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Junichi Yoshikawa

Publications and source records attributed to Junichi Yoshikawa.

At least 37 records · Page 2Linked to original sources

Effects of erythropoietin on cardiac remodeling after myocardial infarction.

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.

Animals↗

Effects of treatment for diabetes mellitus on circulating vascular progenitor cells.

The circulating endothelial progenitor cells (EPCs) have an important role in angiogenesis, and the smooth muscle progenitor cells (SMPCs) participate in atherosclerosis. However, little is known about the effects of treatment of diabetes mellitus (DM) on EPCs and SMPCs. Therefore, we investigated the relations between the number of circulating vasucular progenitor cells before and after the treatment for DM. Ten previously untreated DM patients were enrolled in this study. Blood samples were collected before and after treatment. The peripheral mononuclear cells were purified and cultured to differentiate them into EPCs and SMPCs. After two weeks, the number of EPCs was determined by Dil-labeled acetylated low density lipoprotein and lectin binding. The number of SMPCs was evaluated by immunocytochemical staining of alpha-smooth muscle actin. Before treatment, the number of EPCs and SMPCs was significantly related to hemoglobin A1c and blood sugar. Serial examination revealed that improvement of glycemic control significantly increased the number of both EPCs and SMPCs. DM reduces the number of circulating EPCs and SMPCs according to its severity, and treatment of DM significantly increases the number of EPCs and SMPCs, which may be involved in angiogenesis and atherosclerosis in diabetes.

Actins↗

Inflection point of ascending aortic waveform is a predictive factor for major adverse cardiac events after successful coronary stent placement in acute myocardial infarction.

OBJECTIVE: The reflection waveform in the ascending aortic pressure has been reported to reflect systemic arterial stiffness, and increase the risk of coronary heart disease. The purpose of this study is to evaluate prospectively whether the reflection waveform in the ascending aortic pressure is associated with the risk of major adverse cardiac events (MACE) after successful coronary stenting in acute myocardial infarction (AMI). METHODS AND RESULTS: One hundred and twenty-five patients with AMI and undergoing successful coronary stenting were enrolled in this study. We measured the inflection time to determine the reflection waveform in the ascending aortic pressure at angioplasty. Inflection time was defined as the time interval from initiation of a systolic pressure waveform to the inflection point. During a period of 2945 person-months, we confirmed 42 cases of MACE. Shorter inflection time increased incident MACE. Kaplan-Meier analysis demonstrated a significantly reduced event-free rate in patients with inflection time < or = 86 ms (MACE; p < 0.01, cardiovascular death; p < 0.001 by log-rank test). The multiple-adjusted hazard ratio for a I standard deviation (SD) magnitude decrease in inflection time was 1.46 (95% confidence interval, 1.03 to 2.05) for MACE, and 5.76 (95% confidence interval, 1.78 to 18.67) for cardiovascular death. CONCLUSIONS: Shorter inflection time increased the risk of MACE after successful coronary stenting in patients with AMI.

Aged↗

Coronary artery calcification revisited.

Calcification is a common finding in human coronary arteries. However, there is conflicting evidence for a link between calcification and plaque instability. Current intravascular ultrasound (IVUS) technology allows a definitive detection of the calcification and measurement of the vessel wall. Using preinterventional IVUS images, we clarified that in patients with acute myocardial infarction, small "spotty" calcifications prevailed, associated with a fibrofatty plaque and positive remodeling. Conversely, in patients with stable angina pectoris, extensive calcification was frequent. IVUS allows the detection of vulnerable plaques in coronary arteries, by identifying not only a large lipid core and positive remodeling, but also a spotty pattern of calcification.

Calcinosis↗

Method analysis for optimal continuous imaging using intravascular optical coherence tomography.

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.

Animals↗

[Estimation of myocardial ischemia by diastolic strain analysis in exercise stress echocardiography: comparison with exercise thallium-201 single photon emission computed tomography].

OBJECTIVES: The feasibility of detecting persistent regional left ventricular abnormal relaxation due to myocardial ischemia using strain echocardiography several minutes after exercise was investigated. METHODS: Consecutive 27 patients (mean age 65 +/- 9 years, 21 males, 6 females) with suspected coronary artery disease were enrolled. Strain echocardiographic images were acquired at the mid segments of the left ventricular wall before and 5 min after exercise in the apical long-axis, two-chamber and four-chamber views. Strain curves were obtained at each segment, and peak values of strain at the closure of aortic valve (A) and at one third of diastolic duration (B) were measured. Strain diastolic index (SDI) was calculated as (A - B)/A X 100%. The ratio of SDI before exercise to that after exercise was defined as the SDI ratio and compared with exercise thallium-201 single photon emission computed tomography (SPECT) as the reference standard to detect myocardial ischemia. RESULTS: A total of 162 segments were evaluated. Based on the results of exercise SPECT, 119 segments were classified as non-ischemic segments, and 43 as ischemic segments. Ischemic segments showed significant decreases in SDI before and after exercise, whereas non-ischemic segments showed no significant differences in SDI before and after exercise. SDI ratio was significantly decreased in ischemic segments, but not in non-ischemic segments. SDI ratio with a cut off value of 0.51 had a sensitivity of 91% and a specificity of 89% to detect myocardial ischemia in the receiver-operating characteristics. Conclusions. Strain echocardiography can provide quantitative assessment of myocardial ischemia by detecting post-ischemic regional left ventricular delayed relaxation even 5 min after exercise.

Aged↗

Smoking history and prior surgical resection predict sensitivity to gefitinib in advanced non-small-cell lung cancer.

BACKGROUND: Gefitinib is an inhibitor of epidermal growth factor receptor tyrosine kinase, and induces radiographic regression and symptomatic improvement in patients with non-small cell lung cancer (NSCLC). Phase II trials suggested female sex and adenocarcinoma were associated with response, never smoking history and adenocarcinoma were associated with survival. We attempted to identify additional clinical features associated with response and survival. METHODS: We reviewed medical records and imaging studies of all 68 NSCLC patients treated by gefitinib monotherapy in our institution. We identified patients experiencing disease control and compared their clinical features with those of other patients. We considered partial response, stable disease or incomplete response and stable disease to be evidence of disease control. Univariate and multivariate analysis were performed to determine predictive and prognostic factors associated with disease control and survival. RESULTS: Of 68 patients, 20 (29.4%) experienced disease control. Variables identified as significant for disease control with gefitinib included never smoking history (p=0.0128) and history of curative surgical resection (p=0.0007) on multivariate analysis. Variables identified as significant for overall survival included never smoking history (p=0.0128), history of curative surgical resection (p=0.0007), and performance status (PS) of 0 and 1 (p=0.0001) on multivariate analysis. CONCLUSIONS: Our findings suggest that never smoking history and history of curative surgical resection are key factors for disease control and prognostic factors in patients with NSCLC treated with gefitinib.

Adult↗

Endothelin-converting enzyme expression in the neointima after percutaneous coronary intervention.

Smooth muscle cells (SMCs) are the major cellular component of neointimal tissues after percutaneous coronary intervension (PCI). Endothelin-1 (ET-1) is a powerful vasoconstrictor and has a mitogenic effect on SMCs. Endothelin-converting enzyme (ECE) is a key enzyme in the process of ET-1 generation. However, the expression of ECE in association with post-PCI repair processes has not been reported. Thirteen coronary sites after PCI obtained at autopsy and 6 atherectomy specimens obtained from restenotic sites were investigated. Frozen sections were stained with antibodies against ECE, SMCs, macrophages, and endothelial cells. The immunoreactivity of ECE was quantified using computer-aided planimetry. At the early stage after PCI, most neointimal SMCs expressed ECE. The ECE-positive cell area was significantly (p<0.005) larger in the sites within 3 months after PCI than in the sites from 6 months onward. In atherectomy specimens, neointimal SMCs showed distinct ECE positivity. These findings suggest that ECE is upregulated in the neointima at early stages after PCI injury. ECE may be one of the mediators in the repair processes after PCI in humans.

Aged↗

QT dispersion and left ventricular function after stent placement in acute myocardial infarction.

BACKGROUND: QT dispersion is increased in acute myocardial infarction (AMI), but the relation of QT dispersion to left ventricular (LV) function has not yet been fully elucidated. The purpose of this study was to evaluate the relationship between QT dispersion and LV function in patients with successful coronary stenting in AMI. METHODS: Seventy five patients with AMI who underwent percutaneous transluminal coronary angioplasty (PTCA) were enrolled in this study. Corrected QT dispersion was measured before, immediately after, 24 h after, 48 h after, and 6 months after PTCA. Left ventricular ejection fraction (LVEF) was evaluated by left ventriculography at 6 months after PTCA. RESULTS: Corrected QT dispersion at 24 h after and 48 h after PTCA were significantly related to LVEF by univariate analysis (r=-0.282, p<0.05 and r=-0.326, p<0.01, respectively). In multiple regression model, corrected QT dispersion at 24 h after and 48 h after PTCA revealed significant associations with LVEF (R(2)=0.441, coefficient=-0.283, p=0.006 and R(2)=0.411, coefficient=-0.225, p=0.039, respectively), but corrected QT dispersion before, immediately after, and 6 months after PTCA were not associated with LVEF. CONCLUSIONS: Corrected QT dispersion at 24 h after and 48 h after PTCA in AMI correlate with LVEF at 6 months after PTCA.

Analysis of Variance↗

Comparison of levels of serum matrix metalloproteinase-9 in patients with acute myocardial infarction versus unstable angina pectoris versus stable angina pectoris.

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.

Aged↗

Alterations in T-lymphocyte subsets in the airways of asthmatic patients with active hepatitis C virus infection.

BACKGROUND: The interaction between hepatitis C virus (HCV) infection and certain pulmonary disorders is of considerable interest. We have previously found that active HCV infection in asthmatic patients is associated with impaired responses to inhaled corticosteroid therapy. OBJECTIVES: To examine differences in T-lymphocyte subsets in asthmatic airways with or without HCV infection. METHODS: 12 HCV-negative and 29-HCV positive asthmatics were included in this study. All HCV-positive asthmatics received interferon (IFN) therapy (11 IFN responders and 18 IFN non-responders). T-lymphocyte subsets in induced sputum were analyzed before and 1 year after IFN therapy. RESULTS: Before IFN therapy, percentages of lymphocytes and CD8+ T lymphocytes in induced sputum were higher in HCV-positive asthmatics than in HCV-negative asthmatics. After IFN therapy, there was no significant change in percentages of lymphocytes and T-lymphocyte subsets in IFN non-responders. However, percentage of lymphocytes and CD8+ T lymphocytes in IFN responders significantly decreased, while CD4+ T lymphocytes increased. Therefore, the CD4/CD8 ratio significantly increased following IFN therapy in IFN responders. In IFN responders, forced expiratory volume in 1 s (FEV(1)) after salbutamol administration significantly increased following IFN therapy, while it did not change in non-responders. In addition, in IFN responders, the change in the CD4/CD8 ratio after IFN therapy was significantly correlated with the increase in FEV(1) after salbutamol administration. CONCLUSIONS: The number of CD8+ T lymphocytes increases in the airways of asthmatic patients with active HCV infection, and this may be associated with airway dysfunction in these patients.

Albuterol↗

Granulocyte-colony stimulating factor augments neovascularization induced by bone marrow transplantation in rat hindlimb ischemia.

Because granulocyte-colony stimulating factor (G-CSF) mobilizes bone marrow cells including endothelial progenitor cells, we examined whether G-CSF augments angiogenesis and collateral vessel formation induced by bone marrow-mononuclear cells transplantation (BMT). Unilateral hindlimb ischemia was surgically induced in Lewis rats. One week after surgery, administration of 100 mg/kg per day G-CSF significantly increased the laser Doppler blood perfusion index (LDBPI), number of angiographically detectable collateral vessels (angiographic score), and capillary density determined by alkaline phosphatase staining. In the BMT group (1 x 10(7) cells/rat) and the group with combined G-CSF treatment and BMT, LDBPI was significantly increased compared with that in the vehicle-treated group. In the BMT group, neovascularization was significantly increased as evidenced by the angiographic score and capillary density compared with the vehicle-treated group. Furthermore, the combination of G-CSF treatment and BMT augmented neovascularization compared with BMT alone, as evidenced by the angiographic score and capillary density. Moreover, G-CSF significantly increased vascular endothelial growth factor mRNA and fibroblast growth factor-2 mRNA in hindlimb muscle. In conclusion, G-CSF was found to augment neovascularization in rat hindlimb ischemia. Combined use of G-CSF treatment and BMT may be a useful strategy for therapeutic neovascularization in ischemic tissues.

Alkaline Phosphatase↗

Beneficial effect of candesartan on rat diastolic heart failure.

In this study, we examined whether an angiotensin II type 1 (AT1)-receptor blocker improves diastolic heart failure (DHF) in Dahl salt-sensitive (DS) rats. DHF was prepared by feeding DS rats on 8% NaCl diet from 7 weeks of age. DHF was estimated with echocardiography by measuring E velocity / A velocity (E/A) of left ventricular inflow. DS rats with established DHF were orally given candesartan (1 mg/kg per day) or vehicle. After 13 days of treatment, candesartan significantly improved DHF, as shown by the reduction of E/A from 4.49 +/- 1.04 to 1.98 +/- 0.54 (P<0.05) and prolonged survival rate more than the vehicle. Cardiac fibrosis, apoptosis, and gene expression were estimated by Sirius Red-staining, TUNEL-staining, and Northern blot analysis, respectively. The improvement of DHF by candesartan was accompanied by the decrease in cardiac hypertrophy, fibrosis, and apoptosis, and the reduction of gene expression of brain natriuretic peptide, collagen I, and monocyte chemoattractant protein-1. Moreover, candesartan decreased cardiac inflammatory cells and reactive oxygen species, estimated by counting ED-1-positive cells and the measurement of 4-hydroxy-2-nonenal staining, respectively. These results indicate that candesartan can improve diastolic dysfunction and may slow the progression of cardiac remodelling in DS rats with established DHF.

Aldehydes↗

Lack of large intestinal carcinogenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine at low doses in rats initiated with azoxymethane.

2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), an abundant food-derived heterocyclic amine (HCA), has attracted particular attention as a human colon carcinogen. Humans are in fact exposed to continuous low doses of HCAs during lifetime. Therefore, we focused on rat large intestinal carcinogenicity of PhIP at levels that mimic practical human exposure. A total of 192 6-week-old male F344 rats were subcutaneously injected twice with 15 mg/kg body weight azoxymethane (AOM), then continuously fed various doses (0, 0.001, 0.01, 0.1, 1, 10, 50 and 200 ppm) of PhIP in the diet. At week 16, aberrant crypt foci (ACF) were quantitatively analyzed. At week 36, tumor occurrence was pathologically analyzed. Then immunohistochemical examinations were performed. PhIP was found to enhance strongly AOM-initiated rat large intestinal tumorigenesis at high doses (50 and 200 ppm), while lower doses (0.001-10 ppm) had no apparent effects. High doses also caused variation in tumor histologic types and their distribution throughout the large intestinal segments. Frequencies of ACF/cm(2) did not meaningfully vary between the groups. Cellular proliferation activity in normal-appearing colonic mucosa was significantly increased at high doses. These novel findings may provide evidence of a low-dose potential for PhIP, with a no-observed effect level speculated to be 10 ppm in the present initiation-promotion experimental model.

Animals↗

Acute hemodynamic benefits of bi-atrial atrioventricular sequential pacing with the optimal atrioventricular delay.

OBJECTIVES: We evaluate the acute effects on hemodynamics of bi-atrial (BiA) pacing with the optimal atrioventricular (AV) delays, in comparison with high right atrial (HRA) pacing and coronary sinus (CS) pacing. BACKGROUND: Bi-atrial pacing has been suggested as one of the alternative therapy for preventing the recurrence of atrial fibrillation (AF). There are, however, few reports on the hemodynamic effects of BiA pacing, and the results that exist are controversial. METHODS: Twenty patients were paced from HRA, left lateral site of CS, and both sites with the optimal AV delays at 80 and 100 beats/min, in random order. After 5-min pacing, maximal P-wave duration in a 12-lead electrocardiogram, cardiac output (CO), pulmonary capillary wedge pressure (PCWP), and the transmitral flow pattern by transthoracic echocardiography were measured. RESULTS: Compared with HRA and CS pacing, BiA pacing delivered the shortest P-wave duration (HRA: 130 +/- 14 ms, CS: 132 +/- 19 ms, and BiA: 94 +/- 8 ms, respectively, p < 0.001) and the most improvement in CO and PCWP (HRA: 3.63 +/- 0.67 l/min and 9.2 +/- 4.3 mm Hg, CS: 3.71 +/- 0.70 l/min and 8.8 +/- 3.4 mmHg, and BiA: 3.88 +/- 0.63 l/min and 8.0 +/- 3.1 mmHg, respectively, p < 0.01). Bi-atrial pacing also significantly increased the mitral flow time velocity integral and peak A-wave velocity by transthoracic echocardiography, compared with HRA and CS pacing (HRA: 7.6 +/- 1.4 cm and 68.8 +/- 12.2 cm/s, CS: 7.8 +/- 1.4 cm and 70.5 +/- 14.5 cm/s, and BiA: 8.2 +/- 1.2 cm and 76.3 +/- 14.2 cm/s, respectively, p < 0.01). Bi-atrial pacing most significantly decreased the intervals between the atrial pacing spike and the peak of A-wave (HRA: 180 +/- 28 ms, CS: 165 +/- 21 ms, and BiA: 157 +/- 19 ms, respectively, p < 0.01). These improvements in hemodynamics significantly correlated with interatrial conduction delay. CONCLUSIONS: Bi-atrial pacing made the most significant improvements of hemodynamics. These benefits may be due to the improvements in interatrial conduction delay and atrial dyssynchrony.

Aged↗

Angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium after myocardial infarction.

Osteopontin has been reported to have an important role in cardiac fibrosis. However, little is known about the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin type 1 receptor blockers (ARB) on osteopontin expression in infarcted myocardium. The purpose of this study was to elucidate the effects of an ACEI (perindpril) and an ARB (candesartan cilexitil) on cardiac function as assessed by Doppler echocardiography and cardiac osteopontin expression associated with cardiac remodeling in myocardial infarcted rats. ACEI or ARB was administered after myocardial infarction (MI). At 4 weeks after MI, cardiac function, and mRNAs in non-infarcted myocardium were analyzed. ACEI and ARB equally prevented left ventricular dilatation, reduction of ejection fraction, and the increase in E/A wave velocity ratio and the rate of E wave deceleration by MI. ACEI and ARB significantly suppressed increased mRNA expression of atrial natriuretic peptide, brain natriuretic peptide, osteopontin, and collagen I and III in the non-infarcted ventricle at 4 weeks. Immunohistochemically stained osteopontin was increased in interstitial fibrosis of non-infarcted myocardium. Both ACEI and ARB significantly prevented cardiac fibrosis and osteopontin expression. In conclusion, angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium and prevents cardiac remodeling after MI.

Angiotensin II Type 1 Receptor Blockers↗

Important role of apoptosis signal-regulating kinase 1 in ischemia-induced angiogenesis.

OBJECTIVE: We first examined the role of apoptosis signal-regulating kinase 1 (ASK1), one of mitogen-activated protein kinase kinase kinases, in ischemia-induced angiogenesis. METHODS AND RESULTS: Unilateral hindlimb ischemia was induced surgically in C57BL/6J wild-type (WT) mice or mice deficient in ASK1 (ASK1(-/-)). ASK1 activity in WT mouse hindlimb was increased dramatically after ischemia. By laser Doppler analysis, well-developed collateral vessels and angiogenesis were observed in WT mice in response to hindlimb ischemia, whereas these responses were reduced in ASK1(-/-) mice. Immunostaining revealed that infiltration of macrophages and T lymphocytes was suppressed in the ischemic tissues of ASK1(-/-) mice compared with WT mice. The expression of vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1) proteins in ischemic tissues was weaker in ASK1(-/-) mice compared with WT mice. In vitro study on endothelial cells indicated that dominant-negative ASK1 significantly attenuated hydrogen peroxide-induced VEGF and MCP-1 production. Furthermore, in vivo blockade of MCP-1 by its neutralizing antibody suppressed the recovery of the blood flow and capillary formation after ischemia. CONCLUSIONS: ASK1 pathway promotes early angiogenesis by inducing inflammatory cell infiltration and VEGF and MCP-1 expression. ASK1 may provide the basis for the development of new therapeutic strategy for angiogenesis.

Animals↗

Direct demonstration by transthoracic Doppler echocardiography of adenosine-induced coronary steal in the collateral-dependent vessel.

Coronary flow velocity reserve was measured to assess the frequency of coronary steal in the collateral-dependent coronary arteries using transthoracic Doppler echocardiography. Coronary steal occurred in half the vessels studied. There was no significant difference between coronary flow velocity reserve in poorly and well-developed collaterals.

Adenosine↗