Circulating platelet-derived microparticles are associated with atherothrombotic events: a marker for vulnerable blood.
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Biomedical subjects
Publications and source records attributed to Kenei Shimada.
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OBJECTIVES: We sought to evaluate the effect of acute hyperglycemia on coronary microcirculation by noninvasive measurement of coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). RESEARCH DESIGN AND METHODS: Measurements of CFVR using TTDE and levels of plasma glucose and serum insulin and lipids were determined before and 1 hour after loading with oral glucose (75-g glucose) in 10 young healthy males (mean age, 30 +/- 2 years) or an artificial sweetener in five of the 10 subjects without coronary risk factors. RESULTS: In all subjects, the levels of plasma glucose and serum insulin significantly increased after glucose loading compared with baseline (5.1 +/- 0.6 vs 7.6 +/- 1.2 mM/l, 6 +/- 3 vs 49 +/- 13 microU/ml, respectively; P < 0.0001). CFVR was significantly decreased 1 hour after acute oral glucose loading (4.4 +/- 0.7-3.8 +/- 0.7, respectively; P < 0.01). There was no significant change in CFVR after loading with an artificial sweetener (4.4 +/- 0.6-4.4 +/- 0.5 cm/sec). CONCLUSIONS: TTDE revealed that acute hyperglycemia induced by oral glucose loading suppresses CFVR in healthy young male subjects. This result suggests that acute hyperglycemia may have adverse effects on coronary microcirculation.
Erythropoietin (EPO) has been suggested to have a cardioprotective effect against ischemia. The purpose of this study was to examine the effects of EPO on cardiac remodeling after myocardial infarction (MI). MI was induced by ligation of the coronary artery in Wistar rats. The rats with MI were randomly divided into untreated MI and two EPO-treated MI groups. EPO was administered subcutaneously by injection once a day for 4 days after MI at 5000 U/kg or 3 times a week for 4 weeks at 1000 U/kg. Five days after MI, EPO prevented the increase in activated caspase 3, matrix metalloproteinase-2, and transcriptional activation of activator protein-1 in non-infarcted myocardium. Four weeks after MI, left ventricular weight, left ventricular end-diastolic pressure, and left ventricular dimension were increased, and ejection fraction and E wave deceleration time were decreased. EPO significantly attenuated this ventricular remodeling and systolic and diastolic dysfunction. In addition, EPO significantly attenuated the interstitial fibrosis and remodeling-related gene expression in non-infarcted myocardium. Furthermore, EPO significantly enhanced angiogenesis and reduced apoptotic cell death in peri-infarcted myocardium. In conclusion, when administered after MI, EPO prevents cardiac remodeling and improves ventricular function with enhanced angiogenesis and reduced apoptosis.
OBJECTIVES: Optical coherence tomography(OCT)is a high-resolution imaging method that can clearly visualize vessels through the displacement of blood with flushing agents. Continuous imaging methods have not been established. This study investigated optimal methods for continuous OCT imaging. METHODS: Thirty-four arteries with stent implantation (24 peripheral and 10 coronary arteries)in 14 pigs were examined using OCT with a motorized pullback device. Two imaging methods (flush alone by liquid substance and flush with occlusion) were compared. Adequate image acquisition was defined as the entire circumferential intimal layer being detectable within continuous segments. To investigate factors that could influence image quality, stented regions were divided into 4-5 mm segments. RESULTS: The flush with occlusion method provided better OCT images compared to flush alone (flush with occlusion: 60.9%, flush alone: 8.7%, p = 0.0002). Using the flush with occlusion method, the rate of adequate image acquisition was 64.4% and visualization of > 75% intimal circumference was 83.5%. Intravascular ultrasound could detect all stented regions. Segmental analyses found more adequate images were detected in smaller vessels (adequate segment: 3.8 +/- 0.4 mm, inadequate segment: 4.2 +/- 0.8 mm, p < 0.0001) or with centered image wire position (adequate segment: center 35%, inadequate segment: center 14%, p = 0.003). In addition, side branches did not affect image quality. CONCLUSIONS: To acquire continuous OCT images, the flush with occlusion method was more effective compared to flush alone. Moreover, image quality is affected by vessel size and imaging wire position. These results suggest that optimized OCT imaging can provide continuous vessel detection.
Matrix metalloproteinases (MMPs) are important for resorption of extracellular matrixes and may degrade the fibrous cap of an atherosclerotic plaque, thus contributing to coronary plaque rupture. Histologic studies have shown MMP expression in lesions of acute coronary syndrome. In this study, we evaluated the relation between plaque morphology as obtained by intravascular ultrasound before percutaneous coronary intervention and serum MMP levels in patients who had coronary artery disease. We enrolled consecutive 47 patients who had acute myocardial infarction (AMI), 23 who had unstable angina pectoris (UAP), and 19 who had stable effort angina pectoris and underwent intravascular ultrasound before percutaneous coronary intervention followed by successful primary percutaneous coronary intervention. Peripheral blood was obtained from all patients before angiography and serum levels of MMP-1,-2, and -9 were analyzed. Serum levels of MMP-9 in the AMI and UAP groups were significantly higher than that in the stable effort angina pectoris group (p = 0.007 and 0.04, respectively). From the intravascular ultrasound findings before percutaneous coronary intervention, plaque rupture was detected in 26 patients (55%) in the AMI group and in 11 patients (48%) in the UAP group. In these 2 groups, patients with plaque rupture had significantly higher levels of MMP-9 than patients who did not have plaque rupture (p = 0.03 and 0.01, respectively). Multiple logistic regression analysis showed that MMP-9 was the only independent predictor of plaque rupture (p = 0.004). In conclusion, high levels of MMP-9 in patients who have AMI and UAP are related to the presence of plaque rupture in the culprit lesion.
OBJECTIVES: This study sought to investigate the relationship between multiple plaque ruptures, C-reactive protein (CRP), and clinical prognosis in acute myocardial infarction (AMI). BACKGROUND: Several studies have demonstrated that ruptured or vulnerable plaques exist not only at the culprit lesion but also in the whole coronary artery in some acute coronary syndrome (ACS) patients. Recent studies have reported that a ruptured plaque at the culprit lesion is associated with elevated CRP, which indicates a poor prognosis in patients with ACS. METHODS: We performed intravascular ultrasound in 45 infarct-related arteries and another 84 major coronary arteries in 45 first AMI patients. RESULTS: Plaque rupture was observed in 21 patients (47%) at the culprit site. Intravascular ultrasound revealed 17 additional plaque ruptures at remote sites in 11 patients (24%). Patients with multiple risk factors were more frequently found in our multiple-plaque rupture patients compared with single-plaque rupture or nonrupture patients (82% vs. 40% vs. 29%, p = 0.01). High-sensitive CRP levels had a positive correlation with the number of plaque ruptures (p < 0.01). All culprit lesions were successfully treated by percutaneous coronary intervention. Patients with multiple plaque rupture showed significantly poor prognosis compared with others (p = 0.01). CONCLUSIONS: Multiple plaque rupture is associated with systemic inflammation, and patients with multiple plaque rupture can be expected to show a poor prognosis. Our results suggest that AMI treatment should focus not only on stabilization of the culprit site but also a systemic approach to systemic stabilization of the arteries.
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This study examined the effect of azithromycin therapy on the coronary microcirculation using measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography in 35 patients with coronary artery disease. CFVR increased significantly after azithromycin therapy (3.0 +/- 0.7 vs 3.5 +/- 0.7, p <0.001). The changes in CFVR were negatively correlated with changes in high-sensitivity C-reactive protein levels in patients receiving azithromycin.
BACKGROUND: Calcification is a common finding in human coronary arteries; however, the relationship between calcification patterns, plaque morphology, and patterns of remodeling of culprit lesions in a comparison of patients with acute coronary syndromes (ACS) and those with stable conditions has not been documented. METHODS AND RESULTS: Preinterventional intravascular ultrasound (IVUS) images of 178 patients were studied, 61 with acute myocardial infarction (AMI), 70 with unstable angina pectoris (UAP), and 47 with stable angina pectoris (SAP). The frequency of calcium deposits within an arc of less than 90 degrees for all calcium deposits was significantly different in culprit lesions of patients with AMI, UAP, and SAP (P<0.0001). Moreover, the average number of calcium deposits within an arc of <90 degrees per patient was significantly higher in AMI than in SAP (P<0.0005; mean+/-SD, AMI 1.4+/-1.3, SAP 0.5+/-0.8). Conversely, calcium deposits were significantly longer in SAP patients (P<0.0001; mean+/-SD, AMI 2.2+/-1.6, UAP 1.9+/-1.8, and SAP 4.3+/-3.2 mm). In AMI patients, the typical pattern was spotty calcification, associated with a fibrofatty plaque and positive remodeling. In ACS patients showing negative remodeling, no calcification was the most frequent observation. Conversely, SAP patients had the highest frequency of extensive calcification. CONCLUSIONS: Our observations show that IVUS allows the identification of vulnerable plaques in coronary arteries, not only by identifying a fibrofatty plaque and positive remodeling, but also by identifying a spotty pattern of calcification.
Epidemiologic studies suggest that tea consumption decreases the risk for cardiovascular events. However, there has been no clinical report examining the effects of tea consumption on coronary circulation. The purpose of this study was to evaluate the effects of black tea on coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). This was a double-blind crossover study of 10 healthy male volunteers conducted to compare the effects of black tea and caffeine on coronary circulation. The coronary flow velocity of the left anterior descending coronary artery was measured at baseline and at hyperemia during adenosine triphosphate infusion by TTDE to determine CFVR. The CFVR ratio was defined as the ratio of CFVR after beverage consumption to CFVR before beverage consumption. All data were divided into 2 groups according to beverage type: group T (black tea) and group C (caffeine). Two-way analysis of variance showed a significant group effect and interaction in CFVR before and after beverage consumption (p = 0.001). CFVR significantly increased after tea consumption in group T (4.5 +/- 0.9 vs 5.2 +/- 0.9, p <0.0001). The CFVR ratio of group T was larger than that of group C (1.18 +/- 0.07 vs 1.04 +/- 0.08, p = 0.002). Acute black tea consumption improves coronary vessel function, as determined by CFVR.
Coronary flow reserve was evaluated using transthoracic Doppler echocardiography before and after 3 months of fluvastatin therapy in patients with hypercholesterolemia. Coronary flow reserve increased significantly after lipid-lowering therapy, and coronary microcirculation was improved in patients with hypercholesterolemia.
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OBJECTIVES: The aim of this study was to investigate the relationship between circulating monocytes and in-stent neointimal volume at six-month follow-up. BACKGROUND: In-stent neointimal hyperplasia is the main contributing factor to in-stent restenosis. There is increasing evidence that white blood cells (WBCs), especially monocytes, play a central role in restenosis after stent implantation. METHODS: We performed coronary stent implantation in 107 patients (107 lesions). Peripheral blood was obtained from all patients immediately before coronary angiography and every day for seven days after the intervention, and each WBC fraction count was analyzed. At scheduled six-month follow-up, all patients received angiographic and volumetric intravascular ultrasound analysis. RESULTS: The circulating monocyte count increased and reached its peak two days after stent implantation (from 350 +/- 167 to 515 +/- 149/mm3, p < 0.01). The maximum monocyte count after stent implantation showed a significant positive correlation with in-stent neointimal volume at six-month follow-up (r = 0.44, p < 0.0001). Other fractions showed neither significant serial changes nor a correlation with in-stent neointimal volume. Multiple regression analysis revealed that in-stent neointimal volume was independently correlated with stent volume immediately after implantation (r = 0.45, p < 0.0001) and maximum monocyte count (r = 0.35, p < 0.001). Angiographic restenosis, defined as percent diameter stenosis >50%, was observed in 22 patients (21%), and these patients showed a significantly larger maximum monocyte count than patients without restenosis (642 +/- 110 vs. 529 +/- 77/mm3, p < 0.01). CONCLUSIONS: Circulating monocytes increased after coronary stent implantation, and the peak monocyte count related to in-stent neointimal volume. Our results suggest that circulating monocytes play a role in the process of in-stent neointimal hyperplasia.
Studies have reported a circadian variation in the onset of acute myocardial infarction (AMI). Pathologic studies have revealed that plaque rupture is 1 of the major causes of AMI, but none of these has looked specifically at the circadian variation of plaque rupture. The aim of this study was to use intravascular ultrasound (IVUS) to investigate the circadian variation of plaque rupture in AMI. This study included 174 consecutive patients with AMI who underwent preinterventional IVUS. All patients were assigned to either a rupture group or a nonrupture group according to the preinterventional IVUS. In the 81 patients (47%) in the rupture group, the frequency of the onset of AMI increased significantly in the period from 6 A.M. to 12 P.M. compared with all other time periods (p <0.05). The clinical features of AMI in the rupture group were characterized as occurring significantly more at rest (67% vs 31%, p <0.01) and after significantly less preinfarction angina (22% vs 57%, p <0.01) compared with the nonrupture group. A different circadian variation was identified in the nonrupture group, characterized as a significant nocturnal nadir (12 to 6 A.M. compared with all other periods, p <0.05). The circadian variation of AMI is the result of a morning increase in incidence of plaque rupture.
BACKGROUND: Oolong tea has been studied for its effect on cardiovascular disease and obesity. Plasma adiponectin levels are reduced in obesity, in patients with type 2 diabetes mellitus and in coronary artery disease (CAD). OBJECTIVE: To investigate prospectively, whether intake of Oolong tea influences plasma adiponectin levels, low-density lipoprotein (LDL) particle size, total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL cholesterol, serum triglyceride and plasma glucose levels in patients with CAD. METHODS: Twenty two patients in our study consumed Oolong tea (1000 ml) or water for 1 month in our randomized cross-over study design. RESULTS: There was a significant difference in plasma adiponectin levels before and after 1 month intake of Oolong tea (6.26 +/- 3.26 microg/ml versus 6.88 +/- 3.28 microg/ml, P < 0.05), and in plasma level LDL particle size (25.02+/-0.67 nm versus 25.31+/-0.60 nm, P < 0.01). The water-consuming control group showed no changes (6.28+/-3.28 microg/ml versus 6.23+/-3.21 microg/ml) in adiponectin levels or LDL particle sizes (25.03+/-0.70 nm versus 25.02+/-0.72 nm). We also observed a significant difference in hemoglobin A1c levels (7.23 +/- 4.45% versus 6.99 +/- 4.30%, P < 0.05) before and after intake of Oolong tea. CONCLUSION: Oolong tea may have beneficial effects on the progression of atherosclerosis in patients with CAD.
BACKGROUND: We hypothesized that coronary flow assessment by transthoracic Doppler echocardiography (TTDE) for both intramyocardial collateral channel and epicardial channels would be useful for identifying occluded left anterior descending coronary artery (LAD). METHODS: We assessed flow direction in the LAD and the septal branch (SEP) by TTDE in 302 consecutive patients who were suggested to have ischemic heart disease. We defined antegrade LAD flow as a direction from the base to the apex of the left ventricle in the anterior groove area, and antegrade SEP flow as a direction from anterior to inferior in the anterior interventricular septum. By contrast, we defined retrograde LAD and SEP flow as an inverse direction. We performed angiography on all patients. RESULTS: Retrograde flow was detected in 22 (LAD, 16 patients; SEP, 6 patients) of 23 patients with occluded LAD, and antegrade flow was detected in all patients without occluded LAD. The sensitivity and specificity for identification of occluded LAD by TTDE were 96% and 100%, respectively. CONCLUSIONS: Assessment of flow direction in both LAD and SEP by TTDE is a useful method in identification of occluded LAD.
BACKGROUND: Coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) has been found to be useful for assessing left anterior descending coronary artery (LAD) stenosis. However, this method has been restricted only for the LAD. The purpose of this study was to detect severe right coronary artery (RCA) stenosis by CFVR measurement using contrast-enhanced TTDE. METHODS: In 60 consecutive patients with angina pectoris (mean (SD) age: 60 (11), 18 women), coronary flow velocities in the RCA were recorded in the postero-descending coronary artery by contrast-enhanced TTDE at rest and during hyperemia induced by intravenous infusion of adenosine triphosphate (140 mcg/ml/kg). CFVR was calculated as the ratio of hyperemic to basal peak and mean diastolic flow velocity. CFVR measurements by TTDE were compared with the results of coronary angiography performed within 1 week. RESULTS: Coronary flow velocity was successfully recorded in 49 (82%) of the 60 patients with contrast agent. CFVR (mean (SD)) was 1.4 (0.4) in patients with, and 2.6 (0.6) in patients without significant stenosis in the RCA (%diameter stenosis > 75%, P < 0.001). Using the cutoff value 2.0 for CFVR in the RCA, its sensitivity and specificity in detecting significant stenosis in the RCA were 88% and 91%, respectively. CONCLUSION: CFVR measurement in the postero-descending coronary artery by contrast enhanced TTDE is a new, noninvasive method to detect significant stenosis in the RCA.
BACKGROUND: Several studies have demonstrated the benefit of the patency of infarct-related artery (IRA) in acute myocardial infarction (AMI). However those studies have not been concerned with myocardial viability in the region-at-risk. In the present study the effect of the patency of IRA was investigated in the setting of anterior AMI with poor viable myocardium in the risk region. METHODS AND RESULTS: From 1993 to 1996 patients with a first time anterior AMI and poor viable myocardium in the region-at-risk at 1 month after onset were identified and enrolled. Patients with a totally occluded IRA were included in the Non-Open group (n=44), and patients with a reperfused IRA were included in the Open group (n=49). At 5 years after onset, left ventricular function was better preserved in the Open group than in the Non-Open group (p<0.05). Kaplan-Meier survival curves for cardiac mortality and event-free survival curves revealed poor prognoses in the Non-Open group over a 5-year period (p<0.05, respectively). The advantages of a patent IRA were further seen in health-related quality-of-life outcomes (p<0.05). CONCLUSIONS: Even in patients with poor myocardial viability after an anterior AMI, the patency of the IRA is strongly associated with improved long-term survival, independent of residual myocardium viability.