• The Korean Journal of Nuclear Medicine
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• v.32 no.1
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• pp.50-60
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• 1998

I-123 labelled fatty acids are suitable for investigation of regional myocardial metabolism, so they are on the clinical trial. However, the precise properties of these materials are not characterized yet. We have synthesized phenylpentadecanoic acid and labeled this compound with I-123. The purpose of this study was to examine the stability, biodistribution, metabolism and SPECT imaging of [I-123]15-(p-iodophenyl)pentadecanoic acid(I-123-IPPA) that we made. The stability test of I-123-IPPA in serum of rat, mouse and human showed no free I-123 after 1 hour. In biodistribution study in mice for various time intervals after injection(5, 10, 15, 30, 60 minutes), uptake in myocardium was 14.5%ID/g(5 min), and 1.9%ID/heart(5 min), while uptake in muscles was 2.6%ID/g(5 min). Myocardium to blood ratio and myocardium to lung ratio increased for 5 min after injection and then decreased rapidly. Chromatographic data of rat blood and urine showed that little PPA was found in blood and urine at 15-20 min after injection. The myocardial I-123-IPPA SPECT images of a dog with myocardial infarction showed defects similar to those of Tc-99m-MIBI and F-18-FDG. These data suggest that I-123-IPPA is quite stable in vitro and shows favorable biodistribution in mice. SPECT imaging with I-123-IPPA demonstrated infarct zone as photon defect in dog model of myocardial infarction. I-123-IPPA may be used for the evaluation of fatty acid metabolism in clinical trials in Korea.

• Journal of Chest Surgery
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• v.36 no.9
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• pp.638-645
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• 2003

The purposes of this study were to evaluate the effect of myocardial protection with our cold blood cardioplegic solution and to observe the relationship between ultrastructural study and other evaluation methods and its effectiveness. Material and Method: We evaluated the changes of myocardial ultrastructure using semi-quantitative scoring system, CK-MB fraction, SGOT and LDH1/LDH2, and EKG in 18 patients undergoing valvular heart surgery and coronary artery bypass grafting (CABG). Right atrial auricular biopsies were taken before the cardiopulmonary bypass (CPB) and shortly after the end of CPB. Myocardium-related serum enzymes ＆ EKG were checked for 3 days of postoperative period and their postoperative peak enzyme value and observed new Q wave ＆ ST segment elevation in EKG were choosen. Result: There were 8 males and 10 females, and their mean age was 55.6$\pm$13. Eight patients underwent valvular heart surgery and ten coronary artery bypass grafting, The mean CPB time was 119$\pm$29 minutes and the mean aortic cross-clamp (ACC) time was 75.4$\pm$24 minutes. Before the start of CPB, the mean mitochondrial score was 4.28$\pm$0.53 and after the end of CPB, it significantly increased to 2.35$\pm$0.79. There was no evidence of perioperative myocardial infarction in terms of myocardiumrelated serum enzyme value and Q wave and ST change in EKG. There was no significant relationship between pre-CPB and post-CPB mitochondrial score and the mean time of CPB and ACC, and the mean value of postoperative peak CK-MB, SGOT and LDH1/LDH2, but there was relatively positive correlation of CPB time with peak LDH1/LDH2. Conclusion: Despite the apparent satisfactory results in myocardium-related serum enzymes ＆ EKG, with this study using the cold blood cardioplegic solution, there were many changes in myocardial ultrastructures, and more studies are needed to obtain further information.

• Journal of Chest Surgery
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• v.37 no.7
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• pp.547-552
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• 2004

Recently, autologous bone marrow cell transplantation (CTx) for angiogenesis and myogenesis in ischemic myocardium has been extensively investigated to improve heart functions. This study was designed to evaluate the effects of CTx with off-pump coronary artery bypass grafting (OPCAB) in patients who were not feasible for complete revascularization. Material and Method: Four male patients underwent CTx and OPCAB simultaneously. Bone marrow was aspirated from iliac bone. Mean 1.5 ${\times}$ 10$^{9}$ mononuclear cells including mean 6.7 ${\times}$ 10$^{6}$ CD34 + cells and 3.7 ${\times}$ 10$^{6}$ AC133 + cells were obtained and concentrated with 10 cc. These cells were transplanted into non-graftable ischemic myocardium after OPCAB. The heart function of all patients were evaluated using the MIBI scan, echocardiogram and MRI preoperatively. The effects of CTx was evaluated using MIBI scan and echocardiogram at 1 month postoperatively. Result: An average of 2 grafts were bypassed to left anterior descending artery territory. Other territories were transplanted with isolated mononuclear cell. All patients had uncomplicated postoperative course. After 1 month follow up, there were improvement in symptom, ejection fraction (from 49% to 55%) on echocardiogram and myocardial perfusion on MIBI scan in all patients. Conclusion: These preliminary data showed improvement of heart function and myocardial perfusion and also showed the feasibility and safety of combined therapy with OPCAB and CTx in ischemic myocardium. However, the effectiveness of CTx alone cannot be readily assessed. Further randomized, controlled studies are required to evaluate the effectiveness of CTx alone.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2002.09a
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• pp.314-317
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• 2002

The purpose of this study was to evaluate the clinical application of Patlak tool on GE PET workstation for quantitative analysis of dynamic PET images in cardiac patients. Three patients including coronary artery disease (CAD), myocardial infarction (MI), and angina were studied. All subjects underwent dynamic cardiac PET scan using a GE Advance scanner. After 10 min transmission scan for attenuation correction using two rotating $\^$68/Ge rod sources, three patients with cardiac disease were performed dynamic cardiac PET scan after the administration of approximately 370 MBq of FDG. The dynamic scan consisted of 36 frames with variable frame length (12${\times}$10s, 6${\times}$20s, 6${\times}$60s, 12${\times}$300s) for a total time of 70 min. Blood samples were obtained to determine the plasma substrate concentration. Region of interest of circular and rectangular shape to acquire input functions and tissue data were placed on left ventricle and myocardium. A value of 0.67 was used for lumped constant. Mean plasma substrate concentrations for three patients were 100 mg/dl (CAD), 100 mg/dl (MI), 132 mg/dl (angina), respectively. Regional MMRGlc values (mean${\pm}$SD) at lateral myocardium area for CAD, MI, and angina were 8.43${\pm}$0.24, 4.08${\pm}$0.16, and 6.15${\pm}$0.23 mg/min/100ml, respectively. Patlak tool on GE PET workstation appeared to be useful for quantitative analysis of dynamic PET images in cardiac patients, although further studies may be required for absolute quantitation.

• 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.

• Herbal Formula Science
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• v.31 no.3
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• pp.157-169
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• 2023

Gracilaria Verrucosa (GV), a seaweed used in traditional Korean medicine, was studied for its effects on MI-induced heart failure in rats. MI is caused by a blocked coronary artery, leading to severe cardiac dysfunction. The study used a rat model to assess cardiac changes over time and evaluate the impact of GV on heart failure. Ischemia was induced through LAD ligation surgery, and the extent of ischemic area was measured as a prognostic factor. GV extract administration significantly improved cardiac morphology and reduced cardiac weight compared to the MI group. GV treatment also improved cardiac function, as evidenced by positive effects on chamber dilation during MI-induced heart failure. Parameters such as ejection fraction (EF) and fractional shortening (FS) were measured. The MI group showed decreased EF and FS compared to the sham group, while these parameters improved in the GV group. GV treatment also reduced levels of LDH, CPK, and CK-MB in the serum, indicating reduced myocardial damage. Histological analysis revealed that GV treatment attenuated cardiac hypertrophy and fibrosis, with reduced collagen deposition in the myocardium. Immunohistochemistry analysis showed suppressed expression of TGF-β1 and collagen 1, involved in fibrosis. In conclusion, GV showed potential in improving cardiac function in a rat model of MI-induced heart failure. It alleviated myocardial damage, attenuated cardiac hypertrophy and fibrosis, and suppressed fibrotic markers. Further studies are needed to explore its clinical efficacy and underlying mechanisms in cardiac diseases beyond animal models.

• Korean Journal of Radiology
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• v.20 no.1
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• pp.83-93
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• 2019

Objective: The purpose of this study was to prospectively investigate the value of the myocardial extracellular volume fraction (ECV) in predicting myocardial functional outcome after revascularization of coronary chronic total occlusion (CTO). Materials and Methods: Thirty patients with CTO underwent cardiovascular magnetic resonance (CMR) before and 6 months after revascularization. Three baseline markers of functional outcome were evaluated in the dysfunctional segments assigned to the CTO vessels: ECV, transmural extent of infarction (TEI), and unenhanced rim thickness (RIM). At the global level, the ECV values of the whole myocardium with and without a hyperenhanced region (global and remote ECV) were respectively measured. Results: In per-segment analysis, ECV was superior to TEI and RIM in predicting functional recovery (area under receiver operating characteristic curve [AUC]: 0.86 vs. 0.75 and 0.73, all p values < 0.010), and it emerged as the only independent predictor of regional functional outcome (odds ratio [OR] = 0.83, 95% confidence interval [CI]: 0.77-0.89; p < 0.001) independent of collateral circulation. In per-patient analysis, global baseline ECV was indicative of ejection fraction (EF) at the follow-up examination (β = -0.61, p < 0.001) and changes in EF (β = -0.57, p = 0.001) in multivariate regression analysis. A patient with global baseline ECV less than 30.0% (AUC, 0.93; sensitivity 94%, specificity 80%) was more likely to demonstrate significant EF improvement (OR: 0.38; 95% CI: 0.17-0.85; p = 0.019). Conclusion: Extracellular volume fraction obtained by CMR may provide incremental value for the prediction of functional recovery both at the segmental and global levels in CTO patients, and may facilitate the identification of patients who can benefit from revascularization.

• Korean Journal of Radiology
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• v.21 no.6
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• pp.647-659
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• 2020

Objective: The occurrence of intramyocardial hemorrhage (IMH) and microvascular obstruction (MVO) in myocardial infarction (MI), known as severe ischemia/reperfusion injury (IRI), has been associated with adverse remodeling. APT102, a soluble human recombinant ecto-nucleoside triphosphate diphosphohydrolase-1, can hydrolyze extracellular nucleotides to attenuate their prothrombotic and proinflammatory effects. The purpose of this study was to temporally evaluate the therapeutic effect of APT102 on IRI in rats and to elucidate the evolution of IRI in the acute stage using cardiovascular magnetic resonance imaging (CMRI). Materials and Methods: Fifty-four rats with MI, induced by ligation of the origin of the left anterior descending coronary artery for 60 minutes, were randomly divided into the APT102 (n = 27) or control (n = 27) group. Intravenous infusion of APT102 (0.3 mg/kg) or placebo was administered 15 minutes before reperfusion, and then 24 hours, 48 hours, 72 hours, and on day 4 after reperfusion. CMRI was performed at 24 hours, 48 hours, 72 hours, and on day 5 post-reperfusion using a 7T system and the hearts were collected for histopathological examination. Cardiac function was quantified using cine imaging and IMH/edema using T2 mapping, and infarct/MVO using late gadolinium enhancement. Results: The extent of infarction (p < 0.001), edema (p < 0.001), IMH (p = 0.013), and MVO (p = 0.049) was less severe in the APT102 group than in the control group. IMH size at 48 hours was significantly greater than that at 24 hours, 72 hours, and 5 days after reperfusion (all p < 0.001). The left ventricular ejection fraction (LVEF) was significantly greater in the APT102 group than in the control group (p = 0.006). There was a negative correlation between LVEF and IMH (r = -0.294, p = 0.010) and a positive correlation between IMH and MVO (r = 0.392, p < 0.001). Conclusion: APT102 can significantly alleviate damage to the ischemic myocardium and microvasculature. IMH size peaked at 48 hours post reperfusion and IMH is a downstream consequence of MVO. IMH may be a potential therapeutic target to prevent adverse remodeling in MI.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.4
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• pp.407-416
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• 2023

The regeneration of myocardium following acute circulatory events remains a challenge, despite numerous efforts. Mesenchymal stem cells (MSCs) present a promising cell therapy option, but their differentiation into cardiomyocytes is a time-consuming process. Although it has been demonstrated that PSME4 degrades acetyl-YAP1, the role of PSME4 in the cardiac commitment of MSCs has not been fully elucidated. Here we reported the novel role of PSME4 in MSCs cardiac commitment. It was found that overnight treatment with apicidin in primary-cultured mouse MSCs led to rapid cardiac commitment, while MSCs from PSME4 knock-out mice did not undergo this process. Cardiac commitment was also observed using lentivirus-mediated PSME4 knockdown in immortalized human MSCs. Immunofluorescence and Western blot experiments revealed that YAP1 persisted in the nucleus of PSME4 knockdown cells even after apicidin treatment. To investigate the importance of YAP1 removal, MSCs were treated with shYAP1 and apicidin simultaneously. This combined treatment resulted in rapid YAP1 elimination and accelerated cardiac commitment. However, overexpression of acetylation-resistant YAP1 in apicidin-treated MSCs impeded cardiac commitment. In addition to apicidin, the universal effect of histone deacetylase (HDAC) inhibition on cardiac commitment was confirmed using tubastatin A and HDAC6 siRNA. Collectively, this study demonstrates that PSME4 is crucial for promoting the cardiac commitment of MSCs. HDAC inhibition acetylates YAP1 and facilitates its translocation to the nucleus, where it is removed by PSME4, promoting cardiac commitment. The failure of YAP1 to translocate or be eliminated from the nucleus results in the MSCs' inability to undergo cardiac commitment.

• Korean Circulation Journal
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• v.54 no.5
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• pp.233-252
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• 2024

Background and Objectives: Myocardial ischemia-reperfusion injury (MIRI) refers to the damage of cardiac function caused by restoration of blood flow perfusion in ischemic myocardium. However, long non-coding RNA prostate androgen regulated transcript 1 (PART1)'s role in MIRI remain unclear. Methods: Immunofluorescence detected LC3 expression. Intermolecular relationships were verified by dual luciferase reporter assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry and transferase-mediated dUTP nick-end labeling (TUNEL) assays analyzed cell viability and apoptosis. The release of lactate dehydrogenase was tested via enzyme-linked immunosorbent assay (ELISA). Left anterior descending coronary artery surgery induced a MIRI mouse model. Infarct area was detected by 2,3,5-triphenyltetrazolium chloride staining. Hematoxylin and eosin staining examined myocardial injury. ELISA evaluated myocardial marker (creatine kinase MB) level. Results: PART1 was decreased in hypoxia/reoxygenation (H/R) induced AC16 cells and MIRI mice. PART1 upregulation attenuated the increased levels of Bax, beclin-1 and the ratio of LC3II/I, and enhanced the decrease of Bcl-2 and p62 expression in H/R-treated cells. PART1 upregulation alleviated H/R-triggered autophagy and apoptosis via miR-302a-3p. Mechanically, PART1 targeted miR-302a-3p to upregulate transcription factor activating enhancer-binding protein 2C (TFAP2C). TFAP2C silencing reversed the protected effects of miR-302a-3p inhibitor on H/R treated AC16 cells. We further established TFAP2C combined to dual-specificity phosphatase 5 (DUSP5) promoter and activated DUSP5. TFAP2C upregulation suppressed H/R-stimulated autophagy and apoptosis through upregulating DUSP5. Overexpressed PART1 reduced myocardial infarction area and attenuated MIRI in mice. Conclusion: PART1 improved the autophagy and apoptosis in H/R-exposed AC16 cells through miR-302a-3p/TFAP2C/DUSP5 axis, which might provide novel targets for MIRI treatment.