Abstract 19337: Transcoronary Delivery of Allogeneic Cardiac Stem Cells Reduces Ventricular Arrhythmia Inducibility in a Post Myocardial Infarction Swine Model

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Gerard Loughlin ◽  
Pablo M Ruiz Hernandez ◽  
Pablo Avila ◽  
Veronica Crisostomo ◽  
Ricardo Sanz ◽  
...  

Introduction: Post myocardial infarction (MI) patients are at risk of scar related ventricular tachycardia (VT). Hypothesis: Stem cell therapy reduces post-MI scar size, potentially leading to a reduction in the risk of ventricular arrhythmias (VA). Methods: A post-MI scar model of VT was created by transient occlusion of the mid left anterior descending artery in 56 swine. Five weeks after infarct creation 29 subjects were treated with allogeneic cardiac stem cells (CSC): 10 underwent transcoronary delivery of CSC, 9 direct transepicardial delivery (via a minithoracotomy) and 10 underwent a combined transcoronary and VT substrate guided (late potentials) direct transendocardial CSC delivery procedure using an electroanatomic mapping system. Of the remainder, 8 subjects underwent a “sham” transepicardial procedure and 19 served as controls. Seventeen weeks after infarct creation an electrophysiological study was performed in each subject to assess for ventricular arrhythmia inducibility. VA inducibility was compared in each group vs. the control group. Results: Of the 19 control subjects, 17 were inducible (89,5 %). As presented in the figure, CSC delivery with a combined transcoronary/transendocardial approach was associated with a significant reduction in VT inducibility rates compared to controls (20 % vs. 89,5 %; p value 0,001). Subjects treated with transcoronary CSC also experienced significantly lower VA inducibility rates (40 % vs. 89,5 %; p value 0,009). There were no differences in VA inducibility compared with controls in patients in the “sham” (62,5 % vs 89,5 %; p value 0,136) or the transepicardial group (66,7 % vs 89,5 %; p value 0,290). Conclusions: Combined transcoronary and VT substrate-guided transendocardial CSC delivery is associated with a significant reduction in VA inducibility in a post-MI swine model. Future human studies should evaluate the effects of allogeneic CSC therapy on ventricular arrhythmia burden in post-MI patients.

2012 ◽  
Vol 16 (11) ◽  
pp. 2549-2563 ◽  
Author(s):  
Zhuzhi Wen ◽  
Zun Mai ◽  
Haifeng Zhang ◽  
Yangxin Chen ◽  
Dengfeng Geng ◽  
...  

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
D Arara ◽  
M Fadil ◽  
Y Karani ◽  
RD Nindrea

Abstract Funding Acknowledgements Type of funding sources: None. Background Primary percutaneous coronary intervention (PPCI) is a treatment of choice in ST elevation myocardial infarction patients (STEMI). However, this approach could affect the kidney function due to iodinated contrast exposure to the patient. Remote ischemic post conditioning (RIPostC) is a non-invasive and simple method that not only has cardioprotective but also renoprotective effect for kidney function. Purpose The aim of this study was to investigate the effect of RIPostC to kidney function in STEMI patients undergoing PPCI. Methods This study uses pre and post-test only with control group design with experimental research designs. Data was taken at an Indonesian Heart Center from June 2019 until March 2020, there were 66 patients with ST-segment elevation myocardial infarction (STEMI) being performed RIPostC procedure with intermittent ischaemia and reperfusion applied to the arm through five cycles of 5-min inflation and 5-min deflation of an automated cuff device after crossing wire. Creatinine and eGFR were measured pre and 48 hours post PPCI. Kidney function were determined by eGFR post PPCI, ΔeGFR (pre and 48 hours post PPCI), creatinine post PPCI and Δcreatinine (pre and 48 hours post PPCI). Bivariate analysis was performed to determine the effect RIPostC to kidney function using the Chi-square test.  Result A total of 66 patients who underwent the PPCI procedure were divided into two groups RIPostC (n = 33) and without RIPostC (n = 33). The baseline characteristic in both of group was similar. We found that there were no differences of eGFR (70,46 ± 23,06 vs 65,88 ± 23,36, p = 0,424), ΔeGFR (0 [-34,68 - 37,32] vs 0 [-121,53 - 29,70], p value= 0,406), creatinine (1,00 [0,70 - 4,60] vs 1,20 [0,60-4,10], p value= 0,633) and Δcreatinine (0 [-1,20-1,10] vs 0 [-0,50-0,90], p value= 0,390) RIPostC group had a lower CI-AKI incident if we compare with the non RIPostC (15,2% vs 42,4%, p < 0,05). Conclusion Remote ischaemic conditioning does not significantly improve kidney function (eGFR, ΔeGFR, creatinine and Δcreatinine) in patients with STEMI undergoing PPCI The differences of kidney functionVariableRIPostCControlp valueeGFR post PPCI (ml/min/1,73 m2), mean70,46 ± 23,0665,88 ± 23,360,424aΔeGFR(ml/min/1,73 m2), median0 [-34,68 - 37,32]0 [-121,53 - 29,70]0,406bCreatinine post PPCI (mg/dL), median1,00 [0,70 - 4,60]1,20 [0,60-4,10]0,633bΔcreatinine (mg/dL), median0 [-1,20-1,10]0 [-0,50-0,90]0,390ba = Independent sample T testb = mann whitney testAbstract Figure. ΔeGFR and Δcreatinine pre and post PPCI


ACS Nano ◽  
2017 ◽  
Vol 11 (10) ◽  
pp. 9738-9749 ◽  
Author(s):  
Junnan Tang ◽  
Xiaolin Cui ◽  
Thomas G. Caranasos ◽  
M. Taylor Hensley ◽  
Adam C. Vandergriff ◽  
...  

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
K Eletriby ◽  
A Desoky ◽  
N Shawky ◽  
A Farag

Abstract Aim and objectives The aim of this study was to assess the impact of high intensity statins used prior to primary PCI in patients presenting with acute STEMI (ST-elevation Myocardial Infarction) on myocardial perfusion and in-hospital MACE (major adverse cardiac events). Patients and Methods The study included 170 patients who presented with acute STEMI to the cardiology department of Ain Shams university hospitals and underwent primary PCI (percutaneous coronary intervention). They were divided into two groups where the first group received high intensity statins (40-80mg of atorvastatin or 20-40mg of rosuvastatin) besides guideline recommended therapy before primary PCI and the 2nd group served as a control group and received guideline recommended therapy, and high intensity statins after going back to the coronary care unit after primary PCI. Post interventional thrombolysis in myocardial infarction (TIMI) flow grade and myocardial blush grade (MBG) were recorded and ST-segment resolution was measured. Results The majority of patients in both groups had the LAD as the culprit vessel for their presentation. In the control group there were 4 patients with TIMI I flow and MBG I, 13 with TIMI II flow and MBG II and 68 with TIMI III flow and MBG III. Meanwhile in the cases group there was 1 patient with TIMI I flow and MBG I, 3 with TIMI II flow and MBG II and 81 with TIMI III flow and MBG III. This difference was statistically significant with a P value of 0.010. There were 34 patients in the cases group who showed complete ST-segment resolution (40%) vs 19 patients (22.4%) in the control group which was statistically significant with a P value of 0.013. In addition, ejection fraction measured by M-mode had values of Mean+-SD of 45.91 ± 5.49 in cases group vs 43.01 ± 8.80 in control group which was statistically significant with a P value of 0.011. There was not a statistically significant difference between the two groups regarding in-hospital death of all causes and stroke after primary PCI. Conclusion High intensity statin loading before primary PCI resulted in improved post-procedural TIMI flow, MBG, complete ST-segment resolution and ejection fraction as measured by M-mode but did not decrease incidence of in-hospital MACE.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Masaaki Ii ◽  
Ayumi Yokoyama ◽  
Miki Horii ◽  
Hiroshi Akimaru ◽  
Takayuki Asahara

Background: Recently, human multipotent adipose-derived stem cells (hMADSs) have been isolated featuring extensive expansion capacity ex vivo. However, little is known about the therapeutic efficacy of hMADS in ischemic heart diseases. We tested the hypothesis that hMADS transplantation may contribute to cardiac functional recovery following myocardial infarction (MI). Methods and Results: Nude rats were either transplanted with hMADSs (5x10 5 /rat, n=10) or PBS (control, n=9) in ischemic myocardium immediately following MI induction. The cardiac function, infarct size and capillary density in the peri-infarct area were evaluated by echocardiography and immunostaining 28 days after surgery. The cardiac function was significantly greater with increased capillary density and reduced fibrosis area in the hMADS group than that in the control group. Next, we examined tissue regeneration in the infarct heart by the transplanted hMADSs. However, remarkable differentiation of hMADSs into any cardiac cell lineages was not detected. To explore another mechanism for the favorable effect of hMADSs, we further examined mRNA expression of cytokines in hMADSs under hypoxic conditions. Although hypoxia decreased the expressions, robust VEGF, bFGF, and SDF-1α expressions were detected in hMADSs. Notably, the stem/progenitor chemokine SDF-1α expression in hMADSs was significantly greater than that in human mesenchymal stem cells that are well known to have a therapeutic effect on ischemic heart diseases. We then focused on SDF-1α /CXCR4 axis and examined the contribution of bone marrow (BM)-derived endothelial progenitor cells (EPCs), that have CXCR4 receptor for SDF-1v, to ischemic myocardium using a Tie2/LacZ BM transplantation nude mouse model. β-gal positive EPCs are frequently observed in ischemic myocardium in the hMADS group compared to the control group. Conclusion: hMADSs exhibit a therapeutic effect on cardiac function following MI with the production of VEGF, bFGF, and SDF-1α demonstrating paracrine effects rather than direct contribution to cardiac regeneration. These findings suggest that transplanted hMADSs and recruited EPCs may synergistically promote angiogenesis playing a role in ischemic myocardium.


2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Wangde Dai ◽  
Mary Kearns-Jonker ◽  
Paul Gerczuk ◽  
Mirja Gunthart ◽  
Nandini Girish ◽  
...  

We determined whether co-transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and mesenchymal stem cells (MSCs) had additive effects on left ventricular (LV) function and remodeling compared with hESC-CMs treatment alone in a rat myocardial infarction model. One week after myocardial infarction induced by left coronary ligation, nude rats received hESC-CMs (n=15), hESC-CMs + MSCs (n=16), hESC-CMs + MSCs transduced to over-express hemeoxygenase 1(HO-1) (n=14), or saline (n=19). At 4 weeks after treatment, LV function was assessed by left ventriculography, echocardiography and Millar catheter. Some hearts were processed for histology. The LV ejection fraction (LVEF) in sham noninfarcted hearts was 78.1±1.8% (n=5) in the nude rat model. LVEF in the 3 cell treated groups (hESC-CMs: 67.6±1.4%; hESC-CMs + MSCs: 67.2±1.6%; and hESC-CMs + MSCs with HO-1: 66.3±1.7%) were comparable, and significantly higher than in the saline group (60.6±1.2%, n=19; p=0.0022). There was a trend for less left ventricular akinesis and dyskinesis (expressed as % of LV circumference) assessed by left ventriculography at 8.96±1.9% in hESC-CMs group, 8.37±1.67% in hESC-CMs + MSCs group and 4.57±1% in hESC-CMs + MSCs with HO-1 group compared to 10.73±1.76% in the control group (p=0.056). There was a nonsignificant trend for LV fractional shortening assessed by echocardiography to be greater in the 3 cell groups (32.1±3.9% in hESC-CMs; 30.2±2% in hESC-CMs + MSCs; 31.0±1.9% in hESC-CMs + MSCs with HO-1) compared to 24.8±2.2% in the saline group (p=0.18). Expansion index reflecting thinning and dilatation of the infarct was significantly worse in the control group at 0.71±0.05 versus the other 3 groups at 0.32±0.05 (p=0.0039). Thus, cell therapy by hESC-CMs alone or combination transplantation of hESC-CMs and MSCs (with or without HO-1) significantly improved LV function assessed by left ventriculography and reduced expansion index. However, co-transplantation of hESC-CMs and MSCs did not provide better functional improvement compared with hESC-CMs treatment alone after left coronary artery occlusion in nude rats over a period of 4 weeks, suggesting that there may be a ceiling effect above which LV function can not further improve after cell therapy.


2020 ◽  
pp. 229255032096740
Author(s):  
Qin Yonghong ◽  
Li Aishu ◽  
Yazan Al-Ajam ◽  
Liao Yuting ◽  
Zhang Xuanfeng ◽  
...  

Current wound healing models generally employ full-thickness or irregular split wounds. Consequently, assessing the type of healing at varying wound depths and determining the deepest level at which wounds can regenerate has been a challenge. We describe a wound model that allows assessment of the healing process over a continuous gradient of wound depth, from epidermal to full-thickness dermal loss. Further, we investigate whether green fluorescent protein–labeled bone marrow mesenchymal stem cells (BM-MSCs/GFP) transplantation could regenerate deeper wounds that might otherwise lead to scar formation. A wound gradient was created on the back of 120 Sprague Dawley rats, which were randomized into the BM-MSCs/GFP and control group. These were further subdivided into 6 groups where terminal biopsies of the healing wounds were taken at days 1, 3, 5, 7, 14, and 21 post-operatively. At each observed time point, the experimental animals were anesthetized and photographed, and depending on the group, the animals euthanized and skin taken for rapid freezing, haemotoxylin and eosin staining, and vascular endothelial growth factor (VEGF) immunohistochemistry. We found the deepest layer to regenerate in the control group was at the level of the infundibulum apex, while in the BM-MSCs/GFP group this was deeper, at the opening site of sebaceous duct at hair follicle in which had the appearance of normal skin and less wound contraction than the control group ( P value less than .05). The expression of VEGF in BM-MSCs/GFP group was higher than that in control group ( P value less than .05). The number of vessels increased from 2.5 ± 0.2/phf of control group to 5.0 ± 0.3/phf of BM-MSCs/GFP ( P value less than .05). The progressively deepening wound model we described can identify the type of wound repair at increasing depths. Further, topical transplantation of BM-MSCs/GFP significantly improved regeneration of deeper wounds from infundibulum apex (maximum depth of control group regeneration) to the opening site of sebaceous duct at hair follicle level.


Sign in / Sign up

Export Citation Format

Share Document