Abstract 14321: Administration of Laminin511 Combined With Prostacyclin Agonist Enhances Endogenous Stem Cell Recruitment in Acute Myocardial Infarction Model Rat

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nagako Sougawa ◽  
Shigeru Miyagawa ◽  
Akima Harada ◽  
Noriko Oda-Mochizuki ◽  
Ryoko Sato-Nishiuchi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cell ◽  
Infarct Size ◽  
The Other ◽  
Combination Group ◽  
Control Group ◽  
Therapeutic Effects ◽  
Cell Recruitment ◽  
Endogenous Stem Cell

Backgroud: Although treatment by endogenous stem cell recruitment is one of the promising therapeutic options for the damaged tissues, the therapeutic efficacy is not enough to repair the severely damaged heart. How to enhance migration of stem cells to injured site and confine them there may be key point to improve the therapeutic effects. In this study, we hypothesized that combined strategy of prostacyclin agonist (ONO1301), which is enhancer in stem cell recruitment, and laminin (LM) 511 as stem cell bed may enhance regeneration processes in failed heart. Methods and Results: To examine the therapeutic effect of ONO1301 and LM511, we administrated ONO1301 and LM511 immersed collagen sheet (Combination group), only LM511 immersed collagen sheet (LM group), only ONO1301 immersed collagen sheet (ONO group), and PBS immersed collagen sheet (control) to rat acute infarction model. Four weeks later, qPCR analysis and histological analysis revealed that the expression of cytokines related to cell migration or angiogenesis were significantly higher in the combination group as compared to the other groups. The number of mesenchymal stem cell (PDGFRα and CD90 double positive cells) tended to be higher in the combination group compared to the other groups (combination: 388 ± 7 cells/mm 2 , LM: 292 ± 34 cells/mm 2 , ONO: 216 ± 30 cells/mm 2 , control: 160 ± 34 cells/mm 2 ). In addition, the number of matured arterioles which have both endothelial cells and smooth muscle cells was markedly higher in the combination group compared to the control group (combination: 616 ± 44 cells/mm 2 , control: 226 ± 60cells/mm 2 ; p < 0.05). In addition, infarct size was remarkably reduced in the combination group than the other groups (combination: 11.5 ± 0.1%, LM: 14.8 ± 0.8%, ONO: 23.6 ± 2.9%, control: 29.2 ± 2.0%). Ultrasonographically, ejection fraction significantly improved in the combination group compared to the other groups (combination: 55.0 ± 0.9%, LM: 51.6 ± 1.4%, ONO: 46.9 ± 1.4%, control: 43.5 ± 2.9%). Conclusion: The combined administration of LM511 and ONO1301 promotes arteriogenesis by enhanced endogenous repair with declined infarct size and improved cardiac function in rat acute myocardial infarction model, proposing new therapeutic strategy for ischemic cardiomyopathy.

Glycosylation Engineering Combined with CD26 Inhibitor Enhances Umbilical Blood Cells Engraftment In the NOD/SCID Mouse

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4687-4687
Author(s):  
Zimin Sun ◽  
Chengyang Zhou ◽  
Xingbing Wang ◽  
Jian Wang ◽  
Huilan Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
The Other ◽  
Combination Group ◽  
Control Group ◽  
Overall Survival Rate ◽  
Hematopoietic Stem ◽  
Glycosylation Engineering

Abstract Abstract 4687 Given the tremendous need for and potential of umbilical cord blood (UCB) to be utilized as a donor source for hematopoietic stem cell (HSC) transplantation in adults, there is a strong push to overcome the constraints created by the limited volumes and subsequent limited HSC and hematopoietic progenitor cell (HPC) numbers available for HSC transplantation from a single collection. Hematopoietic stem cell homing is believed to be critical for the development of methodologies to improve transplant efficiency and subsequently immune reconstitution during hematopoietic stem cell transplantation in clinical setting. We have previously described the functional defect of partial homing receptor in cord blood stem cell (the higher activity of CD26 and the lower expression of P/E-selectin ligand) in vitro. Respectively, we had confirmed that using of glycosylation engineering and CD26 inhibitor can fix the defect of stem cell homing. However, there is no evidence can prove whether the combination would improve the ability of homing. In present study, to explore the use of glycosylation combined with CD26 inhibitor as a method of improving the transplant efficiency of CB CD34+ hematopoietic stem cells (expressing CD45), we utilized the xenotransplanted nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model in vivo. 6–8 weeks age of NOD/SCID mice were divided into 5 groups (8 mice per group): blank control group (without stem cells infusion); control group (CD34+ cells infusion alone); glycosylation engineering group; CD26 inhibitor group and combination group (glycosylation engineering combined CD26 inhibitor group). Purified CD34+ stem cells (5×105 per mice) derived from fresh UCB by immunomagnetic beads were injected into lethally irradiated NOD/SCID mice intravenously. To investigate the effect of early engraftment in vivo, we monitored the expression of CD45 in peripheral blood and the overall viability rate weekly until the fourth week by flow cytometry. One week after transplantation, there is no expression of CD45 in peripheral blood in any group, but we observed 2.52±1.41% and 4.8% expression in bone marrow of recipient mice respectively in control and glycosylation engineering groups. All mice in the blank control group were dead and overall viability rate were almost the same for the other four groups (80% in control group,80% in glycosylation engineering group, 100% in CD26 inhibitor group and 100% in combination group). The second week, there is only expression of CD45 in recipient mice for combination group 0.63±0.37%. The overall survival rate among control were significantly lower than the other four groups (40% in control group,80% in glycosylation engineering group, 100% in CD26 inhibitor group and 100% in combination group, P<0.05). In the third week, all groups except the blank control group expressed CD45 in peripheral blood, we observed 0.81±0.12%, 2.81±0.14%, 3.12±0.53% and 7.05±0.87% in peripheral blood of recipient mice for control, glycosylation engineering, CD26 inhibitor treated and combination group. The overall survival rate among CD26 inhibitor treated and combination groups were significantly higher than the other three groups. (40% in control group,40% in glycosylation engineering group, 80% in CD26 inhibitor group and 80% in combination group, P<0.05). In the fourth week, we observed 15.87±0.21%, 30.51±0.62%, 34.33±0.82% and 40.22±1.62% in peripheral blood of recipient mice for control, glycosylation engineering, CD26 inhibitor treated and combination group. The overall survival rate among CD26 inhibitor treated and combination groups were significantly higher than the other three groups. (40% in control group,40% in glycosylation engineering group, 80% in CD26 inhibitor group and 80% in combination group, P<0.05). These results provide the evidence that the combination of two methods have better effect on early implantation than use them respectively. Our results also supported the potential use of CD26 inhibitor combined with glycosylation engineering to treat the umbilical blood which the number of stem cell is less than bone marrow and peripheral blood during hematopoietic stem cell transplantation as a method to improve the transplant efficiency. Furthermore, we aimed to investigate the long-term implantation effect of combination of glycosylation engineering and inhibition of CD26 in vivo. Disclosures: Sun: International Cooperation Research Fund of Anhui Provincial Scientific and Technologic Committee (08080703026): Research Funding; Fund of the Key Medical Project of Anhui Provincial healthy department (2010A005): Research Funding; Anhui Provincial “115” Industrial Innovation Program: Research Funding.

scholarly journals C-Reactive Protein Apheresis as Anti-inflammatory Therapy in Acute Myocardial Infarction: Results of the CAMI-1 Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Wolfgang Ries ◽  
Jan Torzewski ◽  
Franz Heigl ◽  
Christian Pfluecke ◽  
Sebastian Kelle ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Clinical Trial ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Control Group ◽  
Lv Function ◽  
Myocardial Infarct Size ◽  
C Reactive Protein ◽  
Reactive Protein

Background: C-reactive protein (CRP) is a well-known marker of inflammation. It is less known that CRP mediates tissue damage in acute myocardial infarction (AMI) thus potentially worsening prognosis. A newly developed specific CRP adsorber allows efficient lowering of CRP levels and may improve survival.Objectives: Aim of this multi-center, controlled, non-randomized first-in-man CRP apheresis in Acute Myocardial Infarction study (CAMI-1) was to investigate the relationship between CRP levels (CRP gradient), myocardial infarct size and function as well as safety and efficacy of CRP apheresis in the setting of acute ST-segment Elevation Myocardial Infarction (STEMI) in humans.Methods: Eighty-three patients (45 apheresis, 38 controls) were recruited. CRP apheresis was performed 24 ± 12, 48 ± 12, and optionally 72 ± 12 h after onset of symptoms. First aphereses were performed at a median CRP concentration of 23.0 mg/L (range 9–279). In each apheresis session, 5,900 ± 400 mL plasma was processed via peripheral venous access. Primary study endpoint was a reduction in myocardial infarct size after STEMI as determined by cardiovascular magnetic resonance (CMR).Results: In controls, the CRP concentration significantly correlated with infarct size (p = 0.002) and decreased myocardial function (p ≤ 0.001). The CRP concentration in apheresis patients did not correlate with infarct size (p = 0.66) or left ventricular (LV) function (p = 0.79) and global strains and therefore significantly differed from controls (p = 0.03 and p = 0.002). Three major adverse cardiac events occurred in the control group after 12 months, none occurred in the apheresis group. Mean CRP depletion achieved over all apheresis procedures was 53.0 ± 15.1%. Apheresis sessions were well-tolerated. Reduced infarct size in the apheresis group compared to the control group (primary endpoint) was not achieved according to the original statistical analysis plan. Taking into account the individual CRP levels, however, revealed significant results. Modifications of the analysis plan were introduced in order to recruit a sufficient number of patients.Conclusions: This pilot study in humans reveals a correlation between CRP concentration and myocardial infarct size. CRP concentrations in STEMI can effectively be reduced by CRP apheresis without relevant side effects. CRP apheresis has the potential to interfere with deleterious aspects of STEMI. By lowering CRP levels, it resulted in the loss of correlation of CRP concentrations with myocardial infarct sizes as well as LV function. These results encourage a larger, randomized clinical trial.Clinical Trial Registration:https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&amp;TRIAL_ID=DRKS00008988, DRKS00008988.

scholarly journals A study to find out the effect of remote ischemic post conditioning of lower limb in patients of acute myocardial infarction undergoing primary percutaneous coronary intervention

2017 ◽  
Vol 4 (5) ◽  
pp. 1313
Author(s):  
Sreedhara R. ◽  
Vishwa Deepak Tripathi
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Infarct Size ◽  
Lower Limb ◽  
Coronary Intervention ◽  
Reperfusion Therapy ◽  
Control Group ◽  
St Segment ◽  
Percutaneous Coronary ◽  
Infarct Size Reduction

Background: Reperfusion therapy of affected myocardium is among the most successful method for infarct size reduction and achieving the better outcome in patients with ST-segment elevation myocardial infarction (STEMI). Primary percutaneous coronary intervention (pPCI) is among best procedures for successful reperfusion therapy which has effect in reduction of size of infarct, maintaining ventricular function for better outcome. In this study, authors were aimed to assess whether remote ischemic post-conditioning (RIPC) of lower limb could reduce enzymatic infarct size in patients with acute STEMI undergoing pPCI.Methods: A case control, cross sectional, hospital based randomized study was carried out in Institute of Cardiovascular Sciences, IPGMER, Kolkata, from February 2014 to October 2015. Total 40 patients (20 cases and 20 controls) who were undergoing primary PCI for acute myocardial infarction were taken for study. In the active treatment group, the protocol was started with thrombectomy. The lower limb was exposed to 3 cycles of ischemia/reperfusion, each obtained by 5 min cuff inflation at 200mmHg, followed by 5 min complete deflation. End point of the study will be enzymatic infarct size assessed by the area under the curve of creatine kinase-myocardial band (CK-MB) release.Results: The AUC of serum CK release during the first 72 hours of reperfusion was significantly reduced (p=0.0341) in the post-conditioned group compared with the control group, averaging 9632 units in postconditioned compared with 13493 units in control group which represented 26% of reduction of infarct size.Conclusions: Remote ischemic post conditioning of lower limb significantly improves blush grading and enzymatic infarct size reduction with a trend towards significant reduction of mean ST segment deviation.

Preinfarction Angina and Improved Reperfusion of the Infarct-related Artery

1999 ◽  
Vol 82 (S 01) ◽  
pp. 68-72 ◽  
Author(s):  
Alessandro Sciahbasi ◽  
Eugenia De Marco ◽  
Attilio Maseri ◽  
Felicita Andreotti
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Early Reperfusion ◽  
Vast Number ◽  
Beneficial Effects ◽  
Infarct Related Artery ◽  
Cardioprotective Effects ◽  
Collateral Vessels

SummaryPreinfarction angina and early reperfusion of the infarct-related artery are major determinants of reduced infarct-size in patients with acute myocardial infarction. The beneficial effects of preinfarction angina on infarct size have been attributed to the development of collateral vessels and/or to post-ischemic myocardial protection. However, recently, a relation has been found between prodromal angina, faster coronary recanalization, and smaller infarcts in patients treated with rt-PA: those with preinfarction angina showed earlier reperfusion (p = 0.006) and a 50% reduction of CKMB-estimated infarct-size (p = 0.009) compared to patients without preinfarction angina. This intriguing observation is consistent with a subsequent observation of higher coronary recanalization rates following thrombolysis in patients with prodromal preinfarction angina compared to patients without antecedent angina. Recent findings in dogs show an enhanced spontaneous lysis of plateletrich coronary thrombi with ischemic preconditioning, which is prevented by adenosine blockade, suggesting an antithrom-botic effect of ischemic metabolites. Understanding the mechanisms responsible for earlier and enhanced coronary recanalization in patients with preinfarction angina may open the way to new reperfusion strategies.A vast number of studies, globally involving ≈17,000 patients with acute myocardial infarction, have unequivocally shown that an infarction preceded by angina evolves into a smaller area of necrosis compared to an infarct not preceded by angina (Table 1) (1). So far, preinfarction angina has been thought to have cardioprotective effects mainly through two mechanisms: collateral perfusion of the infarctzone (2-4), and ischemic preconditioning of the myocardium (5-7). Here we discuss a further mechanism of protection represented by improved reperfusion of the infarct-related artery.

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