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Biomedical subjects

Hiroaki Matsubara

Publications and source records attributed to Hiroaki Matsubara.

At least 37 records · Page 2Linked to original sources

[A case of takotsubo cardiomyopathy provoked by taking a new quinolone antibiotic drug and a non-steroidal anti-inflammatory drug].

A 97-year-old woman was provoked a convulsion after taking a new quinolone antibiotic drug Levofloxacin and a non-steroidal anti-inflammatory drug Loxoprofen. At a later time, she was suffered from severe chest pain. An electrocardiogram showed ST segment elevation in leads II, III and aVF, and T-wave inversion in leads V1 to V4. Coronary angiography demonstrated no organic stenosis, however biventriculography revealed apical ballooning akinesis and basal hyperkinesis. Positron emission tomography was also performed to assess the uptake of 18F-fluorodeoxyglucose (FDG) after 75 g oral glucose loading for evaluating myocardial glucose metabolism at 10th day. Severely reduced uptake of FDG was observed in the apical ballooning region. Left ventriculography showed normal wall motion at 19th day. Thallium-201 myocardial single-photon emission computed tomography (SPECT) to determine the status of myocardial perfusion at the 20th hospital day showed normal perfusion. Iodine-123-beta-methyl-p-iodophenyl penta-decanoic acid myocardial SPECT to evaluate myocardial fatty acid metabolism at the 23rd day revealed severely reduced uptake in the apical ballooning region. These findings suggested that the coronary microcirculation was impaired in the apical ballooning region.

Aged, 80 and over↗

[Clinical usefulness of 1231I-BMIPP myocardial SPECT in patient with microvascular spasm: a case report].

This patient was a 64-year-old man with chest pain at rest. An electrocardiogram showed depression of the ST segment in V2-V5 leads during chest pain. 123I-BMIPP myocardial SPECT revealed reduced uptake in the apex. Coronary angiographies revealed severely delayed filling of contrast medium without narrowing of epicardial coronary arteries. An intracoronary infusion of isosorbide dinitrate did not improve the delayed filling of contrast medium or the ST segment depression. After an intracoronary infusion of nicorandil, coronary arterial flows were remarkably improved, chest symptoms disappeared, and electrocardiographic findings were improved. Left ventriculography showed severe hypokinesis in the apex. After the medication with nicorandil, reduced 123I-BMIPP myocardial uptake and reduced wall motion on echocardiography were improved. These findings suggest that myocardial ischemia in this case might be explained as having been caused by microcirculation disturbance.

Coronary Circulation↗

[Clinical usefulness of 201Tl/99mTc-PYP dual myocardial quantitative gated SPECT program using low-dose dobutamine loading in assessment of myocardial viability in patient with acute myocardial infarction--a case report].

An 86-year-old man with chest pain was admitted to our hospital. Coronary angiography revealed 99% stenosis of the mid segment of the left anterior descending coronary artery, therefore, a coronary stent was implanted. Immediately after the stent implantation, 99% stenosis occurred at the proximal site of the 1st diagonal artery because of stent jeal. On the 4th hospital day, ECG-gated 201TL/99mTc-PYP dual myocardial quantitative gated SPECT was performed at rest and during low-dose dobutamine loading. The 201Tl scintigraphy revealed moderately reduced uptake in the anterior, septal and apical walls, and 99mTc-PYP uptake was observed in the mid-anterior wall. A three-dimensional surface display of gated 201Tl SPECT images showed severe hypokinesis in the anterior, septal and apical walls at rest. On the other hand, during low-dose dobutamine loading, improved wall motion was observed in the basal anterior and septal walls, while no change was observed in the midanterior and apical wall movements. Three-dimensional surface display of gated 201Tl/99mTc-PYP dual SPECT images revealed similar patterns of wall motion as those of gated 201Tl SPECT images at rest. During low-dose dobutamine loading, on the other hand, a three-dimensional surface display of gated 201Tl/99mTc-PYP dual SPECT images revealed improved wall motion in the basal anterior, septal and apical walls, but worsened wall motion of the mid-anterior wall. After 6 months, a follow-up coronary angiography revealed no re-stenosis of the stent, but 99% stenosis at the proximal aspect of the 1st diagonal artery. Left ventriculography revealed improved wall motion in the apex and akinesis of the mid-anterior wall. These wall motion findings were similar to those visualized in the three-dimensional surface display of gated 201Tl/99mTc-PYP dual SPECT images during low-dose dobutamine loading in the acute phase. These results suggest that 201Tl/99mTc-PYP dual myocardial quantitative gated SPECT using low-dose dobutamine loading could be useful for the assessment of myocardial viability after reperfusion therapy in patients with acute myocardial infarction.

Aged, 80 and over↗

[Coronary artery plaque assessment using Volcano Therapeutics' Virtual Histology intravascular ultrasound and temperature guide wire].

OBJECTIVES: This study investigated the tissue characterization of human coronary artery plaque using Virtual Histology intravascular ultrasound (VH-IVUS) and temperature guide wire. METHODS AND RESULTS: Between August 2005 and December 2005, VH-IVUS examination and guide wire based measurement of coronary temperature were performed in 66 patients: 39 with stable angina pectoris (SAP), and 27 with unstable angina pectoris(UAP). Patients in the acute myocardial infarction with necrotic tissue and thrombus were excluded. After measurement of distal coronary pressure and coronary temperature, the following tissue types of atherosclerotic plaque were evaluated by VH-IVUS: fibrotic, fibro-fatty, dense calcium and necrotic core. Occurrence of fibro-fatty tissue was significantly higher in UAP patients than in SAP patients (17.4 +/- 7.0% vs 11.2 +/- 5.2%, p = 0.04), and coronary temperature was significantly higher in UAP patients than in SAP patients (0.08 +/- 0.05 vs 0.03 +/- 0.02 degrees C, p = 0.01). CONCLUSIONS: These results suggest that the combination of VH-IVUS analysis and measurement of coronary temperature may be able to predict the progression of lesions.

Aged↗

[Therapeutic angiogenesis for peripheral arterial disease and ischemic heart disease by autologous bone marrow cells implantation].

Postnatal neovascularization was initially thought to result exclusively from the migration and proliferation of pre-existing, fully differentiated endothelial cells (a process referred to as angiogenesis). Several lines of experimental evidence, however, demonstrated that circulating endothelial progenitor cells (EPCs) home to sites of neovascularization and differentiate into endothelial cells in situ in a manner consistent with a process termed vasculogenesis. Moreover, recent clinical study, named as the Therapeutic Angiogenesis Using Cell Transplantation (TACT), has demonstrated the efficacy and safety of autologous implantation of bone marrow-mononuclear cells(BM-MNCs) in randomly allocated patients with ischemic limbs of peripheral arterial diseases. Implantation of BM-MNCs is also applied to patients with no-option angina pectoris, demonstrating the usefulness of this therapy for improvement of symptom, myocardial perfusion, and exercise capacity. Moreover, recent accumulating studies demonstrated the possibilities that transplantation of bone marrow-derived or peripheral blood-derived EPCs enhances neovascularization and improves cardiac function after acute myocardial infarction(AMI). There were no serious adverse effects reported in cell transplantation therapy. Thus, bone marrow-derived cell transplantation therapy has been applied to acute and chronic ischemic heart diseases as well as peripheral arterial diseases, demonstrating the safety and effectiveness of therapeutic angiogenesis.

Bone Marrow Transplantation↗

Amelioration of diabetic peripheral neuropathy by implantation of hematopoietic mononuclear cells in streptozotocin-induced diabetic rats.

This study was performed in order to evaluate the angiogenic effect of implantation of either peripheral blood mononuclear cells (PBMNCs) or bone marrow mononuclear cells (BMMNCs) on diabetic peripheral neuropathy. Streptozotocin (50 mg/kg) was injected intravenously into 6-week-old male Lewis rats. Four weeks after the induction of diabetes, 6 x 10(7) of PBMNCs or 1 x 10(8) of BMMNCs were implanted into the left hindlimb muscle. Motor nerve conduction velocity (MNCV) was monitored before and after implantation. At the end of the experiment, bilateral nerve blood flow (NBF) was measured by laser Doppler and the number of vessels in the sciatic nerves quantified by Factor VIII staining of the sections. Diabetes resulted in an approximately 20% reduction (P < 0.01) in sciatic MNCV. Four weeks after implantation, MNCV was improved by 54% with PBMNCs and by 67% with BMMNCs (both P < 0.01). Moreover, the effects of implantation were almost abolished by administration of VEGF-neutralizing antibody. Sciatic NBF was reduced by approximately 50% by diabetes (P < 0.05). This reduction in perfusion was improved by 74% by implantation of PBMNCs and by 62% by implantation of BMMNCs (P < 0.05 and P < 0.01, respectively). These effects were observed only in the implanted limb. Immunohistochemical staining of sciatic nerve sections for Factor VIII showed no significant increase in the number of vessels in the sciatic nerve following implantation of either PBMNCs or BMMNCs. These data suggest that implantation of hematopoietic mononuclear cell fractions is associated with an improvement in MNCV as a result of arteriogenic effects in the sciatic nerve, and that VEGF may contribute to this effect. This improvement occurred in the absence of angiogenesis. Implantation of these cell fractions may therefore be a potential new therapeutic method for treating diabetic peripheral neuropathy.

Analysis of Variance↗

Nox1 is involved in angiotensin II-mediated hypertension: a study in Nox1-deficient mice.

BACKGROUND: Increased production of reactive oxygen species (ROSs) by angiotensin II (Ang II) is involved in the initiation and progression of cardiovascular diseases. NADPH oxidase is a major source of superoxide generated in vascular tissues. Although Nox1 has been identified in vascular smooth muscle cells as a new homolog of gp91phox (Nox2), a catalytic subunit of NADPH oxidase, the pathophysiological function of Nox1-derived ROSs has not been fully elucidated. To clarify the role of Nox1 in Ang II-mediated hypertension, we generated Nox1-deficient (-/Y) mice. METHODS AND RESULTS: No difference in the baseline blood pressure was observed between Nox1(+/Y) and Nox1(-/Y). Infusion of Ang II induced a significant increase in mean blood pressure, accompanied by augmented expression of Nox1 mRNA and superoxide production in the aorta of Nox1(+/Y), whereas the elevation in blood pressure and production of superoxide were significantly blunted in Nox1(-/Y). Conversely, the infusion of pressor as well as subpressor doses of Ang II did elicit marked hypertrophy in the thoracic aorta of Nox1(-/Y) similar to Nox1(+/Y). Administration of a nitric oxide synthase inhibitor (L-NAME) to Nox1(+/Y) did not affect the Ang II-mediated increase in blood pressure, but it abolished the suppressed pressor response to Ang II in Nox1(-/Y). Finally, endothelium-dependent relaxation and the level of cGMP in the isolated aorta were preserved in Nox1(-/Y) infused with Ang II. CONCLUSIONS: A pivotal role for ROSs derived from Nox1/NADPH oxidase was suggested in the pressor response to Ang II by reducing the bioavailability of nitric oxide.

Angiotensin II↗

Sonoporation using microbubble BR14 promotes pDNA/siRNA transduction to murine heart.

Naked plasmid DNA (pDNA) and short interfering RNA (siRNA) duplexes were transduced into adult murine heart by means of sonoporation using the third-generation microbubble, BR14. Plasmid DNAs carrying luciferase, beta-galactosidase (beta-gal), or enhanced green fluorescent protein (EGFP) reporter genes were mixed with BR14 and injected percutaneously into the left ventricular (LV) cavity of C57BL/6 mice while exposed to transthoracic ultrasound at 1MHz for 60s. Sonoporation at an output intensity of 2.0W/cm(2) and a 50% pulse duty ratio resulted in the highest luciferase expression in the heart. Histological examinations revealed significant expression of the beta-gal and EGFP reporters in the subendocardial myocardium of LV. Intraventricular co-injection of siRNA-GFP and BR14 with concomitant ultrasonic exposure resulted in substantial reduction in EGFP expression in the coronary artery in EGFP transgenic mice. The present method may be applicable to gain-of-function and loss-of-function genetic engineering in vivo of adult murine heart.

Animals↗

Interaction between AT1 and AT2 receptors during postinfarction left ventricular remodeling.

The relative contribution of the angiotensin II type 1 and 2 receptors (AT1-R and AT2-R) in postmyocardial infarction (MI) remodeling remains incompletely understood. We studied five groups of C57Bl/6 mice after 1 h of left anterior descending artery occlusion-reperfusion: 1) wild type, untreated (n = 12); 2) wild type, treated with the AT1-R blocker losartan (10-20 mg.kg(-1).day(-1) in drinking water) from day 1 to day 28 post-MI (n = 10); 3) cardiac overexpression of the AT2-R [AT2-transgenic (TG); n = 14]; 4) AT2-TG treated with losartan (n = 13); and 5) AT2-TG and null for the AT1a-R [AT2-TG/AT1 knockout (KO); n = 10]. Cardiac magnetic resonance imaging (CMR) measured ejection fraction and left ventricular end-diastolic and end-systolic volume (EDVI and ESVI) and mass indexed to weight on days 0, 1, 7, and 28 post-MI. Infarct size was measured on day 1 by late gadolinium-enhanced CMR. Regional myocyte hypertrophy and collagen content were measured on day 28 post-MI. Infarct size was similar among groups. Systolic blood pressure was lowest in AT2-TG/AT1KO. By day 28 post-MI, when corrected for baseline differences, EDVI and ESVI were higher and ejection fraction was lower in wild type than other groups. Ejection fraction was highest and EDVI and mass index were lowest in AT2-TG/AT1KO at day 28. The AT2-TG/AT1KO demonstrated less fibrosis in adjacent regions. Regional myocyte hypertrophy was similar in all groups. The AT1-R and AT2-R are intricately intertwined in post-MI remodeling. Pharmacological blockade of AT1-R is equivalent to AT2-R overexpression in attenuating post-MI remodeling. Genetic knockout of the AT1a-R is additive to AT2-R overexpression, due, at least in part, to blood pressure lowering.

Animals↗

Site-selective direct photochemical deposition of copper on glass substrates using TiO2 nanocrystals.

Deposition of copper thin films was achieved by a photocatalytic reaction of site-selectively adsorbed TiO(2) nanocrystals for direct fabrication of copper circuit patterns on glass substrates. The nanocrystal monolayers absorbed on hydrophobic surface templates serve as an effective photocatalyst, producing metallic copper and formic acid via oxidation of methanol in solution. The formic acid generated has also been suggested to serve as an electron donor that accelerates copper deposition through a UV-mediated autocatalytic reaction, even after nanocrystals are embedded into the grown copper films. The thickness of the deposited copper films was easily controlled by varying the UV irradiation time, irradiation power, and initial concentration of methanol as a hole scavenger. The process presented herein provides an effective methodology for resist-free, direct metallization of insulating substrates.

Letter↗

Targeted delivery of bone marrow mononuclear cells by ultrasound destruction of microbubbles induces both angiogenesis and arteriogenesis response.

OBJECTIVE: Ultrasound (US)-mediated destruction of contrast microbubbles causes capillary rupturing that stimulates arteriogenesis, whereas intramuscular implantation (im) of bone marrow mononuclear cells (BM-MNCs) induces angiogenesis. We therefore studied whether US-targeted microbubble destruction combined with transplantation of BM-MNCs can enhance blood flow restoration by stimulating both angiogenesis and arteriogenesis. METHODS AND RESULTS: US-mediated destruction of phospholipid-coated microbubbles was applied onto ischemic hindlimb muscle and subsequently BM-MNCs were transfused. A significant enhancement in blood flow recovery after Bubble+US+BM-MNC infusion (34% increase, P<0.05) was observed compared with Bubble+US (25%). The ratio of capillary/muscle fiber increased by Bubble+US+BM-MNC-i.v (260%, P<0.01) than that in the Bubble+US group (172%), into which BM-MNCs were incorporated (angiogenesis). Smooth muscle alpha-actin-positive arterioles were also increased, and angiography showed augmented collateral vessel formation (arteriogenesis). Platelet-derived proinflammatory factors activated by Bubble+US induces the expression of adhesion molecules (P-selectin and ICAM-1), leading to the attachment of transplanted BM-MNCs on the endothelium. Flow assay confirmed that the platelet-derived factors cause the adhesion of BM-MNCs onto endothelium under laminar flow. CONCLUSIONS: This study demonstrates that the targeted delivery of BM-MNCs by US destruction of microbubbles enhances regional angiogenesis and arteriogenesis response, in which the release of platelet-derived proinflammatory factors activated by Bubble+US play a key role in the attachment of transplanted BM-MNCs onto the endothelial layer.

Angiography↗

Short-term fluctuations in sinus cycle length after premature ventricular beats in patients with hypertrophic cardiomyopathy and myocardial infarction.

BACKGROUND: Sinus cycle length has been reported to fluctuate after a ventricular premature beat (VPB). The purpose of this study was to assess the short-term fluctuations of sinus cycle length in patients with hypertrophic cardiomyopathy (HCM) and prior myocardial infarction (MI). METHODS: The relative deviation of RR intervals from the mean of the last two RR intervals preceding a VPB were calculated during the 20 subsequent beats following the VPB from Holter recordings in 92 patients with non-obstructive HCM, 57 patients with prior MI and 54 healthy controls. RESULTS: In controls, the deviations of the RR intervals were negative for several beats after a VPB and subsequently changed to positive before returning to the baseline. Similar changes in RR intervals following a VPB were exhibited in HCM patients; however, the late positive deviations of RR intervals were more marked than in controls. By contrast, in patients with prior MI, the early negative deviations of RR intervals were smaller compared with controls, and the deviations returned to the baseline without incidence of the positive changes. CONCLUSIONS: Short-term fluctuations in sinus cycle length after a VPB differed exclusively among HCM patients, prior MI patients, and healthy controls.

Adult↗

Carbon dioxide-rich water bathing enhances collateral blood flow in ischemic hindlimb via mobilization of endothelial progenitor cells and activation of NO-cGMP system.

BACKGROUND: Carbon dioxide-rich water bathing has the effect of vasodilatation, whereas it remains undetermined whether this therapy exerts an angiogenic action associated with new vessel formation. METHODS AND RESULTS: Unilateral hindlimb ischemia was induced by resecting the femoral arteries of C57BL/J mice. Lower limbs were immersed in CO2-enriched water (CO2 concentration, 1000 to 1200 mg/L) or freshwater (control) at 37 degrees C for 10 minutes once a day. Laser Doppler imaging revealed increased blood perfusion in ischemic limbs of CO2 bathing (38% increase at day 28, P<0.001), whereas N(G)-nitro-L-arginine methyl ester treatment abolished this effect. Angiography or immunohistochemistry revealed that collateral vessel formation and capillary densities were increased (4.1-fold and 3.7-fold, P<0.001, respectively). Plasma vascular endothelial growth factor (VEGF) levels were elevated at day 14 (18%, P<0.05). VEGF mRNA levels, phosphorylation of NO synthase, and cGMP accumulation in the CO2-bathed hindlimb muscles were increased (2.7-fold, 2.4-fold, and 3.4-fold, respectively) but not in forelimb muscles. The number of circulating Lin-/Flk-1+/CD34- endothelial-lineage progenitor cells was markedly increased by CO2 bathing (24-fold at day 14, P<0.001). The Lin-/Flk-1+/CD34- cells express other endothelial antigens (endoglin and VE-cadherin) and incorporated acetylated LDL. CONCLUSIONS: Our present study demonstrates that CO2 bathing of ischemic hindlimb causes the induction of local VEGF synthesis, resulting in an NO-dependent neocapillary formation associated with mobilization of endothelial progenitor cells.

Animals↗

Heart rate variability in adult patients with isolated left ventricular noncompaction.

BACKGROUND: Isolated left venticular noncompaction (IVNC) is a rare congenital heart disease charactrized by a pattern of an excessively prominent trabecular meshwork with deep intertrabecular recesses. Heart rate variability (HRV) has been reported to be impaired in various heart diseases, though little is known regarding HRV in adult patients with IVNC. METHODS: We measured spectral components of HRV using fast Fourier transformation of 24-h Holter recordings in 10 adult patients with IVNC, 40 patients with myocardial infarction (MI), 40 patients with hypertrophic cardiomyopathy (HCM) and 40 healthy controls. RESULTS: The low frequency component and the high frequency component of HRV were lower in IVNC patients tahn those in controls (265 +/- 213 ms(2) vs. 469 +/- 195 ms(2), p < 0.01; 80 +/- 51 ms(2) vs. 185 +/- 126 ms(2), p < 0.01). Furthermore, 3 IVNC patients with a previous history of heart failure exhibited more decreased HRV (low frequency, 75 +/- 56 ms(2); high frequency, 39 +/- 18 ms(2)). Contrary, the ratio of low frequency to high frequency component was higher in patients with IVNC than controls (3.5+/-0.5 vs. 3.2 +/- 0.3, p < 0.05). The degree of impaired HRV was severest in MI patients, intermediate in IVNC patients and mildest in HCM patients compared with controls. CONCLUSIONS: HRV is impaired in adult patients with IVCN, especially in patients with a previous history of heart failure, suggesting vagal withdrawal or sympathetic enhancement. HRV in IVNC adults is less impaired than in MI patients, and more impaired than in HCM patients of our cohort.

Adult↗

Comparison of the effects of quinapril and losartan on carotid artery intima-media thickness in patients with mild-to-moderate arterial hypertension.

BACKGROUND: Ultrasonographic evidence of increased carotid intima-media thickness (IMT) is known to be associated with generalized atherosclerosis. Therapeutic blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme (ACE) inhibitors reportedly reduces carotid IMT in humans. However, there has been no head-to-head comparison of the effects of ACE inhibitor and angiotensin receptor blocker (ARB), a newer type of RAS inhibitor, on carotid IMT. METHODS: 57 hypertensive patients were randomly assigned to treatment with one of two antihypertensive drugs: ACE inhibitor (quinapril; n = 25, group Q) or ARB (losartan; n = 18, group L). RESULTS: After 1 year of treatment, a similar decrease in mean blood pressure was observed in all groups. Carotid IMT was decreased significantly in group Q (10% decrease, p < 0.05) but did not change in group L. There were no significant changes in other atherosclerotic factors between these two groups. CONCLUSION: Our findings suggest that the antiatherosclerotic effect of quinapril is more potent than that of losartan in hypertensive patients. This effect appears unrelated to the drug's antihypertensive action or to traditional atherosclerotic factors.

Aged↗