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Hiroo Kumagai,
Naoki Oshima,
Tomokazu Matsuura,
Kamon Iigaya,
Masaki Imai,
Hiroshi Onimaru,
Katsufumi Sakata, Motohisa Osaka,
Toshiko Onami,
Chie Takimoto,
Tadashi Kamayachi,
Hiroshi Itoh,
Takao Saruta
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ABSTRACT: Accentuated sympathetic nerve activity (SNA) is a risk factor for cardiovascular events. In this review, we investigate our working hypothesis that potentiated activity of neurons in the rostral ventrolateral medulla (RVLM) is the primary cause of experimental and essential hypertension. Over the past decade, we have examined how RVLM neurons regulate peripheral SNA, how the sympathetic and renin-angiotensin systems are correlated and how the sympathetic system can be suppressed to prevent cardiovascular events in patients. Based on results of whole-cell patch-clamp studies, we report that angiotensin II (Ang II) potentiated the activity of RVLM neurons, a sympathetic nervous center, whereas Ang II receptor blocker (ARB) reduced RVLM activities. Our optical imaging demonstrated that a longitudinal rostrocaudal column, including the RVLM and the caudal end of ventrolateral medulla, acts as a sympathetic center. By organizing and analyzing these data, we hope to develop therapies for reducing SNA in our patients. Recently, 2-year depressor effects were obtained by a single procedure of renal nerve ablation in patients with essential hypertension. The ablation injured not only the efferent renal sympathetic nerves but also the afferent renal nerves and led to reduced activities of the hypothalamus, RVLM neurons and efferent systemic sympathetic nerves. These clinical results stress the importance of the RVLM neurons in blood pressure regulation. We expect renal nerve ablation to be an effective treatment for congestive heart failure and chronic kidney disease, such as diabetic nephropathy.
Hypertension Research 12/2011; 35(2):132-41. · 2.58 Impact Factor
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Akihiro Mori,
Peter Lee,
Takeshi Yokoyama,
Hitomi Oda,
Kaori Saeki,
Yohei Miki,
Satoshi Nozawa,
Daigo Azakami,
Yutaka Momota,
Yuki Makino,
Takako Matsubara, Motohisa Osaka,
Katsumi Ishioka,
Toshiro Arai,
Toshinori Sako
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ABSTRACT: Artificial pancreas technology, involving "closed-loop" controls with real-time blood glucose monitoring, has been increasing in reliability as its potential for clinical use and application grows. One such device, based on this technology, is the STG-22 (Nikkiso Co., Ltd., Tokyo, Japan) artificial pancreas apparatus. In order to assess the reliability and accuracy of the device for measuring blood glucose, it is important to compare its readings to those obtained using a 'gold standard' method, such as the hexokinase method. Therefore, in the present study, canine blood [glucose] measurements using the STG-22 were compared to those obtained using a previously established commercial reagent, Quickauto-Neo GLU-HK. Furthermore, two different sample types (whole blood versus plasma constituent) were compared to determine which sample type results in more accurate and optimal readings with the STG-22. Given that the STG-22 was not primarily designed for canine blood samples, results for canine blood samples were not accurate. Measurements performed by the STG-22 with whole blood were significantly lower than reference [glucose] counterparts. Alternatively, an opposite trend was observed with plasma measurements that were significantly higher. A conversion format using the following formula, Hexokinase [glucose] = STG-22 [glucose] × 1.407 + 1.532, was observed with canine samples in our study.
Journal of Artificial Organs 06/2011; 14(2):133-9. · 1.59 Impact Factor
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ABSTRACT: No reliable precursor of sudden cardiac death is known.
Holter electrocardiograms of 34 patients experiencing a cardiac event (event group, 20 deaths) were compared with 191 controls (no event group). The event group included 25 patients with ventricular fibrillation or acute myocardial infarction (AMI), and 9 with cardiac arrest due to complete atrioventricular block. The logarithms were calculated of the moving average of 5 successive values for the low-frequency component (LF), the high-frequency component (HF), and the ratio LF/HF of heart rate variability: ln(LF), ln(HF) and ln(LF/HF). A V-shaped trough appeared in the curve of ln(LF/HF) [sV-trough] or ln(HF) [pV-trough] before such an event in 31 patients in the event group. The V-trough was marked by a small variation lasting 2 h, an abrupt descent lasting 30 min, and a sharp ascent for 40 min. An sV-trough was observed in 22 patients before the onset of ventricular fibrillation or AMI. A pV-trough was observed in all 9 patients before the onset of complete atrioventricular block. In the no event group, an sV-trough and a pV-trough were observed in 10 subjects (5%) and 20 subjects (10%), respectively. The positive predictive accuracy of an sV-trough for ventricular fibrillation or AMI and that of a pV-trough for complete atrioventricular block was 88% and 100%, respectively.
A previously unidentified V-trough of autonomic activity is a potential precursor of lethal events.
Circulation Journal 09/2010; 74(9):1906-15. · 3.77 Impact Factor
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ABSTRACT: Approximately 5% of motor vehicle deaths are assumed to be occur because of a cardiac event thought to be triggered by multiple factors. One important factor is an imbalance of sympathetic and parasympathetic nervous activities, which can be measured by analyzing heart rate variability (HRV). Therefore, a system has been developed to make electrocardiographic (ECG) recordings outside the driver's awareness from the steering wheel (steering-ECG) with an algorithm to remove noise.
Steering-ECG and ECG from a chest lead (chest-ECG) were recorded simultaneously in 10 normal subjects while they were driving for 90 min. For each of 4 parameters (instantaneous heart rate, low- and high-frequency components of HRV, and the ratio of these components in all subjects), mutual information was used to examine whether the fluctuation from the steering-ECG resembled that from the chest-ECG. The mutual information of each parameter was larger than 0.047 with 95% confidence interval (mutual information values vary from 0 to 1; threshold of significance: 0.047). Hence, the fluctuation of each steering-ECG parameter resembled its chest-ECG counterpart.
This system heralds a new driver-safety strategy by reporting alteration of autonomic nervous activity during driving.
Circulation Journal 11/2008; 72(11):1867-73. · 3.77 Impact Factor
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ABSTRACT: The nonlinearity of cardiovascular regulation is higher in normal physiology, whereas several diseases are characterized by a reduction in this nonlinearity. Reduced nonlinearity of heart rate regulation is a robust risk factor for high mortality in patients with myocardial infarction. We investigated the changes in linear and nonlinear correlations of cardiovascular regulation after administering drugs in hypertensive diabetic rats. Type 1 diabetes was induced in rats by intraperitoneally injecting spontaneously hypertensive rats with streptozotocin. The animals were then divided into 4 groups and each group was given vehicle, candesartan, amlodipine, or insulin for 2 weeks. Blood pressure, heart rate, renal sympathetic nerve activity, and renal blood flow were simultaneously recorded in the conscious state, and the linear and nonlinear correlations were compared by using coherence and the mutual information method. Candesartan and amlodipine decreased blood pressure to a similar extent, but renal sympathetic nerve activity was significantly lower in the candesartan group than in the vehicle group. The renal sympathetic nerve activity in the insulin group was also lower than in the vehicle group. There were no significant differences in linear correlation among the 4 groups. In contrast, the nonlinear correlations between renal sympathetic nerve activity and blood pressure in the candesartan group and the insulin group were significantly higher than in the vehicle group. Candesartan and insulin decreased renal sympathetic nerve activity and increased the nonlinearity. These results suggest that reducing the activity of renin-angiotensin system and insulin that lowers blood glucose level may improve autonomic nervous system dysfunction and neurohumoral regulation of the cardiovascular system in diabetic hypertensive rats.
Hypertension Research 11/2008; 31(10):1941-51. · 2.58 Impact Factor
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Motohisa Osaka
Journal of Nippon Medical School 11/2007; 74(5):330-1.
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ABSTRACT: The mechanism of 1/f scaling of heartbeat intervals remains unknown. We recorded heartbeat intervals, sympathetic nerve activity, and blood pressure in conscious rats with normal or high blood pressure. Using nonlinear analyses, we demonstrate that the dynamics of this system of 3 variables is low‐order chaos, and that sympathetic nerve activity leads to heartbeat interval and blood pressure changes. It is suggested that 1/f scaling of heartbeat intervals results from the low‐order chaos of these variables and that impaired regulation of blood pressure by sympathetic nerve activity is likely to cause experimentally observable steeper scaling of heartbeat intervals in hypertensive (high blood pressure) rats. © 2004 American Institute of Physics
AIP Conference Proceedings. 04/2004; 708(1):306-309.
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I. J. Bifurcation and Chaos. 01/2004; 14:3449-3457.
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Tomoyuki Yambe,
Yasuyuki Shiraishi,
Makoto Yoshizawa,
Akira Tanaka,
Ken-ichi Abe,
Fumihiro Sato,
Hidetoshi Matsuki,
Masayoshi Esashi,
Yoichi Haga,
Shigenao Maruyama, [......],
Yun Luo,
Eiji Okamoto,
Yutaka Kubo, Motohisa Osaka,
Shunsuke Nanka,
Yoshifumi Saijo,
Yoshiaki Mibiki,
Tasuku Yamaguchi,
Mune-ichi Shibata,
Shinichi Nitta
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ABSTRACT: Where is the place which should be helped in a patient with congestive heart failure? The answer may be contraction of the heart. At Tohoku University, development research of "the artificial myocardium" has been conducted, using a ball screw type electromagnetic motor. Furthermore, super-miniaturization is being attempted at present. Thus, a system with shape memory alloy is being developed. The cooling speed problem was solved by the application of the Peltier element. A drive at a speed equal to that of a heartbeat was realized by the application of this system. At present, a ventricular assist device is used for patients waiting for a heart transplant in Japan. An air driven type system disturbs a patient's QOL remarkably because it is connected to the drive device. With our concept, energy is provided by using the electromagnetic force from outside of the body by the use of transcutaneous energy transmission system. Magnetic shielding by amorphous fibers was used at Tohoku University to improve the total efficiency. A natural heart can alter the cardiac output corresponding to the demand. Artificial internal organs must participate in the system of the living body, too. Tohoku University has developed a resistance based artificial heart control algorithm, which simulated a baroreflex system to cope with every demand. Nano level sensing equipment is now under development at Tohoku University. At present, development is being conducted aiming at an "intelligent artificial myocardium".
Biomedecine [?] Pharmacotherapy 11/2003; 57 Suppl 1:122s-125s. · 2.00 Impact Factor
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ABSTRACT: The mechanism of 1/f scaling of heartbeat intervals remains unknown. We recorded heartbeat intervals, sympathetic nerve activity, and blood pressure in conscious rats with normal or high blood pressure. Using nonlinear analyses, we demonstrate that the dynamics of this system of three variables is low-order chaos, and that sympathetic nerve activity leads to heartbeat interval and blood pressure changes. It is suggested that impaired regulation of blood pressure by sympathetic nerve activity is likely to cause experimentally observable steeper scaling of heartbeat intervals in hypertensive (high blood pressure) rats.
Physical Review E 05/2003; 67(4 Pt 1):041915. · 2.26 Impact Factor
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ABSTRACT: Patients with a reduced nonlinear component of heart rate regulation have a poorer outcome.
We investigated whether a nonlinear correlation between renal sympathetic nerve activity (RSNA) and blood pressure or renal blood flow is reduced in conscious, spontaneously hypertensive rats (SHR) by comparing them with normotensive Wistar-Kyoto rats (WKY). We also determined the linearity and nonlinearity of the correlation in SHR who were given an angiotensin II receptor blocker, candesartan, orally for 2 weeks. The RSNA value was higher in SHR than in WKY, and coherence peaks of transfer function were found at 0.05 and 0.80 Hz (ie, below respiratory- and cardiac-related fluctuations). The coherence (linearity) of the transfer function was significantly higher and gain was smaller in SHR than in WKY. Because mutual information values (linear and nonlinear correlation) were similar in both strains, we found the nonlinear correlation to be lower in SHR than in WKY. Time delay values calculated by the mutual information method demonstrated that RSNA preceded blood pressure and renal blood flow by 0.5 to 1.0 s. In SHR given candesartan, the RSNA value was lower, and the linearity was lower and nonlinearity higher than SHR given vehicle.
Linear correlation between RSNA and blood pressure or renal blood flow was higher in SHR than in WKY, whereas the nonlinear correlation was lower. Oral treatment with candesartan increased the nonlinearity and reduced the linearity in SHR. Increased RSNA and the renin-angiotensin system may be responsible for the lower nonlinearity and higher linearity in hypertension.
Circulation 08/2002; 106(5):620-5. · 14.74 Impact Factor
