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Biomedical subjects

Youichi Takeyama

Publications and source records attributed to Youichi Takeyama.

12 recordsLinked to original sources
PubMed2005

High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations.

OBJECTIVES: We carried out a complete screening of the SCN5A gene in 38 Japanese patients with Brugada syndrome to investigate the genotype-phenotype relationship. BACKGROUND: The gene SCN5A encodes the pore-forming alpha-subunit of voltage-gated cardiac sodium (Na) channel, which plays an important role in heart excitation/contraction. Mutations of SCN5A have been identified in 15% of patients with Brugada syndrome. METHODS: In 38 unrelated patients with clinically diagnosed Brugada syndrome, we screened for SCN5A gene mutations using denaturing high-performance liquid chromatography and direct sequencing, and conducted a functional assay for identified mutations using whole-cell patch-clamp in heterologous expression system. RESULTS: Four heterozygous mutations were identified (T187I, D356N, K1578fs/52, and R1623X) in 4 of the 38 patients. All of them had bradyarrhythmic complications: three with sick sinus syndrome (SSS) and the other (D356N) with paroxysmal complete atrioventricular block. SCN5A-linked Brugada patients were associated with a higher incidence of bradyarrhythmia (4 of 4) than non-SCN5A-linked Brugada patients (2 of 34). Families with T187I and K1578fs/52 had widespread penetrance of SSS. Notably, the patient with K1578fs/52, who had been diagnosed as having familial SSS without any clinical signs of Brugada syndrome, showed a Brugada-type ST-segment elevation after intravenous administration of pilsicainide and programmed electrical stimulation-induced ventricular tachycardia. All of the mutations encoded non-functional Na channels, and thus were suggested to cause impulse propagation defect underlying bradyarrhythmias. CONCLUSIONS: Our findings suggest that loss-of-function SCN5A mutations resulting in Brugada syndrome are distinguished by profound bradyarrhythmias.

Adult↗
PubMed2005

Eplerenone suppresses neointimal formation after coronary stent implantation in swine.

BACKGROUND: Enhanced extracellular matrix accumulation rather than cell proliferation contributes to later stages of in-stent restenosis. Aldosterone itself has been shown to increase cardiovascular fibrosis, therefore, we studied the suppressive effects of eplerenone, a new aldosterone receptor antagonist, on neointimal hyperplasia after coronary stent implantation in swine. METHODS: Palmatz-Shatz stents were implanted in the left anterior descending artery of 36 pigs. One hundred milligrams of Eplerenone was orally administered from 1 week before, to 4 weeks after stent implantation in Group E (n=18), and vehicle was given to Group C (n=18). Pigs were sacrificed 1 or 4 weeks after stent implantation. The number of infiltrating macrophages was calculated at 1 week. Morphometrical analysis was performed to measure the area of each layer, and %area of fibrosis and mRNA for collagen I, III and TGF-beta was analyzed by RT-PCR at 4 weeks. RESULTS: The number of infiltrating macrophages was less in Group E than in Group C (p<0.01). The overall size of coronary arteries at 4 weeks was similar in both groups. However, the luminal area was larger in Group E than in Group C (p<0.05), and the intimal area was smaller in Group E than in Group C (p<0.05). The %area of fibrosis was significantly less in Group E than in Group C at 4 weeks (p<0.01). In Group E, the expression of mRNA for collagen I, III and TGF-beta was significantly reduced. CONCLUSION: Orally administered eplerenone attenuated collagen accumulation within the neointima, thereby inhibiting neointimal hyperplasia after stent implantation.

Actins↗
PubMed2005

Marked increase in the histamine content of neointima after stent implantation of pig coronary artery and growth-promoting effects of histamine in cultured smooth muscle cells.

After coronary stent implantation, the unfavorable in-stent restenosis often occurs by the formation of neointima due to the proliferation of smooth muscle cells. Platelet-derived growth factor (PDGF) and other peptide growth factors contribute to this process, but little is known about the role of non-peptide factors in this process. In the present study, the role of histamine, a non-peptide factor, in the formation of neointima was investigated using a pig coronary model of in-stent restenosis and a culture system of coronary smooth muscle cells. A Palmaz-Schatz stent was implanted in the left anterior descending coronary artery of male pigs. At 1, 2 and 4 weeks after stenting, the histamine content of neointima was determined to be 326 +/- 82, 1427 +/- 280 and 440 +/- 69 pmol/mg protein, respectively, by HPLC fluorometry. In contrast, the histamine content of arterial media from the untreated control arteries was only 15.3 +/- 1.6 pmol/mg protein. These results demonstrate that the histamine content of neointima is about 20 to 90-fold that of the normal media. In vitro, histamine by itself did not stimulate the proliferation of cultured smooth muscle cells, but potentiated the PDGF-stimulated proliferation of the cultured cells via a mechanism independent of H1 and H2 histamine receptors. Thus, histamine may be an important non-peptide factor in the pathogenesis of in-stent restenosis.

Animals↗
PubMed2004

[Expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in the pig coronary artery injury model: comparison of plain old balloon angioplasty and stent implantation].

OBJECTIVES: Restenosis after coronary intervention usually occurs due to coronary remodeling or neointimal formation, but inflammation is also important especially after stent implantation. Adhesion molecules are important in the recruitment of inflammatory cells into the neointima and in the phenotypical changes of vascular smooth muscle cells. To examine the role of adhesion molecules in the pathogenesis of restenosis, immunohistochemical expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was investigated in the pig coronary injury model. METHODS: Left anterior descending coronary arteries of pigs were injured using a balloon. Two weeks after the injury, balloon injury was performed again in the balloon group and a Palmaz-Schatz stent was implanted in the stent group. Pigs were sacrificed at 1, 2 and 4 weeks. Immunohistochemical analysis was performed using ICAM-1, VCAM-1, macrophage and alpha-smooth muscle actin antibodies. RESULTS: In non-injured vessels, weak immunoreactivities of ICAM-1 and VCAM-1 were observed in the endothelium and media. In injured sites, ICAM-1 and VCAM-1 were found in the inflammatory cells and smooth muscle cells in the neointima from 1 week, and strong immunoreactivities were seen around the strut in the stent group. Although the immunoreactivities peaked at 2 weeks in the balloon group, strong immunoreactivities were still seen at 4 weeks in the stent group. Regenerated endothelial cells were positive for both antibodies from 2 weeks. CONCLUSIONS: The expression of ICAM-1 and VCAM-1 lasted longer in the stent group than in the balloon group, suggesting the occurrence of late restenosis after stent implantation. Control of the inflammatory response including adhesion molecules is essential for further reduction of restenosis after stent implantation.

Angioplasty, Balloon, Coronary↗
PubMed2003

Mechanism of decrease in the atrial potential after implantation of a single-lead VDD pacemaker: atrial histological changes after implantation of a VDD pacemaker lead in dogs.

The single-lead VDD pacemaker system (VDDPS) enables atrial synchronous ventricular pacing with only one lead in patients with an atrioventricular block. There are some cases in which the atrial potential decreases after implantation of a VDDPS, making physiological pacing difficult. The mechanism of this decrease has not been elucidated yet. To elucidate the possible relationship between the decrease of the atrial potential after implantation of a VDDPS and histopathological changes of the atrium. We implanted a VDDPS from the jugular vein under anesthesia in 10 adult dogs. The tip of the pacing lead was fixed in the right ventricular apex of the heart under fluoroscopic guidance. Then, the lead was ligated and fixed to the jugular vein at a point where a favorable atrial potential was obtained. The end of the lead was passed from the neck to the back subcutaneously; then pulled outside and fixed there to measure the atrial potential. The atrial potential was measured using a pacing system analyzer under anesthesia on days 3 (n = 9) and 7 (n = 8), as well as on weeks 2 (n = 6), 3 (n = 4), and 4 (n = 3), after the implantation. The heart was removed from the dogs on day 3 (n = 2), day 7 (n = 2), week 2 (n = 2), and week 4 (n = 4) to examine the atrial histological findings. The atrial potential was 2.7 +/- 0.7 mV at the time of the implantation, 1.7 +/- 1.1 mV (P < 0.05) on day 3, and 1.7 +/- 0.7 mV on week 4 after the implantation. Macroscopically, the pacemaker lead was covered with thrombus, and adhered to the atrial wall in 80% of animals. Microscopically, the endocardium was hypertrophic due to fibrous tissue; besides RBC extravasation, inflammatory cells infiltration and degeneration of myocardial cells, were observed under the endocardium. Inflammatory changes developed in the atrial wall after implantation of the VDDPS, and this seemed to be one of the mechanisms for the decrease of the atrial potential of the VDDPS.

Animals↗
PubMed2002

Comparison of the morphological changes of restenosis after the implantation of various types of stents in a swine model.

BACKGROUND: Stent design causes the differences of restenosis rate, but the morphological differences after the various types of stent implantation have not been clarified. DESIGN: Seven types of stents were implanted in pig coronary arteries to clarify how the mechanism of restenosis differs with coil stents and tube stents. METHODS: The left anterior descending coronary arteries (LADs) of pigs were injured using coronary angioplasty balloons (diameter: 3.0 mm; length: 20 mm; balloon/artery ratio: 1 : 2). Fourteen days after the injury, four types of coil stents (Cordis, Wiktor, GR-I, and GR-II) and three types of tube stents (Palmaz-Schatz, gfx, and Multilink) were implanted, and the LADs were extracted 28 days after the implantation. RESULTS: The proliferated neointima was eccentric in the coil stents and concentric in the tube stents. Although there was no significant difference in the area of neointima, the area of the lumen was significantly larger in the tube stents than in the coil stents ( < 0.01) because of the larger area of stent. Cells positive for anti-proliferating cell nuclear antigen antibody were mainly observed around the stent struts, and most of these cells were also positive for either anti-macrophage or anti-smooth muscle actin antibodies. CONCLUSIONS: Compared to the coil stents, the tube stents induce less negative remodelling including stent recoil, resulting in a wider luminal area. In order to prevent restenosis, it is crucial to implant a stent that will cause less negative remodelling.

Animals↗
PubMed2002

Thrombus on the tricuspid valve in a patient with primary antiphospholipid syndrome after implantation of an inferior vena cave filter.

A 62-year-old woman with a history of pulmonary embolism and primary antiphospholipid syndrome (PAPS) with positivity for lupus anticoagulant was admitted to hospital with shortness of breath. A filter had been implanted in her inferior vena cava (IVC) 5 years previously. Emergency echocardiography revealed a lobulated, mobile echogenic mass on the tricuspid valve, and on pulmonary perfusion scintigraphy several apparently new defects were noted. Fibrinolytic therapy improved her symptoms and the pulmonary perfusion, then intravenous heparinization was continued for a further week. Repeat echocardiography performed on the 7th day of the admission showed complete disappearance of the mass, which was retrospectively diagnosed as a thrombus based on its resolution with fibrinolytic and anticoagulant therapies.

Antiphospholipid Syndrome↗
PubMed2002

Clinical characteristics and follow-up in patients with microvascular angina.

Arteriosclerosis of the small arteries is one of the main causes of microvascular angina, and although some reports have shown favorable prognoses, there is progressive reduction in left ventricular function. The present study evaluated the prognosis of microvascular angina in 86 Japanese patients (51 women, 35 men; average age, 59+/-9 years) who had ischemic ST segment depression, normal coronary angiograms and small artery sclerosis confirmed by endomyocardial biopsies. The mean follow-up period was 7.2+/-3.4 years. Questionnaires regarding their symptoms, cardiac medication, and new events were sent to all patients. Eighty-five patients (98.9%) were still alive at the end of the follow-up period. Chest pain remained in 35.3%; the degree of pain was unchanged in 18.8%, and had lessened in 11.8%. None of the patients died of cardiac events or suffered from a myocardial infarction. At the end of the follow-up period, calcium antagonist was used in 63.5% of patients. Seventeen patients (20.0%) were free of antianginal medication. The prognosis of microvascular angina diagnosed by strict criteria was favorable.

Aged↗
PubMedDate not supplied

Mechanisms of restenosis after coronary intervention: difference between plain old balloon angioplasty and stenting.

BACKGROUND: Restenosis after coronary intervention remains an unsolved and important clinical problem. We histologically examined the mechanism of restenosis after both balloon injury and stenting. METHODS: Coronary arteries of swine were subjected to balloon injury and stenting. Next, just after stenting or at 7, 14, or 28 days, the animals were sacrificed for the evaluation by morphometric analysis, histological observation, and immunostaining. RESULTS: The neointimal area peaked at 14 days in the balloon injury group (BG) and increased linearly up to 28 days in the stent group (SG). At 28 days, the total vascular area in the BG was reduced to 78% of the control values. In the SG, the total vascular area remained enlarged. According to the phenotypic analysis, the vascular smooth muscle cells (VSMCs) in the neointimal area at 28 days were the contractile type in the BG and the synthetic type in the SG. Proliferating cell nuclear antigen (PCNA) and macrophage-positive cells were not observed in neointima in the BG at 28 days, whereas they were observed around the stent struts in the SG. In addition, numerous inflammatory cells, such as neutrophils and eosinophils, were also present in the SG. CONCLUSIONS: Restenosis after balloon injury consisted of arterial remodeling and neointimal hyperplasia, whereas that after stenting consisted mostly of neointimal hyperplasia. The neointimal area in the SG lasted longer than that in the BG. Continuous inflammation may be an important factor in the restenosis of stenting.

Angioplasty, Balloon, Coronary↗