Delivery of CD151 by Ultrasound Microbubbles in Rabbit Myocardial Infarction

Cardiology ◽  
2016 ◽  
Vol 135 (4) ◽  
pp. 221-227 ◽  
Author(s):  
Shao-Ling Yang ◽  
Ke-Qiang Tang ◽  
Jun-Jia Tao ◽  
Ai-Hong Wan ◽  
Yan-Duan Lin ◽  
...  

Objectives: We aimed to evaluate whether ultrasound (US) and microbubble-mediated delivery of Cluster of Differentiation 151 (CD151) could enhance the therapeutic effects of CD151 on myocardial infarction (MI). Methods: A rabbit model of MI was established by a modified Fujita method. Then, 50 MI rabbits were randomly divided into 5 groups, including G1 (CD151 plasmid and physiological saline in the presence of US); G2 (CD151 and Sonovue in the presence of US); G3 (CD151 and Sonovue in the absence of US); G4 (Sonovue in the absence of US), and a control group (physiological saline in the absence of US). After 14 days of treatment, the expression of CD151 was detected by Western blot. Besides, vessel density of peri-infarcted myocardium was measured by immunohistochemistry, and cardiac function was analyzed by echocardiography. Results: The rabbit model of MI was established successfully. CD151 injection increased the expression of CD151 and microvessel density in the myocardium of MI rabbits. Heart function was significantly improved by CD151, which exhibited increased left ventricular ejection fraction, left ventricular fractional shortening and a reduced Tei index. Besides, US Sonovue significantly increased the expression efficiency of CD151. Conclusion: US microbubble was an effective vector for CD151 delivery. CD151 might be an effective therapeutic target for MI.

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Yumei Ye ◽  
Jose R Perez-Polo ◽  
Manjyot K Nanhwan ◽  
Sven Nylander ◽  
Yochai Birnbaum

Background: Clopidogrel (C) and Ticagrelor (T) are P2Y12 ADP receptor antagonists. In addition, ticagrelor inhibits adenosine cell uptake. In PLATO trial T reduced the incidence of the primary composite endpoint myocardial infarction, stroke or cardiovascular death over C in patients with acute coronary syndromes. Previous data show that 7d pretreatment with T limits infarct size (IS) in rats. We compared the effects of C and T, administered just before reperfusion on IS. We also assessed the effect of T and C, administered just before reperfusion and/or 6w oral treatment on cardiac remodeling. Methods: Rats underwent 30min coronary artery ligation. 1) At 25min of ischemia rats received intraperitoneal (IP) vehicle, T (10 or 30mg/kg), or C (12.5mg/kg). Area at risk (AR) was assessed by blue dye and IS by TTC staining 24h after reperfusion. 2) Rats received vehicle without (sham) or with (control) coronary ischemia, T (30mg/kg) IP (TIP), T (300mg/kg/d) oral for 6w, started a day after reperfusion (TPO), TIP+PO (TIPPO), or C (12.5mg/kg IP +62.5mg/kg/d PO for 6w). LV dimensions and function was assessed by echo at 6w. Results: 1) AR was comparable among groups. IS was 45.3±1.7% of the AR in the control group. T10 (31.5±1.8%; p=0.001) and T30 (21.4±2.6% p<0.001) significantly reduced IS, whereas C (42.4±2.6%) had no effect. Platelet aggregation in the controls was 64.7±1.3% and was comparable in T30 (24.9±1.8%) and C (23.2±1.8%) at 2h post reperfusion. T30 increased Akt, eNOS and ER1/2 phosphorylation 4h after reperfusion, whereas C had no effect. 2) Platelet aggregation at 1w oral treatment was 59.7±3.2% in the control group and was comparable in TIPPO (18.1±1.3%) and C (17.4±0.7%). Left ventricular ejection fraction was 77.6±0.9%*, 44.8±3.5%, 69.5±1.6%*, 69.2±1.0%*, 76.3±1.2%*, and 37.4±3.7% in the sham, vehicle, TIP, TPO, TIPPO and C treated group, respectively (*p<0.001 vs. vehicle). Left ventricular diameters at diastole and systole showed the same pattern. Conclusions: T, but not C, administered just before reperfusion protects against reperfusion injury. Oral T (in combination or not with acute treatment just before reperfusion) treatment for 6w improves heart function. C, despite achieving similar degree of platelet inhibition had no effect on remodeling.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yueqiu Chen ◽  
Jianfeng Zuo ◽  
Weiqian Chen ◽  
Ziying Yang ◽  
Yanxia Zhang ◽  
...  

Abstract Background Interleukin 33 is known to have an important influence in the process of myocardial infarction, and the immunoregulatory function of MSCs could be influenced by cell factors. In this study, we evaluated the therapeutic efficacy of IL-33-overexpressing bone marrow mesenchymal stem cells (IL33-MSCs) on myocardial infarction (MI) and detected the inflammatory level and cardiac function in rats. Methods and results First, we evaluated the proliferation of T cells and polarization of macrophages that had been co-cultured with Vector-MSCs or IL33-MSCs. Co-culture experiments indicated that IL33-MSCs reduced T cell proliferation and enhanced CD206+ macrophage polarization. Second, we determined the inflammation level and cardiac function of PBS-, Vector-MSC-, and IL33-MSC-injected rats. Echocardiography indicated that left ventricular ejection fraction (LVEF) was enhanced in IL33-MSC-injected rats compared with Vector-MSC-injected rats. Postmortem analysis of rat heart tissue showed reduced fibrosis and less inflammation in IL33-MSC-injected rats. Conclusion These studies indicated that the IL33-MSC injection improved heart function and reduces inflammation in rats with MI compared with PBS or Vector-MSC injections. Graphical Abstract IL-33 overexpression enhances the immunomodulatory function and therapeutic effects of MSCs on acute MI via enhancing the polarization of macrophages toward M2, enhancing the differentiation of CD4+ T cells toward CD4+IL4+Th2 cells, and finally, reducing heart inflammation and enhancing heart function.


2007 ◽  
Vol 6 (3) ◽  
pp. 166-171 ◽  
Author(s):  
Jina Choo ◽  
Lora E. Burke ◽  
Kyung Pyo Hong

Background Health-related quality of life (HRQOL) has been used as a primary health outcome in cardiac rehabilitation programs (CRP). Aims This study aimed to evaluate the effects of an 8-week CRP on HRQOL and exercise capacity in myocardial infarction (MI) patients in Korea. Methods After matching on gender, age, and left ventricular ejection fraction, 60 subjects with a first acute MI were allocated to either a CRP group ( n =31) or a Control group ( n =29). The 8-week CRP included hospital-based, supervised exercise training (three times per week, average intensity of 65% VO2peak) and individual education sessions. The Control group was instructed on a home-based exercise regimen without contact during the 8 weeks. At baseline and 8 weeks, HRQOL was assessed by the Quality of Life Index (QLI)–cardiac version III; exercise capacity by a treadmill test. Results After adjusting for education level, the overall QLI, health/functioning and psycho/spiritual scores showed greater increases in the CRP group than the Control group ( p=.014, p=.016, and p=.036, respectively). We observed significant improvements in VO2peak ( p<.0001), anaerobic threshold ( p<.0001), and maximal exercise duration ( p<.0001) in the CRP group, compared to the Control group. Conclusions These findings suggest that the Korean CRP can lead to significant improvements in HRQOL outcomes and exercise capacity.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Yucheng Zhong ◽  
Kunwu Yu ◽  
Xiang Wang ◽  
Xiaoya Wang ◽  
Qingwei Ji ◽  
...  

Objective.Recent studies suggest that IL-38 is associated with autoimmune diseases. Furthermore, IL-38 is expressed in human atheromatous plaque. However, the plasma levels of IL-38 in patients with ST-segment elevation myocardial infarction (STEMI) have not yet to be investigated.Methods.On admission, at 24 h, at 48 h, and at 7 days, plasma IL-38, C-reactive protein (CRP), cardiac troponin I (cTNI), and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels were measured and IL-38 gene in peripheral blood mononuclear cells (PBMCs) was detected in STEMI patients.Results.The results showed that plasma IL-38 levels and IL-38 gene expression in PBMCs were significantly increased in STEMI patients compared with control group and were time dependent, peaked at 24 h. In addition, plasma IL-38 levels were dramatically reduced in patients with reperfusion treatment compared with control group. Similar results were also demonstrated with CRP, cTNI, and NT-proBNP levels. Furthermore, IL-38 levels were found to be positively correlated with CRP, cTNI, and NT-proBNP and be weakly negatively correlated with left ventricular ejection fraction (LVEF) in STEMI patients.Conclusions.The results indicate that circulating IL-38 is a potentially novel biomarker for patients with STEMI and IL-38 might be a new target for MI study.


Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
Jensyn VanZalen ◽  
Takahiro Nakashima ◽  
Annie Phillips ◽  
Joseph Hill ◽  
Alyssa Enciso ◽  
...  

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) improves survival of patients with prolonged cardiac arrest (CA) that is refractory to standard CPR and ACLS. It has been proposed that ECPR accentuates inflammation after CA, potentially limiting its effectiveness. The benefits of leukocyte filters or leukocyte-modulating devices in conjunction with ECPR have not been studied. Hypothesis: When paired with ECPR, inflammation-modulating devices targeting leukocytes may improve recovery of cardiac function after prolonged cardiac arrest. Methods: In a randomized study, 24 swine (40±5kg) underwent 8min of untreated ventricular fibrillation CA followed by CPR with mechanical chest compressions and impedance threshold device for 30 min (total arrest time = 38min), immediately followed by 8h of ECPR with heparin anticoagulation and temperature maintained at 33°C. Group 1 (n=8) had standard ECPR system (control), Group 2 (n=8) had a leukocyte filter device (LF) added to the ECPR circuit, an and Group 3 (n=8) had a leukocyte modulation device (LMOD) added to the ECPR circuit. Recovery of cardiac function was measured using a cardiac resuscitablity score (CRS) and left ventricular ejection fraction (LVEF) via transthoracic echocardiography. Data was collected at baseline (prior CA) and after 8h of ECPR. Data analysis: single-factor ANOVA test (p<0.05 significance). Results: There were no statically significant differences between the groups in CRS (Control = 3.3 ± 2.4, LF = 4.0 ± 2.8, LMOD = 2.1 ± 2.6; p=0.37) or LVEF (Control = 59% ± 27%, LF = 49% ± 29% LMOD = 34% ± 38%: p=0.34) at 8 hours after ECPR initiation (Table 1). Discussion: In this swine model of prolonged cardiac arrest treated with ECPR, addition of a leukocyte filter or leukocyte modulation device to the ECPR circuit did not improve recovery of cardiac function during the first 8 hours after initiating ECPR.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
I Leonova ◽  
M Solovyeva ◽  
S Boldueva

Abstract Funding Acknowledgements Type of funding sources: None. Purpose  to assess the incidence of various forms of atrial fibrillation (AF) among the patients with MI, the prevalence of various types of myocardial infarction (MI) among the patients with AF, the features of the in-hospital prognosis among the patients with MI, and AF compared with those without AF. Materials and methods  1660 cases of patients with MI treated in 2013-18 - the main group (100 patients) were analyzed.  Results  AF occurred in 309 patients (18.6% of the total number of patients with MI). Preexisting AF was in 59.2% of patients. Patients with MI and AF were older than those without AF (mean age 75.2 ± 10.1 versus 64.6 ± 12.8, p &lt;0.0001), among them there were more women (52.4% versus 35.5% in patients without AF, p &lt;0.0001). Type 2 MI occurred 5 times more often among patients with MI and AF (p &lt;0.0001). Further, 2 study groups were formed - the main (100 patients with type 1 MI and preexisting AF) and control (type 1 MI 200 patients without AF), adjusted for sex (58% of women in both groups), age (mean age 75.5 ± 8, 7 in the main group versus 75.2 ± 8.5 in the control group, p = 0.775). DM (45% versus 31.5%, p = 0.030), previous MI (40% versus 25.5%, p = 0.012) and stroke (21% vs. 11.5%, p = 0.037) were more common in the main group than in the control. Patients with MI and AF had lower GFR (56.8 ± 19.4 versus 61.7 ± 17.9 ml / min / 1.73 m2, p = 0.031), LDL (2.8 ± 0.9 versus 3.3 ± 1.0 mmol/L, p = 0.0002). Patients with AF had a lower left ventricular ejection fraction (55.2 ± 10.5 versus 59.8 ± 10.0 %, p = 0.0005). Significant mitral regurgitation was more common in the 1-st group (53.9% versus 30.3% in the control group, p = 0.0002). There were no significant differences in the incidence of acute heart failure (HF) (Killip 3-4) (20% versus 13%, p = 0.127). Patients in the 1-st and 2-nd groups did not differ in the number of affected coronary artery (p = 0.7327), the level of their damage (p = 0.1956), in the frequency of revascularization (p = 0.0686). Patients with MI and AF had worse in-hospital prognosis. Pulmonary embolism (PE) (9% in patients with AF versus 1% in patients without AF, p = 0.0011), minor bleeding (21% versus 9.5%, p = 0.0057), combined endpoint (stroke + PE + mortality) (19% versus 10.5%, p = 0.0415) were more common in the main group. At discharge, patients with AF had chronic HF III NYHA in 21.8% cases versus 5.5% in patients without AF, p = 0.0001. There were no significant differences in other endpoints (recurrent MI, stroke, major bleeding, and total mortality) between the groups during hospitalization. In-hospital mortality was 13% in the main versus 9.5% in the control group (p = 0.4276). Conclusion  AF occurs in 18.6% of patients with MI. Patients with AF and MI are older with the prevalence of females. Patients with type 1 MI and pre-existing AF is a group of high risk. PE, severe chronic HF, minor bleeding, and combined endpoint (stroke + PE + mortality) were significantly common among them.


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Enrico Fabris ◽  
Sara Menzio ◽  
Caterina Gregorio ◽  
Andrea Pezzato ◽  
Davide Stolfo ◽  
...  

Abstract Aims The appropriate timing to administer antithrombotic therapies in ST-elevation myocardial infarction (STEMI) remains uncertain. This study aims to evaluate the role of antithrombotic therapy administration at first medical contact (FMC) compared to the administration in the Cathlab. Methods and results We conducted a ‘before-after’ observational study enrolling STEMI undergoing primary percutaneous coronary intervention (PCI). Outcomes were evaluated during two successive periods, before (control group: aspirin only at FMC) and after (pre-treated intervention group: heparin, aspirin plus ticagrelor at FMC) the introduction of a new regional pre-treatment protocol. 537 consecutive patients (300 in control vs. 237 in intervention group) were enrolled. The pre-treated compared to no pre-treated population showed better basal reperfusion, expressed as basal thrombolysis in myocardial Infarction (TIMI)-flow (p for trend P &lt; 0.001). Pre-treated population showed lower frequency of TIMI 0 (56.5% vs. 73.7%, OR: 0.46, 95% CI: 0.32–0.67, P &lt; 0.001) and higher frequency of TIMI 2–3 (33.3% vs. 19.7%; OR: 2.0; 95% CI: 1.38–2.00, P &lt; 0.001) and TIMI 3 [14.3% vs. 9.7%, OR: 1.56, 95% CI: (0.92–2.65), P = 0.094]. Pre-treated compared to no pre-treated population showed reduced infarct size expressed as Troponin Peak [20 286 (8726–75027) vs. 48 676 (17229–113900), P = 0.001], and higher left ventricular ejection fraction at discharge [53% (44–59) vs. 50% (44–56), P = 0.027]. In-Hospital BARC ≥2 bleeding were similar (2.1% vs. 2.0%, P = 0.929, in pre-treated vs. no pre-treated population, respectively). Conclusions This study provides support for an early pre-treatment strategy in STEMI patients and confirmed the importance of an efficient organization of STEMI networks which allow initiation of antithrombotic treatment at FMC.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Cheng ◽  
X Y Song ◽  
L Chen ◽  
R D Xu ◽  
Q Qin ◽  
...  

Abstract Mesenchymal stem cells derived from bone marrow promotes cardiomyocytes survival under hypoxia through exosomal miR-210 Background A paracrine effect was regarded as the key mechanism involved in the MSC (mesenchymal stem cell)-based treatment for myocardial infarction. In our pilot experiments, hypoxia remarkably promotes MSC to paracrine exosomal miR-210, which could significantly enhance the cardiomyocytes survival in hypoxic incubation, suggesting that exosomal miR-210 played critical roles in the favorable paracrine effect of MSC on cardiomyocytes. Purpose The aim of this study was to investigate the important mechanism by which MSCs promote the tolerance of cardiomyocytes to hypoxia by secreting exosomal miR-210. Methods and results The exosomes were isolated from MSCs conditioned medium through ultracentrifugation, and we detected that miR-210 was the most abundant in MSC-exosome and increased most prominently in the hypoxia. The extracted exosomes were prepared for conditioned medium and the effect on myocardial protection was examined. The viability of control group was much better than the cardiomyocytes treated with hypoxia, but it was further increased in the presence of MSC-exosome, however, measurement was significantly lower in cardiomyocytes in hypoxia with exosomes derived from MSCs treated with GW4869. Subsequently, the co-localization of miR-210 with exosome-specific surface markers CD81 and CD63 were observed by immunofluorescence technique. Continuous magnetic live cell imaging was used to observe the uptake of exosome by cardiomyocytes, and fluorescence localization was used to observe the localization of miR-210 with Cy3 fluorescence in cardiomyocytes. Then, we demonstrated that MSCs exosomal miR-210 exerts the cardioprotective effect by regulating the AIFM3 (apoptosis-inducing factor mitochondria-associated protein 3), and we directly overexpressed miRNA-210 in cardiomyocytes and the results showed that the regulatory activity of the intake of exosomal miR-210 was consistent with that of the biological exosomal miR-210. Finally, we verified the protective effect on the ischemic myocardium by constructing rat myocardial infarction models. The level of apoptosis was detected at 1 week after myocardial infarction. The left ventricular ejection fraction and ventricular remodeling were measured at 4 weeks. In vivo, we demonstrated that explanted miR-210 from transplanted MSCs significantly reduced myocardial necrosis and apoptosis induced by ischemia and improved cardiac function and myocardial remodeling. Conclusion Here, we show that the exosomal miR-210 secreted by MSCs significantly increase the viability of cardiomyocytes and cardiac function. These findings suggest that exosomal miR-210 is a key effector that mediates the protection against hypoxia. Acknowledgement/Funding National Natural Science Foundation of China (Grant Nos. 81470467)


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Matthias Koestering ◽  
Tobias Zeus ◽  
Michael Brehm ◽  
Thomas Bartsch ◽  
Christina M Schannwell ◽  
...  

Introduction: Remodeling of the left ventricle (LV) after myocardial infarction (MI) represents a major cause of infarct-related heart failure and death. After acute myocardial infarction transplantation of bone marrow cells (BMCs) leads to regeneration of infarcted zones due to neovascularization and regeneration of myocardium. We investigated cardiac performance of intracoronary transplantation of autologous BMCs in patients with chronic ischemic heart disease, suffered from transmural myocardial infarction. Methods: We treated 120 consecutive patients (51±14 years) with chronic myocardial infarction by intracoronary transplantation of autologous bone marrow mononuclear cells (BMCs) and compared them with a consecutive enrolled representative control group (n=45, 53±11 years). Bone marrow was harvested from the hip (~80 ml) and mononuclear cells were identified including CD34+, AC133+ and CD 34−, CD45−, CD14− cells. The median number of mononuclear cells harvested after overnight culture was 104 x 10 6 Results: After 3 months in the transplantation group, infarct size was reduced from (32±9 to 25±9%) significantly (p<0.001), and global left ventricular ejection fraction (45±9 to 51±10%) significantly (p<0.001); as well as infarction wall movement velocity (1.86 ± 0.72 to 3,12 ± 0.78cm/s) significantly (p<0.001), while in the control group no significant changes were observed during 3 months follow-up in infarct size (29±9 to 28±9%), in left ventricular ejection fraction (48±10 to 50±15%) and in wall movement velocity of infarcted area (1.81 ± 0.76 to 1.92 ± 0.78cm/s). After bone marrow cell transplantation, there was an significantly (p<0.05) improvement of maximum oxygen uptake (VO2max, +12%) and significantly (p<0.05) of regional 18F-Fluor-Desoxy-Glucose (FDG) uptake (PET) into infarcted tissue (+15%). Conclusions: These results demonstrate that selective intracoronary transplantation of autologous BMCs may reduce infarct size and improve LV function and myocardial glucose uptake in chronic ischemic heart disease after chronic infarcted myocardium.


Ozone Therapy ◽  
2016 ◽  
Vol 1 (1) ◽  
pp. 10
Author(s):  
Sergio Pandolfi ◽  
Claudio Di Giovanni ◽  
Eleonora Marinari ◽  
Marianno Franzini

Here we present the case of a 76-year-old patient who suffered from ischemic cardiopathy and myocardial infarction in January 2014, arterial hypertension, kidney failure, Parkinsonism, vascular multinfarctual ischemic cerebropathy, cerebral ictus, neurogenic bladder, and inguinal hernia. The left ventricular ejection fraction evaluated through repeated echocardiographic examinations remained reduced to 33% from January 2014 to March 2015. The left ventricular ejection fraction, after 14 months from acute myocardial infarction and despite the coronary angioplasty and medical therapy, remained constantly reduced to 33%. On 3<sup>rd</sup> July 2015 he started the oxygen-ozone therapy with 2 autohemoinfusions of ozonated blood per week. Over the first two months of therapy we noticed a marked improvement of his heart conditions with a net reduction in asthenia and neurological status, the improvement of heart conditions was corroborated by the echocardiogram of 5<sup>th</sup> November 2015 which showed an increase in the left ventricular ejection fraction from 33% to 50%. In this case the heart function improvement of left ventricular ejection fraction was noticed only after having started the systemic oxygen-ozone therapy through large autohemoinfusion. In April 2015, before starting the oxygen-ozone therapy we assessed the patient’s inguinal hernia to be inoperable due to the lapsed heart conditions, while the subsequent reassessment in December 2015, after the patient underwent oxygen-ozone therapy for 5 months, we assessed him to be operable considering the heart function improvement.


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