scholarly journals Delta-1 functionalized hydrogel promotes hESC-cardiomyocyte graft proliferation and maintains heart function post-injury

2019 ◽  
Author(s):  
Kaytlyn A Gerbin ◽  
Katie A Mitzelfelt ◽  
Xuan Guan ◽  
Amy M Martinson ◽  
Charles E Murry
Keyword(s):  
Myocardial Infarction ◽  
Heart Function ◽  
Fold Increase ◽  
Post Injury ◽  
Graft Size ◽  
Cell Dose ◽  
Current Cell ◽  
Functional Benefit ◽  
3D Presentation

ABSTRACTCurrent cell transplantation techniques are hindered by small graft size, requiring high cell doses to achieve therapeutic cardiac remuscularization. Enhancing the proliferation of transplanted human stem cell-derived cardiomyocytes (hESC-CMs) could address this, allowing an otherwise subtherapeutic cell dose to prevent disease progression after myocardial infarction. Here, we designed a hydrogel that activates Notch signaling through 3D presentation of the Notch ligand Delta-1 to use as an injectate for transplanting hESC-CMs into the infarcted rat myocardium. After four weeks, hESC-CM proliferation increased 2-fold and resulted in a 3-fold increase in graft size with the Delta-1 hydrogel compared to controls. To stringently test the effect of Notch-mediated graft expansion on long-term heart function, a normally subtherapeutic dose of hESC-CMs was implanted into the infarcted myocardium and cardiac function was evaluated by echocardiography. Transplantation of the Delta-1 hydrogel + hESC-CMs augmented heart function and was significantly higher at three months compared to controls. Graft size and hESC-CM proliferation were also increased at three months post-implantation. Collectively, these results demonstrate the therapeutic approach of a Delta-1 functionalized hydrogel to reduce the cell dose required to achieve functional benefit after myocardial infarction by enhancing hESC-CM graft size and proliferation.

scholarly journals P1587 Echochardiographic estimation of the impact of long-term treatment with Trimetazidine on myocardial dysfunction in patients with ST elevation myocardial infarction

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
T Svanidze ◽  
T Saralidze ◽  
I Mamatsashvili ◽  
T Bediashvili
Keyword(s):  
Myocardial Infarction ◽  
Heart Function ◽  
Myocardial Dysfunction ◽  
Reperfusion Therapy ◽  
Left Ventricular ◽  
Control Group ◽  
Long Term Treatment ◽  
St Elevation ◽  
The Impact

Abstract Outcome of ST elevation acute myocardial infarction (STEMI) is usually complicatedby congestive heart failure (HF) that impacts quality of life and prognosis. Spectrum of myocardial injury depends on intensity of impaired myocardial perfusion and on existing metabolic state. Metabolic changes occurring during early hours of myocardial infarction include increased secretion of catecholamines and production of circulating free fatty acids (FFAs). As myocardium depends on aerobic metabolism increased FFAs exert toxic effect on myocardium resulting in metabolic mismatch, decreased cardiac function and arrhythmias. Our aim was to diminish signs of HF after STEMI especially in patients (P)who could not undergo reperfusion therapy because of different reasons.We used long-term metabolic therapy (MT) with TrimetazidineMR(TMZ)just from the first day of STEMI during 3 months. Evaluation of heart function was based on ECG, Holter monitoring and echocardiographic (Echo) data received before and after treatment. We observed 50 P with STEMI who could not undergo reperfusion therapy. All were treated with standard therapy according to guideline. 35 of them (I group) additionally were treated with TMZ 80 mg p/o once a day for 3 months. The rest15 patients represented II - control group. P including in these groups were comparable according to echocardiographic data. These Patients did not reveal any life-threatening arrhythmias in the acute stage of MI and any prognostically indifferent arrhythmias in the following period. Echoinvestigation in dynamic (before treatment and after 3 months) showed significant improvement of ejection fraction (EF by 14,2%) and stroke volume (SVby14,8%) in patients with STEMI treated with TMZwhile in control group EF (by 4,5%) and SV (by 6,8%) wereincreasedslightly. After 3 months improvement of diastolic function was also prominent in patients treated with TMZ that was revealed by decreased diastolic volume. In patients treated with MT end diastolic diameter (EDD) diminished by 4,8%, end systolic diameter (ESD) - by 5,7%, end diastolic volume (EDV) - by 9,3% and end systolic volume (ESV) - by 14,9% while in control group EDD was decreased by 1,9%, ESD - by 2,8%, EDV - by 4,7% and ESV - by 4,1%. Diastolic dysfunction was also estimatedaccording to left ventricular filling pressure (LVFP) E/ethat was especially interesting in P with HF with mid-range and preserved EF. Before treatment (LVFP) was increased in 17 P from the first group and in 7 P in control group. In the first group increased LVFP significantly decreased in 12 P and moderately in 5, while in control group LVFPwas only decreased moderately in 4and slightly in 3 P. The received data make it relevant to useTMZmetabolic therapy for effective treatment of HF in patients with STEMI. MT not only improves the course of disease, but diminishes rehabilitation period as well.

Abstract 3603: Extreme Lipoprotein(a) Levels Predict a 3–4 Fold Increase in Risk of Myocardial Infarction in the General Population

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Pia R Kamstrup ◽  
Marianne Benn ◽  
Anne Tybjćrg Hansen ◽  
Børge G Nordestgaard
Keyword(s):  
Myocardial Infarction ◽  
General Population ◽  
Fold Increase ◽  
Threshold Effect ◽  
Lipoprotein A ◽  
Hazard Ratios ◽  
Heart Study ◽  
Increased Risk ◽  
Increase In Risk

Background: Elevated lipoprotein(a) levels associate with increased risk of myocardial infarction in some, but not all studies. Limitations of previous studies include lack of risk estimates for extreme lipoprotein(a) levels, measurements in long-term frozen samples and no correction for regression dilution bias. We tested the hypothesis that extreme lipoprotein(a) levels predict myocardial infarction in the general population, measuring levels shortly after sampling and correcting for regression dilution bias. Methods and Results: We examined 9330 men and women from the Danish general population, The Copenhagen City Heart Study. During 10 years follow-up, 498 participants developed myocardial infarction. In women, multifactorially adjusted hazard ratios for myocardial infarction for elevated lipoprotein(a) levels were 1.1(95% confidence interval 0.6 –1.9) for 5–29 mg/dL, 1.7(1.0 –3.1) for 30 – 84 mg/dL, 2.6(1.2–5.9) for 85–119 mg/dL (>90 th percentile), and 3.6(1.7–7.7) for ≥120 mg/dL (>95 th percentile) versus levels <5 mg/dL (figure , p-values are test for trend of hazard ratios). Equivalent values in men were 1.5(0.9 –2.3), 1.6(1.0 –2.6), 2.6(1.2–5.5), and 3.7(1.7– 8.0). Conclusions: We observed a stepwise increase in risk of myocardial infarction with increasing levels of lipoprotein(a) in both genders, with no evidence of a threshold effect. Extreme lipoprotein(a) levels predict a 3– 4 fold increase in risk of myocardial infarction in the general population. Figure. Risk of myocardial infarction by levels of lipoprotein(a)

scholarly journals Compliance as the major effectiveness determinant in preventive acetylsalicylic acid therapy

2011 ◽  
Vol 10 (2) ◽  
pp. 102-109
Author(s):  
V. V. Rafalskiy ◽  
A. N. Baglikov
Keyword(s):  
Myocardial Infarction ◽  
Acetylsalicylic Acid ◽  
Cardiovascular Events ◽  
Information Technologies ◽  
Treatment Compliance ◽  
Fold Increase ◽  
Acid Therapy ◽  
Therapy Compliance ◽  
Enteric Coated

Acetylsalicylic acid (ASA) treatment of patients with cardiovascular disease (CVD) is one of the most effective methods for CVD event prevention. In a substantial proportion of the patients, however, long-term preventive ASA treatment compliance is low (44-71%). Low compliance is associated with reduced antiplatelet effects of ASA and a 2-3-fold increase in the risk of myocardial infarction (MI), ischemic stroke (IS), and other cardiovascular events. ASA therapy compliance could be improved by achieving better collaboration between doctors and patients, while educating patients and explaining the importance of following the doctors’ advice. In addition, enteric-coated ASA forms could play an important role in improving treatment tolerability and, therefore, increasing compliance. Other potentially effective measures include the use of modern packaging (calendar blisters) and information technologies (telephone communication, MGMM).

Abstract P387: Deceasing Tissue Stiffness Improves The Efficacy Of Extracellular Matrix-based Therapy For Myocardial Infarction

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Xinming Wang ◽  
Samuel Senyo
Keyword(s):  
Myocardial Infarction ◽  
Extracellular Matrix ◽  
Molecular Mechanisms ◽  
Heart Function ◽  
Extracellular Proteins ◽  
Molecular Evidence ◽  
Mouse Heart ◽  
Heart Regeneration ◽  
Tissue Stiffness ◽  
Post Injury

Hypothesis and objective: We hypothesize that lowering heart stiffness improves heart regeneration induced by extracellular matrix (ECM) proteins. In this study we investigated heart post-injury responses in non-regenerative mice hearts with modulated tissue stiffness and ECM hydrogel. The objectives are 1) determining if heart stiffness affects heart regeneration in response to extracellular biomolecules; and 2) identifying specific signaling pathways that regulate fibroblasts and cardiomyocytes mechanosensitivity to extracellular proteins. Methods: P5 mouse heart stiffness was modulated by BAPN and genipin injections. Solubilized porcine fetal ECM was injected immediately after ligating coronary artery. Heart function and histology were conducted on day 3 and week 3 post-myocardial infarction (MI). A mice ventricle explant model was used to investigate the molecular mechanisms. Results: Heart stiffness was lowered from 50kPa to 9kPa by BAPN and increased to 142kPa by genipin. We observed that fetal ECM treatment preserved cardiac output, reduced fibrosis, and promoted cardiomyocyte cell cycle activity. Decreasing tissue stiffness further improved the therapeutic efficacy of fetal ECM on heart post-MI response (Fig.1). Decreasing tissue stiffness lowered fibrosis in non-ECM treated MI control hearts, but did not affect the other aspects. Using a ventricle explant model of various stiffness, molecular evidence demonstrated that agrin-YAP signaling pathway is involved in the mechano-regulation of fetal ECM-induced heart regeneration. Agrin expression was elevated and cardiomyocyte YAP activation was not affected by changing tissue stiffness in control (no-ECM) mechano-modulated explants. However, YAP activation in fetal-ECM treated explants was increased by softening tissue. We also demonstrated that ECM hydrogel inhibits fibroblast to myofibroblast differentiation through CAPG protein.

Influence of platelet function on long-term LV performance in myocardial infarction treated with primary angioplasty

2008 ◽  
Vol 7 ◽  
pp. 126-126
Author(s):  
Z HUCZEK ◽  
K FILIPIAK ◽  
J KOCHMAN ◽  
R PIATKOWSKI ◽  
M ROIK ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Platelet Function ◽  
Primary Angioplasty
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