• International Journal of Stem Cells
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• v.17 no.1
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• pp.70-79
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• 2024

The efficacy of adipose-derived stem cells (ASCs) on myocardial infarction is limited due to poor survival and engraftment. Integrin-mediated cell adhesion is a prerequisite for its survival and homing. ASCs expressed insufficient integrin 𝛼₄, limiting their homing capacity. This study aims to characterize integrin 𝛼₄⁺ ASC subpopulation and investigate their therapeutic efficacy in myocardial infarction. We used fluorescence-activated cell sorting to harvest integrin 𝛼₄⁺ ASCs subpopulation, which were characterized in vitro and transplanted into myocardial infarction model. Positron emission tomography imaging were performed to measure infarction size. Cardiac cine magnetic resonance imaging was used to evaluate heart contractile function. Compared with the unfractionated ASCs, integrin 𝛼₄⁺ ASCs subpopulation secreted a higher level of angiogenic growth factors, migrated more rapidly, and exhibited a stronger anti-apoptotic capacity. Vascular cell adhesion molecule-1 was obviously up-regulated at 3 days after myocardial infarction, which interacted with integrin α₄ receptor on the surface of ASCs to enhance the survival and adhesion. Thus, we implanted unfractionated ASCs or integrin α₄⁺ ASCs subpopulation into the 3-day infarcted myocardium. Integrin α₄⁺ ASCs subpopulation exhibited more robust engraftment into the infarcted myocardium. Integrin α₄⁺ ASCs subpopulation more effectively decreased infarct size and strengthen cardiac function recovery than did the unfractionated ASCs. Integrin α₄⁺ ASCs subpopulation is superior to unfractionated ASCs in ameliorating ischemic myocardial damage in animal model. Mechanistically, their more robust engraftment into the infarct area, higher migratory capacity and their increased release of paracrine factors contribute to enhanced tissue repair.

• Korean Journal of Radiology
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• v.21 no.12
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• pp.1294-1304
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• 2020

Objective: To determine whether T1 mapping could monitor the dynamic changes of injury in myocardial infarction (MI) and be histologically validated. Materials and Methods: In 22 pigs, MI was induced by ligating the left anterior descending artery and they underwent serial cardiovascular magnetic resonance examinations with modified Look-Locker inversion T1 mapping and extracellular volume (ECV) computation in acute (within 24 hours, n = 22), subacute (7 days, n = 13), and chronic (3 months, n = 7) phases of MI. Masson's trichrome staining was performed for histological ECV calculation. Myocardial native T1 and ECV were obtained by region of interest measurement in infarcted, peri-infarct, and remote myocardium. Results: Native T1 and ECV in peri-infarct myocardium differed from remote myocardium in acute (1181 ± 62 ms vs. 1113 ± 64 ms, p = 0.002; 24 ± 4% vs. 19 ± 4%, p = 0.031) and subacute phases (1264 ± 41 ms vs. 1171 ± 56 ms, p < 0.001; 27 ± 4% vs. 22 ± 2%, p = 0.009) but not in chronic phase (1157 ± 57 ms vs. 1120 ± 54 ms, p = 0.934; 23 ± 2% vs. 20 ± 1%, p = 0.109). From acute to chronic MI, infarcted native T1 peaked in subacute phase (1275 ± 63 ms vs. 1637 ± 123 ms vs. 1471 ± 98 ms, p < 0.001), while ECV progressively increased with time (35 ± 7% vs. 46 ± 6% vs. 52 ± 4%, p < 0.001). Native T1 correlated well with histological findings (R² = 0.65 to 0.89, all p < 0.001) so did ECV (R² = 0.73 to 0.94, all p < 0.001). Conclusion: T1 mapping allows the quantitative assessment of injury in MI and the noninvasive monitoring of tissue injury evolution, which correlates well with histological findings.

• Investigative Magnetic Resonance Imaging
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• v.7 no.2
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• pp.132-136
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• 2003

Purpose : To evaluate the usefulness of breath-hold T2-weighted MR imaging in patients with myocardial infarction. Materials and Methods : We investigated 11 patients with myocardial infarction who shown delayed enhancement on MR imaging. Infarcted myocardium on T2-weighted MR imaging was classified as high, iso, and low signal area comparing with normal myocardium. The intensity and transmural extent of infracted myocardium was also analyzed. On the basis of clinical information, the stage of infracted myocardium on T2-weighted MR imaging was assessed. Results : It was observed high signal area in 12 segments of 5 patients, low in 12 segments of 6 patients on T2-weighted MR imaging. The high signal intensity of infarcted myocardium was shown as $175{\pm}9\%$ comparing with that of the normal myocardium, low signal intensity as $73{\pm}5\%\;(p\;<\;0.05)$. In the evaluation of transmural extent, the high signal areas on T2-weighted MR imaging were larger than infarct area on delayed enhancement imaging $(100\%\;vs.49\%{\pm}17\%)$, whereas low signal areas on T2-weighted MR imaging correlated. High signal area was visualized on T2-weighted MR imaging within 11 days, whereas low-signal area was seen after 7 months. Conclusion : Breath-hold T2-weighted MR imaging is useful in the evaluation of stage as well as edema and fibrous scar in patients with myocardial infarction.

• Journal of Chest Surgery
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• v.47 no.4
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• pp.434-436
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• 2014

Left ventricular thrombus is a common complication related to acute myocardial infarction. Removing this with an incision of the free wall of the left ventricle may cause fatal cardiac dysfunction or arrhythmias. Furthermore, performing incision and suture on the fragile myocardium of an acute myocardial infarction patient may cause serious bleeding complications. If there is a patient with left ventricular thrombus who needs thoracotomy for another reason, the case is attempted with the thought that if effective intraventricular visualization and manipulation can be done, fatalities caused by incision and suture may be reduced. For patients undergoing cardiopulmonary bypass, if intracardiac manipulation is required, an endoscope can be used, and given the potential complications after the incision and suturing of the infarcted tissue, the benefits are deemed sufficient.

• Korean Circulation Journal
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• v.53 no.6
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• pp.367-386
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• 2023

Ischemic heart disease remains the primary cause of morbidity and mortality worldwide. Despite significant advancements in pharmacological and revascularization techniques in the late 20th century, heart failure prevalence after myocardial infarction has gradually increased over the last 2 decades. After ischemic injury, pathological remodeling results in cardiomyocytes (CMs) loss and fibrosis, which leads to impaired heart function. Unfortunately, there are no clinical therapies to regenerate CMs to date, and the adult heart's limited turnover rate of CMs hinders its ability to self-regenerate. In this review, we present novel therapeutic strategies to regenerate injured myocardium, including (1) reconstruction of cardiac niche microenvironment, (2) recruitment of functional CMs by promoting their proliferation or differentiation, and (3) organizing 3-dimensional tissue construct beyond the CMs. Additionally, we highlight recent mechanistic insights that govern these strategies and identify current challenges in translating these approaches to human patients.

• Journal of Chest Surgery
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• v.33 no.6
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• pp.494-501
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• 2000

Background: Transmyocardial laser revascularization(TMLR) for revascularizing ischemic myocardium in patients was originally based on the assumption that laser channels remain their patency much longer. But recent studies show that laser channels did not remain open and that TMLR could achieve treatment benefits without long-term channel patency. The angiongencesis is currently thought to be induced by non-specific inflammatory response to mechanical tissue injury. This study is to evaluate hypothesis that various transmyocaridal mechanical revascularization(TMMR) may induce the angiogenic responses similar to that seen with TMLR, and transmyocaridal polymer stent revascularization(TMSR), the polymer stent in the myocardial tissue is hydrolyzed in 2 weeks, may enhance the non-specific inflammatory reaction resulting angiogenesis. Furthermore, polymer myocaridal stent channels remain long-term patency. Material and Method: Eight domestic pigs underwent ligation of the proximal circumflex artery, and 2 weeks later they were randomized to undergo transmycardial acupunctural revascularization (TMPR, Group I) of the left lateral wall with 18-G needle(n=2), to undergo transmyocardial (TMDR, Group II) with industrial 2mm steel drill(n=2), to undergo transmyocardial polymer stent revascularization (TMSR, Group III) after drilling the infarcted myocardium(n=2), the stent is poly(lactic acid-co-glycolic acid), which is self-degradated in the myocardium, and to a control group the ischemic zone was unterated(n=2). All the pigs were sacrificed after 4 weeks TMMR. Sections from the ischemic zone were submitted for vascular endothelial growth factor (VEGF) ELISA and histology. Result: There were makedly increase in the VEGF immunoassay in the ischemic zone of the TMMR group compared to the ischemic zone of the control group(control: each 30.85 and 43.15pg/mg protein, TMPR: each 44.14 and 68.61 pg/mg protein, TMDR: each 65.92 and 78.65 pg/mg protein, TMSR: each 177.39 and 168.87 pg/mg protein). TMSR channels caused greatest VEGF expression than channels made by other group and the polymer stent channels remained vacuole after 4 weeks. Conclusion: Transmyocardial polymer stent revascularization promoted the most angiogenci response by the VEGF immunoassay, although our study did not show the statistical significancy. The channels remained but the flow patency was not verified. Transmyocardial polymer stent revascularization (TMSR) is desirable in future experimental trials and in view of the significant cost implications comparable to that of laser.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.3
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• pp.259-266
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• 2020

Cardiovascular diseases are the primary reason of mortality, among which myocardial infarction (MI) is the most dominant and prevalent. This study was considered to examine D-Limonene protective action against isoproterenol (ISO) induced MI. Wister male rats were dispersed into four groups. Normal and D-Limonene control group in which rats administered saline or D-Limonene. ISO control animals were administered saline for 21 days then challenged with ISO (85 mg/kg, subcutaneously) on 20th and 21st day for MI induction. D-Limonene pretreated group in which animals were pretreated with D-Limonene 50 mg/kg orally for 21 days then administered ISO on 20th and 21st day. MI prompted variations were assessed by myocardial infarction area determination, blood pressure (BP) alterations, cardiac injury biomarkers and inflammatory mediators measurements. For more depth investigation, both the apoptotic status was evaluated via measuring mRNA expression of Bcl-2 and Bax as well as mitogen-activated protein kinase-extracellular signal-regulated kinase (MAPK-ERK) signal transduction were investigated via Western blotting. MI group revealed significant infarcted area, blood pressure alterations, myocardial injury enzymes intensification together with inflammatory cytokines amplification. MI was associated with activation of MAPK-ERK signal pathway and apoptotic status within the myocardium. On the other hand, pretreated with D-Limonene demonstrated deterred infracted area, reduced myocardial enzymes, improved BP indices, lessened inflammatory levels. Furthermore, D-Limonene pretreatment caused a decline in MAPK proteins pathway and Bax relative mRNA expression, while intensifying Bcl-2 mRNA expression promoting that D-Limonene may constrain MI induced myocardial apoptosis. D-Limonene mitigated MI injury through MAPK/NF-κB pathway inhibition and anti-apoptotic effect.

• Archives of Plastic Surgery
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• v.34 no.2
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• pp.149-155
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• 2007

Purpose: This study was to investigate how the heparin, which has been known to induce neovascularization by MMP in the infarcted tissue of the myocardium, had influence on the expression of mRNA of MMP 1,2,9 of the skin wound of rat. Methods: Full depth skin wounds were created on the dorsum of Sprague-Dawley 60 rats. The experimental rats were divided into two groups according to the concentration of heparin($100{\mu}g/ml$ in 20, $300{\mu}g/ml$ in 20). Heparin soaked gelatin sponges in different concentration were inserted into the pocket of experimental rats and the wounds were closed. Normal saline soaked gelatin sponges were used in control rats. Wounds were harvested at 48 and 72 hours after closure. We performed histologic study in H-E stain. RNA was isolated from the harvested tissue and then real time polymerase chain reaction was performed to determine the gene expression of MMP-1,2,9. Results: We observed that inflammatory cell decreased in heparin soaked group and heparin increased the expression of MMP-1,9 mRNA of dorsal wound of rat at 72 hours (p < 0.05). Conclusion: This result suggest that heparin may be used inducing another factor inducing scarless wound healing by increasing MMP.

• Journal of Chest Surgery
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• v.31 no.10
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• pp.924-927
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• 1998

Background: Myocardial cell death after myocardial infarction or reperfusion is classified into necrosis and apoptosis. Bcl-2 protein is a cytoplasmic protein, which inhibits apoptosis and is expressed in acute stage of myocardial infarction but not in normal heart. This study was performed to investigate whether Bcl-2 protein was expressed respectively to the reperfusion time. Materials and methods: Thirty nine New Zealand white rabbits weighing 1.5-4.8 kg (mean, 2.9kg) were alloted into 7 groups (n=5 in each group) which underwent left anterior descending coronary artery(LAD) occlusion for 30 minutes, followed by reperfusion. The animals were sacrificed at 1, 4, 8, 12, 24 hours, and 3, 7 days after occlusion. Ventricle was excised immediately after intervention. Tissues were fixed in 10% buffured formalin and embedded in paraffin. Bcl-2 protein was detected by immunohistochemical stain with using monoclonal antibody against Bcl-2 protein. Results: The positive immunohistochemical reactivity for Bcl-2 protein was observed in 12, 24 hours, and 3 days reperfusion groups. Bcl-2 protein was detected in salvaged myocytes surrounding the infarcted area. Conclusions: Bcl-2 protein is expressed at the late acute stage of infarct. Therefore, the expression of Bcl-2 protein may not protect acute cell death, but may play a role in the prevention of late cell death after myocardial is chemia-reperfusion.