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1.  Determinants of Brachial-Ankle Pulse Wave Velocity and Carotid-Femoral Pulse Wave Velocity in Healthy Koreans 
Journal of Korean Medical Science  2014;29(6):798-804.
The aim of this study was to determine the normal value of brachial-ankle pulse wave velocity (baPWV) and carotid-femoral pulse wave velocity (cfPWV) according to age group, gender, and the presence of cardiovascular risk factors in healthy Koreans, and to investigate the association between PWV and risk factors such as prehypertension, dyslipidemia, smoking, and obesity. We measured an arterial stiffness in 110 normal subjects who were 20 to 69 yr-old with no evidence of cardiovascular disease, cerebrovascular accident or diabetes mellitus. The mean values of baPWV and cfPWV were 12.6 (±2.27) m/sec (13.1±1.85 in men, 12.1±2.51 in women; P=0.019) and 8.70 (±1.99) m/sec (9.34±2.13 in men, 8.15±1.69 in women; P=0.001), respectively. The distribution of baPWV (P<0.001) and cfPWV (P=0.006) by age group and gender showed an increase in the mean value with age. Men had higher baPWV and cfPWV than women (P<0.001). There was a difference in baPWV and cfPWV by age group on prehypertension, dyslipidemia, current smoking, or obesity (P<0.001). In multiple linear regression, age and prehypertension were highly associated with baPWV and cfPWV after adjustment for confounding factors (P<0.001). The present study showed that baPWV and cfPWV are associated with age, gender, and prehypertension in healthy Koreans.
Graphical Abstract
PMCID: PMC4055813  PMID: 24932081
Prehypertension; Gender Identity; Age Groups; Ankle Brachial Index; Carotid-Femoral; Pulse Wave Analysis
2.  Clinical Utility of Coronary CT Angiography with Stress Perfusion CT in Preoperative Cardiac Risk Evaluation 
Korean Circulation Journal  2014;44(3):170-176.
Background and Objectives
Vascular surgery carries high operative risk. Recently developed cardiac computed tomography (CT) provides excellent imaging of coronary artery disease (CAD), as well as myocardial perfusions. We investigated the role of stress perfusion CT with coronary computed tomography angiography (CCTA) using 128-slice dual source CT (DSCT) in preoperative cardiac risk evaluation.
Subjects and Methods
Patients scheduled for vascular surgery were admitted and underwent the adenosine stress perfusion CT with CCTA using DSCT. Patients who presented with unstable angina, recent myocardial infarction, decompensated heart failure, or renal failure were excluded. Stress perfusion CT was first acquired using sequential mode during adenosine infusion, after which, scanning for CT angiography was followed by helical mode. Perioperative events were followed up for 1 month.
Ninety-one patients completed the study. Most patients (94.5%) had coronary atherosclerosis, with 36 (39.6%) patients had more than 50% coronary artery stenosis. Perfusion defects with significant stenosis were found in 12 cases (13.2%). Revascularization after DSCT was rarely performed. Four patients (4.4%) experienced cardiac events in the perioperative period: two experienced heart failure and two had non-fatal myocardial infarction.
We cannot conclude that the stress perfusion CT, with CCTA using DSCT, plays a significant role in preoperative risk evaluation from this study. However, the coronary atherosclerosis and the significant CAD were commonly found. The perfusion defects with significant lesions were found in only small fraction of the patients, and did not contribute to perioperative myocardial infarction or heart failure.
PMCID: PMC4037639  PMID: 24876858
Vascular surgical procedure; Coronary artery disease; Multidetector computed tomography; Myocardial perfusion imaging
3.  Immunoglobulin G4 Non-Related Sclerosing Disease with Intracardiac Mass Mimicking Mitral Stenosis: Case Report 
Journal of Korean Medical Science  2013;28(12):1830-1834.
The cardiovascular system may be one of the target organs of both immunoglobulin G4 related and non-related systemic multifocal fibrosclerosis. We present a case of IgG4 non-related systemic multifocal fibrosclerosis mimicking mitral stenosis on echocardiography. For a more detailed differential diagnosis, we used multimodal imaging techniques. After surgical biopsy around the abdominal aortic area in the retroperitoneum, histological examination revealed IgG4 non-related systemic multifocal fibrosclerosis. We describe the multimodal imaging used to diagnose IgG4 non-related systemic multifocal fibrosclerosis and a positive response to steroid treatment. There have been no previous case reports of IgG4 non-related systemic multifocal fibrosclerosis with intracardiac involvement. Here, we report a case of IgG4 non-related systemic multifocal fibrosclerosis mimicking mitral stenosis.
PMCID: PMC3857383  PMID: 24339717
Immunoglobulin G4 Non-Related Sclerosing Disease; Periaortitis; Left Atrium Mass; Mitral Valve Stenosis
4.  Comparison of Cardiovascular Risk Factors for Peripheral Artery Disease and Coronary Artery Disease in the Korean Population 
Korean Circulation Journal  2013;43(5):316-328.
Background and Objectives
The objective of this study was to analyze and compare risk factors for peripheral artery disease (PAD) and coronary artery disease (CAD).
Subjects and Methods
The sample included 7936 Korean patients aged ≥20 years who were hospitalized from 1994 to 2004. Of the 7936 subjects, PAD (n=415), CAD (n=3686), and normal controls (Control) (n=3835) were examined at the Health Promotion Center, Samsung Medical Center.
The mean age (years) of PAD subjects was 64.4 (±9.3), while CAD subjects was 61.2 (±9.9), and Control subjects was 59.9 (±9.1) (p<0.01). The proportion of males was 90.6% for PAD, 71.4% for CAD, and 75.5% for Control subjects (p<0.01). The adjusted odds ratios (ORs) for hypertension, diabetes mellitus, hypercholesterolemia, smoking, metabolic syndrome and chronic kidney disease were significantly higher in subjects with PAD or CAD compared to those in Control. However, the ORs for high density lipoprotein, being overweight, and being obese were significantly lower in PAD subjects compared to those in Control.
We found that cardiovascular risk factors were in fact risk factors for both PAD and CAD.
PMCID: PMC3675306  PMID: 23755078
Peripheral artery disease; Coronary artery disease; Risk factors
5.  Dose fentanyl injection for blunting the hemodynamic response to intubation increase the risk of reflex bradycardia during major abdominal surgery? 
Korean Journal of Anesthesiology  2012;63(5):402-408.
Although supplemental fentanyl has been widely used to blunt the hemodynamic responses to laryngoscopic intubation, its residual vagotonic effect may increase the risk of reflex bradycardia. We compared the incidence and severity of significant reflex bradycardia after a bolus injection of equivalent doses of fentanyl and remifentanil (control drug).
In this prospective, randomized, double-blind study, 220 adult patients undergoing major abdominal surgery were randomly assigned to receive fentanyl (1.5 µg/kg) or remifentanil (1.5 µg/kg). No anticholinergic prophylaxis was administered. Symptomatic reflex bradycardia was defined as a sudden decrease in heart rate to < 50 beats per minute (bpm) or to 50-59 bpm associated with a systolic arterial pressure < 70 mmHg in connection with surgical maneuvers. If bradycardia or hypotension developed, atropine or ephedrine was administered following a predefined treatment protocol.
In total, 188 subjects (remifentanil, 95; fentanyl, 93) were included. The proportion of subjects with symptomatic reflex bradycardia in the fentanyl group was similar to that in the remifentanil group (30.1% vs. 28.4%, respectively). Atropine and/or ephedrine were needed similarly in both groups. The differences between the group of 55 patients who presented with symptomatic reflex bradycardia were not statistically significant with respect to the lowest heart rate, anesthetic depth-related data (bispectral index and end-tidal sevoflurane concentration), or the proportion of causative surgical maneuvers.
Fentanyl (1.5 µg/kg) administered intravenously during anesthetic induction is unlikely to increase the incidence and severity of significant reflex bradycardia in patients undergoing major abdominal surgery.
PMCID: PMC3506848  PMID: 23198032
Bradycardia; Fentanyl; Reflex; Surgical procedures
6.  Hereditary Thrombophilia in Korean Patients with Idiopathic Pulmonary Embolism 
Yonsei Medical Journal  2012;53(3):571-577.
Hereditary thrombophilia (HT) is a major risk factor for idiopathic pulmonary embolism (iPE) and shows different prevalence among ethnic groups. The prevalence and clinical characteristics of HT in Korean patients with iPE were investigated.
Materials and Methods
Patients with PE on computed tomography (CT) scan were recruited, and those with malignancy were excluded. Patients were divided into iPE and provoked PE (pPE) groups. The presence of HT in the iPE group was assessed by DNA sequencing of the corresponding gene in patients who had low levels of natural anticoagulants. The clinical characteristics of iPE with HT (iPE/HT+) were compared with those of iPE without HT (iPE/HT-) and pPE.
Out of 161 patients, 84 patients had iPE and 77 patients had pPE. Among 54 patients in the iPE group whose coagulation profiles were tested, 28 patients were diagnosed with HT (51.9%; 28/54). Compared with the iPE/HT- and pPE groups, the iPE/HT+ group showed the highest proportion of male patients (71.4%; p<0.001); the youngest mean age (44±14 years; p<0.001); and the highest frequencies for history of venous thromboembolism (64.3%; p<0.001), concurrent deep vein thrombosis (75.0%; p=0.021), and adverse clinical outcomes (42.9%, p<0.001). Protein C deficiency was the most common HT. On molecular genetic tests, causative mutation was identified in 13 patients.
In this study of Korean patients, about half of the patients with iPE had HT. Patients with iPE and HT were mostly young males with deep venous thrombosis (DVT), previous venous thromboembolism (VTE), and frequent adverse clinical outcomes. Therefore, Korean patients with iPE should be tested for HT.
PMCID: PMC3343445  PMID: 22477002
Pulmonary embolism; hereditary thrombophilia; protein C deficiency; Korea
7.  Angiopoietin-1 Gene Therapy Attenuates Hypertension and Target Organ Damage in Nitric Oxide Synthase Inhibited Spontaneously Hypertensive Rats 
Korean Circulation Journal  2011;41(10):590-595.
Background and Objectives
In our previous study, we found that the gene transfer of a potent derivative of cartilage oligomeric matrix protein Angiopoietin-1 (COMP-Ang-1) substantially prevented hypertension, microvascular rarefaction, and target organ damage in spontaneously hypertensive rats (SHRs). The purpose of the present study was to examine the role of nitric oxide (NO) in the therapeutic effects observed after COMP-Ang-1 gene transfer.
Materials and Methods
To exclude the NO-mediated effects in COMP-Ang-1 gene therapy, the SHRs were treated with an NO synthase (NOS) inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME) before the electrophoretic gene transfer.
The pretreatment with L-NAME induced a severe and sustained increase in systolic blood pressure (BP) in a LacZ plasmid transferred control SHR. However, the electrophoretic transfer of a COMP-Ang-1 plasmid instead of LacZ plasmid in L-NAME-pretreated SHRs substantially blocked the development of hypertension without any significant difference in comparison with L-NAME-untreated COMP-Ang-1 plasmid transferred groups. In addition, the COMP-Ang-1 plasmid transfer substantially attenuated microvascular rarefaction and arteriole remodeling in the heart and kidney, which might account for the mild histological alterations observed in the COMP-Ang-1 plasmid transferred group, in contrast to the severe fibrosis and necrosis seen in the LacZ plasmid controls.
These therapeutic outcomes of COMP-Ang-1 gene transfer even in NOS inhibited SHRs suggested that the antihypertensive effect of COMP-Ang-1 was not merely secondary to NO-mediated vasorelaxation, but it may be associated with its ability to protect the vascular endothelium probably via an NO-independent mechanism which serves to attenuate microvascular rarefaction and target organ damage, and also to prevent hypertension by reducing peripheral vascular resistance.
PMCID: PMC3221901  PMID: 22125558
Angiopoietin-1; Endothelium; Hypertension; Nitric oxide
8.  Analysis of expert consultation referrals for anesthesia-related issues (December 2008-July 2010): KSA legislation committee report 
Korean Journal of Anesthesiology  2011;60(4):260-265.
Since 2009, database construction of anesthesia-related adverse events has been initiated through the legislation committee of the Korean Society of Anesthesiologists (KSA), based on expert consultation referrals provided by police departments, civil courts, and criminal courts.
This study was a retrospective descriptive analysis of expert consultation referrals on surgical anesthesia-related cases between December 2008 and July 2010.
During the given period, 46 surgical anesthesia-related cases were referred to the KSA legislation committee for expert consultation. Because six cases were excluded due to insufficient data, 40 cases were included in the final analysis. Of 40 cases, 29 (72.5%) resulted in death. Respiratory events were most common in both surviving/disabled and dead patients (36.4 vs. 51.7%, respectively; P > 0.05). Overall, respiratory depression due to the drugs used for monitored anesthesia care (MAC) was the most common specific mechanism (25%), in which all but one case (profound brain damage) resulted in death. In all of these cases, surgeons or physicians provided MAC without the help of anesthesiologists.
Overall, the most common damaging mechanism was related to respiratory depression due to sedatives or anesthetics used for MAC. Almost all MAC injury cases are believed to be preventable with the use of additional or better monitoring and an effective response to initial physiological derangement. Thus, it is essential to establish practical MAC guidelines and adhere to these guidelines strictly to reduce the occurrence of severe anesthesia-related adverse outcomes.
PMCID: PMC3092961  PMID: 21602976
Complications; Malpractice; Medical legislation; Outcome assessment
9.  Genetic Analysis of Three Korean Patients with Clinical Features of Ehlers-Danlos Syndrome Type IV 
Journal of Korean Medical Science  2007;22(4):698-705.
Ehlers-Danlos syndrome (EDS) is a hereditary disorder of the connective tissue. EDS type IV (EDS IV), the vascular type of the disease, is characterized by easy bruising, thin skin with visible veins, and spontaneous rupture of the large arteries, uterus, or bowel. EDS IV is caused by mutations in the gene for type III procollagen (COL3A1). However, recent studies suggest that the causative mutation of EDS IV is not homogeneous. We report our experience with three patients presenting with clinical features of type IV EDS. A 48-yr-old woman presented with acute aortic dissection (patient 1) and 36-yr-old and 21-yr-old women presented with carotid-cavernous fistula (patients 2 and 3, respectively). All three patients bruised easily. Two patients (patients 1 and 3) had thin transparent skin with visible veins. Genetic analysis of COL3A1 revealed a Gly732Val (c.2195G>T) mutation in patient 1 and a duplication of 15 base pairs (c.3221_3235dup) which resulted in an interposition of five amino acids (p.Gly1074_Pro1078dup) in patient 2. However, no mutations were observed in COL3A1 or transforming growth factor β receptors 1 and 2 in patients 3, which might be either due to a deletion of single or multiple exons in the COL3A1 gene or due to a genetic heterogeneity. This is the first report of genetically confirmed cases of EDS IV in Korea.
PMCID: PMC2693823  PMID: 17728513
Ehlers-Danlos Syndrome Type IV; COL3A1; Mutation; Dissection; Carotid-cavernous Sinus Fistula
10.  Cardiac Dysrhythmias, Cardiomyopathy and Muscular Dystrophy in Patients with Emery-Dreifuss Muscular Dystrophy and Limb-Girdle Muscular Dystrophy Type 1B 
Journal of Korean Medical Science  2005;20(2):283-290.
Emery-Dreifuss muscular dystrophy (EDMD) and limb-girdle muscular dystrophy type 1B (LGMD1B) are characterized by cardiac dysrhythmias, late-onset cardiomyopathy, slowly progressive skeletal myopathy and contractures of the neck, elbows and ankles. The causative mutation is either in the emerin gene (X-linked recessive EDMD) or lamin A/C gene (autosomal dominant EDMD2 or LGMD1B). We report three cases of EDMD, EDMD2 and LGMD1B. A 14-yr-old boy showed limitation of cervical flexion and contractures of both elbows and ankles. Sinus arrest with junctional escape beats was noted. He was diagnosed as X-linked recessive EDMD (MIM 310300). A 28-yr-old female showed severe wasting and weakness of humeroperoneal muscles. Marked limitation of cervical flexion and contractures of both elbows and ankles were noted. Varying degrees of AV block were noted. She was diagnosed as autosomal dominant EDMD2 (MIM 181350). A 41-yr-old female had contractures of both ankles and limb-girdle type muscular dystrophy. ECG revealed atrial tachycardia with high grade AV block. She was diagnosed as autosomal dominant LGMD1B (MIM 159001). Cardiac dysrhythmias in EDMD and LGMD1B include AV block, bradycardia, atrial tachycardia, atrial fibrillation, and atrial standstill, causing sudden death necessitating pacemaker implantation. Cardiologists should know about these unusual genetic diseases with conduction defects, especially in young adults.
PMCID: PMC2808607  PMID: 15832002
Muscular Dystrophies; Cardiomyopathies; emerin; Lamins; Heart Conduction System
11.  Aldosterone Upregulates Connective Tissue Growth Factor Gene Expression via p38 MAPK Pathway and Mineralocorticoid Receptor in Ventricular Myocytes 
Journal of Korean Medical Science  2004;19(6):805-811.
The effect of aldosterone on connective tissue growth factor (CTGF) was examined in rat embryonic ventricular myocytes. Upon aldosterone treatment, CTGF expression was significantly increased in a dose and time-dependent manner. To explore the molecular mechanism for this upregulation, we examined the role of mineralocorticoid receptor. Pre-treatment of an antagonist (spironolactone) at 5-fold excess of aldosterone blocked the CTGF induction by aldosterone, suggesting that the upregulation was mediated by mineralocorticoid receptor. Aldosterone treatment resulted in activation of ERK1/2, p38 MAPK, and JNK pathways with a more transient pattern in p38 MAPK. Blocking studies using pre-treatment of the inhibitor of each pathway revealed that p38 MAPK cascade may be important for aldosterone-mediated CTGF upregulation as evidenced by the blocking of CTGF induction by SB203580 (p38 MAPK inhibitor), but not by PD098059 (ERK1/2 inhibitor) and JNK inhibitor I. Interestingly, JNK inhibitor I and PD098059 decreased the basal level of CTGF expression. On the other hand, pre-treatment of spironolactone abrogated the p38 MAPK activation, indicating that mineralocorticoid receptor mechanism is linked to p38 MAPK pathway. Taken together, our findings suggest that aldosterone induces CTGF expression via both p38 MAPK cascade and mineralocorticoid receptor and that cross-talk exists between the two pathways.
PMCID: PMC2816296  PMID: 15608389
Connective Tissue Growth Factor; Aldosterone; Mitogen-activated Protein Kinase p38; Spironolactone; Receptor, Mineralocorticoid
12.  Comparative measurement of aortic root by transthoracic echocardiography in normal Korean population based on two different guidelines 
Aortic root size is an important parameter in vascular diseases and can be easily assessed by transthoracic echocardiography. However, measurements values may vary according to cardiac cycle and the definition used for edge. This study aimed to define normal values according to the measurement method specified by two different guidelines to determine the influence of the different methods on echocardiographic measurements.
Healthy Korean adults were enrolled. The aortic root diameters were measured twice at four levels (aortic annulus, sinuses of Valsalva, sinotubular junction, and ascending aorta) by the 2005 American Society of Echocardiography (ASE) guidelines (measured from leading edge to leading edge during diastole) and the 2010 ASE pediatric guidelines (measured from inner edge to inner edge during systole).
One hundred twelve subjects aged 20–69 years were enrolled. The aortic diameters (cm) determine by the aforementioned two guidelines showed significant difference. Measurements were larger in 2005 ASE guideline at aortic annuls, sinuses of Valsalva, and sinotubular junction level, but smaller at ascending aortic level with 2-3mm of differences. Intraobserver variability was similarly good, but interobserver variability was slightly higher than intraobserver variability in both measurement methods. BSA and age was most important determinant for aortic root size.
The measurement method of aortic root can affect the echocardiographic result. The measurement method should be noted when assessing clinical significance of aortic root measurement.
PMCID: PMC3751523  PMID: 23941562
Aortic root measurement; Normal reference; Transthoracic echocardiography
13.  Evaluation of Montanide™ ISA 71 VG Adjuvant during Profilin Vaccination against Experimental Coccidiosis 
PLoS ONE  2013;8(4):e59786.
Chickens were immunized subcutaneously with an Eimeria recombinant profilin protein plus Montanide™ ISA 70 VG (ISA 70) or Montanide™ ISA 71 VG (ISA 71) water-in-oil adjuvants, or with profilin alone, and comparative RNA microarray hybridizations were performed to ascertain global transcriptome changes induced by profilin/ISA 70 vs. profilin alone and by profilin/ISA 71 vs. profilin alone. While immunization with profilin/ISA 70 vs. profilin alone altered the levels of more total transcripts compared with profilin/ISA 71 vs. profilin alone (509 vs. 296), the latter was associated with a greater number of unique biological functions, and a larger number of genes within these functions, compared with the former. Further, canonical pathway analysis identified 10 pathways that were associated with genes encoding the altered transcripts in animals immunized with profilin/ISA 71 vs. profilin alone, compared with only 2 pathways in profilin/ISA 70 vs. profilin alone. Therefore, ISA 71 was selected as a candidate adjuvant in conjunction with profilin vaccination for in vivo disease protection studies. Vaccination with profilin/ISA 71 was associated with greater body weight gain following E. acervulina infection, and decreased parasite fecal shedding after E. maxima infection, compared with profilin alone. Anti-profilin antibody levels were higher in sera of E. maxima- and E. tenella-infected chickens vaccinated with profilin/ISA 71 compared with profilin alone. Finally, the levels of transcripts encoding interferon-γ, interleukin (IL)-2, IL-10, and IL-17A were increased in intestinal lymphocytes from E. acervulina-, E. maxima-, and/or E. tenella-infected chickens vaccinated with profilin/ISA 71 compared with profilin alone. None of these effects were seen in chickens injected with ISA 71 alone indicating that the adjuvant was not conferring non-specific immune stimulation. These results suggest that profilin plus ISA 71 augments protective immunity against selective Eimeria species in chickens.
PMCID: PMC3620231  PMID: 23593150
14.  Peripheral Artery Disease in Korean Patients Undergoing Percutaneous Coronary Intervention: Prevalence and Association with Coronary Artery Disease Severity 
Peripheral artery disease (PAD) is an important marker for the risk stratification of patients with coronary artery disease (CAD). We investigated the prevalence of PAD in patients undergoing percutaneous coronary intervention (PCI) with CAD and the relationship between ankle-brachial pressure index (ABPI) and CAD severity. A total of 711 patients undergoing PCI for CAD from August 2009 to August 2011 were enrolled. PAD diagnosis was made using the ABPI. The prevalence of PAD was 12.8%. In PAD patients, mean values of right and left ABPI were 0.71 ± 0.15 and 0.73 ± 0.15. Patients with PAD had a higher prevalence of left main coronary disease (14.3% vs 5.8%, P = 0.003), more frequently had multivessel lesions (74.9% vs 52.1%, P < 0.001) and had higher SYNTAX score (18.2 ± 12.3 vs 13.1 ± 8.26, P = 0.002). Using multivariate analysis, we determined that left main CAD (OR, 2.954; 95% CI, 1.418-6.152, P = 0.004) and multivessel CAD (OR, 2.321; 95% CI, 1.363-3.953, P = 0.002) were both independently associated with PAD. We recommend that ABPI-based PAD screening should be implemented in all patients undergoing PCI with CAD, especially in severe cases.
PMCID: PMC3546110  PMID: 23341717
Peripheral Artery Disease; Coronary Artery Disease; Atherosclerosis
15.  Successful Management of Pulmonary and Inferior Vena Cava Tumor Embolism from Renal Cell Carcinoma 
Pulmonary tumor embolism can be a cause of respiratory failure in patients with cancer even though it occurs rarely. We describe a 56-year-old man who underwent a pulmonary tumor embolectomy using cardiopulmonary bypass on beating heart combined with inferior vena cava embolectomy and right radical nephrectomy. Aggressive surgical treatment in this severe case is necessary not only to reduce the fatal outcome of pulmonary embolism in the short run, but also to improve the oncological prognosis in the long term.
PMCID: PMC3487017  PMID: 23130307
Pulmonary embolism; Cancer; Great vessels; Embolectomy
16.  Plasma N-Terminal Pro-B-Type Natriuretic Peptide Is Predictive of Perioperative Cardiac Events in Patients Undergoing Vascular Surgery 
Identification of patients at high risk for perioperative cardiac events (POCE) is clinically important. This study aimed to determine whether preoperative measurement of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) could predict POCE, and compared its predictive value with that of conventional cardiac risk factors and stress thallium scans in patients undergoing vascular surgery.
Patients scheduled for non-cardiac vascular surgery were prospectively enrolled. Clinical risk factors were identified, and NT-proBNP levels and stress thallium scans were obtained. POCE was the composite of acute myocardial infarction, congestive heart failure including acute pulmonary edema, and primary cardiac death within 5 days after surgery. A modified Revised Cardiac Risk Index (RCRI) was proposed and compared with NT-proBNP; a positive result for ischemia and a significant perfusion defect (≥ 3 walls, moderate to severely decreased, reversible perfusion defect) on the thallium scan were added to the RCRI.
A total of 365 patients (91% males) with a mean age of 67 years had a median NT-proBNP level of 105.1 pg/mL (range of quartile, 50.9 to 301.9). POCE occurred in 49 (13.4%) patients. After adjustment for confounders, an NT-proBNP level of > 302 pg/mL (odds ratio [OR], 5.7; 95% confidence interval [CI], 3.1 to 10.3; p < 0.001) and a high risk by the modified RCRI (OR, 3.9; 95% CI, 1.6 to 9.3; p = 0.002) were independent predictors for POCE. Comparison of the area under the curves for predicting POCE showed no statistical differences between NT-proBNP and RCRI.
Preoperative measurement of NT-proBNP provides information useful for prediction of POCE as a single parameter in high-risk patients undergoing noncardiac vascular surgery.
PMCID: PMC3443723  PMID: 23019395
Pro-B-type natriuretic peptide; Vascular surgical procedures; Postoperative complications
17.  Clinical Characteristics of Acute Aortic Syndrome in Korean Patients: From the Korean Multi-Center Registry of Acute Aortic Syndrome 
Korean Circulation Journal  2012;42(8):528-537.
Background and Objectives
Acute aortic syndrome (AAS) is a heterogeneous group of disorders that often present with severe chest or back pain. It includes acute aortic dissection (AD), intramural hematoma (IMH), dissecting aneurysm, and penetrating aortic ulcer (PAU). The clinical picture of AAS and its prognosis have not been studied in a large number of Korean patients. Therefore, we organized a multi-center registry to identify the clinical characteristics and treatment patterns, as well as long-term outcomes in Korean patients with AAS.
Subjects and Methods
Five-hundred twenty-eight patients, who had been diagnosed with AAS, were enrolled into this registry from 10 centers. On a retrospective basis, we collected demographic, laboratory, imaging data, as well as follow-up clinical outcomes by reviewing medical records from individual centers. All the data were collected in core lab and analyzed in detail.
The mean patient age was 60.1±14.5 years; the male-to-female ratio was M : F=297 : 231. The prevalent risk factors for AAS included hypertension (361, 68.4%) and diabetes (52, 11.1%). The components of AAS that are included in this study are acute AD (446, 84.5%), IMH (57, 10.7%), and PAU (11, 2.1%). By type of AAS, patients diagnosed with Stanford A were 45.6% of enrolled patients, whereas those with Stanford B were 54.4% of enrolled patients. Among nearly half of the patients were treated with medicine (55.7%) alone, whereas 40.0% underwent surgery and 4.3% underwent endovascular treatment. Overall, the in-hospital event rate was 21.2% and the in-hospital death rate was 8.1%. The mean follow-up duration was 42.8 months and there showed 22.9% of total event and 10.1% of death during this period.
By organizing a multi-center registry of AAS, we could identify the characteristics of AAS in real-world Korean patients. Further, prospective study is warranted with a larger number of patients.
PMCID: PMC3438262  PMID: 22977448
Aortic diseases; Dissection; Hematoma; Population characteristics
18.  Impact of Lysophosphatidylcholine on the Plasminogen Activator System in Cultured Vascular Smooth Muscle Cells 
Journal of Korean Medical Science  2012;27(7):803-810.
The balance between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) regulates fibrinolysis. PAI-1 expression increases in atherosclerotic arteries and vascular smooth muscle cells (VSMCs) are one of major constituents of atheroma. We investigated the impact of lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, on the plasminogen activator system of the rat VSMCs. The lysoPC stimulated the protein and gene expressions of PAI-1 but did not affect the protein expression of t-PA. Fibrin overlay zymography revealed that lysoPC increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA. Vitamin E inhibited the lysoPC-induced PAI-1 expression. Further, lysoPC increased the intracellular reactive oxygen species (ROS) formation. Caffeic acid phenethyl ester, an inhibitor of NF-κB, blocked this lysoPC effect. Indeed, lysoPC induced the NF-κB-mediated transcriptional activity as measured by luciferase reporter assay. In addition, genistein, an inhibitor of protein-tyrosine kinase (PTK), diminished the lysoPC effect, while 7,12-dimethylbenz[a]anthracene, a stimulator of PTK, stimulated PAI-1 production. In conclusion, lysoPC does not affect t-PA expression but induces PAI-1 expression in the VSMC by mediating NF-κB and the genistein-sensitive PTK signaling pathways via oxidative stress. Importantly, lysoPC stimulates the enzyme activity of PAI-1 and suppresses that of t-PA.
PMCID: PMC3390732  PMID: 22787379
Lysophosphatidylcholines; NF-kappa B; Oxidative Stress; Plasminogen Activator Inhibitor 1; Protein-Tyrosine Kinase; Muscle, Smooth, Vascular
19.  Ischemic Stroke in Takayasu's Arteritis: Lesion Patterns and Possible Mechanisms 
Background and Purpose
The purpose of the present study was to use brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) to identify the mechanism of stroke in patients with Takayasu's arteritis (TA).
Among a retrospective cohort of 190 TA patients, 21 (3 males and 18 females) with a mean age of 39.9 years (range 15-68 years) who had acute cerebral infarctions were included in lesion pattern analyses. The patients' characteristics were reviewed, and infarction patterns and the degree of cerebral artery stenosis were evaluated. Ischemic lesions were categorized into five subgroups: cortical border-zone, internal border-zone, large lobar, large deep, and small subcortical infarctions.
In total, 21 ischemic stroke events with relevant ischemic lesions on MRI were observed. The frequencies of the lesion types were as follows: large lobar (n=7, 33.3%), cortical border zone (n=6, 28.6%), internal border zone (n=1, 4.8%), small cortical (n=0, 0%), and large deep (n=7, 33.3%). MRA revealed that 11 patients had intracranial artery stenosis.
Hemodynamic compromise in large-artery stenosis and thromboembolic mechanisms play significant roles in ischemic stroke associated with TA.
PMCID: PMC3391615  PMID: 22787494
vasculitis; thromboembolism; intracranial artery stenosis
20.  Risk factors for delayed recanalization of calf vein thrombosis 
To determine the risk factors of delayed recanalization of isolated calf vein thrombosis (CVT).
One hundred fifty limbs of 110 patients with CVT between September 2007 and April 2010 were enrolled. We used ultrasonography for the diagnosis and follow-up examinations of CVT. We calculated recanalization rates at 1 and 3 months after initial diagnosis and analyzed the risk factors associated with delayed recanalization of CVT.
CVTs were located in the muscular calf vein in 110 (73.3%), in the deep calf vein in 18 (12%), and in both in 22 cases (14.7%). Among all CVTs, 94 limbs (63%) were symptomatic. Major risk factors for CVT were orthopedic surgery (87.3%), malignancy (21.3%), and immobilization (15.3%). Sixty-seven patients (60.9%) were treated with oral anticoagulation therapy, while 43 patients by low molecular weight heparin (n = 19) or by conservative methods including elastic compression stockings and ambulation (n = 21). The cumulative recanalization rate at 1 and 3 months was 23% and 82% and it was significantly higher in patients who underwent oral anticoagulation therapy compared with patients without oral anticoagulation therapy (84% vs. 65%, P = 0.008 by log-rank test). Malignancy (odds ratio [OR], 2.789; P = 0.043) and immobilization (OR, 4.191; P = 0.029) were independent risk factors for delayed recanalization of CVT and oral anticoagulation (OR, 0.300; P = 0.020) was an independent factor in promoting recanalization in multivariate analysis.
For patients with isolated CVT, no oral anticoagulation resulted in higher rates of delayed recanalization compared to oral anticoagulation treatment. Immobilization and having malignancy were independent risk factors for delayed recanalization.
PMCID: PMC3341480  PMID: 22563538
Thrombosis; Venous thrombosis; Deep vein thrombosis
21.  Assessment of coagulation with 6% hydroxyethyl starch 130/0.4 in cesarean section 
Korean Journal of Anesthesiology  2012;62(4):337-342.
Third-generation hydroxyethyl starch (HES) solutions have been developed to minimize negative effects on hemostasis. In normal pregnancy, the coagulation activity increases, reaching a maximum around term. This study examined the effects of hemodilution with HES 130/0.4 (6%) on blood coagulation in parturients in vivo and in vitro.
Forty parturients scheduled for cesarean sections were assigned randomly to receive either 500 or 1,000 ml of HES 130/0.4 (6%). Rotation thromboelastometry (ROTEM®) measurements were performed before and after administering HES 130/0.4 (6%). In addition, blood samples obtained from 20 randomly selected parturients were diluted 10% to 40% using HES 130/0.4 (6%), and ROTEM® measurements were performed before and after dilution. The changes from baseline and the effects of dilution were analyzed by ROTEM® parameters.
Infusions of 500 or 1,000 ml of HES 130/0.4 (6%) in the parturients altered the clot formation time, α angle, and maximal clot firmness, although all remained within normal ranges. HES 130/0.4 (6%) affected in vitro blood coagulation in parturients' blood containing 10, 20, 30, and 40% HES. The clotting time was prolonged at each dilution percentage, but remained within the normal range. Other parameters showed an impairment of the coagulation system.
Blood coagulation in parturients may be compromised at high dilution ratios of HES 130/0.4 (6%) to blood. Nevertheless, the infusion of 1,000 ml of HES 130/0.4 (6%) in normal parturients did not significantly affect blood coagulation.
PMCID: PMC3337380  PMID: 22558500
Cesarean section; Coagulation; Hydroxyethyl starch; Pregnancy
22.  Spectral entropy for assessing the depth of propofol sedation 
Korean Journal of Anesthesiology  2012;62(3):234-239.
For patients in the intensive care unit (ICU) or under monitored anesthetic care (MAC), the precise monitoring of sedation depth facilitates the optimization of dosage and prevents adverse complications from underor over-sedation. For this purpose, conventional subjective sedation scales, such as the Observer's Assessment of Alertness/Sedation (OAA/S) or the Ramsay scale, have been widely utilized. Current procedures frequently disturb the patient's comfort and compromise the already well-established sedation. Therefore, reliable objective sedation scales that do not cause disturbances would be beneficial. We aimed to determine whether spectral entropy can be used as a sedation monitor as well as determine its ability to discriminate all levels of propofol-induced sedation during gradual increments of propofol dosage.
In 25 healthy volunteers undergoing general anesthesia, the values of response entropy (RE) and state entropy (SE) corresponding to each OAA/S (5 to 1) were determined. The scores were then analyzed during each 0.5 mcg/ml- incremental increase of a propofol dose.
We observed a reduction of both RE and SE values that correlated with the OAA/S (correlation coefficient of 0.819 in RE-OAA/S and 0.753 in SE-OAA/S). The RE and SE values corresponding to awake (OAA/S score 5), light sedation (OAA/S 3-4) and deep sedation (OAA/S 1-2) displayed differences (P < 0.05).
The results indicate that spectral entropy can be utilized as a reliable objective monitor to determine the depth of propofol-induced sedation.
PMCID: PMC3315652  PMID: 22474549
Entropy; Propofol; Sedation
23.  Comparative Microarray Analysis of Intestinal Lymphocytes following Eimeria acervulina, E. maxima, or E. tenella Infection in the Chicken 
PLoS ONE  2011;6(11):e27712.
Relative expression levels of immune- and non-immune-related mRNAs in chicken intestinal intraepithelial lymphocytes experimentally infected with Eimeria acervulina, E. maxima, or E. tenella were measured using a 10K cDNA microarray. Based on a cutoff of >2.0-fold differential expression compared with uninfected controls, relatively equal numbers of transcripts were altered by the three Eimeria infections at 1, 2, and 3 days post-primary infection. By contrast, E. tenella elicited the greatest number of altered transcripts at 4, 5, and 6 days post-primary infection, and at all time points following secondary infection. When analyzed on the basis of up- or down-regulated transcript levels over the entire 6 day infection periods, approximately equal numbers of up-regulated transcripts were detected following E. tenella primary (1,469) and secondary (1,459) infections, with a greater number of down-regulated mRNAs following secondary (1,063) vs. primary (890) infection. On the contrary, relatively few mRNA were modulated following primary infection with E. acervulina (35 up, 160 down) or E. maxima (65 up, 148 down) compared with secondary infection (E. acervulina, 1,142 up, 1,289 down; E. maxima, 368 up, 1,349 down). With all three coccidia, biological pathway analysis identified the altered transcripts as belonging to the categories of “Disease and Disorder” and “Physiological System Development and Function”. Sixteen intracellular signaling pathways were identified from the differentially expressed transcripts following Eimeria infection, with the greatest significance observed following E. acervulina infection. Taken together, this new information will expand our understanding of host-pathogen interactions in avian coccidiosis and contribute to the development of novel disease control strategies.
PMCID: PMC3225369  PMID: 22140460
24.  Comparison of Transthoracic Echocardiography With N-Terminal Pro-Brain Natriuretic Peptide as a Tool for Risk Stratification of Patients Undergoing Major Noncardiac Surgery 
Korean Circulation Journal  2011;41(9):505-511.
Background and Objectives
The role of preoperative transthoracic echocardiography (TTE) for the risk stratification has not been well investigated yet. We compared the predictive power of TTE with N-terminal pro-brain natriuretic peptide (NT-proBNP), a representative biomarker that predicts perioperative cardiovascular risk, and investigated whether these tests have incremental value to the clinically determined risk.
Subjects and Methods
We evaluated the Revised Cardiac Risk Index (RCRI), TTE, and NT-proBNP in 1,923 noncardiac surgery cases. The primary endpoint was a perioperative major cardiovascular event (PMCE), which was defined by any single or combined event of secondary endpoints including myocardial infarction, development of pulmonary edema, or primary cardiovascular death within 30 days after surgery.
All echocardiographic parameters including left ventricular ejection fraction, regional wall motion score index, and transmitral early diastolic velocity/tissue Doppler mitral annular early diastolic velocity (E/E') were predictive of PMCE (c-statistics=0.579±0.019 to 0.589±0.015), but none of these parameters were better than the clinically determined RCRI (c-statistics=0.594±0.019) and were inferior to NT-proBNP (c-statistics=0.748±0.019, p<0.001). The predictive power of RCRI {adjusted relative risk (RR)=1.4} could be improved by addition of echocardiographic parameters (adjusted RR=1.8, p<0.001), but not to that extent as by addition of NT-proBNP to RCRI (adjusted RR=3.7, p<0.001).
TTE was modestly predictive of perioperative cardiovascular events but was not superior to NT-proBNP. Moreover, it did not have incremental value to the clinically determined risk. The results of our study did not support the use of routine echocardiography before noncardiac surgery.
PMCID: PMC3193041  PMID: 22022325
Cardiovascular disease; Postoperative complications; Echocardiography; Natriuretic peptides
25.  The effects of magnesium on the course of atrial fibrillation and coagulation in patients with atrial fibrillation undergoing mitral valve annuloplasty 
Korean Journal of Anesthesiology  2011;61(3):210-215.
Atrial fibrillation (AF) is the most common cardiac arrhythmia. Magnesium has been reported to be effective in reducing the incidence or prophylaxis of AF. Magnesium is also an essential constituent of many enzyme systems and plays a physiological role in coagulation regulation. The aim of the present study was to examine the effects of magnesium, whether magnesium infusion might decrease the incidence of AF and induce hypocoagulable state in patients with AF, who were undergoing mitral valve annuloplasty.
This prospective laboratory study was performed using blood from patients with AF undergoing mitral valve annuloplasty. The radial artery was punctured with a 20 gauge catheter and used for monitoring continuous arterial pressure and blood sampling. After anesthesia induction, 4 g of magnesium was mixed with 100 ml normal saline and infused for 5 minutes. Magnesium, calcium, activated clotting time (ACT) and thromboelastographic parameters were checked before and 60 minutes after the magnesium infusion. The electrocardiography changes after magnesium infusion were also checked before commencing cardiopulmonary bypass.
After magnesium infusion, the serum level of magnesium increased significantly but serum calcium did not change significantly. ACT did not change significantly before or after magnesium infusion. The thromboelastographic parameters showed no significant changes before or after magnesium infusion. None of the patients converted to sinus rhythm from AF after the magnesium infusion.
A magnesium infusion did not influence the course of AF and coagulation in patients during prebypass period with AF undergoing mitral valve annuloplasty.
PMCID: PMC3198181  PMID: 22025942
Atrial fibrillation; Magnesium; Mitral valve annuloplasty; Thromboelastography

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