OBJECTIVES: The renin-angiotensin system(RAS) had an important role in the pathogenesis of ischemic heart disease(IHD). Angiotensinogen(ATG), angiotensin-converting enzyme(ACE), and angiotensin II receptor are key components of RAS and reported to have polymorphisms. We studied to investigate the separate and interactive effects of ACE (I/D) and ATG (M235T) gene polymorphisms on the pathogenesis of IHD, and to compare the genetic influences between on the chronic stable angina(CSA) and on the acute coronary syndrome(ACS). METHODS: We studied total 468 patients who underwent CAG. Control group comprised 159 patients who did not have a significant coronary lesion. IHD group was subgrouped according to clinical manifestation into CSA group(n=90) and ACS group(n=219). To determine the frequency of ACE and ATG genotype, polymerase chain reaction (PCR) and enzyme digestion was done. RESULTS: 1) In ACS group, genotype frequency of ACE(II:ID:DD) was 0.27:0.48:0.25 and ATG (MM:MT:TT) was 0.31:0.59:0.10, which was significantly different from control group (ACE II:ID:DD =0.38:0.45:0.17 and ATG MM:MT:TT =0.51:0.40:0.09) (p<0.05). 2) There was no significant difference in genotype frequency of ACE, ATG gene between CSA group and control. 3) In multiple logistic regression analysis, sex, age, ATG and ACE genotype were independent risk factors for ACS. The relative risk for ACS in ACE DD compared to II genotype was 3.52 (95% CI: 1.52-8.13) and that in ACE ID compared to ACE II genotype was 1.55 (95% CI: 0.82-2.94), which showed that the risk increased with the number of ACE D-allele. In contrast, sex, age, and DM were independent risk factors for CSA, whereas ATG and ACE genotype were not. 4) In combined analysis including both ACE and ATG gene polymorphism, the relative risk for ACS associated with ATG genotype increased with the number of ACE D-allele. CONCLUSION: ACE and ATG gene polymorphism are associated with the development of ACS but not CSA, which suggests that ACE and ATG genes may be involved in the plaque unstabilization or thrombosis rather than the chronic progression of coronary atherosclerosis.
Acute Coronary Syndrome* ; Angina, Stable* ; Angiotensinogen* ; Angiotensins* ; Coronary Artery Disease ; Digestion ; Genotype ; Heart ; Humans ; Logistic Models ; Myocardial Ischemia ; Polymerase Chain Reaction ; Receptors, Angiotensin ; Renin-Angiotensin System ; Risk Factors ; Thrombosis

OBJECTIVES: This study was performed to verify the incidence and prognosis of aortic dissection without intimal tear(aortic intramural hemorrhage, IMH) who took only medical treatment in special reference to Stanford type A. METHODS: We analysed the patients of IMH confirmed by TEE, CT, MRI, angiography or CT-angiography in Seoul National University Hospital between 1987 and 1995, retrospectively. RESULTS: The diagnosis of IMH was established in 20 of 143 patients(14%). Nine patients were Stanford type A, 11 patients were type B. The longitudinal extent varied between 8 and 30cm, and IMH size varied between 10 and 30mm. Surgery was performed in two of type A patients because of persistent chest pain and one of type B patients because of progressive aortic dilatation despite of medical treatment. Follow-up imaging studies (mean follow-up period of 20.0+/-2.0 months) were done in 10/17 patients who were treated medically. Complete resolution of IMH was observed in seven cases, four of them were Stanford type A, and the mean size of IMH was 12mm(10-l7mm). Partial resolution was observed in one case, Stanford type A, with the IMH size of 15mm. There was no significant change in the size of IMH in two cases. Initial mean size of IMH was 25mm. In no case, aortic rupture or death was observed during the follow up period. CONCLUSION: In the management of the patient with IMH, same surgical indications as classic aortic dissection have been advocated based on similar prognosis. However our study showed better prognosis in IMH patients treated medically compared to the previous publications. Therefore, even in cases of proximal IMH, medical treatment should be seriously considered.
Angiography ; Aortic Rupture ; Chest Pain ; Diagnosis ; Dilatation ; Follow-Up Studies ; Hemorrhage ; Humans ; Incidence* ; Magnetic Resonance Imaging ; Prognosis* ; Retrospective Studies ; Seoul

BACKGROUND: The mechanism of the closure of umbilical vessels is known to be multifactorial. In order to verify that apoptosis is one of the possible closure mechanisms, we studied to identify apoptosis in umbilical vessels and evaluate its mechanism by studying apoptosis-related gene and the relationship between the pattern of apoptosis and gestational age (GA). METHODS: Twelve umbilical cords of GA of 37-42 weeks were obtained immediatly (less than 10 min. for minimal ongoing external influences) after birth. The presence of apoptotic cells was demonstrated by electron microscopy (EM) and terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling (TUNEL). Immunohistochemical staining and Western blotting were used for the analysis of the proteins of apoptosis-related gene. RESULTS: Apoptosis of the smooth muscle cells of media and intima of umbilical vessels was identified at EM, regardless of GA from 37 to 42 weeks. The proportion of TUNEL (+) cells was 80% in intima, 40% in media, 80% in connective tissue of umbilical cord. The expressions of bax-alpha, bcl-Xs/L were strong in intima, in media and connective tissue, but those of bcl-2 were detected in only in connective tissue, regardless of GA in immunohistochemistry. The ratios of expressions of bax-alpha to bcl-2, bcl-Xs to bcl-XL, did not change with increasing GA from 37 to 42 weeks in Western blotting. CONCLUSION: Apoptosis was identified in umbilical vessels. The closure of umbilical vessels can be explained by apoptosis where the ratios of bax-alpha/bcl-2, bcl-Xs/ bcl-XL play an important role. The fact that there were no differences in the extent of apoptosis and the expressions of bax-alpha/bcl-2, bcl-Xs/bcl-XL according to GA, suggests that apoptosis of umbilical vessels is more dependent on the external stimuli during delivery than GA.
Apoptosis* ; Blotting, Western ; Connective Tissue ; Gestational Age ; Humans* ; Immunohistochemistry ; In Situ Nick-End Labeling ; Microscopy, Electron ; Myocytes, Smooth Muscle ; Parturition* ; Umbilical Cord

BACKGROUND: Cardiac transplantation has been established as a treatment of choice for patients with end- stage heart failure. However, the experiences of cardiac transplantation are still limited in Korea. METHODS: Seventeen adult cardiac transplantations (13 males and 4 females) were performed in Seoul National University Hospital since March 1994. Clinical outcome & course, acute rejection, and complications among transplanted patients were reviewed. RESULTS: Underlying cardiac conditions leading to cardiac transplantation were dilated cardiomyopathy in 9, valvular heart disease with severe LV dysfunction after prosthetic valve replacement in 3, restrictive cardiomyopathy in 2, ischemic cardiomyopathy in 1, intractable ventricular tachyarrhythmia in 1 and hypertrophic cardiomyopathy with severe LV dysfunction in 1 patient. Ages of recipients were between 22 and 54 (median:38). Mean follow up duration was 27 months (1-45 months). The frequencies of rejection decreased with time and were similar to those of previous reports: 1.23 episodes of rejections per patients during first 3months after transplantation, 0.25 during second 3months, 0.17 and 0.08 during third and fourth 3 months. Infectious complications developed in 21.4% of patients during the first year after transplantation and infectious agents were Cytomegalovirus (CMV), gram negative bacteria, and Candida. One-year survival rate of recipients was 81.9%. Systemic CMV infection in 1, aortic rupture in 1, and sudden death in 1 patient were the causes of mortality, all of which developed during early post-transplantation period. CONCLUSION: Cardiac transplantation seems to be a reasonable therapeutic regimen for patient with end stage heart failure even in this country with limited experience; however, close attention and management against acute rejection and infectious complications, especially during the early post-transplantation period, are critical for long term survival.
Adult* ; Aortic Rupture ; Candida ; Cardiomyopathies ; Cardiomyopathy, Dilated ; Cardiomyopathy, Hypertrophic ; Cardiomyopathy, Restrictive ; Cytomegalovirus ; Death, Sudden ; Follow-Up Studies ; Gram-Negative Bacteria ; Heart Failure ; Heart Transplantation* ; Heart Valve Diseases ; Humans ; Korea ; Male ; Mortality ; Seoul ; Survival Rate ; Tachycardia

BACKGROUND: Left ventricular remodeling after myocardial infarction is closely related to the prognosis of the patients with infarction and can be modified by angiotensin converting enzyme inhibitor. In experimental transmural infarction rat model, captopril decreases the ventricular compliance and simultaneously decrease the ventricular volume, but its effects on the nontransmurally infarcted heart are not elucidated. METHODS: Female Sprague-Dawley rats underwent 45-minute left coronary artery occlusion followed by reperfusion to produce nontransmural myocardial infarction. At 5 days after infarction, rats were randomized into two groups : untreated(n=8) and captopril-treated(captopril 2g/liter drinking water)(n=8). After 21 days of treatment, the hearts were arrested at diastole and excised. Passive pressure-volume curve of the left ventricle was plotted, and the stiffness modulus and mean compliance were calculated in the range of 5 to 30mmHg of pressure. Infarct size was also measured to confirm each group has similar size of lesion. The extent of fibrosis(relative area of fibrosis to randomly-selected peri-infarcted zone) was quantified on Masson's trichrome-stained ventricular slices by automatic image analysis software. RESULTS: Compared with untreated group, captopril-treated rats showed significantly decreased ventricular weight-to-body weight ratio(2.60+/-0.18mg/g vs. 2.84+/-0.20, p<0.05), decreased ventricular stiffness modulus(7.24+/-0.61 vs. 8.28+/-0.57, p<0.005), increased mean compliance(9.71+/-0.75 1/mmHg vs. 7.55+/-0.67, p<0.0001), and decreased fibrosis extent(0.82+/-1.49% vs. 5.53+/-5.33, p<0.01). CONCLUSION: These findings suggest that captopril increases the compliance of nontransmurally-infarcted left ventricle at least partly by the suppression of fibrosis, in contrast with previous findings that captopril decresed the passive compliance of transmurally-infarcted ventricle.
Animals ; Captopril ; Compliance ; Coronary Vessels ; Diastole ; Drinking ; Female ; Fibrosis ; Heart ; Heart Ventricles ; Humans ; Infarction ; Models, Animal ; Myocardial Infarction* ; Peptidyl-Dipeptidase A ; Prognosis ; Rats* ; Rats, Sprague-Dawley ; Reperfusion ; Ventricular Remodeling*

BACKGROUND: Atherosclerosis is the most important disease that may cause ischemic syndrome in many organs including heart. It is supposed that apoptosis of vascular smooth muscle cells(VSMCs) is closely related to the progression and rupture of atheromatous plaque. Recent studies have documented evidence for elevated level of nitric oxide(NO) within advanced human atheroma and evidence of regression of atheroma by NO. So this study is designed to evaluate whether exogenous NO from NO donors can induce apoptosis of cultured rat VSMCs and which proapoptotic gene(s) is involved in this type of apoptosis. METHODS: Rat VSMCs were cultured and used for experiment at passage 5 through 7. For NO donor, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine(SNAP) of 0.5, 1, 2, 4mM were exposed to subconfluent VSMCs. The cells were harvested at 6, 12, 24, 48, 72hours after exposure of NO donors. Apoptosis was to be identified by 4, 6-diamidino-2-phenylindole dihydrochloride(DAPI) staining of nuclei and in-situ nick end labeling(TUNEL). The amount of fragmented DNA was analyzed semiquantitatively by diphenylamine(DPA) assay. Immunocytochemical(ICC) staining and western bolt analyses were designed to detect apoptosisrelated gene products, such as Bax-a, Fas and Bcl-2. RESULTS: 1) Decreased mitotic activity was shown after 12 hours exposure of exogenous NO donors, and condensation and margination of chromatin was identified agter 24 hours exposure, by DAPI staining. 2) Percent DNA fragmentation assessed by DPA method was 0,2,9,48,45% at 0,6,12,24,48 hours after exposure of 2mM of NO donors respectively. 3) The expression of Bax-a and Bcl-2 proteins was demonstrated in apoptotic cells by ICC staining. 4) The expression of Bax-a protein in cells under 24 hours exposure of NO donors was elevated by more than 18% of control level on densitometric analysis of western blot. The level of Bcl-2 was suppressed by 26% of control. So, Bax-a/Bcl-2 ratio in cells under exposure of NO donors was elevated to 2.0 from 1.2 of control level. CONCLUSIONS: Exogenous NO from NO donors can induce apoptosis of cultured rat VSMCs, and it is considered that bax-a and bcl-2 genes are involved in this type of apoptosis.
Animals ; Apoptosis* ; Atherosclerosis ; Blotting, Western ; Chromatin ; DNA ; DNA Fragmentation ; Genes, bcl-2 ; Heart ; Humans ; Muscle, Smooth, Vascular* ; Nitric Oxide ; Nitroprusside ; Plaque, Atherosclerotic ; Rats* ; Rupture ; Tissue Donors

BACKGROUND: Familial hypercholesterolemia(FH) is an autosomal dominant inharited disorder. Total cholesterl level of FH heterozygotes is two to fourfold higher than that of normal population. Substained hypercholesterolemia results in cholesterol deposition on various organs or tissues and Achilles tendon xanthoma due to cholesterol deposition is one of the specific clinical findings of FH. One of the lipid lowering drugs, 3-hydroxy-3-methylglutaryl coenzyme A(HMG Co-A) reductase inhibitor effectively lowers the blood cholesterol level in patients with FH, but whether the cholesterol deposition can be regressed by the lipid lowering drugs is rarely reported. This study attemted to determine whether the tendon xanthoma can be regressed by lipid lowering drugs commonly used in patients with FH. METHODS: We analyzed procepectively the serum lipid levels of patients with heterozygous FH before and after lipid lowering therapy with HMG Co-A reductase inhibitor alone(Lovastatin or Pravastatin) or in combination with bile acid sequestrating resin(Cholestyramine). The Achilles tendon thickness was measured radiographically by using soft tissue technique. RESULT: Total 18 patients with heterozygotes FH(M : F=8 :10, mean age; 51.7+/-9.0 years) were treated with the HMG Co-A reductase inhibitor alone or combined with bile acid sequestrating resin and followed for mean 31.9+/-11.9 months. During that period, serum total cholesterol and low density lipoprotein cholesterol significantly fell from 329+/-42 mg/dl to 230+/-29 mg/dl and from 246+/-56 mg/dl to 151+/-28 mg/dl, respectively(p<0.001). Serum high density lipoprotein level increased and maintained 15.3% higher than basal level(p<0.01). Achilles tendon thickness decreased significantly from 13.3+/-3.1 mm to 11.9+/-3.2 mm(p<0.001) with percent reduction of 9.8+/-10.5%(range; 3.1-36.4%). The amount of change of tendon thickness was significantly correlated only with percent reductionof LDL(p=0.029) and female sex(p0.020) on univariate analysis, but it was found to be significantly correlated only with percent reduction of LDL on multivariate analysis(r=0.514,p=0.029). CONCLUSION: Achilles tendon xanthoma can be regressed by effective lipid lowering therapy with HMG Co-A reductase inhibitor alone or with bile acid sequestrating resin in patients with heterozygous FH. the regression of tendon xanthoma is likely to be related to reduction of serum LDL.
Achilles Tendon* ; Bile* ; Cholesterol ; Cholesterol, LDL ; Female ; Heterozygote ; Humans ; Hypercholesterolemia ; Hyperlipoproteinemia Type II* ; Lipoproteins ; Oxidoreductases* ; Tendons ; Xanthomatosis*

OBJECTIVE: In order to evaluate the prevalence of cytomegalovirus infection to terminally failing heart, cytomegaloviral DNA was detected in the explanted hearts of transplantation recipients. METHODS: DNA extractions were performed from explanted failing hearts(N=22) and normal hearts (N=5) and polymerase chain reactions(PCRs) were done for detection of late gene sequence coded pp150 phosphoprotein. The products were confirmed with electrophoresis on 1% agarose gel. In order to improve the sensitivity of detection in cytomegaloviral genome, nested PCRs were executed with the primers designed for the original 607 bp products. RESULTS: All patients had IgG anti-cytomegalovirus antibody and did not have IgM anti-cytomegalovirus antibody. Cytomegaloviral genomes in myocardium were detected by polymerase chain reaction. The 607bp products by PCRs were found in both explanted failing hearts(3 cases/22, 13.5%) and normal hearts(1 case/5, 20.0%). In nested PCRs, 186bp products were found in both failing hearts(LV 4/22, LA 3/20, RV 5/22, HA 0/17) and normal hearts(LV 2/5, LA 1/4, RV 1/5, RA 2/5). There was no significant change in the presence of cytomegaloviral DNA between failing and normal hearts. Total positivity of cytomegaloviral genome in explanted hearts was 44.4% according to nested PCR results. CONCLUSION: Cytomegalovirus was rarely observed in explanted hearts of terminal heart failure and nested PCR could enhance the sensitivity of cytomegaloviral genome detection. But cytomegalovirus might have no direct causal relationship in the development of terminal heart failure.
Cardiomyopathy, Dilated ; Cytomegalovirus Infections* ; Cytomegalovirus* ; DNA ; Electrophoresis ; Genome ; Heart Failure ; Heart* ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Myocardium ; Polymerase Chain Reaction ; Prevalence* ; Sepharose

BACKGROUND: It is well known that collateral circulation has important roles in ischemic heart disease. It reduce ventricular remodelingand infarct size to improve ventricular function and survival. Extents and duration of ischemia are critical stimulants of the development of coronary collaterla circulation. We hypothesize that collateral circulation is poor in patients with lisions at branching points because atherosclerosis progress more rapidly not to allow the collateral circulation to develop. METHOD: We studied total 330 coronary angiography, which have more than 50% stenosis in any coronary artery, normal letf ventriculography and no history of myocardial infarction. In each coronary angiography, severity, site, proximity, length of lesions were analyzed, classified, and collaterale circulation was graded. We also observed whether the lesions involve branching point or not. RESULTS: While coronary collateral circulation developed well when stenosis was more than 90% in the severity, it was poor when the lesions involve branching points. Collateral circulation tended to be poor in case of eccentric lesion, but it was statistically insignificant. The above findings support our hypothesis of the accelerated atherosclerosis at branching points. CONCLUSIONS: The facts that the development of coronary collaterals is poor with lesions involving branching points suggest that atherosclerosis is accelerated at these lesions that is characterized by blood stasis, turbulence and lower arterial wall tension.
Angina Pectoris* ; Atherosclerosis ; Collateral Circulation* ; Constriction, Pathologic ; Coronary Angiography ; Coronary Vessels ; Humans ; Ischemia ; Myocardial Infarction ; Myocardial Ischemia ; Ventricular Function