• Clinical and Experimental Pediatrics
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• v.60 no.11
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• pp.365-372
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• 2017

Purpose: The mechanism for the pathogenesis of adriamycin (ADR)-induced cardiomyopathy is not yet known. Different hypotheses include the production of free radicals, an interaction between ADR and nuclear components, and a disruption in cardiac-specific gene expression. Apoptosis has also been proposed as being involved in cardiac dysfunction. The purpose of this study was to determine if apoptosis might play a role in ADR-induced cardiomyopathy. Methods: Male Sprague-Dawley rats were separated into 2 groups: the control group (C group) and the experimental group (ADR 5 mg/wk for 3 weeks through intraperitoneal injections; A group). Echocardiographic images were obtained at week 3. Changes in caspase-3, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), interleukin (IL)-6, tumor necrosis $factor-{\alpha}$, brain natriuretic peptide (BNP), troponin I, collagen 1, and collagen 3 protein expression from the left ventricle tissues of C and A group rats were determined by Western blot. Results: Ascites and heart failure as well as left ventricular hypertrophy were noted in the A group. Ejection fraction and shortening fraction were significantly lower in the A group by echocardiography. The expression of caspase-3, Bax, IL-6, BNP, collagen 1, and collagen 3 were significantly higher in the A group as compared with the C group. Protein expression of Bcl-2 decreased significantly in the A group compared with the C group. Conclusion: ADR induced an upregulation of caspase-3, Bax, IL-6, and collagen, as well as a depression in Bcl-2. Thus, apoptosis and fibrosis may play an important role in ADR-induced cardiomyopathy.

• Korean Circulation Journal
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• v.53 no.6
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• pp.406-417
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• 2023

Background and Objectives: Pathophysiological changes of right ventricle (RV) after repair of tetralogy of Fallot (TOF) are coupled with a highly compliant low-pressure pulmonary artery (PA) system. This study aimed to determine whether pulmonary vascular function was associated with RV parameters and exercise capacity, and its impact on RV remodeling after pulmonary valve replacement. Methods: In a total of 48 patients over 18 years of age with repaired TOF, pulmonary arterial elastance (Ea), RV volume data, and RV-PA coupling ratio were calculated and analyzed in relation to exercise capacity. Results: Patients with a low Ea showed a more severe pulmonary regurgitation volume index, greater RV end-diastolic volume index, and greater effective RV stroke volume (p=0.039, p=0.013, and p=0.011, respectively). Patients with a high Ea had lower exercise capacity than those with a low Ea (peak oxygen consumption [peak VO₂] rate: 25.8±7.7 vs. 34.3±5.5 mL/kg/min, respectively, p=0.003), while peak VO₂ was inversely correlated with Ea and mean PA pressure (p=0.004 and p=0.004, respectively). In the univariate analysis, a higher preoperative RV end-diastolic volume index and RV end-systolic volume index, left ventricular end-systolic volume index, and higher RV-PA coupling ratio were risk factors for suboptimal outcomes. Preoperative RV volume and RV-PA coupling ratio reflecting the adaptive PA system response are important factors in optimal postoperative results. Conclusions: We found that PA vascular dysfunction, presenting as elevated Ea in TOF, may contribute to exercise intolerance. However, Ea was inversely correlated with pulmonary regurgitation (PR) severity, which may prevent PR, RV dilatation, and left ventricular dilatation in the absence of significant pulmonary stenosis.

• Journal of Chest Surgery
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• v.39 no.9 s.266
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• pp.659-667
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• 2006

Background: Experimental studies of vascular remodeling in the pulmonary arteries have been performed actively. These models required a persistent vascular insult for intimal injury induced by chronic hypoxia, monocrotaline intoxication or chronic air embolism and characterized medial hypertrophy and neointimal formation by active synthesis of the extracellular matrix protein. The purpose of this study was to determine the pattern of pulmonary vascular remodeling after obstruction of the pulmonary vein. Material and Method: Obstruction of the right pulmonary vein with a metal clip was performed in Sprague-Dawley rats $(352{\pm}18g,\;n=10)$ to cause pulmonary vascular disease. Fifteen days later, experimental studies were done and finally the both lungs and hearts were extirpated for experimental measurement. Pulmonary arterial pressure, weight ratio of right ventricle (RV) to left ventricle (LV) and ventricular septum (S) (RV/LV +S weight ratio), and pulmonary artery morphology (percent wall thickness, %WT) were evaluated and compared with normal control groups. Result: Pulmonary hypertension $(38{\pm}12mmHg\;vs\;13{\pm}4mmHg;\;p<0.05)$ and right ventricular hypertrophy (right ventricular/left ventricular and septal weight ratio, $0.52{\pm}0.07\;vs\;0.35{\pm}0.04;\;p<0.05$) with hypertrophy of the muscular layer of the pulmonary arterial wall (percent wall thickness, $22.4{\pm}6.7%\;vs\;6.7{\pm}3.4%;\;p<0.05$) were developed by 15 days after obstruction of the pulmonary vein. Conclusion: Obstruction of the pulmonary vein developed elevation of pulmonary blood pressure and medial hypertrophy of the pulmonary artery. These results are a part of the characteristic vascular remodeling. Theses results demonstrate that obstruction of the pulmonary vein can develope not only high pulmoanry blood flow of contralateral lung but also intima injury inducing vascular remodeling.

• Journal of Chest Surgery
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• v.37 no.9
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• pp.755-761
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• 2004

We evaluated the efficacy of Dor procedure in patients with ischemic left ventricular dysfunction. Material and Method: Between April 1998 and December 2002, 45 patients underwent the Dor procedure con-comitant with coronary artery bypass grafting (CABG). Left ventricular ejection fraction (LVEF) and left ventricular end-diastolic/end-systolic volumes (LVEDV/LVESV) were measured by echocardiography, myocardial SPECT, and cardiac catheterization and angiography performed at the sequence of preoperative, early postoperative, and one year postoperative stage. Result: Cardiopulmonary bypass and aortic clamp times were mean 141$\pm$64, 69$\pm$24 minutes, respectively. Intraaortic balloon pump (IABP) therapy was required in 19 patients (42%; 7 preoperatively, 9 intraoperatively, 3 postoperatively). Operative mortality rate was 2.2% (1/45). Postoperative morbidities were low cardiac output syndrome (12), atrial fibrillation (5), acute renal failure (4), and postoperative bleeding (4). Functional class (NYHA) was improved from classes 2.8 to 1.1 (p < 0,01). When we compared between the preoperative and early postoperative values, LVEF was improved from 32$\pm$9% to 52$\pm$11% (p<0.01). The asynergy portion decreased from 57$\pm$12% to 22$\pm$9%, and LVEDV/LVESV indexes improved from 125$\pm$39 mL/$m^2$, 85$\pm$30 mL/$m^2$ to 66$\pm$23 mL/$m^2$, 32$\pm$16 mL/$m^2$ (p<0.01). Although these changes in volumes were relatively preserved at postoperative one year, the left ventricular volumes showed a tendency to increase. Conclusion: After the Dor procedure for ischemic left ventricular dysfunction, LVEF improvement and left ventricular volume reduction were maintained till postoperative one year. The tendency for left ventricular volume to increase at postoperative one year suggested the requirement of strict medical management.

• The Korean Journal of Nuclear Medicine
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• v.34 no.1
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• pp.30-38
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• 2000

Purpose: We investigated the role of myocardial perfusion SPECT in prediction of ventricular dilatation and the role of revascularization including thrombolytic therapy and PTCA in prevention of ventricular dilatation after an acute myocardial infarction (AMI). Materials and Methods: We performed dipyridamole stress, 4 hour redistribution, and 24 hour reinjection Tl-201 SPECT in 16 patients with AMI two to nine days after attack. Perfusion and wall motion abnormalities were quantified by perfusion index (PI) and wall motion index (WMI). Left ventricular ejection fraction (LVEF), WMI and ventricular volume were measured within 1 week of AMI and after average of 6 months. According to serial changes of left ventricular end-diastolic volume (LVEDV), patients were divided into two groups. We compared WMI, PI and LVEF between the two groups. Relationships among degree of volume, stress-rest PI, WMI, CKMB, Q wave, LVEF and revascularization were analysed using multivariate analysis. Results: Only initial rest perfusion index was significantly different between the two groups (p<0.05). While initial LVEF, stress PI, CKMB, trial of revascularization procedure, presence of Q wave and WMI were not significantly different between the two groups. Eight of 16 patients (50%) showed LV dilatation on follow-up echocardiography. Three of 3 patients (100%) who did not undergo revascualrization procedure documented LV dilatation. And only 5 (38%) of the remaining 13 patients who underwent revascularization revealed LV dilatation. There was no difference in infarct location between the two groups. By multivariate linear regression analysis in patients only undergoing revascularization, rest perfusion index was the only significant factor. Conclusion: Myocardial perfusion SPECT performed prior to revascularization was useful in prediction of LV dilatation after an AMI. Rest perfusion index on myocardial perfusion plays as a significant predictor of left ventricular dilatation after AMI. And revascularization appears to be a valuable procedure in alleviating LV dilatation after AMI with or without viable myocardium in a limited number of patients studied retrospectively.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.2
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• pp.87-94
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• 2022

Myocardial infarction promotes cardiac remodeling and myocardial fibrosis, thus leading to cardiac dysfunction or heart failure. Peiminine has been regarded as a traditional anti-fibrotic Chinese medicine in pulmonary fibrosis. However, the role of peiminine in myocardial infarction-induced myocardial injury and fibrosis remained elusive. Firstly, rat model of myocardial infarction was established using ligation of the left coronary artery, which were then intraperitoneally injected with 2 or 5 mg/kg peiminine once a day for 4 weeks. Echocardiography and haemodynamic evaluation results showed that peiminine treatment reduced left ventricular end-diastolic pressure, and enhanced maximum rate of increase/decrease of left ventricle pressure (± dP/dt max) and left ventricular systolic pressure, which ameliorate the cardiac function. Secondly, myocardial infarction-induced myocardial injury and infarct size were also attenuated by peiminine. Moreover, peiminine inhibited myocardial infarction-induced increase of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α production, as well as the myocardial cell apoptosis, in the rats. Thirdly, peiminine also decreased the myocardial fibrosis related protein expression including collagen I and collagen III. Lastly, peiminine reduced the expression of p38 and phosphorylation of extracellular signal-regulated kinase 1/2 in rat model of myocardial infarction. In conclusion, peiminine has a cardioprotective effect against myocardial infarction-induced myocardial injury and fibrosis, which can be attributed to the inactivation of mitogen-activated protein kinase pathway.

• Journal of Chest Surgery
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• v.56 no.5
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• pp.295-303
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• 2023

Background: The use of Adriamycin (ADR), also known as doxorubicin, as a chemotherapy agent is limited by its detrimental adverse effects, especially cardiotoxicity. Recent studies have emphasized the crucial role of angiotensin II (Ang-II) in the development of ADR-induced cardiomyopathy. This study aimed to explore the potential cardioprotective effects of losartan in a rat model of ADR-induced cardiomyopathy. Methods: Male Sprague-Dawley rats were randomly divided into 3 groups: a control group (group C), an ADR-treated group (ADR 5 mg/kg/wk for 3 weeks via intraperitoneal injections; group A), and co-treatment of ADR with losartan group (same dose of ADR and losartan; 10 mg/kg/day per oral for 3 weeks; group L). Western blot analysis was conducted to demonstrate changes in brain natriuretic peptide, collagen 1, tumor necrosis factor (TNF)-α, interleukin-6, matrix metalloproteinase (MMP)-2, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), and caspase-3 protein expression levels in left ventricular (LV) tissues from each group. Results: Losartan administration reduced LV hypertrophy, collagen content, and the expression of pro-inflammatory factors TNF-α and MMP-2 in LV tissue. In addition, losartan led to a decrease in the expression of the pro-apoptotic proteins Bax and caspase-3 and an increase in the expression of the anti-apoptotic protein Bcl-2. Moreover, losartan treatment induced a reduction in the apoptotic area compared to group A. Conclusion: In an ADR-induced cardiomyopathy rat model, co-administration of ADR with losartan presented cardioprotective effects by attenuating LV hypertrophy, pro-inflammatory factors, and apoptosis in LV tissue.

• Journal of the Korean Society of Visualization
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• v.16 no.2
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• pp.31-37
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• 2018

Ischemic mitral regurgitation (IMR) is the primary mitral valve (MV) pathology in the aftermath of myocardial infarction as a consequence of regional left ventricular (LV) remodeling. We investigated the effect of asymmetric papillary muscle (PM) displacement and annular dilation on IMR development. Virtual MV modeling was performed to create a normal human MV. Asymmetric PM displacement, asymmetric annular dilation, and the combination of these two pathologic characteristics were modeled. Dynamic finite element evaluation of MV function was performed across the complete cardiac cycle for the normal and three different IMR MV models. While the normal MV demonstrated complete leaflet coaptation, each pathologic MV model clearly revealed deteriorated leaflet coaptation and abnormal stress distributions. The pathologic MV model having both asymmetric PM displacement and annular dilation showed the worst leaflet malcoaptation. Simulation-based biomechanical evaluation of post-ischemic LV remodeling provides an excellent tool to better understand the pathophysiologic mechanism of IMR development.

• 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.

• Korean Journal of Radiology
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• v.24 no.5
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• pp.395-405
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• 2023

Objective: This study aimed to develop and validate models using radiomics features on a native T1 map from cardiac magnetic resonance (CMR) to predict left ventricular reverse remodeling (LVRR) in patients with nonischemic dilated cardiomyopathy (NIDCM). Materials and Methods: Data from 274 patients with NIDCM who underwent CMR imaging with T1 mapping at Severance Hospital between April 2012 and December 2018 were retrospectively reviewed. Radiomic features were extracted from the native T1 maps. LVRR was determined using echocardiography performed ≥ 180 days after the CMR. The radiomics score was generated using the least absolute shrinkage and selection operator logistic regression models. Clinical, clinical + late gadolinium enhancement (LGE), clinical + radiomics, and clinical + LGE + radiomics models were built using a logistic regression method to predict LVRR. For internal validation of the result, bootstrap validation with 1000 resampling iterations was performed, and the optimism-corrected area under the receiver operating characteristic curve (AUC) with 95% confidence interval (CI) was computed. Model performance was compared using AUC with the DeLong test and bootstrap. Results: Among 274 patients, 123 (44.9%) were classified as LVRR-positive and 151 (55.1%) as LVRR-negative. The optimism-corrected AUC of the radiomics model in internal validation with bootstrapping was 0.753 (95% CI, 0.698-0.813). The clinical + radiomics model revealed a higher optimism-corrected AUC than that of the clinical + LGE model (0.794 vs. 0.716; difference, 0.078 [99% CI, 0.003-0.151]). The clinical + LGE + radiomics model significantly improved the prediction of LVRR compared with the clinical + LGE model (optimism-corrected AUC of 0.811 vs. 0.716; difference, 0.095 [99% CI, 0.022-0.139]). Conclusion: The radiomic characteristics extracted from a non-enhanced T1 map may improve the prediction of LVRR and offer added value over traditional LGE in patients with NIDCM. Additional external validation research is required.