• Molecules and Cells
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• v.43 no.8
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• pp.671-685
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• 2020

The regulator of calcineurin (RCAN) was first reported as a novel gene called DSCR1, encoded in a region termed the Down syndrome critical region (DSCR) of human chromosome 21. Genome sequence comparisons across species using bioinformatics revealed three members of the RCAN gene family, RCAN1, RCAN2, and RCAN3, present in most jawed vertebrates, with one member observed in most invertebrates and fungi. RCAN is most highly expressed in brain and striated muscles, but expression has been reported in many other tissues, as well, including the heart and kidneys. Expression levels of RCAN homologs are responsive to external stressors such as reactive oxygen species, Ca²⁺, amyloid β, and hormonal changes and upregulated in pathological conditions, including Alzheimer's disease, cardiac hypertrophy, diabetes, and degenerative neuropathy. RCAN binding to calcineurin, a Ca²⁺/calmodulin-dependent phosphatase, inhibits calcineurin activity, thereby regulating different physiological events via dephosphorylation of important substrates. Novel functions of RCANs have recently emerged, indicating involvement in mitochondria homeostasis, RNA binding, circadian rhythms, obesity, and thermogenesis, some of which are calcineurin-independent. These developments suggest that besides significant contributions to DS pathologies and calcineurin regulation, RCAN is an important participant across physiological systems, suggesting it as a favorable therapeutic target.

• The Journal of Internal Korean Medicine
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• v.27 no.1
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• pp.102-113
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• 2006

Objectives & Methods : To obtain the 50% lethal dose(LD50), approximated lethal dose(ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study into such things as repeated dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male SD rats according to KFDA Guideline 1999-61[KFDA, 1999] at dosage levels of 2,000, 1,000, 500, 250 and 125 mg/kg/$10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. Results & Conclusions : After 2 or 3 days of dosing, 1 or 2 animals in 2,000 mg/kg-dosing groups died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and survivors recovered to normal within 3 or 4 days after dosing. Significant decrease in body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group, from 1 days after dosing compared to those of vehicle control group. Significantly diminished body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy and hemorrhage of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. The value for LD50 found in this study was 2,218.57 mg/kg. ALD in this study was 2,000 mg/kg, and the target organs are considered to be the heart and the kidney.

• Journal of Chest Surgery
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• v.17 no.4
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• pp.593-606
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• 1984

With the ligation of patent ductus arteriosus by Gross in 1938, surgeons first entered the field of congenital heart disease. Interruption of a ductus is one of the most satisfactory and curative operations in the field of surgery for congenital heart disease. 27 cases of isolated patent ductus arteriosus were operated from Jan. 1978 to July 1984 at the Department of Thoracic & Cardiovascular Surgery in Kyung-Hee University Hospital. Retrospective clinical analysis of these patients were: 1. Sex ratio, female: male, was 2:1. 2. Mean age at operation was 9.85\ulcorner.58 years. The youngest patient was a 23 month-old girl and the oldest one was a 24 year-old male. 3. More than half of the patients had less than 50 percentile of growth retardation. 4. Chief complaints of the patients were frequent URI [52%], dyspnea on exertion [33%], generalized weakness [22%], palpitation [7%], but 7 patients [26%] had no subjective symptoms. 5. Continuous machinery murmur could be heard at the 2nd or 3rd intercostal space on the left sternal border in 22 patients [81%]. The other S patients made systolic murmur with accentuation of the second heart sound and those were associated with pulmonary hypertension. 6. Radiologic findings of Chest P-A were cardiac enlargement in 15 patients [55%], enlargement of pulmonary conus and/or increasing density of pulmonary vascularity in 20 patients [74%]. 7. Electrocardiographic findings of the patients were within normal limit in 13 patients [48%], LVH in 4 patients [15%], biventricular hypertrophy in 3 patients [11%]. 8; echocardiogram was obtained from 11 patients. Ductus was directly visualized in 7 patients. Left atrial enlargement is the secondary change of left to right shunt, 10 patients had LA/Ao ratio more than 1.2. 9. Cardiac catheterization performed in 25 patients. The mean value of the results were:SO2[PA-RV]= 14.72\ulcorner6.01%, Qp/Qs=2.22\ulcorner.80, peak systolic pulmonary arterial pressure=48.28\ulcorner1.60 mmHg. 10. 26 patients were operated through the left posterolateral thoracotomy: closure of ductus by double ligation in 14 cases, triple ligation in 5 cases, and division with suture in 8 cases. One patient suffer from aneurysmal rupture of main pulmonary artery, endocarditis, hemopericardium was treated with cardiopulmonary bypass via median sternotomy and closure of ductus through the ruptured main pulmonary artery. 11.There was no death associated with the operation, but 3 cases were experienced with intraoperative rupture around the ductus resulting in massive bleeding. The other complications were transient hoarseness in one patient, atelectasis in left lower lobe in 3 patients, and postoperative systemic hypertension in 4 patients with unknown etiology. 12. Pulse pressure was reduced, 11.47+5.92 mmHg, postoperatively, as compare to preoperative status. 13. Intraoperative wedge lung biopsy from lingular segment for the evaluation of the pulmonary vascular disease was taken in S patients with severe pulmonary hypertension. The result was Heath-Edward grade I in one case, grade II in two cases, and grade III in two cases.

• Journal of Chest Surgery
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• v.23 no.6
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• pp.1180-1190
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• 1990

96 patients underwent cardiac valve replacement for valvular heart diseases consecutively between February 1986 to February 1990 in the Department of Thoracic and Cardiovascular Surgery of Yeungnam University Hospital. The follow up period was between 6 months and 4.5 years postoperatively[mean 23.4$\pm$13.1 months]. 75 cases got mitral valve replacement, 6 cases, aortic valve replacement, 15 cases, double valve replacement. 30[31.2%] patients were male and 66[68.8%] were female and the age ranged from 14 to 66 years old. Early hospital death within 30 days postoperation were 5 patients[5.2%], consisting of by low cardiac output in 2, infective endocarditis in 1, multiple organ failure with sepsis in 1 patient. There was no late postoperative death. Most common early postoperative complication was wound disruption [8.7%] and then low cardiac output, pneumothorax, pleural effusion in order. Most common late postoperative complications were minor bleeding episodes[8.7%] related to anticoagulant therapy which were consisted of frequent epistaxis in 3, gum bleeding in 2, hemorrhagic gastritis in 1, hypermenorrhea in 1, hematoma in right arm in 1 patient. Valve-related complications included valve thrombosis [1.6%/ patient-year], valve failure due to pannus formation[1.1% /patient-year], prosthetic valve endocarditis[1, 1%o/patient-year] and minor anticoagulant hemorrhage[4.4% /patient-year]. 5 cases of reoperations were performed in 4 patients due to valve failure and all of them were in the mitral positions[2.7% /patient-year]. Cardiothoracic ratios in the chest X-ray decreased at the 6th month and 1st year postoperation in all patients. But in New York Heart Association[NYHA] functional class IV, no change in cardiothoracic ratio was found between 6 months and 1 year postoperation. In the echocardiogram, the size of the cardiac chambers decreased, but ejection fraction increased postoperatively in each functional class. In the electrocardiogram, decreases were found in the incidence of atrial fibrillation, left atrial enlargement, left ventricular hypertrophy with right bundle branch block increasing postoperatively in each functional class. The actuarial survival rate was 98.4% for all patients, 98.7% for mitral valve replacement, 83.8% for aortic valve replacement, and 80% for double valve replacement at the end of a 4.5 year follow up period. Meanwhile the actuarial freedom rate was 91.5% for prosthetic valve endocarditis, 91.6% for thromboembolism, 89.0% for prosthetic valve failure and 83.7% for minor anticoagulant hemorrhage. Preoperative NYHA class III and IV were 75% of all patients, but 95% of all patients were up graded to NYHA class I and II postoperatively.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.442-448
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• 2006

To obtain the 50% lethal dose (LD50), approximated lethal dose (ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study like repeat dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male ICR mouse according to KFDA Guideline 1999-61 [KFDA, 1999] at a dosage level of 2,000, 1,000, 500, 250 and $125\;mg/kg/10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. After 2 or 3 days of dosing, 1 or 2 animals in 2,000 and 1,000 mg/kg-dosing groups were died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and they were recovered to normal within 4 days after dosing in case of survivors. A significant decrease of body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group from 1 days after dosing compared to those of vehicle control group. A significant decrease of body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. LD50 in this study was detected as 2,242.42 mg/kg. ALD in this study was detected as 1,000 mg/kg and the target organ was considered as the heart and kidney.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.6
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• pp.607-616
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• 2018

The effect of melatonin on juveniles with cardio fibrosis is poorly understood. We investigated whether HDACs participate in the anti-fibrotic processes regulated by melatonin during hypertrophic remodeling. Abdominal aortic constriction (AAC) was employed in juvenile rats resulting in pressure overload-induced ventricular hypertrophy and melatonin was subsequently decreased via continuous light exposure for 5 weeks after surgery. AAC rats displayed an increased cross-sectional area of myocardial fibers and significantly elevated collagen deposition compared to sham-operated rats, as measured by HE and Masson Trichrome staining. Continuous light exposure following surgery exacerbated the increase in the cross-sectional area of myocardial fibers. The expression of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 genes were all significantly enhanced in AAC rats with light exposure relative to the other rats. Moreover, the protein level of $TNF-{\alpha}$ was also upregulated in the AAC light exposure groups when compared with the sham. However, Smad4 protein expression was unchanged in the juveniles' hearts. In contrast, beginning 5 weeks after the operation, the AAC rats were treated with melatonin (10 mg/kg, intraperitoneal injection every evening) or vehicle 4 weeks, and sham rats were given vehicle. The changes in the histological measures of cardio fibrosis and the gene expressions of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 were attenuated by melatonin administration. The results reveal that melatonin plays a role in the development of cardio fibrosis and the expression of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 in cardiomyocytes.

• Journal of Chest Surgery
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• v.38 no.3 s.248
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• pp.197-203
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• 2005

Homograft aortic valve replacement (AVR) has many advantages such as excellent hemodynamic performance, faster left ventricular hypertrophy regression, resistance to infection and excellent freedom of thromboembolism. To find out the results of homograft AVR, we reviewed our surgical experiences. Material and Method: Eighteen patients (male female=16 : 2, mean age=39.3$\pm$16.2 years, range: 14$\~$68 years) who underwent homo-graft aortic valve replacement between May 1995 and May 2004 were reviewed. The number of homografts was 20 (17 aortic and 3 pulmonic homografts) including two re-operations. Ten patients had a history of previous aortic valve surgery. Indications for the use of a homograft were native valve endocarditis (n=7), prosthetic valve endocarditis (n=5), or Behcet's disease (n=8). The homograft had been implanted predominantly as a full root except in one patient in the subcoronary position. Result: Mean follow-up was 41.3 $\pm$ 26.2 months. There was one operative mortality. Postoperative complications included postoperative bleeding in 3 patients, and wound infection in 1. There was no late death. Three patients underwent redo-AVR. The etiology of the three reoperated patients was Behcet's disease (p=0.025). Freedom from reoperation was $87.5\pm8.3\%$, $78.8\pm11.2\%$ at 1, 5 years respectively, In patients with infective endocarditis, there was no recurrence of endocarditis. There was no thromboembolic complication. Conclusion: Although longer term follow-up with larger numbers of patients is necessary, the operative and mid-term results for homograft AVR was good when we took into account the operative risks of Behcet's disease or infective endocarditis. Behest's disease was a risk factor for reoperation after the homograft AVR. We think homograft AVR is the procedure of choice, particularly in patients with infective endocarditis.

• Journal of Chest Surgery
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• v.36 no.9
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• pp.651-658
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• 2003

Since the first implanted in September 1997, the use of On-X prosthetic heart valve has been increasing around in the world. This study was designed to assess the feasibility, safety, and the postoperative hemodynamics with this new valve in clinical setting. Material and Method: The current study was carried out on 52 patients undergoing aortic valve replacement with this prosthesis between April 1999 to August 2002 at Chonnam National University Hospital to evaluate the surgical results. 52％ of the patients were male and the average age at implant was 50$\pm$13 years. The study followed the guidelines of the AATS/STS. Preoperatively, 32(61.5％) patients were in NYHA functional class III or IV and 2 patients had previous aortic valve surgery. Concomitant cardiac surgery was performed in 71.1％. The implanted valve sizes were 19 mm in 13 patients, 21 mm in 26, 23 mm in 10 and 25 mm in 3, respectively. Mean follow-up was 16.6$\pm$10.5 months (1∼39 months). Echocardiographic assessment was performed pre- and immediate postoperatively, as well as 3, 6, 12 months after surgery, evaluating pressure loss and regression of left ventricular hypertrophy. Result: Mean cardiopulmonary bypass time was 191$\pm$94.7 minutes with an aortic cross-clamp time of 142$\pm$51.7 minutes. There was no early and late mortality, Freedom from adverse events at 1 year in the study were as follows: thromboembolism, 95.6$\pm$6％; bleeding events, 90.2$\pm$4％; paravalvular leakage 92.3$\pm$4％; and overall valve-related morbidity at 1 year was 76.6$\pm$3％. There were no cases of valve thrombosis, prosthetic valve endocarditis and structural or non-structural failure. Left ventricular function at 12 months after surgery (EF=62.7$\pm$9.8％) revealed a statistically significant improvement compared to preoperative investigation (EF=55.8$\pm$15.9％, p=0.006). Left ventricular mass index was 247.3$\pm$122.3 g/$m^2$ on preoperative echocardiographic study, but regressed to 155.5$\pm$58.2 g/$m^2$ at postoperative 1 year (p=0.002). Over the follow-up period a further decrease of peak transvalvular gradients was observed in all patients: 62.5$\pm$38.0 mmHg on preoperative assessment, 18.2$\pm$6.8 mmHg at immediate postoperative period (p < 0.0001), 7.6$\pm$5.09 mmHg (p<0.0001) at 6 month, 18.0$\pm$10.8 mmHg (p<0.0001) at 1 year. Conclusion: The On-X prosthetic heart valve performs satisfactorily in the first 1 year period. Clinical outcome by examining NYHA functional classification revealed especially good results. Effective regression of left ventricular hypertrophy and statistically significant decrease of transvalvular gradient were observed over the first year, but longer-term follow-up of this patient group is needed to establish the expected rates for late valve-related events as well as the long-term clinical efficacy of this valve.

• Clinical and Experimental Pediatrics
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• v.56 no.6
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• pp.235-241
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• 2013

Repair of tetralogy of Fallot (TOF) has shown excellent outcomes. However it leaves varying degrees of residual hemodynamic impairment, with severe pulmonary stenosis (PS) and free pulmonary regurgitation (PR) at both ends of the spectrum. Since the 1980s, studies evaluating late outcomes after TOF repair revealed the adverse impacts of residual chronic PR on RV volume and function; thus, a turnaround of operational strategies has occurred from aggressive RV outflow tract (RVOT) reconstruction for complete relief of RVOT obstruction to conservative RVOT reconstruction for limiting PR. This transformation has raised the question of how much residual PS after conservative RVOT reconstruction is acceptable. Besides, as pulmonary valve replacement (PVR) increases in patients with RV deterioration from residual PR, there is concern regarding when it should be performed. Regarding residual PS, several studies revealed that PS in addition to PR was associated with less PR and a small RV volume. This suggests that PS combined with PR makes RV diastolic property to protect against dilatation through RV hypertrophy and supports conservative RVOT enlargement despite residual PS. Also, several studies have revealed the pre-PVR threshold of RV parameters for the normalization of RV volume and function after PVR, and based on these results, the indications for PVR have been revised. Although there is no established strategy, better understanding of RV mechanics, development of new surgical and interventional techniques, and evidence for the effect of PVR on RV reverse remodeling and its late outcome will aid us to optimize the management of TOF.

• Clinical and Experimental Pediatrics
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• v.55 no.9
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• pp.350-353
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• 2012

An 18-year-old boy was admitted with chest discomfort, nausea, and dyspnea at rest. At the age of 3 years, he underwent muscle biopsy and dystrophin gene analysis owing to an enlarged calf muscle and elevated serum kinase level (6,378 U/L) without overt weakness; based on the results, Becker muscular dystrophy (BMD) was diagnosed. The dystrophin gene showed deletion of exons 45 to 49. He remained ambulant and could step upstairs without significant difficulties. A chest roentgenogram showed cardiomegaly (cardiothoracic ratio, 54%), and his electrocardiogram (ECG) showed abnormal ST-T wave, biatrial enlargement, and left ventricular hypertrophy. The 2-dimensional and M-mode ECGs showed a severely dilated left ventricular cavity with diffuse hypokinesis. The systolic indices were reduced, including fractional shortening (9%) and ejection fraction (19%). Despite receiving intensive medical treatment, he died from congestive heart failure 5 months after the initial cardiac symptoms. We report a case of BMD with early-onset dilated cardiomyopathy associated with deletion of exons 45 to 49. Early cardiomyopathy can occur in BMD patients with certain genotypes; therefore, careful follow-up is required even in patients with mild phenotypes of BMD.