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Biomedical subjects

Eiji Toyota

Publications and source records attributed to Eiji Toyota.

At least 19 recordsLinked to original sources
PubMed2006

Assessment of coronary arterial thrombus by optical coherence tomography.

We analyzed optical coherence tomographic (OCT) characteristics of different types of coronary thrombi that had been confirmed at postmortem histologic examination. We examined 108 coronary arterial segments of 40 consecutive human cadavers. OCT images of red and white thrombi were obtained and the intensity property of these thrombi was analyzed. Red and white thrombi were found in 16 (17%) and 19 (18%) of the 108 arterial segments, respectively. Red thrombi were identified as high-backscattering protrusions inside the lumen of the artery, with signal-free shadowing in the OCT image. White thrombi were identified as low-backscattering projections in the OCT image. There were no significant differences in peak intensity of OCT signal between red and white thrombi (130+/-18 vs 145+/-34, p=0.12). However, the 1/2 attenuation width of the signal intensity curve, which was defined as the distance from peak intensity to its 1/2 intensity, was significantly different between red and white thrombi (324+/-50 vs 183+/- 42 microm, p<0.0001). A cut-off value of 250 microm in the 1/2 width of signal intensity attenuation can differentiate white from red thrombi with a sensitivity of 90% and specificity of 88%. We present the first detailed description of the characteristics of different types of coronary thrombi in OCT images. Optical coherence tomography may allow us not only to estimate plaque morphology but also to distinguish red from white thrombi.

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PubMed2006

Assessment of coronary arterial plaque by optical coherence tomography.

The purpose of this study was to analyze the ability of optical coherence tomography (OCT) to identify coronary arterial plaque diagnosed by histologic examination. We examined 166 sections from 108 coronary arterial segments of 40 consecutive human cadavers (24 men and 16 women; mean age 74 +/- 7 years). The plaque type was classified as fibrous (n = 43), fibrocalcific (n = 82), or lipid-rich (n = 41). The accuracy of OCT and intravascular ultrasound (IVUS) in characterizing the plaque type was studied, with the histologic consensus diagnosis serving as the gold standard. OCT, as well as IVUS, had high sensitivity and specificity for characterizing the different types of atherosclerotic plaque. OCT had a higher sensitivity for characterizing lipid-rich plaques than IVUS (85% vs 59%, p = 0.03). In conclusion, the high resolution of OCT permitted evaluation of lipid-rich plaques more accurately than IVUS.

Aged↗
PubMed2006

Identification of a receptor-independent activator of G protein signaling (AGS8) in ischemic heart and its interaction with Gbetagamma.

As part of a broader effort to identify postreceptor signal regulators involved in specific diseases or organ adaptation, we used an expression cloning system in Saccharomyces cerevisiae to screen cDNA libraries from rat ischemic myocardium, human heart, and a prostate leiomyosarcoma for entities that activated G protein signaling in the absence of a G protein coupled receptor. We report the characterization of activator of G protein signaling (AGS) 8 (KIAA1866), isolated from a rat heart model of repetitive transient ischemia. AGS8 mRNA was induced in response to ventricular ischemia but not by tachycardia, hypertrophy, or failure. Hypoxia induced AGS8 mRNA in isolated adult ventricular cardiomyocytes but not in rat aortic smooth muscle cells, endothelial cells, or cardiac fibroblasts, suggesting a myocyte-specific adaptation mechanism involving remodeling of G protein signaling pathways. The bioactivity of AGS8 in the yeast-based assay was independent of guanine nucleotide exchange by Galpha, suggesting an impact on subunit interactions. Subsequent studies indicated that AGS8 interacts directly with Gbetagamma and this occurs in a manner that apparently does not alter the regulation of the effector PLC-beta(2) by Gbetagamma. Mechanistically, AGS8 appears to promote G protein signaling by a previously unrecognized mechanism that involves direct interaction with Gbetagamma.

Animals↗
PubMed2006

Measurement of the thickness of the fibrous cap by optical coherence tomography.

BACKGROUND: Identification of the fibrous cap is important because its thickness is a major determinant of plaque vulnerability in lipid-rich plaque. Thus, a high-resolution imaging technique may be a promising method for the identification of the fibrous cap within lipid-rich plaque. The purpose of this study was to investigate the feasibility of using optical coherence tomography (OCT) to measure the thickness of the fibrous cap within lipid-rich plaque. METHODS AND RESULTS: We examined 35 lipid-rich plaques from 102 coronary arterial segments of 38 human cadavers (22 men and 16 women; mean ages, 74 +/- 7 years). Optical coherence tomography and corresponding histological images were digitized for measurement of the thickness of fibrous cap, and the results between OCT and histological examination were compared. There was good correlation of the thickness of the fibrous cap between OCT and histological examination (y = 0.97x + 28.49; r = 0.90; P < .001). A Bland-Altman test showed good agreement of the thickness of the fibrous cap between OCT and histological examination (mean difference, -24 +/- 44 microm). CONCLUSIONS: Optical coherence tomography provides an accurate representation of the thickness of the fibrous cap and may prove useful in assessing plaque vulnerability in lipid-rich plaque.

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PubMed2006

Geometric differences of the mitral valve tenting between anterior and inferior myocardial infarction with significant ischemic mitral regurgitation: quantitation by novel software system with transthoracic real-time three-dimensional echocardiography.

We sought to investigate the 3-dimensional geometric differences of mitral leaflet tenting in ischemic mitral regurgitation, comparing inferior and anterior myocardial infarction (MI). Using real-time 3-dimensional echocardiography, we obtained transthoracic volumetric images for patients with significant ischemic mitral regurgitation (9 inferior and 7 anterior). With our novel software system, 3-dimensional images of the leaflets were reconstructed for quantitation. Mitral leaflet configuration was then represented in contour in which the degree of the tenting could be observed. Calculated percent of tethered leaflet area (>5-mm tenting from the annular level) was compared in inferior and anterior MI. Percent of tethered leaflet area was significantly smaller in inferior than anterior MI, reflecting the localized leaflet tenting in inferior MI (16.7 +/- 18.8% vs 38.9 +/- 9.7%, P = .01). In anterior MI, mitral valve leaflets were widely tethered toward the left ventricle, in contrast with inferior MI showing localized tenting of the leaflet.

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PubMed2006

Rate of progression of valvular aortic stenosis in patients undergoing dialysis.

BACKGROUND: In patients undergoing dialysis, aortic valve calcification and aortic stenosis are frequently found. However, the rate of progression of aortic stenosis is still unclear. METHODS: In all, 55 consecutive patients undergoing dialysis were followed up by echocardiography for a period of 12 months. Patients were divided into two groups: noncalcification (no or mildly calcified aortic valve) and calcification (moderate or heavily calcified aortic valve). RESULTS: The rate of progression of maximum aortic jet velocity and degression of aortic valve area were more rapid in calcification group than in noncalcification group (0.37 +/- 0.36 m/s and 0.17 +/- 0.29 m/s, P = .027; 0.17 +/- 0.15 cm2 and 0.04 +/- 0.07 cm2, P < .001, respectively). CONCLUSIONS: The degree of aortic stenosis progressed more rapidly in patients undergoing dialysis with aortic valve calcification than without aortic valve calcification.

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PubMed2005

Vascular endothelial growth factor is required for coronary collateral growth in the rat.

BACKGROUND: The goal of this study was to determine whether the expression of vascular endothelial growth factor (VEGF) is critical for coronary collateral growth. Previous studies have provided an association between coronary collateral growth and VEGF, but none have allowed determination of a causal role. METHODS AND RESULTS: We measured coronary collateral growth in rats subjected to repetitive episodes of myocardial ischemia (RI; one 40-second occlusion every 20 minutes for 2 hours 40 minutes, followed by 5 hours 20 minutes of rest, with this 8-hour cycle repeated 3 times per day for 10 days). Collateral growth was measured from blood flow (radioactive microspheres), visualization of arterial-arterial anastomoses (x-ray micro-CT), and maintenance of function during complete coronary occlusion in 3 groups of animals: sham (received instrumentation but no RI), experimental (subjected to RI), and anti-vascular endothelial growth factor (RI+anti-VEGF 0.6 mg/100 g per day) to block the endogenous actions of VEGF. In the 3 groups, native collateral flow (measurement for RI or sham protocol) averaged 0.2 to 0.3 mL x min(-1) x g(-1) of tissue. In the sham group, collateral flow did not increase during the protocol. Collateral flow in the control RI group increased by approximately 6-fold to 1.63 mL x min(-1) x g(-1) tissue, but in the anti-VEGF group, collateral flow did not increase after the RI protocol (0.22 mL x min(-1) x g(-1)). In acute experiments, collateral flow was unchanged during vasodilation with dipyridamole, indicating the increases in collateral flow are due to collateral growth and not vasodilation. X-ray micro-CT analysis revealed a 3-fold increase (versus sham group) in the number of arterial-arterial anastomoses per heart after RI, which was prevented by treatment with anti-VEGF. The growth of the collateral circulation was functional in the RI group because complete coronary occlusion did not induce any untoward effects on hemodynamics or arrhythmias. In the sham or anti-VEGF groups, coronary occlusion at the end of the protocol induced many arrhythmias and deterioration of function. CONCLUSIONS: From these results, we conclude that the expression of VEGF is critical to the growth of coronary collaterals.

Animals↗
PubMed2005

Mitral annulus flattens in ischemic mitral regurgitation: geometric differences between inferior and anterior myocardial infarction: a real-time 3-dimensional echocardiographic study.

BACKGROUND: New surgical strategies to restore the saddle shape of the mitral annulus are expected to increase annuloplasty effectiveness. Preoperative and postoperative configuration of the curved annulus, however, is difficult to quantify with 2-dimensional echocardiography. We sought to investigate the geometric deformity in the mitral annulus in ischemic mitral regurgitation (MR), comparing inferior and anterior myocardial infarction (MI) with the use of a custom quantitation software system with transthoracic 3-dimensional echocardiography. METHODS AND RESULTS: We performed real-time 3-dimensional echocardiography in 23 patients with ischemic MR attributable to inferior MI or anterior MI and in 10 controls. Three-dimensional data were cropped into 18 radial planes, and we manually marked the annulus in mid systole. Three-dimensional annular images were reconstructed, and annular circumferences, areas, and heights were quantified. Annulus was significantly more dilated and flattened in ischemic MR than in controls and was further deformed in anterior MI as compared with inferior MI (control: circumference 9.9+/-0.7 cm, area 9.6+/-0.5 cm2, height 5.0+/-0.7 mm; inferior MI: circumference 11.5+/-1.2 cm [P<0.01 compared with control], area 11.4+/-2.0 cm2 [P<0.05 compared with control], height 3.5+/-1.6 mm [P<0.05 compared with control]; anterior MI: circumference 14.2+/-2.4 cm [P<0.0001 compared with control, P<0.05 compared with inferior MI], area 13.7+/-2.8 cm2 [P<0.01 compared with control, P<0.05 compared with inferior MI], height 1.7+/-1.5 mm [P<0.0001 compared with control, P<0.05 compared with inferior MI]). CONCLUSIONS: Mitral annulus flattens in ischemic MR. Deformity of the mitral annulus was greater in anterior MI group than in the inferior MI group.

Aged↗
PubMed2005

Quantitation of mitral valve tenting in ischemic mitral regurgitation by transthoracic real-time three-dimensional echocardiography.

OBJECTIVES: We sought to investigate the geometric changes of the mitral leaflets and annulus, clarify the maximum tenting site of the leaflets, and quantify the valve tenting in ischemic mitral regurgitation (MR) using three-dimensional (3D) echocardiography. BACKGROUND: Although the understanding of the mechanisms of ischemic MR has advanced recently, the geometric changes of the mitral leaflets and annulus have been assessed by two-dimensional echocardiography in the clinical setting, despite the unique configuration of the leaflets and annulus. METHODS: Utilizing real-time 3D echocardiography, we obtained transthoracic volumetric images in 12 patients with ischemic MR presenting with global left ventricular dysfunction and in 10 controls. Original software was used to crop the 3D data into 18 radial planes, and we marked the mitral annulus and leaflets in each plane in mid-systole. The 3D images of the leaflets and annulus were reconstructed for the quantitative measurements. RESULTS: In ischemic MR, the annulus flattened with apparent tenting of the leaflets. Maximum and mean tenting length were longer and tenting volume was larger in ischemic MR than control subjects (maximum tenting length: 9.8 +/- 2.0 mm vs. 3.1 +/- 1.2 mm, p < 0.0001, mean tenting length: 3.7 +/- 0.9 mm vs. 0.7 +/- 0.5 mm, p < 0.0001, tenting volume: 4.09 +/- 1.22 ml vs. 0.45 +/- 0.29 ml, p < 0.0001). The maximum tenting site was located in anterior leaflet in all patients. CONCLUSIONS: We clearly demonstrated 3D geometric deformity of the mitral leaflets and annulus in ischemic MR using novel software for creating images by 3D echocardiography. This technique will be helpful in making a proper decision for the surgical strategy in each patient.

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PubMed2005

Direct measurement of nipradilol-derived nitric oxide in the vascular wall of canine femoral arteries.

Nipradilol (NP: 3,4-dihydro-8-[2-hydroxy-3-isopropylamino]propoxy-3-nitroxy-2H-1-benzopyran) shows not only beta-adrenoreceptor-blocking effects but also nitroglycerin-like vasodilatory action. We aimed to directly measure NP-derived nitric oxide (NO) in the vascular wall. An NO-sensitive microelectrode was inserted into the vascular media (the vasodilatory action site of NO) of isolated perfused canine femoral arteries. Each vessel was perfused with 15 microM NP in the presence or absence of 1 mM N-ethylmaleimide (NEM; a thiol alkylator). Intravascular-wall NO concentration increased 181+/-34 nM during NP perfusion (P<0.001 vs basal, n=10) with an average base-to-peak reaction time of 1.5+/-0.1 min (P<0.0001, n=8). Concomitant perfusion of NEM with NP attenuated the intravascular-wall NO production significantly (P<0.0001 vs NP only). It is concluded that NP is metabolized to NO in the vascular wall of an isolated canine femoral artery in large part through a metabolic process involving thiols with a base-to-peak reaction time of about 1.5 min.

Adrenergic beta-Antagonists↗
PubMed2005

Assessment of coronary intima--media thickness by optical coherence tomography: comparison with intravascular ultrasound.

BACKGROUND: Optical coherence tomography (OCT) is a new imaging method. With a resolution of approximately 10-20 Em, which is approximately 10-fold higher than that of intravascular ultrasound (IVUS). METHODS AND RESULTS: This study compared the coronary intima - media thickness (IMT) and the intimal thickness of 54 coronary arterial segments evaluated by histological examination with the results of OCT and IVUS. There was better agreement in IMT between OCT and histological examination than between IVUS and histological examination (r = 0.95, p < 0.001, mean difference = -0.01+/-0.07 mm for OCT; r = 0.88, p < 0.001, mean difference = -0.03+/-0.10 mm for IVUS). There was good agreement in the intimal thickness between OCT and histological examination (r = 0.98, p < 0.001, mean difference = 0.01+/-0.04 mm). CONCLUSIONS: IMT could be measured more accurately by OCT than IVUS. In addition, the intimal thickness could be evaluated by OCT and correlated well with the histological examination.

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PubMed2005

Visualization of neointima formation by optical coherence tomography.

Optical coherence tomography (OCT) has recently been proposed as a high-resolution imaging method. Our male patient, who had been treated with a coronary stent, died due to acute leukemia. Coronary artery images using intravascular ultrasound (IVUS) and OCT were obtained postmortem. We also compared the image of neointima formation after stent implantation evaluated by histopathological examination with that evaluated by IVUS and OCT. OCT visualized well-apposed stent struts and neointima formation, which could not be visualized completely by IVUS. OCT may be useful for monitoring structural changes after stent implantation.

Coronary Stenosis↗
PubMed2004

Dynamics of flow velocities in endocardial and epicardial coronary arterioles.

The subendocardium is the most vulnerable area of the left ventricle to the effects of hypoperfusion and ischemia. Despite this well-acknowledged observation, the mechanisms underlying this susceptibility are not elucidated, although numerous explanations including differences in transmural distribution of hemodynamics, metabolism, and wall stresses have been proposed. Our goal was to make dynamic measurements of endocardial and epicardial flow velocities, which reflect hemodynamic and wall stresses, to approach this problem. We measured blood flow velocities in subendocardial and subepicardial coronary arterioles of in vivo beating canine hearts using a high-speed, charge-coupled device, intravital videomicroscope with a rod-probe lens. Subendocardial flow was characterized by remarkable systolic flow-velocity reversal (systolic slosh ratio, 84%; measurable velocity of retrograde flow, faster than -40 mm/s), which contrasted to predominant forward-flow velocity during systole in the subepicardial arterioles (systolic slosh ratio, 25%; maximum velocity, approximately -20 mm/s; P < 0.0005 and 0.05 vs. subendocardial arterioles, respectively). We speculate that this retrograde flow is "wasteful," because this volume must be refilled during the subsequent diastole, which thereby detracts from the net perfusion as well as the time for perfusion. Accordingly, we also believe that the retrograde systolic blood flow contributes to the vulnerability of the subendocardium to ischemia.

Animals↗
PubMed2004

Exogenous NO suppresses flow-induced endothelium-derived NO production because of depletion of tetrahydrobiopterin.

Exogenous nitric oxide (NO) suppresses endothelium-derived NO production. We were interested in determining whether this is also the case in flow-induced endothelium-derived NO production. If so, then is the mechanism because of intracellular depletion of tetrahydrobiopterin [BH4; a cofactor of NO synthase (NOS)], which results in superoxide production by uncoupled NOS? Isolated canine femoral arteries were perfused with 100 microM S-nitroso-N-acetylpenicillamine (SNAP; an NO donor) and/or 64 microM BH4. Perfusion of SNAP suppressed flow-induced NO production, which was evaluated as a change in the slope of the linear relationship between perfusion rate and NO production rate (P < 0.02 vs. control; n = 7). Subsequent BH4 perfusion returned the slope to the control level. Concomitant perfusion of SNAP and BH4 retained the control-level NO production (n = 7). Concomitant perfusion of SNAP and 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron; 1 mM; a membrane-permeable superoxide scavenger) also retained the control-level NO production (n = 7), whereas perfusion of Tiron after SNAP could not return the NO production to the control level (P < 0.02 vs. control; n = 7). We also found a significant decrease in BH4 concentration in the endothelial cells after SNAP perfusion. In conclusion, these results indicate that exogenous NO suppresses the flow-induced, endothelium-derived NO production by superoxide released from uncoupled NOS because of intracellular BH4 depletion.

Animals↗
PubMed2004

Myocardial angiogenesis.

Coronary angiogenesis and collateral growth are chronic adaptations to myocardial ischemia, which are aimed at restoring coronary blood flow and salvaging myocardium in an ischemic region. Although we have assumed that myriad numbers of growth factors are involving in this adaptation, details in the underlying mechanisms, i.e., number of angiogenic factors, angiostatic factors, their receptors/signaling cascades, interactions/crosstalk among the signaling pathways and receptors, and the time course of expression/function of a particular factor or pathway during the successful adaptation are still unclear; they are, probably, harmonized like a symphony. Although there is as of yet no consensus about the mechanisms and causal factors for these cononary adaptations to ischemia, recent evidence strongly suggests that a balance between growth factors and growth inhibitors is critical. In this review we introduce vascular endothelial growth factor, angiopoietins, and angiostatin, as factors playing pivotal roles in coronary angiogenesis and collateral growth.

Angiopoietins↗
PubMed2004

Global heterogeneity of glomerular volume distribution in early diabetic nephropathy.

BACKGROUND: Morphologic characteristics in early stage of nephropathy of noninsulin-dependent diabetes mellitus (NIDDM) have not been determined despite the fact thatdiagnosis in this stage of the disease is important for the prognosis. We hypothesized that heterogeneity in glomerular volume-distribution may be a sensitive index of early stage of diabetic nephropathy in NIDDM. METHODS: In spontaneous diabetic rats [Otsuka Long-Evans Tokushima Fatty (OLETF) rat (N= 5)] of 27 to 28 weeks, an experimental model of early diabetic nephropathy in human NIDDDM and age-matched control rats [Long Evans Tokushima Lean (LETO) rat (N= 5)], we completely filled the kidney with contrast medium. Glomeruli were visualized as three-dimensional images using x-ray micro-computed tomography (micro-CT). Glomerular volumes (N= 400 in each kidney) were directly measured and evaluated as absolute volume and normalized values to kidney weight and body weight. Scattering of glomerular volume-distribution was evaluated as coefficient variation (CV) (SD/mean). RESULTS: The CV was significantly larger in OLETF rat (0.195) comparing to LETO rat (0.146, P < 0.01). This difference was even consistent under the normalization to kidney weight and body weight. Absolute glomerular volume was larger in OLETF rat compared to LETO rat (P < 0.005); however, when glomerular volume was normalized, this variable was comparable between two groups. CONCLUSION: We visualized three-dimensional glomerular images in the early stages of diabetic nephropathy using micro-CT and quantified the heterogeneity in glomerular volume distribution throughout the cortex by direct measurement of the individual. We propose that heterogeneity in glomerular volume distribution is a sensitive parameter to ascertain early diabetic nephropathy in NIDDM.

Animals↗
PubMed2004

Three-dimensional microstructural abnormality of the coronary capillary network after myocardial reperfusion--comparison between 'reflow' and 'no-reflow'.

BACKGROUND: The 3-dimensional (D) structural abnormalities of the coronary capillary network and capillary volume changes after myocardial reperfusion were investigated using confocal laser scanning microscopy. METHODS AND RESULTS: Using open-chest anesthetized rats' hearts, the left anterior descending artery (LAD) was occluded for 7 min followed by reperfusion. The hearts were divided into 2 groups: (1) reperfused area stained well by intravenous indocyanine green after reperfusion (Reflow), and (2) lack of staining in the reperfused area (No-reflow). The entire coronary microvasculature was filled with contrast medium using a Langendorff's perfusion system. Capillaries were observed 3-dimensionally in the control and reperfused areas in both the Reflow and No-reflow group and the capillary volume fraction was computed from the 3-D images. The reperfused area in both groups showed decreased capillary diameter with waving and shrinkage configuration. In the No-reflow group, marked interruption of capillary network was observed. In the Reflow group the capillary volume fraction was significantly reduced in the reperfused area compared with the control area (14.8+/-4.1% vs 22.2+/-5.6%, p<0.05). Capillary volume fraction was further decreased in the No-reflow group compared with Reflow (5.3+/-1.4% vs 14.8+/-4.1%, p<0.01). CONCLUSION: The morphological changes in coronary capillaries after reperfusion were characterized by waving and shrinkage, which resulted in a reduction in capillary volume.

Animals↗