Junya Takagawa

Toyama Medical and Pharmaceutical University, Тояма, Toyama, Japan

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Publications (12)50.42 Total impact

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    ABSTRACT: Influences of slow and deep respiration on steady-state sympathetic nerve activity remain controversial in humans and could vary depending on disease conditions and basal sympathetic nerve activity. To elucidate the respiratory modulation of steady-state sympathetic nerve activity, we modeled the dynamic nature of the relationship between lung inflation and muscle sympathetic nerve activity (MSNA) in 11 heart failure patients with exaggerated sympathetic outflow at rest. An autoregressive exogenous input model was utilized to simulate entire responses of MSNA to variable respiratory patterns. In another 18 patients, we determined the influence of increasing tidal volume and slowing respiratory frequency on MSNA; 10 patients underwent a 15-min device-guided slow respiration and the remaining 8 had no respiratory modification. The model predicted that a one-liter, step increase of lung volume decreased MSNA dynamically; its nadir (-33 ± 22 %) occurred at 2.4 sec; and steady-state decrease (-15 ± 5 %), at 6 sec. Actually, in patients with the device-guided slow and deep respiration, respiratory frequency effectively fell from 16.4 ± 3.9 to 6.7 ± 2.8/min (p<0.0001) with a concomitant increase in tidal volume from 499 ± 206 to 1177 ± 497 ml (p<0.001). Consequently, steady-state MSNA was decreased by 31 % (p<0.005). In patients without respiratory modulation, there were no significant changes in respiratory frequency, tidal volume, and steady-state MSNA. Thus, slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with high levels of resting sympathetic tone as in heart failure.
    AJP Heart and Circulatory Physiology 08/2014; 307(8). DOI:10.1152/ajpheart.00109.2014 · 3.84 Impact Factor
  • Journal of Cardiac Failure 10/2013; 19(10):S173-S174. DOI:10.1016/j.cardfail.2013.08.489 · 3.05 Impact Factor
  • Journal of Cardiac Failure 10/2012; 18(10):S173. DOI:10.1016/j.cardfail.2012.08.258 · 3.05 Impact Factor
  • Journal of Cardiac Failure 09/2010; 16(9). DOI:10.1016/j.cardfail.2010.07.201 · 3.05 Impact Factor
  • Journal of Cardiac Failure 09/2009; 15(7). DOI:10.1016/j.cardfail.2009.07.131 · 3.05 Impact Factor
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    ABSTRACT: The present study was designed to develop a method to continuously measure Holter electrocardiogram (ECG) and physical activity in terms of metabolic costs to examine circadian dynamics of RR intervals and physical activity in patients with heart failure. A total of 7 healthy subjects and 3 heart failure patients performed cardiopulmonary exercise test using four-stage graded treadmill walking at 0% grade to examine whether the acceleration signals in the vertical direction could reflect actual body energy expenditure during physical activity. Then, using this new method, 24-hr monitorings of ECG and physical activity were performed in 24 inpatients with heart failure while they were allowed to walk around freely. Our results showed the integral of rectified acceleration signals was closely correlated with actual metabolic cost in all subjects. Instantaneous changes in heart rate were quite concordant with physical activity. As compared with the asymptomatic patients (n = 12), the symptomatic patients (n = 12) had lower energy expenditure during 8-hr daytime periods but higher mean heart rate. Furthermore, a more prominent ultradian rhythm of circadian changes in heart rate and physical activity was found in 50% of all subjects studied. The simultaneous analysis of Holter ECG and physical activity as the same time series revealed that in patients with heart failure, sympathovagal balance shifted toward sympathotonic conditions and their physical activity could become subject to intrinsic ultradian dynamics of body's homeostasis.
    Clinical and Experimental Hypertension 07/2009; 27(2-3):241-9. DOI:10.1081/CEH-200048870 · 1.23 Impact Factor
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    ABSTRACT: Abnormal sleep dynamics in patients with heart failure is one of the mechanisms for the relative predominance of central sympathetic outflow over parasympathetic tone. This study was designed to examine whether central sympathoinhibition could improve the sympathovagal imbalance related to rapid-eye-movement (REM)/non-REM ultradian sleep rhythm in these patients. Beat-by-beat RR intervals of overnight electrocardiogram were serially subject to power spectral analysis in 14 patients with chronic heart failure and 13 age-matched subjects with normal cardiac function. To assess autonomic sleep dynamics, the ultradian rhythm was extracted from all-night consecutive high-frequency (HF) components of heart rate variability (HRV) before and after administration of an (alpha2)-adrenergic agonist, guanfacine. Night-time HRV in heart failure was characterized by an attenuated ultradian rhythm of HF-components with a concomitant reduction in averaged HF power. Guanfacine reduced blood pressure, heart rate, and plasma norepinephrine concentrations by 7%, 8%, and 34% (p < 0.01), respectively. After guanfacine, HF power rose by 154% (p < 0.01) with a prominent augmentation of the all-night ultradian rhythm (+361%, p < 0.01). Central sympathoinhibition augments a sleep-related ultradian rhythm of parasympathetic tone, suggesting a potential benefit to autonomic balancing and sleep quality in patients with chronic heart failure.
    Circulation Journal 09/2005; 69(9):1052-6. DOI:10.1253/circj.69.1052 · 3.94 Impact Factor
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    ABSTRACT: Enhanced central hypercapnic chemosensitivity is known to mediate excessive exercise ventilation and to indicate a poor prognosis in patients with chronic heart failure. The present study was designed to elucidate the role of central sympathetic activity in the enhancement of hypercapnic chemosensitivity. Central hypercapnic chemosensitivity and plasma norepinephrine were measured in 99 patients with chronic heart failure. In 40 patients, the alpha index was derived from simultaneous analysis of R-R interval and systolic blood pressure variability. The effects of a central sympatholytic agent, guanfacine (0.25 mg/day), on hypercapnic chemosensitivity and exercise ventilatory response were studied in 20 of these patients. Hypercapnic chemosensitivity was enhanced in 76% of the patients and correlated significantly with plasma norepinephrine levels (r = 0.49, P < .01) at rest. There was a significant inverse relationship between central chemosensitivity and the alpha index (r = -0.41, P < .01). Guanfacine significantly reduced plasma norepinephrine levels by 29% (P < .01) and chemosensitivity by 31% (P < .01). The beneficial effect of central sympathoinhibition with guanfacine was observed specifically in patients who had enhanced chemosensitivity prior to drug administration. Similarly, the patients with excessive exercise ventilation showed a greater reduction in exercise ventilation with this agent. The present findings suggest that central sympathoexcitation could play an important role in the pathogenesis of enhanced hypercapnic chemosensitivity and a resultant increase in exercise ventilation in chronic heart failure.
    American heart journal 12/2004; 148(6):964-70. DOI:10.1016/j.ahj.2004.05.030 · 4.46 Impact Factor
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    ABSTRACT: Enhanced hypercapnic chemoreflex in chronic heart failure could modulate sympathetic nerve activity in a different manner depending on the severity of heart failure. This study was designed to evaluate the dynamic aspects of sympathoexcitation caused by central hypercapnic chemoreflex in patients with chronic heart failure. In 21 patients with chronic heart failure, wavelet analysis was applied to elucidate the spectral components of muscle sympathetic nerve activity (MSNA) and instantaneous ventilation during hypercapnic chemoreceptor stimulation. Hypercapnia increased MSNA (83+/-8 versus 29+/-9 %, P<.01) and ventilation (209+/-27 versus 190+/-21%, P<.05) more in 12 symptomatic patients than in 9 asymptomatic patients. This hypercapnic chemoreflex exerted a greater influence on the sympathetic limb than on the ventilatory limb in the symptomatic patients. The wavelet analysis revealed that the within-breath sympathoinhibition in the symptomatic patients was attenuated as compared with that in the asymptomatic patients (0.33+/-0.03 vs. 0.44+/-0.04, P<.05). The enhanced chemoreflex sympathetic drive and relative attenuation of ventilatory sympathoinhibition could contribute to exaggerated sympathoexcitation in patients with heart failure when they are exposed to carbon dioxide during exercise or sleep apnea.
    Journal of Cardiac Failure 06/2004; 10(3):236-43. DOI:10.1016/j.cardfail.2003.09.005 · 3.05 Impact Factor
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    ABSTRACT: The purpose of the study was to evaluate the dynamic nature of heart rate baroreflex under closed-loop conditions. We applied pressure perturbation with a random-interval cuff inflation to parametric system identification of the baroreflex. In 10 healthy men (six young, 27 +/- 3.9 years old, and four older, 50 +/- 3.8 years old), blood pressure variations were produced by a random-interval (0.06-0.50 Hz) cuff inflation around bilateral thighs to identify characteristics of the baroreflex with an autoregressive moving average model with exogenous input. The model faithfully described the dynamic relationship between mean blood pressure and RR interval. A theoretical 1 mmHg step input of mean blood pressure caused a rapid increase in RR intervals toward the steady state within 10 s in younger subjects. In older subjects, however, the step response showed a delayed and gradual increase in RR interval over 20 s. The steady-state gain obtained from the autoregressive moving average model with exogenous input was significantly greater than that determined from the slope of the pressure-RR relationship. The conclusion was that the dynamic baroreflex gain was quantified using a parametric system identification technique and blood pressure perturbation by means of a random-interval cuff inflation. This method would potentially be of great use in helping us gain insights into a closed-loop system of complex and dynamic cardiovascular regulation in humans.
    Journal of Cardiovascular Pharmacology 01/2004; 42 Suppl 1:S11-3. DOI:10.1097/00005344-200312001-00004 · 2.14 Impact Factor
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    ABSTRACT: This study was designed to elucidate the influence of cardiac sympathetic denervation on the sympathoexcitatory response to acute myocardial ischemia during balloon coronary occlusion (BCO) in humans. Alterations of cardiac sympathetic nerve function could modulate sympathetic reflexes originating from the ischemic area. In 23 patients with angina pectoris, we quantified the baseline cardiac sympathetic denervation of the ischemia-related area by iodine-123 metaiodobenzylguanidine ((123)I-MIBG), and transient changes in sympathetic activity during BCO by wavelet analysis of RR interval variability. Balloon coronary occlusion resulted in a transient augmentation of low-frequency (LF: 0.04 to 0.14 Hz) spectral components of RR interval variability in 4 of 12 patients with cardiac denervation and in 8 of 11 patients without denervation (p < 0.01 by the chi-square test). Consequently, the increase in LF components was significantly less during BCO in patients with cardiac denervation (34%) than in those without denervation (273%) (interaction: p < 0.05). In seven patients with severe ischemia provoked by a fall of > or = 10% in the left ventricular ejection fraction, LF components increased by 506% during BCO, regardless of the condition of cardiac denervation. In contrast, in patients with mild ischemia provoked by a fall of <10% in the ejection fraction, changes of LF components during BCO were significantly less in patients with denervation than in those without denervation (84 vs. 344%, p < 0.05). These findings suggest that if the provoked ischemia is not severe, cardiac sympathetic denervation could prevent ischemia-induced sympathoexcitation.
    Journal of the American College of Cardiology 02/2002; 39(3):436-42. DOI:10.1016/S0735-1097(01)01770-3 · 16.50 Impact Factor
  • Journal of Cardiac Failure 09/1998; 4(3):84-84. DOI:10.1016/S1071-9164(98)90368-2 · 3.05 Impact Factor