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

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

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: 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: 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

BACKGROUND: Idiopathic left ventricular tachycardia(ILVT) with no structural heart disease is not an uncommon disease and characterized by the ECG feature of right bundle branch block. This study was performed to evaluate the effectiveness of radiofrequency catheter ablation (RFCA) for the treatment of ILVT and the usefulness of Purkinje potential(P-potential) in determining the site of successful ablation and to compare the biophysical parameter according to the modes of energy application. METHOD: From January 1993 to July 1996, 18 patients with symptomatic ILVT underwent RFCA. The ablation site were guided by pace mapping, ventricular activation mapping or P-potential. RESULTS: Of the 18 patients, there were 14 male and 4 female patients with a mean age of 34.1 years-old. RFCA eliminated VT successfully in 14 of total 18 patients(78%), 11 of 12 in leftaxis VT, 2 of 3 in right axis VT and 1 of 3 in northwest axis VT. Successful sites of wall in 3 patients with right axis deviation or northwest axis. Ablations in 5 of the 9 patients, guided by pace mapping or ventricular activation mapping, were successful and in 9 all patients, guided by P-potential, were successful. In 9 patients guided by the P-potential, the earliest P-potential appeared 22.7+/-7.7msec earlier than the QRS complex during sinus rhythm and 32.0+/-11.5msec earlier during VT. Pace mapping with similar QRS was not necessarily essential for a successful ablation. In comparing the biophysical parameters according to energy delivery modes, more energy was delivered safety during successful ablation in temperature mode(mean 1148.3J) than constant power mode(520.9J). No acute and late complication was developed during ablation and for a mean of 25 months follow-up. One case of VT with right axis deviation relapsed 2 months after successful ablation. CONCLUSION: RFCA is useful for the effective and safe treatment of ILVT. The earliest P-potential might be a better guide than mapping or earliest ventriclar activation for the determination of ablation sites in ILVT with left axis deviation. More energy was delivered safety during successful ablation in temperature mode than constant power mode.
Axis, Cervical Vertebra ; Bundle-Branch Block ; Catheter Ablation* ; Electrocardiography ; Female ; Follow-Up Studies ; Heart Diseases ; Humans ; Male ; Tachycardia, Ventricular*

BACKGROUND: Patients with essential hypertension have abnormal endothelium-dependent vasodilation due to reduced release of nitric oxide(NO). But it is uncertain whether this defect is selective for some pathways of nitric oxide production or a more generalized abnormality of endothelial function. The purpose of this study was to determine whether this defect is due to an impairment at the specific intracellular signal-transduction pathway level or is a more generalized endothelial dysfunction METHOD: Forearm blood flow was measured in 10 patients with essential hypertension (mean blood pressure, 129+/-16.6mmHg ; aged 48+/-10 years old) and 10 control subjects(mean blood pressure, 99.7+/-6.6mmHg ; aged 41+/-10 years old) using strain-gauge plethysmography. The endothelium-dependent vasodilators were acetylcholine(7.5, 15, and 30ug/min), which uses a pertussis toxin-sensitive signal transduction pathway, and bradykinin(100, 200, and 400ng/min), which uses a pertussis toxin-insensitive signal transduction pathway to activate nitric oxide production. Sodium nitroprusside(0.8, 1.6, and 3.2ug/min) was used as an endothelium-independent vasodilator. All drugs were infused into the brachial artery and the order was determined randomly. RESULTS: The maximum flow in response to acetylcholine was markedly impaired in hypertensive patients compared with control subjects(5.29+/-1.86 vs 11.04+/-2.46ml/min/100ml forearm tissue, p<0.001). But the maximum forearm blood flow in response to bradykinin was similar in the two groups(11.96+/-3.57 vs 12.48+/-1.92ml/min/100ml forearm tissue, p=0.69) and that in response to sodium nitroprusside was also similar(10.63+/-3.74 vs 10.51+/-2.39ml/min/100ml forearm tissue, p=0.94). CONCLUSION: Patients with essential hypertension have impaired endothelium-dependent vasodilator response only to acetylcholine, while the response to bradykinin is preserved. This finding indicates that the impairment of endothelial vasodilator function is selective, and suggests the defect occurs at the level of the intracellular signal transduction pathway.
Acetylcholine ; Blood Pressure ; Brachial Artery ; Bradykinin ; Endothelium ; Endothelium-Dependent Relaxing Factors ; Forearm ; GTP-Binding Proteins ; Humans ; Hypertension* ; Nitric Oxide ; Nitroprusside ; Plethysmography ; Signal Transduction ; Sodium ; Vasodilation* ; Whooping Cough

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*

OBJECTIVE: The aim of this study is to analyze the mitochondrial DNA in failing and normal hearts. METHODS: Genomic DNA was extracted from 18 failing and 4 normal hearts. The DNA was digested with each 50 units of BamH I, Pvu II, Pst I, and hybridized using DNA fragments encoding CO II (cytochrome oxidase II) and CO IU. They were detected using 'Fluorescein Gene Images' system. RESULTS: The light microscopic feature of failing myocardium was compatible with that of primary cardiomyopathy. In southern blot analysis, there was no significant difference in mitochondrial DNA amounts between normal and failing hearts. The amount of mitochondrial DNA in hearts, whether normal or failing, was greater than that in lymphocytes. There were no abnormal bands except 16.6kb-normal band using the enzyme BamH I, Pvu II from failing and normal hearts. After digesting with Pst I, 2.1kb band was found using probe CO II and 14.5kb band using probe CO III. CONCLUSION: The amount of mitochondrial DNA in hearts, whether normal or failing, was greater than that in lymphocytes, which suggests that the heart is an active organ in the energy metabolism. Abnormal band was not found in southern blot analysis of the mitochondrial DNA from failing and normal hearts. The more sensitive method such as PCR is required to detect the presence of sma11 amount of mutated DNA.
Blotting, Southern ; Cardiomyopathies ; DNA ; DNA, Mitochondrial* ; Energy Metabolism ; Heart Failure ; Heart* ; Lymphocytes ; Myocardium ; Oxidoreductases ; Polymerase Chain Reaction