LB30057, a Direct Thrombin Inhibitor, the Effect of Restenosis in Porcine Coronary Injury Model

BACKGROUND AND OBJECTIVES: In a previous study, LB30057 was found to inhibit smooth muscle cell proliferation in a dose dependent manner, and prolonged 1 4-day oral administration of LB30057 is effective in reducing the neointimal hyperplasia in a rat carotid balloon injury model. The prolonged administration of LB30057, an orally active direct thrombin inhibitor, was evaluated and found to be a potential inhibitor of restenosis in a porcine coronary injury model. MATERIALS AND METHODS: An oversized balloon injury and a stent injury were given to the right coronary artery and left anterior descending artery, respectively, in the porcine model. LB30057 (50mg/kg) or a placebo was administrated for 28 days, using an osmotic pump, starting 6 hours prior to the injury until sacrifice on the 28th day. The drug concentration and antithrombotic effects (aPTT, thrombin-anti thrombin complex levels) were measured, and a histo-morphometric analysis performed 28 days later. RESULTS: The drug concentrations were 271+/-1 24 and 67+/-52 ng/mL on days 1 and 28 after injury in the drug group. The TAT (thrombin-antithrombin complex) levels were significantly lower in the drug than the control group on the 2nd and 7th days after injury (p<0.05). There were no significant differences in the injury scores, and the luminal, intimal and medial areas between the two groups. CONCLUSION: Prolonged administration of LB30057, using an osmotic pump, was not effective in reducing the restenosis in our pig coronary injury model.

The Clinical Significance of Serum-Hydroxyproline in Acute Coronary Syndrome

BACKGROUND AND OBJECTIVES: The serum hydroxyproline level (SHL) has been regarded as evidence of collagen breakdown or extra-cellular matrix reorganization. The role of SHL as a diagnostic parameter in acute coronary syndrome, and the SHL changes depending on the left ventricular remodeling after acute myocardial infarction, was evaluated. SUBJECTS AND METHODS: Venous blood samples were obtained from 122 patients with AMI at the time of admission, and on days 7, 21 and 90, and once from 15 patients with stable angina, 15 with unstable angina and 12 healthy subjects. The SHL was measured using the amino acid analysis system (HPLC). The regional wall motion index (RWMI), LVEF and LV dimensions were determined in the early (0.05). However, there was a significant elevation in the SHL 14 day after AMI in the patients of the non-reperfusion group (4.36+/-1.46, 7.63+/-2.69 microgram/L, p=0.032). After 2 week, there was no significant difference in the SHL. There was a significant relationship between the late left ventricular ejection fraction and the SHL (r=-0.414, p=0.037), but no significant relationship between the other factors and the SHL (p>0.05). CONCLUSION: The serum hydroxyproline levels were significantly increased in patients with acute coronary syndrome, which reflect the early change in left ventricular remodeling in acute myocardial infarction.

LB30057, A Direct Thrombin Inhibitor, Inhibits Vascular Smooth Muscle Cell proliferation in vitro and the Neointimal Hyperplasia in Rat Carotid Injury Model

BACKGROUND: Recent data showed prolonged administration of direct thrombin inhibitor might be needed to counteract the persistent thrombin activity and reduce the neointimal hyperplasia after arterial injury. We hypothesized that prolonged administration of LB30057, orally active direct thrombin inhibitor, might inhibit the vascular smooth muscle cell (SMC) proliferation in vitro and neointimal hyperplasia in rat carotid injury model. METHODS: In phase I, thrombin stimulated [methyl-3H] thymidine uptake was measured after LB30057 administration in cell culture study using rat aortic SMC. In phase II, LB30057 (low-dose: 5mg/kg, bid: mid-dose: 25mg/kg, bid: high-dose: 50mg/kg, bid) or placebo was administrated orally twice a day starting from 30minutes before injury until sacrifice for 14days in separated 2 sets of experiment. The histo-morphometric analysis for lumen area, intimal area, medial area, intima-to-medial ratio was performed. RESULTS: In vitro rat aortic SMC culture study, LB30057 inhibited thrombin-induced thymidine uptake. The mean neointimal area was significantly less in high-dose and mid-dose group than placebo group (high-dose vs. placebo: 0.14+/-0.02mm2 vs. 0.25+/-0.02mm2: mid-dose vs. placebo: 0.16+/-0.02mm2 vs. 0.29+/-0.03mm2, p<0.005) respectively and the mean ratio of neointima to medial area were significantly less in high-dose and mid-dose group than in placebo group (high-dose vs. placebo: 1.20+/-0.57 vs. 1.94+/-0.67, mid-dose vs. placebo: 1.58+/-0.29 vs. 2.39+/-0.27, p<0.05). There was no significant difference in the mean area of internal elastic lamina, external elastic lamina and mean luminal area between groups. In 2nd set experiment, the mean neointimal area (placebo: 0.29+/-0.03mm2, mid-dose: 0.16+/-0.02mm2: p<0.005), the mean area of internal elastic lamina and external elastic lamina were significantly less in mid-dose group than in placebo group. The mean ratio of neointima to medial area was significantly less in mid-dose group(1.58+/-0.29) than in placebo group (2.39+/-0.27) (p<0.05). CONCLUSION: LB30057 inhibits SMC proliferation in a dose dependent manner. Prolonged 14-day oral administration of LB30057 is effective in reducing the neointimal hyperplasia in rat carotid balloon injury model.

A Case of Primary Antiphospholipid Antibody Syndrome with Multiple Thromboses Including Thrombotic Occlusion of Abdominal Aorta

In antiphospholipid antibody syndrome (APS), multiple thromboses affecting large arteries and veins through the whole body is rare. In this report, a case of a 65 year old women suffering from APS with multiple thromboses of the renal and iliac artery, the infrarenal abdominal aorta, the deep vein, and a pulmonary thromboembolism is presented. The patient was treated successfully with intensive anticoagulation and steroid pulse therapy. There was no evidence of recurrent thrombotic complications during a three year follow-up period with oral warfarin and prednisolone

Reconsideration for current guideline of lipid-lowering therapy in patients with coronary artery disease

BACKGROUND AND OBJECTIVES: Despite the proven benefit of cholesterol- lowering therapy in patients with CAD, there is no consensual opinion on guideline of cholesterol-lowering therapy in patients with CAD in Korea. The aim of this study is to evaluate the risk of CAD according to the cholesterol level and to consider current guideline of cholesterol-lowering therapy for the secondary prevention in patients with CAD. MATERIALS AND METHODS: Consecutive 600 patients were assigned into two groups - coronary artery disease group (364 patients) and normal coronary artery group (236 patients) - depending on the coronary angiographic findings. Lipid profiles (total cholesterol, Triglyceride, HDL-cholesterol, LDL-cholesterol) were obtained and the odd ratio of CAD was evaluated according to the national cholesterol education program treatment guideline (NCEP: LDL cholesterol > or = 130 mg/dl) and the national heath insurance treatment guideline (NHI: total cholesterol > or = 220 mg/dl) by multi-variate logistic regression analysis. RESULTS: According to the NHI and NCEP guideline, the proportion of patients with CAD indicated on cholesterol-lowering therapy were 25%, 36.5% respectively and the odd ratio of CAD was 1.00 (95% CI 0.52 - 1.89, p=0.99), 4.89 (95% CI 2.78 - 8.60, p or = 130 mg/dl only reflected the risk of CAD in both guidelines and more proportion of the patients were indicated on cholesterol-lowering therapy in NCEP guideline than in NHI guideline.

A Case of Behcet's Disease Presenting with Aneurysm of Abdominal Aorta and Hemorrhagic Ulcerative Lesion of Terminal Ileum

Behcet's disease is a disorder of a multisystemic involvement with unknown etiology. Involvement of the cardiovascular system and intestinal tract are rare, but serious complications. We present a case with Behcet's disease demonstrating aneurysm of the abdominal aorta as well as hemorrhagic ileal ulcerative lesions and requiring surgical treatment.

The Study of Branching Anomaly and Tortuosity of Radial Artery for Trans-Radial Coronary Procedure

BACKGROUND AND PURPOSE: The radial artery has currently been regarded as a useful vascular access site for coronary procedures. We want to evaluate the incidence and clinical significance of anomalous branching pattern and tortuosity of radial artery. MATERIALS AND METHOD: From May 1997 to May 1999, retrograde radial artery angiography was performed in 1191 cases. Branching anomaly and tortuosity of upper extremity artery, procedure times and local vascular complications were analyzed. RESULTS: 1) Anomalous radial arterial branching was found in 3.2%. Most common one was high origin of the radial artery (2.4%). 2) Tortuosity of radial artery was found in 4.2%. Most common tortuosity were S shape in 1.8% and omega shape in 1.8% of cases. 3) Cross over to other artery, radial artery occlusion and perforation occurred in 24 cases, 6 cases and 4 cases, respectively. Prolonged procedure times, crossover to other artery and radial artery perforation was related with tortuosity of radial artery, not with anomalous branching. CONCLUSION: The incidence in branching anomaly and tortuosity of radial artery was not frequent in our study. Radial artery tortuosity was associated with old age, prolonged procedure time and radial artery perforation. In selected cases, pre- or intra-procedural angiographic assessment of radial artery might be helpful in performing safe procedure.

Guidewire-Induced Perforation of Distal Circumflex Artery Treated with Transcatheter Embolization of Polyvinyl Alcohol Form

Coronary artery perforation is a rare and serious complication in coronary angioplasty. Some patients complicated by coronary perforation may develop cardiac tamponade, which is generally due to massive hemorrhage in the pericardial space between the epicardium and the pericardium. We report a case of coronary artery perforation producing impending tamponade, which was successfully treated by transcatheter embolization of distal circumflex artery using polyvinyl alcohol.

A Case of Transradial Approach to Carotid Artery Angioplasty and Stenting in Left Internal Carotid Stenosis

Surgical endarterectomy has been shown to be superior to medical treatment in the management of severe carotid stenosis. Endarterectomy, although effective, does have limitations, and percutaneous transluminal angioplasty with stent may offer an alternative modality of treatment. We report on a patient with severe coronary disease that femoral arterial cannulation was not possible due to aorto-femoral shunt operation and absent pulse. The transradial approach was used for aortography, bilateral carotid angiography and successful elective stent deployment in the left internal carotid artery. The transradial approach might be useful alternative in case of problems with femoral approach.

The Severity of Extent of Coronary Atherosclerosis Related to Plasma Homocysteine

BACKGROUND AND PURPOSE: Hyperhomocysteinemia is supposed to be a risk factor for vascular occlusive disease. We want to evaluate the relationship between plasma homocysteine and the severity of coronary artery disease (CAD). METHODS: In 121 consecutive patients (men:62%: age:60+/-10 years) undergoing coronary angiography, plasma homocysteine, vitamin B(12), vitamin B(6) and folate levels were measured and angiographic findings were evaluated for the number of diseased vessels (diameter stenosis 50%), severity of stenosis of CAD and extent of CAD. Extent of CAD was defined as an index derived by assigning a score of 0-3 per segment depending on the proportion of lumen length irregularity and dividing the sum by the number of visualized segments. RESULTS: Twenty-two patients had normal coronary artery: 35 patients, minimal CAD (diameter stenosis < 50%): 30 patients, 1 vessel disease (VD): 22 patients, 2VD and 12 patients, 3VD. Homocysteine levels w+re not significantly different between the groups (normal:7.6+/-4.2 mmol/L: minimal CAD:8.4+/-3.1mmol/L: 1VD: 8.0+/-4.8mmol/L: 2VDs: 10.2+/-6.0 mmol/L: 3VDs: 9.2+/-5.3 mmol/L). There was no relation between the stenosis scores of CAD and homocysteine levels (r=0.1). The extent scores of CAD were weakly correlated to the plasma homocysteine levels (r=0.22, p<0.05) and low density lipoprotein (LDL) cholesterol levels (r=0.28, p<0.01), and reversely correlated to high density lipoprotein (HDL) cholesterol levels (r=-0.31, p<0.01). The plasma homocysteine levels were reversely correlated to vitamin B12 (r=-0.27, p<0.01) and folate (r=-0.23, p<0.05) levels. In conclusion, the plasma homocysteine level was weakly but significantly correlated with the extent of CAD, not with the severity of stenosis.

The changes of radial arterial diameter and procedural outcomes of repeated-use radial artery in transradial

BACKGROUND AND OBJECTIVES: Practical concerns about transradial approach are increasing in consideration of high procedural success rate, low local complications, and patient's convenience. There was no available data about repeated-use of radial artery for coronary procedures. We evaluate the changes of radial arterial diameter and procedural outcomes of repeated transradial procedure. MATERIALS AND METHOD: Of consecutive 1771 transradial coronary procedures, 117 patients received repeated transradial procedures through the same radial artery. Radial arterial diameter, vascular access time and procedural outcomes were evaluated in between the group of first-use and repeated-use of radial artery. RESULTS: Among 117 patients of second transradial coronary procedure in the repeated-use group, 47 patients (41.6%) underwent coronary intervention and 66 patients (58.4%) underwent coronary angiography. The right radial approach was used in 82.9% of the cases. There was no significant difference in radial artery mean diameter between pre-procedure and 1 day after procedure in patients with first-use and repeated-use group. There was no significant change of radial arterial diameter after first-use depending on the SAR (the ratio of sheath outer diameter to radial artery inner diameter). However, after repeated-use of radial artery, there was significant reduction of radial arterial diameter 1 day after procedure in the patients with SAR more than 0.9 (p<0.05). In repeated-use group, the mean radial arterial diameter was 2.63 +/- 0.35mm mm before the procedure and 2.51 +/- 0.29mm during follow-up (136 +/- 123 days) (p<0.05). There was no significant difference of the vascular access time between the first-use and repeated-use procedures (2.9+/-3.1 vs 3.3+/-3.6 minutes, p<0.05). The procedural success and vascular complication rate of repeated-use of radial artery were as similar to those of the first-use, but total occlusion of radial artery was higher in the repeated-use group (2.6% vs 0.7%, p<0.05). CONCLUSION: The diameter of radial artery after transradial procedures was significantly reduced during follow-up and the incidence of asymptomatic radial artery occlusion was more frequent after repeated-use. However, repeated-use of radial artery was feasible in most patients with high procedural success rate and low vascular complications.

A Case of Cardiac Tamponade due to Penetration of the Right Ventricule by an Acupunture Needle

The heart may be critically damaged by objects of unimpressive size or appearance. We report a case of cardiac tamponade due to penetration of the right ventricle by an acupunture needle. A 59-year-old man was admitted due to dyspnea and chest pain. He had recieved acupuncture therapy during 10 years for chronic right upper abdominal pain. He was diagnosed as cardiac tamponade due to hemopericardium caused by an broken a cupuncture needle detected on fluoroscopy, computerized tomography and trans-esophageal echocardiography, and the needle was successfully removed by cardiac surgery. The patient was discharged uneventfully and followed at the outpatient department.

A Case of Stent Embolizations into the Left Renal and Right Common Iliac Artery during Primary PTCA

Coronary stent embolization is a rare event but may result in clinically relevant cardiac ischemia or peripheral embolization during the procedure. We report a case of systemic embolizations of two coil stents during the primary PTCA in acute myocardial infarction, who were treated successfully with a double wire helix technique and a gooseneck snare. Although in our experience this rare complication did not produce any clinical complications, care should be taken to prevent this possibility, especially in patients with significant vessel tortuosity, calcification, total occlusion, or mild stenosis proximal to the target lesion.

The Effect of Local Delivery of IBMX on the Neointimal Proliferation in Rat Carotid Balloon Injury Model

BACKGROUND: Hyperplastic neointima is one of the major mechanisms of restenosis following balloon angioplasty in selected patients with symptomatic angina pectoris. Elevation of cellular cyclic nucleotide levels such as cAMP and cGMP are known to inhibit the proliferation of vascular smooth muscle cells. 3-isobutyl-1-methylxanthine (IBMX) increases intracellular cAMP and cGMP by nonselective inhibition of phosphodiesterases (PDEs). We conducted this study under the hypothesis that local delivery of IBMX could inhibit neointimal hyperplasia after balloon injury of the rat carotid artery. METHODS: Left common carotid artery of 10 week old male Sprague-Dawley rats were subjected to arterial injury by 2F Fogarty balloon catheter. After injury, animals were allocated to the control groups (control 1: injury control and control 2: pluronic gel plus DMSO control) and IBMX group, which received pluronic polymer gel, DMSO and IBMX mixture periadventitially. After 3 weeks, the rats were killed by overdose of ketamine, and the injured left arteries were pressure-fixed with 10% formalin and subjected to histomorphological analysis. RESULTS: Mean body weight of rats was not statistically different among study groups. The mean area of neointima (control group 1:0.28+/-0.05 mm2,Control group 2:0.27+/-0.08 mm2 , IBMX group:0.18+/-0.08 mm2 : p<0.05) and the mean ratio of neointima to medial area[versus (control group 1:1.89+/-0.37, control group 2:1.95+/-0.41, IBMX group: 1.41+/-0.47: p<0.05)] were significantly less in IBMX group. The mean area of external elastic lamina was significantly larger in control group 1 than IBMX group (0.57+/-0.07 mm2 versus 0.47+/-0.10 mm2 ) and mean luminal area showed no significant difference among groups (control group1:0.14+/-0.07 mm2 , control group 2: 0.10+/-0.05 mm2 , control group 3: 0.16+/-0.06 mm2). CONCLUSION: Peri-adventitial single administration of IBMX showed its effectiveness in reducing the neointimal proliferation in rat carotid balloon injury model. Furthermore we observed the positive correlation between intimal area and EELA suggesting vascular remodeling depending on the intima volume.

The Effect of Local Delivery of IBMX on the Neointimal Proliferation in Rat Carotid Balloon Injury Model

BACKGROUND: Hyperplastic neointima is one of the major mechanisms of restenosis following balloon angioplasty in selected patients with symptomatic angina pectoris. Elevation of cellular cyclic nucleotide levels such as cAMP and cGMP are known to inhibit the proliferation of vascular smooth muscle cells. 3-isobutyl-1-methylxanthine (IBMX) increases intracellular cAMP and cGMP by nonselective inhibition of phosphodiesterases (PDEs). We conducted this study under the hypothesis that local delivery of IBMX could inhibit neointimal hyperplasia after balloon injury of the rat carotid artery. METHODS: Left common carotid artery of 10 week old male Sprague-Dawley rats were subjected to arterial injury by 2F Fogarty balloon catheter. After injury, animals were allocated to the control groups (control 1: injury control and control 2: pluronic gel plus DMSO control) and IBMX group, which received pluronic polymer gel, DMSO and IBMX mixture periadventitially. After 3 weeks, the rats were killed by overdose of ketamine, and the injured left arteries were pressure-fixed with 10% formalin and subjected to histomorphological analysis. RESULTS: Mean body weight of rats was not statistically different among study groups. The mean area of neointima (control group 1:0.28+/-0.05 mm2,Control group 2:0.27+/-0.08 mm2 , IBMX group:0.18+/-0.08 mm2 : p<0.05) and the mean ratio of neointima to medial area[versus (control group 1:1.89+/-0.37, control group 2:1.95+/-0.41, IBMX group: 1.41+/-0.47: p<0.05)] were significantly less in IBMX group. The mean area of external elastic lamina was significantly larger in control group 1 than IBMX group (0.57+/-0.07 mm2 versus 0.47+/-0.10 mm2 ) and mean luminal area showed no significant difference among groups (control group1:0.14+/-0.07 mm2 , control group 2: 0.10+/-0.05 mm2 , control group 3: 0.16+/-0.06 mm2). CONCLUSION: Peri-adventitial single administration of IBMX showed its effectiveness in reducing the neointimal proliferation in rat carotid balloon injury model. Furthermore we observed the positive correlation between intimal area and EELA suggesting vascular remodeling depending on the intima volume.