The Inhibition of Neointimal Hyperplasia by Combination of External Radiation and Paclitaxel in A Rat Carotid Injury Model

BACKGROUND AND OBJECTIVES: Radiation therapy is one of the promising new treatment for restenosis, which is a major problem for the long-term success after angioplasty. We compared radiation therapy only and combined therapy of paclitaxel and radiation on neointimal hyperplasia after injury of rat carotid artery to see whether we can reduce the effective dosage of radiation and thus diminish untoward consequence of radiation if paclitaxel could function as a cell-cycle selective radiosensitizer. MATERIAL AND METHODS: A standardized carotid balloon catheter arterial injury was produced in 65 rats. First group was composed of a single dose of paclitaxel 1 mg/kg body weight, 2 mg/kg or 4 mg/kg, which was administrated intraperitoneally at 2 hours after injury. Second group received external radiation at doses of 2.5 or 5 Gy at 24 hours after injury. Third group was treated with combined paclitaxel-radiation: paclitaxel was injected at 2 hours after injury and then external radiation was delivered 24 hours later. At 21 days after injury, the cross-sectional area of neointima and the ratio of intima/medial area were determined from axial sections using image analysis. RESULTS: Single dose of paclitaxel had no effect in reducing smooth muscle cell proliferation. Minimum effective single dose to inhibit neointimal hyperplasia was 5 Gy. Combined paclitaxel-radiation group except subgroup with paclitaxel 1 mg/kg and 2.5 Gy radiation showed significant reduction of neointimal area compared to group with 2.5 Gy radiation. CONCLUSION: Low-dose external radiation combined with paclitaxel can more effectively inhibit smooth muscle cell pro-liferation and neointimal hyperplasia than radiation only in the rat carotid injury model.

Assessment of change of coronary artery flow using corrected TIMI frame count following abciximab adminstration during primary angioplasty for acute myocardial infarction

BACKGROUND: In spite of the successful reperfusion therapy, coronary blood flow in infarcted myocardium was known to decrease for a long time. Abciximab is known to inhibit the final pathway of platelet aggregation and maintenance the large vessel patency. But abciximab may have another important effect beyond the these effect. TIMI frame count method is simple, reproducible, objective and quantitative index of coronary flow. We tried to define the effect of abciximab that used with primary angioplasty on the coronary blood flow using TIMI frame count methods. METHODS: We consecutively studied 30 patients who admitted for acute myocardial infarction without cardiogenic shock from September 1997 to August 1999. We analyzed the changes of corrected TIMI frame count(CTFC) between the baseline(immediate after the angioplasty) and follow-up(post-op 7th day) coronary angiogram and compared the results between the group of primary angioplasty with abciximab(abciximab group, n=1) and the group of primary angioplasty without abciximab(non-abciximab group, n=9). RESULTS: There were no differences between abciximab group and non-abciximab group in baseline characteristics, treatment modalities and angiographic results. According to the results of the comparison of deltaCTFC, changing rate of CTFC, deltavelocity and changing rate of velocity, there were significant improvement of the coronary blood flow in infarct related artery in the abciximab group than non-abciximab group. But there were no differences in the changes of coronary blood flow in non-infarct related artery between two groups. The frequency of major adverse coronary events during follow up periods(mean 6 months) were similar(9.1% and 5.2% each other, p>0.05). CONCLUSIONS: Abciximab used with primary angioplasty in acute myocardial infarction improved the coronary blood flow significantly in infarcted myocardium. This finding may be related that abciximab enhance the perfusion and function of microvasculature in infarcted myocardium.

Evaluation of Left Ventricle Diastolic Function by Color M-Mode Doppler Echocardiography in Coronary Artery Disease

PURPOSE: The aims of this study were to evaluate the usefulness of the propagation velocity (Vp) measured by transthoracic color M-mode Doppler in patients with coronary artery disease and compare Vp with conventional diastolic function index using transmitral and pulmonary vein flow. METHODS: Study subjects were classified into two groups according to the presence of coronary artery disease (CAD): 44 subjects (M:F=22:22, mean age 63+/-12 yrs) with CAD (AMI; n=13 , unstable angina; n=5, stable angina; n=26); 31 normal subjects (M:F=13:18, mean age 43+/-15 yrs). Vp of early flow into left ventricular cavity measured by color M-mode Doppler was proposed as an index of left ventricular diastolic function. Vp was compared with conventional diastolic function index. RESULTS: 1. Vp in CAD patients (32.8+/-9.1 cm/sec) was lower than control (63.6+/-14.1 cm/sec)(p>0.01). Among CAD patients, Vp in CAD patients (30.1+/-8.6 cm/sec) with left ventricular hypertrophy (LVH) was lower than Vp in CAD patients without LVH (35.9+/-8.9 cm/sec)(p>0.01). 2. Vp was correlated with left ventricular ejection fraction (r=0.602, p>0.01), with D wave of pulmonary vein flow (r=0.540, p>0.01) and with E/A velocity ratio of mitral inflow (r=0.517, p>0.01) and negatively correlated with left ventricular mass index (r=-0.576, p>0.01). CONCLUSION: The propagation velocity measured by color M-mode Doppler is a useful index for evaluation of diastolic function of left ventricle in the patients with coronary artery disease.

The Usefulness of Echocardiographic Severity Index for Prediction of Severity of Pulmonary Embolism

BACKGROUND: Pulmonary embolism is associated with varying degrees of pulmonary vascular obstruction. This study was undertaken to establish whether the extent of perfusion defect in lung scintigraphy can be predicted from analysis of echocardiographic measurements in patients with pulmonary embolism. METHODS: We retrospectively studied 28 patients who presented with clinical evidence of pulmonary embolism. In order to compare the extent of perfusion defect in lung scintigraphy, we devised a scoring system (echocardiographic severity index, ESI) for various echocardiographic parameters, which include right ventricle size, area, shape, systolic function, and pulmonary artery pressure. [ESI=sum of scores/number of parameters measured]. RESULTS: The mean values (+/-SD) of each parameter were as follow; right ventricular end-diastolic dimension (RVedD), 34.5+/-5.7 mm; LVedD, 40.9+/-5.2 mm; ratio of RVedD to LVedD, 0.87+/-0.2; right ventricular end-diastolic area (RVedA), 24.7+/-9.5 cm2; right ventricular end-systolic area (RVesA), 17.8+/-7.8 cm2; fractional area change, 28.8+/-9.7%; angle between IVS and RV, 96.0+/-14.8degrees; RV hypokinesia, absence or mild in 29%, moderate in 50%, severe in 21%; TR grade, absence or mild in 25%, moderate in 43%, severe in 32%; pulmonary artery systolic pressure, 50 mmHg 11% of patients. The echocardiographic severity index (ESI) in patients with pulmonary embolism was 0.52+/-0.24, and the perfusion defect score was 0.21+/-0.14. There was a close correlation between the ESI and the extent of perfusion defect (r=0.622, p<0.01). CONCLUSION: The echocardiographic severity index may reflect the extent of the perfusion defects in patients with pulmonary embolism, therefore it is potentially applicable in clinical practice for evaluating patients with pulmonary embolism and furthermore in their follow-up over a period of time.

Transthoracic Echocardiographic Assessment of Adriamycin-induced Cardiomyopathy in Rats with a 15 MHz Transducer

BACKGROUND: Adriamycin (doxorubicin) is one of the widely used drugs in the treatment of a variety of solid and hematologic malignancies. However, the adriamycin-induced cardiomyopathy limits the prolonged use of this effective drug. Transthoracic echocardiography is the excellent tool in early detection and follow-up studies of adriamycin-induced cardiomyopathy. The aim of this study was to assess the cardiac function and morphology using a 15 MHz high-frequency imaging in rats. METHODS: Adriamycin was administrated intraperitoneally by six equal injections at a dose of 2.5 mg/kg over a period of 2 weeks for total cumulative dose of 15 mg/kg body weight in 12 male Sprague-Dawley rats (weight 367+/-39 g). Transthoracic echocardiography with a 15 MHz linear-array transducer was performed at baseline and additionally at 3 weeks to measure the left ventricular wall thickness and dimension from the parasternal short axis view with 2D guided M-mode and pulsed Doppler signals of mitral inflow. Within 2 days of echocardiography, the heart was harvested for electron microscopic evaluation after potassium-induced cardiac arrest. RESULTS: 1) The mortality rate during the experimental period was 0%. 2) Transthoracic echocardiography provided adequate 2D guided M-mode images and pulsed Doppler signals of mitral inflow in all rats. 3) In follow-up echocardiography, pericardial effusion was detected in 7out of 12 rats (58%). 4) Compared to baseline, end-diastolic dimensions were increased from 7.01+/-0.69 to 7.74+/-1.25 mm (p<0.001), end-systolic dimensions were increased from 4.13+/-0.69 to 5.22+/-1.12 mm (p<0.05), and interventricular septal and posterior wall thickness at end-systole and end-diastole were significantly decreased (p<0.05, respectively). 5) Fractional shortening was decreased from 43.0+/-6.8 to 32.7+/-8.0%, compared to baseline (p<0.05). 6) E/A ratio of mitral inflow changed significantly from 1.63+/-0.36 to 2.78+/-1.0, compared to baseline (p<0.05). CONCLUSION: Adriamycin administration at total cumulative dose of 15 mg/kg body weight over 2 weeks creates a reliable model of non-ischemic dilated cardiomyopathy in rats with a high success rate. Transthoracic echocardiography using a 15 MHz transducer provides adequate images for assessing the cardiac function and morphology in follow-up studies in adriamycin-induced cardiomyopathy of rats. These results suggest that transthoracic echocardiography using a 15 MHz Transducer is a promising tool for an assessment of adriamycin-induced cardiomyopathy in small animals.

Assessment of Autonomic Nervous System by the Analysis of Heart Rate Variability in Patients with Variant Angina

BACKGROUND AND OBJECTIVES: Autonomic nervous discharge had been implicated in the pathogenesis of coronary artery spasm although the precise mechanisms by which coronary spasm is triggered remain to be elucidated. The purpose of this study was to assess the pattern of the autonomic nervous system in patients with variant angina through the analysis of heart rate variability. MATERIALS AND METHODS: We compared the pattern of cardiac sympathetic and parasympathetic activity through the time domain and frequency domain analysis of heart rate variability with 24-hour Holter monitoring between 14 patients with variant angina and 14 healthy control subjects. None of the patients had organic coronary artery stenosis as determined by angiography. RESULTS: 1) Among the time domain indices, the percent of successive normal NN intervals difference greater than 50 msec (pNN50) and the square root of the mean squared differences of successive NN intervals (rMSSD) in the patient group were significantly lower than those in the normal control (p <0.05, repectively). 2) In the patient group, mean R-R intervals were significantly shortened from night to early morning compared to control group (p <0.05). 3) With frequency domian analysis, low frequency (0.04 to 0.15Hz)spectrum, which is correlated with sympathetic activity, was revealed no significant difference between two groups. From night to early morning, significant increase of high frequency (0.15 to 0.4 Hz) spectrum, which is specific index for vagal activity, and significant decrease of the ratio of low to high frequency, which represents sympatho-vagal interaction, was blunted in the patient group (p <0.05). CONCLUSIONS: In variant angina, cardiac vagal influence on the heart rate was blunted and sympathetic activity was predominant at night and in the early morning.

Inhibition of Neointimal Hyperplasia by External Radiation in Rat Carotid Injury Model-The Possible Role of Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1-

BACKGROUND AND OBJECTIVES: Despite significant improvement in the field of angioplasty, restenosis remains a major obstacle to the long-term success of the procedure. Radiation can effectively inhibit neointimal hyperplasia by causing the arrest of mitosis during cell division and limiting proliferation by reducing the number of regenerating clonal progenitors. Balloon injury could induce the cell adhesion molecule, ICAM-1 and VCAM-1, on SMCs and regenerating endothelial cells (ECs). ICAM-1 and/or VCAM-1 may play a role in the progression of neointimal hyperplasia induced by balloon injury and external radiation may effectively inhibit neointimal hyperplasia by attenuating their expression. The purpose of this study was to examine the effect of external radiation against ICAM-1 and VCAM-1 on neointimal hyperplasia after balloon injury in rat carotid arteries. MATERIAL AND METHODS: A standardized carotid balloon catheter arterial injury was produced in 51 rats and external beam radiation with doses from 5-20 Gy were delivered in 28 rats (radiation treated group) at 24 hours after injury. To investigate the effect of the external radiation on neointimal hyperplasia, the intima area and the intima/medial area of arteries were measured at day 14 after injury. The expressions of ICAM-1 and VCAM-1 at day 2, day 7, and day 10 after injury were studied in control group and radiation treated group by immunohistochemistry. RESULTS: Means of intimal area and intima/medial ratio in radiation treated group were significantly lower than those in control group and significantly reduced with increasing radiation dosage. At day 2 after injury, medial SMCs of injury group extensively expressed ICAM-1, while it was focally expressed with 10 Gy radiation treated group. At day 7 and day 10 after injury, ICAM-1 expression on medial SMCs was attenuated and neointimal ICAM-1 expression was increased. As compared with control group, ICAM-1 expression after radiation was weak and focal just around the internal elastic lamina. At 2 days after injury, medial SMCs moderately expressed VCAM-1, which was weakly and focally expressed with 10 Gy radiation treated group. At day 7 and day 10 after injury, focal expression of VCAM-1 was noted around the internal elastic lamina, but there was no VCAM-1 expression on neointima with radiation. CONCLUSION: External radiation after carotid arterial injury may potentially inhibit SMC proliferation and neointimal hyperplasia, and balloon injury-induced or upregulated expressions of ICAM-1 and VCAM-1 may be attenuated with external radiation.

The Clinical Study On Inflammatory Myopathies / 대한류마티스학회지

OBJECTIVE: To determine possible similarities and differences in clinical and laboratory features and prognosis between patients with inflammatory myopathies diagnosed at Kangnam St. Mary's hospital and other reported series. METHODS: Medical records of 52 patients diagnosed as inflammatory myopathies by Bohan and Peter criteria who were admitted to Kangnam St. Mary's hospital between January 1989 and August 1994, were reviewed. The patients were further classified into 5 groups proposed by Bohan and Peter ; group I primary polymyositis(PM), group II primary dermatomyositis(DM), group III polymyositis/dermatomyositis(PM/DM) with neoplasia, group IV juvenile PM/DM, group V PM/DM associated with connective tissue disease. RESULTS: 1) There were 52 PM/DM cases with mean age at diagnosis of 34. 4 ranging from 6 to 67 years, and significantly more females(male:female = 9:43). 2) Of 52 patients, group II was the most frequent group(36.5%), and the next were as follows ; group I 28.8%, group V 25%, group IV 5.7%, group 3.8%. Systemic lupus erythematosus(SLE) was the commonest connective tissue disease, and malignancy was associated in 2 cases including breast cancer and small cell carcinoma of lung. 3) At presentation, 86.5% had proximal muscle weakness, 61.5% had arthralgia/arthritis and 44. 2% had Raynaud phenomenon. 4) The elevated serum LDH, aldolase and creatine kinase were found in 84. 6%, 84. 1%o, 71.2% of the patients respectively. Positive electromyography and muscle biopsy consistent with inflammatory myopathy were also found in 91.4%, 88.8% respectively. 5) Positive antinuclear antibody, rheumatoid factor, anti-Ro, anti-nRNP were found in 59.6%, 17.3%, 16.7%, 8.3% of patients respectively, mainly in group V. Anti-Jo-1 antibody was present in 25.8% of patients tested(8/31), including group II 4 cases, group V 3 cases and group I I case. 6) All 8 patients with anti-Jo-1 antibody had interstitial lung disease(ILD) and Raynaud phenomenon with statistical significance, compared with those without anti-Jo-1 antibody(P<0.01). 7) Among the 43 patients in whom follow up was available, 10 patients died(mortality rate 23.2%). The main cause of death were infection(4 cases), and respiratory muscle weakness, respiratory failure due to ILD, malignancy 2 cases respectively. CONCLUSION: The results of the study demonstrated that clinical expression of PM/DM were similar to previously reported series except relatively high frequency of primary dermatomyositis in this study. Anti-Jo-1 antibody was main autoantibody in inflammatory myopathies, which was associated with extramuscular manifestations, such as ILD and Raynaud's phnomenon.