stimulus-responsive hydrogels have garnered considerable attention for their capacity to deliver therapeutic drugs precisely and controllably at the MI site. Here, a smart stimulus-responsive hydrogel with a dual-crosslinked network structure is designed, which enables the precise and controlled release of therapeutic drugs in different pathological stages for the treatment of MI. The hydrogel can rapidly release curcumin (Cur)in the inflammatory phase of MI to exert anti-apoptotic/anti-inflammatory effects. Recombinant humanized collagen type III (rhCol III) is loaded in the hydrogel and released as the hydrogel swelled/degraded during the proliferative phase to promote neovascularization. RepSox (a selective TGF-β inhibitor) releases from Pluronic F-127 grafted with aldehyde nanoparticles (PF127-CHO@RepSox NPs) in the remodeling phase to against fibrosis. The results in vitro and in vivo suggest that the hydrogel improves cardiac function and alleviates cardiac remodeling by suppressing inflammation and apoptosis, promoting neovascularization, and inhibiting myocardial fibrosis. A whole-course-repair system, leveraging stimulus-responsive multifunctional hydrogels, demonstrates notable effectiveness in enhancing post-MI cardiac function and facilitating the restoration of damaged myocardial tissue.

Local delivery of stem cell spheroids with protein/polyphenol self-assembling armor to improve myocardial infarction treatment via immunoprotection and immunoregulation

Stem cell therapies have shown great potential for treating myocardial infarction (MI) but are limited by low cell survival and compromised functionality due to the harsh microenvironment at the disease site. Here, we presented a Mesenchymal stem cell (MSC) spheroid-based strategy for MI treatment by introducing a protein/polyphenol self-assembling armor coating on the surface of cell spheroids, which showed significantly enhanced therapeutic efficacy by actively manipulating the hostile pathological MI microenvironment and enabling versatile functionality, including protecting the donor cells from host immune clearance, remodeling the ROS microenvironment and stimulating MSC's pro-healing paracrine secretion. The underlying mechanism was elucidated, wherein the armor protected to prolong MSCs residence at MI site, and triggered paracrine stimulation of MSCs towards immunoregulation and angiogenesis through inducing hypoxia to provoke glycolysis in stem cells. Furthermore, local delivery of coated MSC spheroids in MI rat significantly alleviated local inflammation and subsequent fibrosis via mediation macrophage polarization towards pro-healing M2 phenotype and improved cardiac function. In general, this study provided critical insight into the enhanced therapeutic efficacy of stem cell spheroids coated with a multifunctional armor. It potentially opens up a new avenue for designing immunomodulatory treatment for MI via stem cell therapy empowered by functional biomaterials.

Comparison between myocardial infarction with non-obstructive coronaries (MINOCA) and myocardial infarct patients with coronary artery disease (MI-CAD): A single-center retrospective cohort study.

The coronary angiography results in a group of patients with myocardial infarction (MI) are normal or near-normal; which is diagnosed as myocardial infarction with non-obstructive coronary arteries (MINOCA). This study aimed to compare the mortality rate and risk factors between MINOCA and myocardial infarction with obstructive coronary artery (MI-CAD). This retrospective cohort study was conducted from January 1, 2018, to December 31, 2019. A total of 679 patients admitted to Afshar Hospital in Yazd with a diagnosis of ST-elevation myocardial infarction (STEMI) from 2018-2019 who underwent primary Percutaneous Coronary Intervention (PCI) were enrolled in the study. Demographic, and clinical variables, ECG finding and one-year mortality, were extracted using MI registry data from the Yazd Cardiac Research Center. The estimated frequency of MINOCA was 4.6%. Patients with MINOCA (47.14±6.2) were younger than patients with MI-CAD (57.61±9.1) (P <0.0001). MINOCA patients (47.4±9.47) had a considerably greater left ventricular ejection fraction (LVEF) than MI-CAD patients (43.5±6.8) (P =0.018). The majority site of MI in MINOCA patients was located in the non-anterior wall (p <0.0001). A comparison of MINOCA and MI-CAD patients' one-year mortalityrevealed no significant difference (P =0.07). The prevalence of patients with MINOCA in Yazd was similar to other communities. Although these patients probably do not have a better prognosis, despite being younger and having better LV systolic function and lower CAD risk factors.

A Biomimetic Nanocarrier Strategy Targets Ferroptosis and Efferocytosis During Myocardial Infarction.

Myocardial infarction (MI) is characterized by irreversible cardiomyocyte death resulting from an inadequate supply of oxygenated blood to the myocardium. Recent studies have indicated that ferroptosis, a form of regulated cell death, exacerbates myocardial injury during MI. Concurrently, the upregulation of CD47 on the surface of damaged myocardium following MI impairs the clearance of dead cells by macrophages, thereby hindering efferocytosis. In this context, simultaneously inhibiting ferroptosis and enhancing efferocytosis may represent a promising strategy to mitigate myocardial damage post-MI. In this study, we engineered platelet membrane-coated hollow mesoporous silicon nanoparticles (HMSN) to serve as a drug delivery system, encapsulating ferroptosis inhibitor, Ferrostatin-1, along with an anti-CD47 antibody. We aimed to assess the potential of these nanoparticles (designated as Fer-aCD47@PHMSN) to specifically target the site of MI and evaluate their efficacy in reducing cardiomyocyte death and inflammation. The platelet membrane coating on the nanoparticles significantly enhanced their ability to successfully target the site of myocardial infarction (MI). Our findings demonstrate that treatment with Fer-aCD47@PHMSN resulted in a 38.5% reduction in cardiomyocyte ferroptosis under hypoxia, indicated by decreased lipid peroxidation and increased in vitro. Additionally, Fer-aCD47@PHMSN improved cardiomyocyte efferocytosis by approximately 15% in vitro. In MI mice treated with Fer-aCD47@PHMSN, we observed a substantial reduction in cardiomyocyte death (nearly 30%), decreased inflammation, and significant improvement in cardiac function. Our results demonstrated that the cooperation between the two agents induced anti-ferroptosis effects and enhanced dead cardiomyocyte clearance by macrophage as well as anti-inflammation effects. Thus, our nanoparticle Fer-aCD47@PHMSN provides a new therapeutic strategy for targeted therapy of MI.

Abstract 220: Transradial Access Versus Transfemoral Approach for Carotid Artery Stenting: A Systematic Review and Meta‐analysis

Introduction Carotid artery stenting (CAS) has emerged as a viable alternative to carotid endarterectomy for managing carotid artery stenosis in high‐risk patients (1). While the transfemoral arterial approach (TF) remains the preferred method, it is associated with inherent limitations and potential complications (2‐4). Consequently, exploring the transradial artery access (TR) as a potential option becomes crucial in optimizing patient outcomes and procedural success rates. Limited data exists comparing the outcomes of TR approach in CAS to TF approach. This study aims to systematically review and meta‐analyze the outcomes and complication rates between TR and TF access for CAS. Methods A systematic electronic search was conducted in four databases up to May 10th, 2023. Studies with randomized or non‐randomized designs, involving CAS through TR or TF approach, were included. Outcomes of interest were stroke, transient ischemic attack (TIA), death, myocardial infarction (MI), and access site complications. A meta‐analysis was performed, analyzing pooled odds ratios (ORs) and 95% confidence intervals (CI) to assess the effect size of the vascular access approaches. Results Six studies with a total of 6,917 patients were included, out of which 602 (8.7%) underwent the TR approach, and 6,315 (91.3%) underwent the TF approach. Meta‐analysis results showed no significant difference in stroke occurrence between TR and TF groups (TR: 1.7% vs. TF: 1.9%; OR = 0.98; 95% CI 0.49 – 1.96; I2 = 0%). Similarly, no significant difference was found in death (TR: 1% vs. TF: 0.9%; OR = 0.95; 95% CI 0.38 – 2.37; I2 = 0%), MI (TR: 0.2% vs. TF: 0.3%; OR = 1.53; 95% CI 0.20 – 11.61; I2 = 0%), TIA (TR: 0.4% vs. TF: 1%; OR = 0.46; 95% CI 0.11 – 1.95; I2 = 0%), and access site complications (TR: 2.2% vs. TF: 1%; OR = 0.97; 95% CI 0.48 – 1.98; I2 = 0%). Conclusion In the comparison of TR and TF approaches for CAS, no significant differences were observed in stroke, death, MI, TIA, or access site complications. TR approach shows promise as an alternative method for CAS, offering potential benefits without increased risk of complications. However, further studies are needed to confirm these findings and establish guidelines for optimal access site selection.

Surface hydrolysis-designed AuNPs-zwitterionic-glucose as a novel tool for targeting macrophage visualization and delivery into infarcted hearts.

Macrophages, innate immune cells, are key players in the maintenance of myocardial homeostasis under normal conditions and tissue repair after injury. The infiltration of macrophages into the injured heart makes them a potentially appealing vehicle for noninvasive imaging and targeted drug delivery of myocardial infarction (MI). In this study, we demonstrated the use of surface hydrolysis-designed AuNPs-zwitterionic-glucose to label macrophages and track their infiltration into isoproterenol hydrochloride (ISO)-induced MI sites noninvasively using CT. The AuNPs-zwitterionic-glucose did not affect the viability or cytokine release of macrophages and were highly taken up by these cells. The in vivo CT images were obtained on Day 4, Day 6, Day 7, and Day 9, and the attenuation was seen to increase in the heart over time compared to the Day 4 scan. In vitro analysis also confirmed the presence of macrophages around injured cardiomyocytes. Additionally, we also addressed the concern of cell tracking or merely AuNP tracking, which is the inherent problem for any form of nanoparticle-labeled cell tracking by using zwitterionic and glucose-functionalized AuNPs. The glucose coated on the surface of AuNPs-zwit-glucose will be hydrolyzed in macrophages, forming only zwitterionic protected AuNPs that cannot be taken up again by endogenous cells in vivo. This will greatly improve the accuracy and precision of imaging and target delivery. We believe this is the first study to noninvasively visualize the infiltration of macrophages into MI hearts using CT, which could be used for imaging and evaluating the possibility of macrophage-mediated delivery in infarcted hearts.

Regeneration of infarcted hearts by myocardial infarction-responsive injectable hydrogels with combined anti-apoptosis, anti-inflammatory and pro-angiogenesis properties

Current treatments including drug therapy, medical device implantation, and organ transplantation have considerable shortcomings for myocardial infarction (MI), such as high invasiveness, the scarce number of donor organs, easy thrombosis, immune rejection, and poor therapeutic effects. Therefore, the development of new solutions to repair infarcted hearts is urgently needed. Smart responsive injectable hydrogels have served as a good foundation in biomedical engineering, especially for cardiac regeneration. Herein, we synthesized an injectable hydrogel that responds to the inflammatory microenvironment at the site of MI to provide the drug curcumin (Cur) and tailored recombinant humanized collagen type III (rhCol III) in a controlled manner for myocardial repair. The excellent antioxidant and anti-inflammatory properties of Cur could effectively reduce the ROS level and cell apoptosis and inhibit inflammatory reactions after MI. The tailored rhCol III promoted cell proliferation, migration, and angiogenesis. The therapeutic hydrogel resulted in the rapid recovery of cardiac function after MI by elevating the expression of the cardiac markers α-actinin and CX 43. In vitro and in vivo data showed that the combined anti-apoptosis, anti-inflammatory and pro-angiogenesis treatment strategies were an auspicious tactic for the treatment of MI, and had significant clinical application value. Furthermore, the work also demonstrated the great application potential of our tailored rhCol III in promoting the repair and regeneration of infarcted hearts.

Mendelian randomization study of the effect of coronary artery calcification on atherosclerotic cardiovascular diseases

Calcium calcification in the wall of arteries (CAC) leads to a higher risk of atherosclerosis related outcomes, especially myocardial infarction (MI). Nevertheless, the causal role of CAC on other related outcomes is unclear. In this study, we used Mendelian randomization (MR) to systematically investigate the causal role of CAC across a broad range of atherosclerotic cardiovascular diseases including coronary heart disease, angina, MI, ischemic heart disease, stroke, and peripheral vascular disease. Publicly available data from the UK biobank and other data sources were used. Using the two-sample Mendelian randomization (MR) approach, we applied 3 MR models including the inverse variance weighted, the weighted-median, and the weighted-mode methods. Eight SNPs associated with CAC were selected as instrumental variables. We observed causal evidence of CAC on MI consistently across all MR models (PIVW = 1.0 × 10−4, PW-Median = 1.1 × 10−4, PW-Mode = 3.8 × 10−2) and this causation is shown in an acute transmural MI of inferior wall (PIVW = 1.5 × 10−4, PW-Median = 4.8 × 10−5, PW-Mode = 3.2 × 10−2) but not consistently observed in an anterior wall. As each site of acute MI was suggested to have relatively specific mechanisms, our finding suggested that the causal role of CAC on MI is in an inferior wall possibly as a consequence of large calcification from a prolonged process, whereas non-calcified artery plaque or other underlying mechanisms may predominantly play role in an anterior infarction during an advanced atherosclerotic process.

Targeted trapping of endogenous endothelial progenitor cells for myocardial ischemic injury repair through neutrophil-mediated SPIO nanoparticle-conjugated CD34 antibody delivery and imaging

Endothelia progenitor cell (EPC)-based revascularization therapies have shown promise for the treatment of myocardial ischemic injury. However, applications and efficacy are limited by the relatively inefficient recruitment of endogenous EPCs to the ischemic area, while implantation of exogenous EPCs carries the risk of tumorigenicity. In this study, we developed a therapeutic protocol that relies on the capacity of neutrophils (NEs) to target lesions and release preloaded EPC-binding molecules for high efficiency capture. Neutrophils were loaded with superparamagnetic iron oxide nanoparticles conjugated to an antibody against the EPC surface marker CD34 (SPIO-antiCD34/NEs), and the therapeutic efficacy in ischemic mouse heart following SPIO-antiCD34/NEs injection was monitored by SPIO-enhanced magnetic resonance imaging (MRI). These SPIO-antiCD34/NEs exhibited unimpaired cell viability, superoxide generation, and chemotaxis in vitro as well as satisfactory biocompatibility in vivo. In a mouse model of acute myocardial infarction (MI), SPIO-antiCD34 accumulation could be observed 0.5 h after intravenous injection of SPIO-antiCD34/NEs. Moreover, the degree of CD133+ EPC accumulation at MI sites was three-fold higher than in control MI model mice, while ensuing microvessel density was roughly two-fold higher than controls and left ventricular ejection fraction was > 50%. Therapeutic cell biodistribution, MI site targeting, and treatment effects were confirmed by SPIO-enhanced MRI. This study offers a new strategy to improve the endogenous EPC-based myocardial ischemic injury repair through NEs mediated SPIO nanoparticle conjugated CD34 antibody delivery and imaging. Statement of SignificanceThe efficacy of endogenous endothelial progenitor cell (EPC)-based cardiovascular repair therapy for ischemic heart damage is limited by relatively low EPC accumulation at the target site. We have developed a method to improve EPC capture by exploiting the strong targeting ability of neutrophils (NEs) to ischemic inflammatory foci and the capacity of these treated cells to release of preloaded cargo with EPC-binding affinity. Briefly, NEs were loaded with superparamagnetic iron oxide nanoparticles conjugated to an antibody against the EPC surface protein CD34 (SPIO-antiCD34). Thus, we explored sites targeting with nanocomposites cargo for non-invasive EPCs interception and therapy tracking. We demonstrate that SPIO-antiCD34 released from NEs can effectively capture endogenous EPCs and thereby promote heart revascularization and functional recovery in mice. Moreover, the entire process can be monitored by SPIO-enhanced magnetic resonance imaging including therapeutic cell biodistribution, myocardial infarction site targeting, and tissue repair.

Correlation of Standard ECG with 2D-Echo and Serum Troponin I in Locating the Site of Myocardial Infarction and its ExtentAn Observational Study

Introduction: Cardiovascular diseases are the leading causes of death in developed countries, and its incidence is on the rise in developing countries. Electrocardiogram (ECG), 2 Dimensional Echocardiography (2D-Echo) and myocardial injury biomarkers help in the diagnosis, prognostification of Myocardial Infarction (MI). Aim: To correlate the findings of ECG, 2D-Echo and Troponin I levels in locating the site and extent of MI. Materials and Methods: This observational study was conducted in the cardiology Intensive Care Unit (ICU)/ward, PES Hospital, Kuppam, Andhra Pradesh, India, from January 2019 to June 2020. A total of 95 patients of acute MI were studied at baseline, and repeat 12 lead ECG, 2D-Echo and serum troponin I levels were recorded. Ejection Fraction (EF) was estimated from the QRS score by means of a formula, and Echocardiographic correlation was obtained on the same day with ECG-QRS scoring by direct estimation of EF in ‘Q’ wave infarction. High sensitivity cardiac Troponin – I was measured at the time of hospitalisation and repeated at six hours if required, and its levels were correlated to the extent of MI i.e., Left Ventricular Ejection Fraction (LVEF). The categorical data were analysed using Chi-square test and p&lt;0.05 was considered as statistically significant. Regression analysis was done for associated factors. Results: There was better correlation between EF calculated from ECG-QRS scoring system and 2D-Echo (r value-0.78, p-value &lt;0.001). There was poor correlation between serum Troponin I levels at admission, and extent of MI i.e., LVEF as estimated by ECG and 2D-Echo (r=-237.13, p=0.334 and r=-120.78, p=0.585). There was a significant correlation between serum Troponin I levels at 72 hours of chest pain or peak values and extent of MI i.e., LVEF as estimated by ECG and 2D-Echo (r=-1446.14, p&lt;0.001 and r=-1354.42, p&lt;0.001). Conclusion: The location of MI, seen on ECG, correlated broadly with those seen on 2D-Echo. 2D-Echo was able to elaborate regional wall motion abnormalities in detail when compared to the ECG. LVEF can be calculated from ECG at bedside in Q wave infarction, which correlated fairly with 2D-Echo findings.

Cardiomyocyte Induction and Regeneration for Myocardial Infarction Treatment: Cell Sources and Administration Strategies.

Occlusion of coronary artery and subsequent damage or death of myocardium can lead to myocardial infarction (MI) and even heart failure-one of the leading causes of deaths world wide. Notably, myocardium has extremely limited regeneration potential due to the loss or death of cardiomyocytes (i.e., the cells of which the myocardium is comprised) upon MI. A variety of stem cells and stem cell-derived cardiovascular cells, in situ cardiac fibroblasts and endogenous proliferative epicardium, have been exploited to provide renewable cellular sources to treat injured myocardium. Also, different strategies, including direct injection of cell suspensions, bioactive molecules, or cell-incorporated biomaterials, and implantation of artificial cardiac scaffolds (e.g., cell sheets and cardiac patches), have been developed to deliver renewable cells and/or bioactive molecules to the MI site for the myocardium regeneration. This article briefly surveys cell sources and delivery strategies, along with biomaterials and their processing techniques, developed for MI treatment. Key issues and challenges, as well as recommendations for future research, are also discussed.

Electroconductive Graphene-Containing Polymeric Patch: A Promising Platform for Future Cardiac Repair.

Myocardial infarction (MI) is one of the leading causes of death worldwide. The complications associated with MI can lead to the formation of nonconductive fibrous scar tissues. Despite the great improvement in electroconductive biomaterials to increase the physiological function of bio-engineered cardiac tissues in vivo, there are still several challenges in creating a suitable scaffold with appropriate mechanical and electrical properties. In the current study, a highly hydrophilic fibrous scaffold composed of polycaprolactone/chitosan/polypyrrole (PCP) and combined with functionalized graphene, to provide superior conductivity and a stronger mechanical cardiopatch, is presented. The PCP/graphene (PCPG) patches were optimized to show mechanical and conductive properties close to the native myocardium. Also, the engineered patches showed strong capability as a drug delivery system. Heparin, an anticoagulant drug, was loaded within the fibrous patches, and the adsorption of the bovine serum albumin (BSA) protein was evaluated. The optimized cardiopatch shows great potential to be used to provide mechanical support and restore electromechanical coupling at the site of MI to maintain a normal cardiac function.

Chemical Engineering of Cell Therapy for Heart Diseases.

Cardiovascular disease (CVD) is a major health problem worldwide. Since adult cardiomyocytes irreversibly withdraw from the cell cycle soon after birth, it is hard for cardiac cells to proliferate and regenerate after myocardial injury, such as that caused myocardial infarction (MI). Live cell-based therapies, which we term as first generation of therapeutic strategies, have been widely used for the treatment of many diseases, including CVD. However, cellular approaches have the problems of poor retention of the transplanted cells and the significant entrapment of the cells in the lungs when delivered intravenously. Another big problem is the low storage/shipping stability of live cells, which limits the manufacturability of living cell products. The field of chemical engineering focuses on designing large-scale processes to convert chemicals, raw materials, living cells, microorganisms, and energy into useful forms and products. By definition, chemical engineers conceive and design processes to produce, transform, and transport materials. This matches the direction that cell therapies are heading toward: "produce", from live cells to synthetic artificial cells; "transform", from bare cells to cell/matrix/factor combinations; and "transport". from simple systemic injections to targeted delivery. Thus, we hereby introduce the "chemical engineering of cell therapies" as a concept. In this Account, we summarize our recent efforts to develop chemical engineering approaches to repair injured hearts. To address the limitations of poor cellular retention and integration, the first step was the artificial manipulation of stem cells before injections (we term this the second generation of therapeutic strategies). For example, we took advantage of the natural infarct-targeting ability of platelet membranes by fusing them onto the surface of cardiac stromal/stem cells (CSCs). By doing so, we improved the rate at which they were delivered through the vasculature to sites of MI. In addition to modifying natural CSCs, we described a bioengineering approach that involved the encapsulation of CSCs in a polymeric microneedle patch for myocardium regeneration. The painless microneedle patches were used as an in situ delivery device, which directly transported the loaded CSCs to the MI heart. In addition to low cell retention, there are some other barriers that need to be addressed before further clinical application is viable, including the storage/shipping stability of and the evident safety concerns about live cells. Therefore, we developed the third generation of therapeutic strategies, which utilize cell-free approaches for cardiac cell therapies. Numerous studies have indicated that paracrine mechanisms reasonably explain stem cell based heart repair. By imitating or adapting natural stem cells, as well as their secretions, and using them in conjunction with biocompatible materials, we can simulate the function of natural stem cells while avoiding the complications association with the first and second generation therapeutic options. Additionally, we can develop approaches to capture endogenous stem cells and directly transport them to the infarct site. Using these third generation therapeutic strategies, we can provide unprecedented opportunities for cardiac cell therapies. We hope that our designs will promote the use of chemical engineering approaches to transform, transport, and fabricate cell-free systems as novel cardiac cell therapeutic agents for clinical applications.

Engineering a naturally-derived adhesive and conductive cardiopatch

Myocardial infarction (MI) leads to a multi-phase reparative process at the site of damaged heart that ultimately results in the formation of non-conductive fibrous scar tissue. Despite the widespread use of electroconductive biomaterials to increase the physiological relevance of bioengineered cardiac tissues in vitro, there are still several limitations associated with engineering biocompatible scaffolds with appropriate mechanical properties and electroconductivity for cardiac tissue regeneration. Here, we introduce highly adhesive fibrous scaffolds engineered by electrospinning of gelatin methacryloyl (GelMA) followed by the conjugation of a choline-based bio-ionic liquid (Bio-IL) to develop conductive and adhesive cardiopatches. These GelMA/Bio-IL adhesive patches were optimized to exhibit mechanical and conductive properties similar to the native myocardium. Furthermore, the engineered patches strongly adhered to murine myocardium due to the formation of ionic bonding between the Bio-IL and native tissue, eliminating the need for suturing. Co-cultures of primary cardiomyocytes and cardiac fibroblasts grown on GelMA/Bio-IL patches exhibited comparatively better contractile profiles compared to pristine GelMA controls, as demonstrated by over-expression of the gap junction protein connexin 43. These cardiopatches could be used to provide mechanical support and restore electromechanical coupling at the site of MI to minimize cardiac remodeling and preserve normal cardiac function.

Abstract 204: Temporal Assessment of Human iPSC-Derived Cardiomyocytes to Assess the Maturity for Cardiac Repair Applications

Cardiovascular disease is the major cause of heart failure following myocardial infarction (MI), which leads to death in acute condition. In the recent year, stem cell therapy has shown a great potential to repair the damaged heart tissue following an MI. Both adult and embryonic stem cells (ES) have potential to repair and regenerate tissue to compensate cell death during MI. Apart from ethical concern, there are several advantages of using human iPSC cardiomyocytes (hiPSC-CMs) over human ES. Most important, the hiPSC-CMs provides autologous cells source which one side eliminate the possibility of cellular rejection while on the other side enhance the possibility of its survival in damaged cardiac tissue. However, the lack of maturity in hiPSC-CMs is a major challenge to replicate and/or replace the adult cardiomyocytes with mature cardiomyocytes at the site of MI. Temporal assessment of cardiac maturity markers and structural gene in hiPSC-CMs cultured in vitro for up to four weeks and comparison with non-failing human heart (NF). The wk-4 hiPSC-CMs has shown an increase in cardiac transcription factor (2-fold, NKX-2.5); Myosin genes (2-3 fold, MYH7, MYHL2); cardiac troponin-T (3-4 fold, TNNI3 and TNNT3); K + channel genes (20-fold, KCNJ2); Ca 2+ related genes (10-fold, CASQ2); Gap-junction genes (2-fold, GJA1) and Na + Channel gene (5-fold, SCN5A). Further, TEM showed that the myofibrils in the wk-4 cardiomyocytes were more compact, aligned and organized. The Z and I-band and specifically M-band were also prominent in the wk-4 sarcomeres. Furthermore, the maturity of hiPSC-CMs was compared with the NF human heart. This study showed a time-course assessment of cardiomyocytes morphology, structural and expression of cardiac maturity genes in hiPSC-CMs cultured for up to four weeks in vitro . Based on the study of the cardiac transcription factor, Na-K channel-related gene and TEM analysis, wk-4 cardiomyocytes showed more maturity than week-1 cardiomyocytes. Studies are ongoing to compare the contractility and action potential of hiPSC-CMs. Finally, the mature hiPSC-CMs will provide autologous cell source and have a significant impact on the functional outcome of patients with acute MI.