Faculty Profiles - MORITA Hiroshi

心不全を合併した心房細動症例に対するアミオダロンの効果、安全性について検討した。心室性不整脈に対してアミオダロンを処方した124例を対象とした。処方時に発作性・持続性心房細動を合併していた症例は43例で、そのうち6ヵ月間経過観察できた心房細動症例は30例であった。アミオダロン投与による洞調律維持は18例で可能であった。洞調律維持群をsinus群、洞調律に回復しなかった群をAF群として検討した。LVEFはAF群では改善する傾向がみられた。心拍数はsinus群で低下傾向を示した。LADは両群ともに変化は認めなかった。BNP値はsinus群で有意に低下し、AF群では低下傾向を示した。KL-6は投与前後で有意差を認めず、KL-6が急上昇した1例は、CT所見で間質の線維化を認めたためアミオダロン投与を中止し、KL-6は投与前の数値にまで回復した。

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Brugada症候群における下壁側壁誘導でのJ waveの意義 Brugada症候群における下壁側壁誘導での早期再分極の影響

時岡浩二, 草野研吾, 谷山真規子, 杜徳尚, 吉田賢司, 三好亨, 西井伸洋, 永瀬聡, 中村一文, 河野晋久, 森田宏, 伊藤浩, 大江透

心電図 32 ( Suppl.1 ) S - 87 2012.2

Acute vasoreactivity testing with nicardipine in patients with pulmonary arterial hypertension.

Yukihiro Saito, Kazufumi Nakamura, Katsumasa Miyaji, Satoshi Akagi, Hiroki Mizoguchi, Aiko Ogawa, Soichiro Fuke, Hideki Fujio, Takahiko Kiyooka, Satoshi Nagase, Kunihisa Kohno, Hiroshi Morita, Kengo F Kusano, Hiromi Matsubara, Tohru Ohe, Hiroshi Ito

Journal of pharmacological sciences 120 ( 3 ) 206 - 12 2012

Language：English Publishing type：Research paper (scientific journal)

Acute vasoreactivity testing for patients with pulmonary arterial hypertension (PAH) has been reported to be useful to identify patients with sustained beneficial response to oral calcium-channel blockers (CCBs), but there is a risk of exacerbation during the testing with oral CCBs. Therefore, we developed a testing method utilizing intravenous nicardipine, a short-acting CCB, and examined the safety and usefulness of acute vasoreactivity testing with nicardipine in PAH patients. Acute vasoreactivity testing with nicardipine was performed in 65 PAH patients. Nicardipine was administered by short-time continuous infusion (1 μg·kg⁻¹·min⁻¹ for 5 min and 2 μg·kg⁻¹·min⁻¹ for 5 min) followed by bolus injection (5 μg/kg). Hemodynamic responses were continuously measured using a right heart catheter. Acute responders were defined as patients who showed a decrease in mean pulmonary artery pressure of at least 10 mmHg to an absolute level below 40 mmHg with preserved or increased cardiac output. Two acute responders and sixty-three non-acute responders were identified. There was no hemodynamic instability requiring additional inotropic agents or death during the testing. Acute responders had good responses to long-term oral CCBs. The acute vasoreactivity testing with nicardipine might be safe and useful for identifying CCB responders in PAH patients.

PubMed

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Sustained monomorphic ventricular tachycardia in patients with Brugada syndrome

Take Yutaka, Morita Hiroshi, Toh Norihisa, Nishii Nobuhiro, Hashimoto Katsushi, Nagase Satoshi, Nakamura Kazuhumi, Kohno Kunihisa, Kusano Kengo, Ohe Tohru, Ito Hiroshi

Shinzo 44 ( 2 ) S2_55 - S2_55 2012

J Wave in Brugada Syndrome -- Comparison to Early Repolarization Syndrome --

Shimizu Wataru, Kawata Hiro, Morita Hiroshi, Ito Hiroshi, Kamakura Shiro

Japanese Journal of Electrocardiology 32 ( 3 ) 300 - 304 2012

Intermittent arm ischemia induces vasodilatation of the contralateral upper limb.

Kenki Enko, Kazufumi Nakamura, Kei Yunoki, Toru Miyoshi, Satoshi Akagi, Masashi Yoshida, Norihisa Toh, Mutsuko Sangawa, Nobuhiro Nishii, Satoshi Nagase, Kunihisa Kohno, Hiroshi Morita, Kengo F Kusano, Hiroshi Ito

The journal of physiological sciences : JPS 61 ( 6 ) 507 - 13 2011.11

Language：English Publishing type：Research paper (scientific journal)

Intermittent arm ischemia before percutaneous coronary intervention induces remote ischemic preconditioning (RIPC) and attenuates myocardial injury in patients with myocardial infarction. Several studies have shown that intermittent arm ischemia increases coronary flow and is related to autonomic nerve system. The aim of this study was to determine whether intermittent arm ischemia induces vasodilatation of other arteries and to assess changes in the autonomic nerve system during intermittent arm ischemia in humans. We measured change in the right brachial artery diameter during intermittent left arm ischemia through three cycles of 5-min inflation (200 mmHg) and 5-min deflation of a blood-pressure cuff using a 10-MHz linear array transducer probe in 20 healthy volunteers. We simultaneously performed power spectral analysis of heart rate. Ischemia-reperfusion of the left arm significantly dilated the right brachial artery time-dependently, resulting in a 3.2 ± 0.4% increase after the 3rd cycle. In the power spectral analysis of heart rate, the high-frequency domain (HF), which is a marker of parasympathetic activity, was significantly higher after the 3rd cycle of ischemia-reperfusion than baseline HF (P = 0.02). Intermittent arm ischemia was accompanied by vasodilatation of another artery and enhancement of parasympathetic activity. Those effects may play an important role in the mechanism of RIPC.

DOI： 10.1007/s12576-011-0172-9

PubMed

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PSL単独での治療に難渋し、MTX併用が有用であった心サルコイドーシスの1例

三好章仁, 草野研吾, 久保元基, 西井伸洋, 永瀬聡, 河野晋久, 森田宏, 伊藤浩

日本サルコイドーシス/肉芽腫性疾患学会雑誌 31 ( サプリメント号 ) 40 - 40 2011.10

Beta-Blockers and Oxidative Stress in Patients with Heart Failure. International journal

Kazufumi Nakamura, Masato Murakami, Daiji Miura, Kei Yunoki, Kenki Enko, Masamichi Tanaka, Yukihiro Saito, Nobuhiro Nishii, Toru Miyoshi, Masashi Yoshida, Hiroki Oe, Norihisa Toh, Satoshi Nagase, Kunihisa Kohno, Hiroshi Morita, Hiromi Matsubara, Kengo F Kusano, Tohru Ohe, Hiroshi Ito

Pharmaceuticals (Basel, Switzerland) 4 ( 8 ) 1088 - 100 2011.8

Language：English Publishing type：Research paper (scientific journal)

Oxidative stress has been implicated in the pathogenesis of heart failure. Reactive oxygen species (ROS) are produced in the failing myocardium, and ROS cause hypertrophy, apoptosis/cell death and intracellular Ca(2+) overload in cardiac myocytes. ROS also cause damage to lipid cell membranes in the process of lipid peroxidation. In this process, several aldehydes, including 4-hydroxy-2-nonenal (HNE), are generated and the amount of HNE is increased in the human failing myocardium. HNE exacerbates the formation of ROS, especially H₂O₂ and ·OH, in cardiomyocytes and subsequently ROS cause intracellular Ca(2+) overload. Treatment with beta-blockers such as metoprolol, carvedilol and bisoprolol reduces the levels of oxidative stress, together with amelioration of heart failure. This reduction could be caused by several possible mechanisms. First, the beta-blocking effect is important, because catecholamines such as isoproterenol and norepinephrine induce oxidative stress in the myocardium. Second, anti-ischemic effects and negative chronotropic effects are also important. Furthermore, direct antioxidative effects of carvedilol contribute to the reduction of oxidative stress. Carvedilol inhibited HNE-induced intracellular Ca(2+) overload. Beta-blocker therapy is a useful antioxidative therapy in patients with heart failure.

DOI： 10.3390/ph4081088

PubMed

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Ezetimibe improves postprandial hyperlipemia and its induced endothelial dysfunction Reviewed

Kei Yunoki, Kazufumi Nakamura, Toru Miyoshi, Kenki Enko, Kunihisa Kohno, Hiroshi Morita, Kengo F. Kusano, Hiroshi Ito

ATHEROSCLEROSIS 217 ( 2 ) 486 - 491 2011.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

Objective: Postprandial hyperlipemia has been shown to impair endothelial function and contribute to the development of atherosclerosis. We investigated the association between postprandial lipid profiles and endothelial function, and we examined the effects of ezetimibe on postprandial hyperlipemia and lipemia-induced endothelial dysfunction.
Methods: A randomized prospective trial in which 10 mg/day of ezetimibe was administered to 10 subjects for 4 weeks and not administered to 10 subjects (control group) was performed. Lipid profiles and endothelial function, assessed by brachial artery flow-mediated dilation (FMD) during a fasting state and at 2, 4, 6 and 8 h after an oral cookie loading test, were determined before and after treatment for 4 weeks.
Results: In all subjects before treatment, the maximum reduction in postprandial % FMD was significantly correlated with the maximum increases in postprandial triglyceride (TG) (r = -0.499, P < 0.05) and apolipoprotein B-48 (apoB-48) concentrations (r = -0.551, P < 0.05). Ezetimibe treatment for 4 weeks significantly suppressed postprandial elevation in TG (area under the incremental curve, from 1419 +/- 594 to 968 +/- 321 mg h/dl, P < 0.05), remnant lipoprotein cholesterol (from 66.9 +/- 27.6 to 38.9 +/- 15.4 mg h/dl, P < 0.01) and apoB-48 (from 58.8 +/- 27.5 to 36.2 +/- 17.0 mu gh/ml, P < 0.05) concentrations, and postprandial endothelial dysfunction assessed by % FMD (maximum reduction in % FMD, from -2.6 +/- 1.1% to -1.2 +/- 0.8%, P < 0.05), whereas no significant changes were observed in the control group.
Conclusion: Postprandial hyperlipemia is closely correlated with transient endothelial dysfunction. Ezetimibe improves postprandial hyperlipemia and its induced endothelial dysfunction. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.atherosclerosis.2011.04.019

Web of Science

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Impact of Hypertriglyceridemia on Endothelial Dysfunction During Statin +/- Ezetimibe Therapy in Patients With Coronary Heart Disease Reviewed

Kei Yunoki, Kazufumi Nakamura, Toru Miyoshi, Kenki Enko, Motoki Kubo, Masato Murakami, Yoshiki Hata, Kunihisa Kohno, Hiroshi Morita, Kengo F. Kusano, Hiroshi Ito

AMERICAN JOURNAL OF CARDIOLOGY 108 ( 3 ) 333 - 339 2011.8

Language：English Publishing type：Research paper (scientific journal) Publisher：EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC

Despite the use of statin therapy and achieving the target for low-density lipoprotein cholesterol, a substantial number of coronary events are not prevented, and residual risk factors remain unsettled. Recently, ezetimibe has been shown to reduce not only low-density lipoprotein cholesterol but also triglyceride (TG) levels. The aim of this study was to investigate the associations of residual risk factors, mainly hypertriglyceridemia, with endothelial function during statin therapy in patients with coronary heart disease and examine the effect of ezetimibe add-on therapy. A total of 109 consecutive patients with coronary heart disease during statin therapy were enrolled. Lipid profile was measured and endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery in a fasting state. Next, 32 patients with high TG levels (>= 150 mg/dl) were prospectively assigned to the ezetimibe add-on group or the no-ezetimibe group, and endothelial function was assessed after 3 months. Multivariate linear regression analysis demonstrated that serum TG and high-density lipoprotein cholesterol levels were independent determinants of percentage FMD (beta = -0.210 and 0.208, respectively, p <0.05). In patients with high TG levels, ezetimibe add-on therapy significantly improved percentage FMD (from 3.3 +/- 1.1% to 4.0 +/- 1.1%, p <0.005), whereas no significant change was observed in the no-ezetimibe group. Moreover, the improvement in percentage FMD was significantly associated with reduction in serum TG levels (beta = -0.387, p <0.05) independent of the change in serum low-density lipoprotein cholesterol levels. In conclusion, hypertriglyceridemia is independently associated with endothelial dysfunction in patients with coronary heart disease during statin therapy. Ezetimibe add-on therapy improves endothelial function in these high-risk populations. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:333-339)

DOI： 10.1016/j.amjcard.2011.03.049

Web of Science

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How can we stabilize QT variability? International journal

Hiroshi Morita

Heart rhythm 8 ( 8 ) 1243 - 4 2011.8

Spontaneous electrocardiogram alterations predict ventricular fibrillation in Brugada syndrome. International journal

Yutaka Take, Hiroshi Morita, Jiashin Wu, Satoshi Nagase, Shiho Morita, Norihisa Toh, Nobuhiro Nishii, Kazufumi Nakamura, Kengo F Kusano, Tohru Ohe, Hiroshi Ito, Douglas P Zipes

Heart rhythm 8 ( 7 ) 1014 - 21 2011.7

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Patients with Brugada syndrome (BS) often have spontaneous changes in their electrocardiogram (ECG). OBJECTIVE: To evaluate the significance of ECG alterations, we investigated the relationships between the ECG and the occurrence of ventricular fibrillation (VF) in both patients and an experimental model of BS. METHODS: In study 1, we evaluated ECG alterations in BS patients with (VF+, n = 33) and without (VF-, n = 41) spontaneous VF. We defined type 0 ECG as coved-type ST elevation without a negative T wave, which represents the existence of loss-of-dome (LOD) type action potentials (APs). In study 2, we optically mapped epicardial APs and recorded transmural ECGs in 34 canine right ventricular tissues with a drug-induced BS model by a combination of pinacidil and pilsicainide. RESULTS: In study 1, changes in ST level ≥0.2 mV were more frequent in the VF+ group than in the VF- group (P <.01). Spontaneous ECG alterations and appearances of types 1 and 0 ECGs were more frequent in the VF+ group than in the VF- group (P <.01). In study 2, BS model with spike-and-dome (SAD) epicardial APs exhibited type 1 ECG. Deepening of the phase 1 notch of the APs induced heterogeneous conversion of the APs (SAD→LOD) and resulted in ECG conversion from type 1 to type 0. Significant AP heterogeneity often appeared during AP alterations and initiated phase 2 reentry. Tissues having ventricular tachycardia (VT; n = 20) had more frequent alterations in APs and ECG than in tissues without VT (n = 14; P <.01). CONCLUSION: ECG alterations, especially conversion between types 0 and 1, are associated with significant AP heterogeneity that can initiate VF in BS.

DOI： 10.1016/j.hrthm.2011.02.009

PubMed

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心臓突然死予知のための新しい診断法 Fragmented QRSによるBrugada症候群突然死の予知

森田宏, 永瀬聡, 草野研吾, 大江透, 伊藤浩

心電図 31 ( Suppl.1 ) S - 36 2011.5

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Papers - MORITA Hiroshi