Abstract 5731: An Increase of Intrinsic Endothelial Progenitor Cells after Acute Myocardial Infarction was Associated with Spontaneous Neovascularization but not with Improvement of Left Ventricula Remodeling

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Motoo Date ◽  
Hiroshi Ito ◽  
Katsuomi Iwakura ◽  
Atsunori Okamura ◽  
Yasushi Koyama ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Left Ventricular ◽  
Volume Index ◽  
Left Ventricular Ejection ◽  
Infarct Zone ◽  
Endothelial Progenitor ◽  
Ventricular Ejection Fraction

Endothelial progenitor cells (EPC) increase after acute myocardial infarction and may contribute to neovascularization in the infarct zone. The aim of this study was to elucidate the relation of EPC release to recovery of microvascualr and myocardial function. Eighteen patients with acute myocardial infarction (AMI) undergoing primary PCI within 12 hours after onset were enrolled. CD34 + cells were counted at days-1, 7 and 14 as an index of EPC. We performed triggered end-systolic myocardial contrast echocardiography (MCE) at every 6 cardiac cycles with continuous infusion of Levovist at days-2 and 14. We performed left ventriculography 6 months later to calculate left ventricular ejection fraction (LVEF) and end-diastolic volume index (LVEDVI). The number of EPC at day-7 was significantly higher than that at day-1 (1.29+/−0.75 vs. 2.10+/−1.25/micL, p<0.001). It was correlated with myocardial blood volume (MBV), that implies microvascular integrity, at day-14 measured from MCE image (r 2 =0.652, p<0.005) and with an increase in MBV from day-1 to day-7 (r 2 =0.533, p<0.005). To evaluate the correlation between EPC and LV function, we divided patients into two groups according to the number of EPC at day-7. LVEF and LVEDVI were comparable between the higher number of EPC and the lower number of EPC groups (49.3+/−12.2 vs. 52.4+/−8.1%, 65.2+/−13.1 vs. 69.1+/−16.6ml/m 2 ). EPC spontaneously released after AMI and number of released EPC is correlated to the amount of neovascularization in the infarct zone. The number of EPC was not necessarily related to the functional improvement or attenuation of LV remodeling.

scholarly journals Transplantation of Endothelial Progenitor Cells in the Treatment of Coronary Artery Microembolism in Rats

2020 ◽  
Vol 29 ◽  
pp. 096368972091268
Author(s):  
Yajun Xue ◽  
Boda Zhou ◽  
Jian Wu ◽  
Guobin Miao ◽  
Kun Li ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cardiac Function ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Low Dose ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
High Dose ◽  
Endothelial Progenitor ◽  
Ventricular Ejection Fraction

As the impairment of myocardial microenvironments due to coronary microembolization (CME) compromises the treatment effect of percutaneous coronary intervention and leads to adverse prognosis, we hypothesized that endothelial progenitor cells (EPCs) transplantation could improve cardiac function in the condition of CME. Low- (2 × 105) and high- (2 × 106) dose rat bone marrow-derived EPCs were transplanted in a model of CME. To develop a CME model, rats were injected with autologous micro-blood-clots into the left ventricle. Echocardiograph was examined before and 1, 7, and 28 days after EPC transplantation; serum cardiac troponin I (cTNI), von Willebrand factor (vWF), and cardiac microRNA expression were examined one day after EPCs transplantation. Heart morphology and vascular endothelial growth factor (VEGF), vWF, and basic fibroblast growth factor (bFGF) expression were examined one day after EPC transplantation. After 10 days of culture inductions, BM-EPCs have high purity as confirmed by flow cytometry. Cardiac function reflected by left ventricular ejection fraction significantly decreased after CME treatment and rescued by low-dose EPC. Compared to the sham group, cTNI and vWF serum levels increased significantly after CME treatment and rescued by low-dose EPC and high-dose EPC. Low-dose EPC treatment decreased myocardial necrosis and fibrosis and elevated cardiac expression of VEGF and vWF, while decreasing the cardiac expression of bFGF. Low-dose EPC treatment significantly suppressed cardiac expression of microRNA-19a but significantly enhanced microRNA-21, microRNA-214, and microRNA-486-3p expression. In conclusion, our results indicate that low-dose EPC transplantation may play a proangiogenic, antifibroblast, antifibrosis, and antinecrosis role and enhance cardiac function in a rat model of CME through a microRNA-related pathway.

scholarly journals Relationship between left ventricular global longitudinal strain, infarct size and left ventricular function in patients with acute myocardial infarction in a stem cell therapy study

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
L Drabik ◽  
A Mazurek ◽  
L Czyz ◽  
M Skubera ◽  
E Kwiecien ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Emission Computed Tomography ◽  
Two Dimensional ◽  
Infarct Zone ◽  
Ventricular Ejection Fraction

Abstract Introduction It is critically important to determine the accuracy, and relationships between, non-invasive imaging modalities, such as two-dimensional echocardiography (TTE), gated single-photon emission computed tomography (SPECT) and cardiac magnetic resonance imaging (cMRI) in patients with recent acute myocardial infarction (AMI) because these are used as clinical trial endpoints. Modest improvements in the left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV) and infarct zone size (IS) have been reported in AMI stem cells therapy trials (SCT). Purpose The aim of the study was to evaluate left-ventricular global longitudinal strain (GLS) in patients with AMI enrolled to SCT and assess its relation with infarct zone, LVEF and LVEDV using multimodality imaging including TTE, cMRI and SPECT. Methods Twenty-eight patients (21 male, 7 female, mean age 60.0±8.7 years) with first AMI, 2–5 days after left anterior descending percutaneous coronary intervention (PCI) and IS ≥10% were enrolled. GLS was evaluated with two-dimensional speckle tracking echocardiography (aCMQ, Philips Epiq 7). Infarct zone was measured using SPECT (E.CAM, Siemens) and gadolinium-enhanced cMRI (Siemens Magnetom Sonata 1.5T). LVEF and LVEDV were assessed with TTE (Auto-ROI, Philips), SPECT (GSQUAN, Siemens) and cMRI (MASS Medis). Measurements were obtained independently by blinded analysts. Results Mean GLS was −11.0±2.5% and showed a positive correlation with infarct zone by SPECT and MRI, negative with TTE-LVEF and cMRI-LVEF (Figure 1) and borderline with SPECT-LVEF (r=−0.35, p=0.08). There was no correlation between GLS and TTE-LVEDV (r=−0.25, p=0.25); SPECT-LVEDV (r=−0.38, p=0.077) and MRI-LVEDV (r=−0.20, p=0.365). Patients in the third and fourth GLS quartile had a smaller IS measured by MRI and a trend toward a smaller infarct zone by SPECT (table 1). Patients in the GLS fourth quartile had higher TTE-LVEF and a trend toward higher cMRI-LVEF compared with other quartiles. LVEF measured with TTE and cMRI was higher compared with SPECT-LVEF (+2.6±6.8%, p=0.006 and +4.2±7.8%, p=0.030, respectively) with no difference between TTE-LVEF and MRI-LVEF (p=0.823) (Table 1). LVEDV evaluated by SPECT and MRI was higher compared with TTE-LVEDV (+48.3±24.9 ml, +47.7±29.5 ml, both p&lt;0.001) with no difference between SPECT-LVEDV and MRI-LVEDV (p=0.984) Conclusions In patients with anterior wall AMI, 2–5 days after PCI, GLS showed a good correlation with infarct zone quantified by SPECT and MRI and with LVEF measured with TTE and cMRI. GLS might thus be a valuable tool in the evaluation of myocardial injury in SCT. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): STRATEGMED 265761 “CIRCULATE” National Centre for Research and Development/Poland/ZDS/00564 Jagiellonian University Medical College Table 1 Figure 1

Randomized, double blind, placebo-controlled, safety and efficacy study of dutogliptin in combination with filgrastim in early recovery post-MI: rationale, design and first interim analysis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Von Lewinski ◽  
B Merkely ◽  
I Buysschaert ◽  
R.A Schatz ◽  
G.G Nagy ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Adverse Events ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Early Recovery ◽  
Ventricular Ejection Fraction ◽  
Combined Application

Abstract Background Regenerative therapies offer new approaches to improve cardiac function after acute ST-elevation myocardial infarction (STEMI). Mobilization of stem cells and homing within the infarcted area have been identified as the key mechanisms for successful treatment. Application of granulocyte-colony stimulating factor (G-CSF) is the least invasive way to mobilize stem cells while DDP4-inhibitor facilitates homing via stromal cell-derived factor 1 alpha (SDF-1α). Dutogliptin, a novel DPP4 inhibitor, combined with stem cell mobilization using G-CSF significantly improved survival and reduced infarct size in a murine model. Purpose We initiated a phase II, multicenter, randomized, placebo-controlled efficacy and safety study (N=140) analyzing the effect of combined application of G-CSF and dutogliptin, a small molecule DPP-IV-inhibitor for subcutaneous use after acute myocardial infarction. Methods The primary objective of the study is to evaluate the safety and tolerability of dutogliptin (14 days) in combination with filgrastim (5 days) in patients with STEMI (EF &lt;45%) following percutaneous coronary intervention (PCI). Preliminary efficacy will be analyzed using cardiac magnetic resonance imaging (cMRI) to detect &gt;3.8% improvement in left ventricular ejection fraction (LV-EF). 140 subjects will be randomized to filgrastim plus dutogliptin or matching placebos. Results Baseline characteristics of the first 26 patients randomized (24 treated) in this trial reveal a majority of male patients (70.8%) and a medium age of 58.4 years (37 to 84). During the 2-week active treatment period, 35 adverse events occurred in 13 patients, with 4 rated as serious (hospitalization due to pneumonia N=3, hospitalization due to acute myocardial infarction N=1), and 1 adverse event was rated as severe (fatal pneumonia), 9 moderate, and 25 as mild. 6 adverse events were considered possibly related to the study medication, including cases of increased hepatic enzymes (N=3), nausea (N=1), subcutaneous node/suffusion (N=1) and syncope (N=1). Conclusions Our data demonstrate that the combined application of dutogliptin and G-CSF appears to be safe on the short term and feasible after acute myocardial infarction and may represent a new therapeutic option in future. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This research is funded by the sponsor RECARDIO, Inc., 1 Market Street San Francisco, CA 94150, USA. RECARDIO Inc. is funding the complete study. The Scientific Board of RECARDIO designed the study. Data Collection is at the participating sites. Interpretation of the data by the Scientific Board and Manuscript written by the authors and approved by the Sponsor

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