Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility.

Decreased contractility in the non-ischemic border zone surrounding a MI is in part due to degradation of cardiomyocyte sarcomeric components by intracellular matrix metalloproteinase-2 (MMP-2). We recently reported that MMP-2 levels were increased in the border zone after a MI and that treatment with doxycycline for two weeks after MI was associated with normalization of MMP-2 levels and improvement in ex-vivo contractile protein developed force in the myocardial border zone. The purpose of the current study was to determine if there is a sustained effect of short term treatment with doxycycline (Dox) on border zone function in a large animal model of antero-apical myocardial infarction (MI). Antero-apical MI was created in 14 sheep. Seven sheep received doxycycline 0.8 mg/kg/hr IV for two weeks. Cardiac MRI was performed two weeks before, and then two and six weeks after MI. Two sheep died prior to MRI at six weeks from surgical/anesthesia-related causes. The remaining 12 sheep completed the protocol. Doxycycline induced a sustained reduction in intracellular MMP-2 by Western blot (3649±643 MI+Dox vs 9236±114 MI relative intensity; p = 0.0009), an improvement in ex-vivo contractility (65.3±2.0 MI+Dox vs 39.7±0.8 MI mN/mm2; p<0.0001) and an increase in ventricular wall thickness at end-systole 1.0 cm from the infarct edge (12.4±0.6 MI+Dox vs 10.0±0.5 MI mm; p = 0.0095). Administration of doxycycline for a limited two week period is associated with a sustained improvement in ex-vivo contractility and an increase in wall thickness at end-systole in the border zone six weeks after MI. These findings were associated with a reduction in intracellular MMP-2 activity

Japanese VLBI Network observations of radio-loud narrow-line Seyfert 1 galaxies

We performed phase-reference very long baseline interferometry (VLBI) observations on five radio-loud narrow-line Seyfert 1 galaxies (NLS1s) at 8.4 GHz with the Japanese VLBI Network (JVN). Each of the five targets (RXS J08066+7248, RXS J16290+4007, RXS J16333+4718, RXS J16446+2619, and B3 1702+457) in milli-Jansky levels were detected and unresolved in milli-arcsecond resolutions, i.e., with brightness temperatures higher than 10^7 K. The nonthermal processes of active galactic nuclei (AGN) activity, rather than starbursts, are predominantly responsible for the radio emissions from these NLS1s. Out of the nine known radio-loud NLS1s, including the ones chosen for this study, we found that the four most radio-loud objects exclusively have inverted spectra. This suggests a possibility that these NLS1s are radio-loud due to Doppler beaming, which can apparently enhance both the radio power and the spectral frequency.Comment: 8 pages, 2 figures, accepted for publication in PAS

VLBI Detections of Parsec-Scale Nonthermal Jets in Radio-Loud Broad Absorption Line Quasars

We conducted radio detection observations at 8.4 GHz for 22 radio-loud broad absorption line (BAL) quasars, selected from the Sloan Digital Sky Survey (SDSS) Third Data Release, by a very-long-baseline interferometry (VLBI) technique. The VLBI instrument we used was developed by the Optically ConnecTed Array for VLBI Exploration project (OCTAVE), which is operated as a subarray of the Japanese VLBI Network (JVN). We aimed at selecting BAL quasars with nonthermal jets suitable for measuring their orientation angles and ages by subsequent detailed VLBI imaging studies to evaluate two controversial issues of whether BAL quasars are viewed nearly edge-on, and of whether BAL quasars are in a short-lived evolutionary phase of quasar population. We detected 20 out of 22 sources using the OCTAVE baselines, implying brightness temperatures greater than 10^5 K, which presumably come from nonthermal jets. Hence, BAL outflows and nonthermal jets can be generated simultaneously in these central engines. We also found four inverted-spectrum sources, which are interpreted as Doppler-beamed, pole-on-viewed relativistic jet sources or young radio sources: single edge-on geometry cannot describe all BAL quasars. We discuss the implications of the OCTAVE observations for investigations for the orientation and evolutionary stage of BAL quasars.Comment: 10 pages, no figure, 3 tables, accepted for publication in PAS

マンセイ キョケツ シンキン ニ オイテ ユウケイ タイモウ ト ゾウショク インシ ノ フクゴウ リョウホウ ワ arteriogenesis オ ソクシンシ シンキン キョクショ ケツリュウリョウ オ ゾウカサセル

京都大学0048新制・課程博士博士(医学)甲第12884号医博第3044号新制||医||939(附属図書館)UT51-2007-H157京都大学大学院医学研究科外科系専攻(主査)教授 野間 昭典, 教授 中尾 一和, 教授 開 祐司学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

The development of new biomechanical strategy for the treatment of post-MI ventricular remodeling

In-vivo豚心にて行う予定であったが、動物用MRIが廃棄処分となったため、PLL濃度/PMN濃度（％）を変えて異なる粘性のナノコンポジット・ジェルをEx-vivo豚心に注入し、一般用MRIを用いて心筋内での心筋線維の錯綜配列を定量化して比較検討した。その結果、４％のジェルが最も理想的な広がりを心筋内で示すことが判明した。コロナ感染拡大によりMRI実験そのものが不可能となったため、立命館大学生命情報学科の協力で臨床CT画像データを用いて胸部大動脈の形状モデルを作成して血流シミュレーションを行い、血管形状モデル曲面の曲率半径の分布から壁張力を求める簡便で有用な方法を開発した。The MRI for animals was discarded as its aging. Then, we had to change our research method from using in-vivo to ex-vivo porcine heart. We injected the nanocomposite gels with various viscosity into the apex of ex-vivo heart, by changing the ratio of PMN to PLL（％). And then we calculated the complexity of myofiber angles from DW images by using the MRI for patients. By analyzing these data, we showed that the best ratio for intra-myocardial gel distribution was 4%. However, the MRI study was severely restricted and became practically impossible, because of COVID-19 pandemic. We had to start the clinical simulation research with the help of Bioinformatics laboratory, Ritsumeikan University. Using the clinical chest CT images, we created configuration models of the aorta and applied blood flow simulations on these models. By using these simulation data, we developed the novel and feasible method to estimate the wall tension from the distribution of the curvature radius of the aorta.研究分野：循環器病学におけるバイオメカニクス応

Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility.

Decreased contractility in the non-ischemic border zone surrounding a MI is in part due to degradation of cardiomyocyte sarcomeric components by intracellular matrix metalloproteinase-2 (MMP-2). We recently reported that MMP-2 levels were increased in the border zone after a MI and that treatment with doxycycline for two weeks after MI was associated with normalization of MMP-2 levels and improvement in ex-vivo contractile protein developed force in the myocardial border zone. The purpose of the current study was to determine if there is a sustained effect of short term treatment with doxycycline (Dox) on border zone function in a large animal model of antero-apical myocardial infarction (MI). Antero-apical MI was created in 14 sheep. Seven sheep received doxycycline 0.8 mg/kg/hr IV for two weeks. Cardiac MRI was performed two weeks before, and then two and six weeks after MI. Two sheep died prior to MRI at six weeks from surgical/anesthesia-related causes. The remaining 12 sheep completed the protocol. Doxycycline induced a sustained reduction in intracellular MMP-2 by Western blot (3649±643 MI+Dox vs 9236±114 MI relative intensity; p = 0.0009), an improvement in ex-vivo contractility (65.3±2.0 MI+Dox vs 39.7±0.8 MI mN/mm2; p<0.0001) and an increase in ventricular wall thickness at end-systole 1.0 cm from the infarct edge (12.4±0.6 MI+Dox vs 10.0±0.5 MI mm; p = 0.0095). Administration of doxycycline for a limited two week period is associated with a sustained improvement in ex-vivo contractility and an increase in wall thickness at end-systole in the border zone six weeks after MI. These findings were associated with a reduction in intracellular MMP-2 activity

Moderate Ischemic Mitral Regurgitation After Posterolateral Myocardial Infarction in Sheep Alters Left Ventricular Shear but Not Normal Strain in the Infarct and Infarct Borderzone.

BackgroundChronic ischemic mitral regurgitation (CIMR) is associated with poor outcome. Left ventricular (LV) strain after posterolateral myocardial infarction (MI) may drive LV remodeling. Although moderate CIMR has&nbsp;been previously shown to affect LV remodeling, the effect of CIMR on LV strain after posterolateral MI remains unknown. We tested the hypothesis that moderate CIMR alters LV strain after posterolateral MI.MethodsPosterolateral MI was created in 10 sheep. Cardiac magnetic resonance imaging with tags was performed 2 weeks before and 2, 8, and 16 weeks after MI. The left and right ventricular volumes were measured, and regurgitant volume indexed to body surface area (regurgitant volume index) was calculated as the difference between left ventricle and right ventricle stroke volumes divided by body surface area. Three-dimensional strain was calculated.ResultsCircumferential strain (Ecc) and longitudinal strain (Ell) were reduced in the infarct proper, MI borderzone, and remote myocardium 16 weeks after MI.&nbsp;In addition, radial circumferential (Erc) and radial longitudinal (Erl) shear strains were reduced in remote myocardium but increased in the infarct and borderzone 16&nbsp;weeks after MI. Of all strain components, however, only Erc was affected by regurgitant volume index (p&nbsp;=&nbsp;0.0005). There was no statistically significant effect of regurgitant volume index on Ecc, Ell, Erl, or circumferential longitudinal shear strain (Ecl).ConclusionsModerate CIMR alters radial circumferential shear strain after posterolateral MI in sheep. Further studies are needed to determine the effect of shear strain on myocyte hypertrophy and the effect of mitral repair on myocardial strain