Shuji Shimizu

National Cerebral and Cardiovascular Center, Ōsaka, Ōsaka, Japan

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Publications (53)106.9 Total impact

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    ABSTRACT: To examine the effects of cariporide, a Na(+)/H(+) exchanger-1 inhibitor, on cardiac norepinephrine (NE) and myoglobin releases during myocardial ischemia/reperfusion by applying a microdialysis technique to the rabbit heart.
    Life sciences. 08/2014;
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    ABSTRACT: In elderly patients, open surgery for patent ductus arteriosus (PDA) is more difficult than that in children and often requires a cardiopulmonary bypass. We report the case of a 67-year-old patient with a PDA that was successfully treated with thoracic endovascular aortic repair (TEVAR). The patient was diagnosed with congestive heart failure (ejection fraction, 36 %) and PDA (9.7 mm in diameter). TEVAR was successfully performed to exclude the PDA. After TEVAR, the patient's heart failure was well controlled by diuretics. TEVAR may be a good alternative to open surgery.
    General thoracic and cardiovascular surgery. 07/2014;
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    ABSTRACT: Arterial aneurysm rupture is one of the most critical complications in patients with vascular-type Ehlers-Danlos syndrome (vEDS). Here, we report a case of recurrent aneurysm rupture successfully treated by endovascular embolization. A 38-year old woman who underwent brachial artery ligation for a ruptured aneurysm was diagnosed postoperatively with vEDS. Impending rupture of a collateral artery aneurysm was encountered 5 months after the initial open surgery. Endovascular embolization with a liquid embolic agent was successfully performed. Given that arterial rupture can occur repeatedly in patients with vEDS, careful life-long follow-up is necessary.
    Interactive Cardiovascular and Thoracic Surgery 07/2014; · 1.11 Impact Factor
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    ABSTRACT: To identify the contribution of myelinated (A-fibre) and unmyelinated (C-fibre) baroreceptor central pathways to the baroreflex control of sympathetic nerve activity and arterial pressure. Two binary white noise stimulation protocols were used to electrically stimulate the aortic depressor nerve and activate reflex responses from either A-fibre (3V, 20-100Hz) or C-fibre (20V, 0-10Hz) baroreceptor in anesthetized Sprague-Dawley rats (n=10). Transfer function analysis was performed between stimulation and sympathetic nerve activity (central arc), sympathetic nerve activity and arterial pressure (peripheral arc), and stimulation and arterial pressure (Stim-AP arc). The central arc transfer function from nerve stimulation to splanchnic sympathetic nerve activity displayed derivative characteristics for both stimulation protocols. However, the modeled steady-state gain (0.28±0.04 vs. 4.01±0.2 %·Hz(-1), P<0.001) and coherence at 0.01Hz (0.44±0.05 vs. 0.81±0.03, P<0.05) were significantly lower for A-fibre stimulation compared with C-fibre stimulation. The slope of the dynamic gain was higher for A-fibre stimulation (14.82±1.02 vs. 7.21±0.79dB·decade(-1), P<0.001). The steady-state gain of the Stim-AP arc was also significantly lower for A-fibre stimulation compared with C-fibre stimulation (0.23±0.05 vs. 3.05±0.31mmHg·Hz(-1), P<0.001). These data indicate that the A-fibre central pathway contributes to high frequency arterial pressure regulation and the C-fibre central pathway provides more sustained changes in sympathetic nerve activity and arterial pressure. A sustained reduction in arterial pressure from electrical stimulation of arterial baroreceptor afferents is likely mediated through the C-fibre central pathway.
    Life sciences 04/2014; · 2.56 Impact Factor
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    ABSTRACT: Background: To identify a pharmacological agent that can selectively activate cardiac vagus nerve for potential use in vagal activation therapy against heart failure, the effects of medetomidine on autonomic nerve activities in both the heart and stomach were examined. Methods and Results: In anesthetized rabbits, microdialysis probes were implanted into both the right atrial and gastric walls. Dialysate acetylcholine (ACh) and norepinephrine (NE) concentrations were measured by high-performance liquid chromatography. First, the effects of 100μg/kg of intravenous medetomidine on vagal ACh and sympathetic NE releases were examined. Medetomidine significantly increased cardiac ACh release (4.7±1.1 to 7.8±0.9nmol/L, P<0.05), but suppressed gastric ACh release (8.0±2.6 to 3.5±1.5nmol/L, P<0.01). In contrast, medetomidine suppressed both cardiac and gastric NE releases. Second, the effects of medetomidine on ACh releases induced by electrical vagus nerve stimulation (VNS; 10Hz) were examined. Electrical VNS significantly increased both cardiac (6.7±1.2 to 14.8±1.8nmol/L, P<0.01) and gastric (3.8±0.8 to 181.3±65.6nmol/L, P<0.01) ACh releases. Medetomidine did not alter the VNS-induced increases in ACh release. Conclusions: Medetomidine suppresses both cardiac and gastric sympathetic nerve activities. In contrast, medetomidine activates cardiac vagus nerve but inhibits gastric vagal activity. Medetomidine might be one of the potential pharmacological agents for vagal activation therapy against heart failure without the risk of gastric adverse effects.
    Circulation Journal 04/2014; · 3.58 Impact Factor
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    ABSTRACT: We tested whether 6-week vagal stimulation (VS) treatment improved open-loop baroreflex function in rats after myocardial infarction (MI). The following three groups of Sprague-Dawley rats were examined: normal control (NC, n = 9), MI with no treatment (MI-NT, n = 8) and MI treated with VS (MI-VS, n = 7). Under anesthesia, a stepwise input ranging from 60 to 180 mmHg was imposed on isolated carotid sinus baroreceptor regions, while the responses in splanchnic sympathetic nerve activity (SNA) and arterial pressure (AP) were measured. The response range of percent SNA was greater in the MI-VS than in the MI-NT group (63.8 ± 4.9% vs. 33.1 ± 3.8%, P < 0.01). The slope of the AP response to percent SNA was not different between the MI-VS and MI-NT groups (0.611 ± 0.076 vs. 0.781 ± 0.057 mmHg/%). The difference in the response range of AP between the MI-VS and MI-NT groups did not reach statistical significance (40.7 ± 6.2 vs. 26.4 ± 3.5 mmHg). In conclusion, the 6-week VS treatment significantly improved the baroreflex control of SNA, but the effect was limited for the baroreflex total-loop function due to the lack of significant improvement in the AP response to percent SNA.
    Journal of Applied Physiology 03/2014; · 3.48 Impact Factor
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    ABSTRACT: Non-anastomotic graft rupture is a rare but critical complication after abdominal aortic aneurysm (AAA) repair. Therefore, identifying the rupture sites is important to perform endovascular stent grafting. A 78-year old man who had undergone Y-grafting for infrarenal AAA before 17 years was referred to our hospital with the complaints of abdominal pain. Computed tomography revealed acute pancreatitis and an enlargement around the grafted abdominal aorta. Contrast-enhanced ultrasonography revealed an extravazation from the graft body 1.5 cm distal to the proximal anastomosis, and endovascular stent grafting was successfully performed. Contrast-enhanced ultrasonography might be useful in detecting the graft rupture.
    Interactive Cardiovascular and Thoracic Surgery 11/2013; · 1.11 Impact Factor
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    ABSTRACT: Dynamic characteristics of arterial pressure (AP) regulation are important components in our understanding of rapid AP restoration by the arterial baroreflex system. The present study examined the effects of an L-type Ca(2+) channel blocker nifedipine on baroreflex-mediated dynamic AP regulation. In anesthetized and vagotomized rats, carotid sinus pressure was externally perturbed using a Gaussian white noise signal, and the neural arc transfer function from pressure input to efferent sympathetic nerve activity (SNA) and the peripheral arc transfer function from SNA to AP were identified. The peripheral arc transfer function approximated a second-order low-pass filter with pure dead time. Intravenous administration of nifedipine significantly decreased the steady-state gain and increased the damping ratio of the peripheral arc without affecting the dynamic characteristics of the neural arc. When the step response of AP was calculated based on the peripheral arc transfer function alone, nifedipine prolonged 80% rise time by 26%. When the closed-loop AP response was simulated based on both the neural arc and peripheral arc transfer functions and the dynamic gain of the baroreflex total loop was assumed to be 2.0, nifedipine prolonged 80% recovery time by 107%. In conclusion, L-type Ca(2+) channel blockade may compromise the baroreflex-mediated AP control not only in the magnitude but also in the speed of AP restoration.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 07/2013; 2013:3805-3808.
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    ABSTRACT: AIM: To examine whether sympathetic afferent stimulation (SAS) inhibits central vagal activation induced by α2 -adrenergic stimulation METHODS: In anaesthetized Wistar Kyoto rats, a cardiac microdialysis technique was applied to the left ventricle, and the effect of α2 -adrenergic stimulation by medetomidine on myocardial interstitial acetylcholine (ACh) levels was examined in the absence (n = 6) or the presence (n = 6) of SAS delivered from the left stellate ganglion. The effect of electrical vagal efferent stimulation on myocardial interstitial ACh release was also examined in the absence or the presence of SAS (n = 6). RESULTS: Intravenous medetomidine (0.1 mg·kg(-1) ) significantly increased myocardial interstitial ACh levels in the absence of SAS (from 1.95 ± 0.79 to 3.36 ± 1.61 nM, P < 0.05) but not in the presence of SAS (from 1.67 ± 0.67 to 2.01 ± 0.78 nM). In contrast, electrical vagal nerve stimulation increased myocardial interstitial ACh level to the same degree regardless of SAS (from 1.66 ± 0.16 to 3.93 ± 0.72 nM without SAS vs. 4.05 ± 0.89 nM with SAS). CONCLUSION: SAS inhibited medetomidine-induced ACh release but not electrical stimulation-induced ACh release, suggesting that SAS inhibited medetomidine-induced vagal activation via central mechanisms. While central vagal activation by α2 -adrenergic agonists could be an alternative to electrical vagal activation, blocking sympathetic afferent input may be important to increase the efficacy of α2 -adrenergic agonists in enhancing vagal nerve activity. This article is protected by copyright. All rights reserved.
    Acta Physiologica 05/2013; · 4.38 Impact Factor
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    ABSTRACT: AIMS: Cilnidipine is a unique Ca(2+) channel blocker that inhibits both L-type and N-type Ca(2+) channels. The present study aimed to assess the effects of intravenous cilnidipine on sympathetic outflow and sympathetic arterial pressure (AP) and heart rate (HR) regulations. MAIN METHODS: Carotid sinus baroreceptor regions were isolated from the systemic circulation in anesthetized and vagotomized Wistar Kyoto rats. Changes in efferent sympathetic nerve activity (SNA), AP and HR in response to a stepwise input of carotid sinus pressure were examined before and during intravenous cilnidipine administration (30 μg/kg bolus + 100 μg kg(-1)h(-1) infusion, n = 6). KEY FINDINGS: Cilnidipine significantly reduced the AP response range (from 68.0 ± 10.2 to 34.6 ± 4.1 mmHg, P = 0.007) but did not affect the SNA response range (from 90.4 ± 10.3 to 84.7 ± 9.5%, P = 0.297) or the HR response range (from 50.4 ± 10.1 to 48.1 ± 6.2 beats/min, P = 0.719). SIGNIFICANCE: Cilnidipine, at a depressor dose used in the present study, does not acutely suppress sympathetic outflow from the central nervous system. Also, it spared the sympathetic HR response, suggesting that N-type Ca(2+) channel blocking action at the cardiac sympathetic nerve endings may be a modest one.
    Life sciences 05/2013; · 2.56 Impact Factor
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    ABSTRACT: We applied a microdialysis technique to the left ventricular myocardium of anesthetized mice and tried to monitor acetylcholine (ACh) release from cardiac vagal nerves. Transection of bilateral cervical vagal nerves decreased dialysate ACh concentration. Electrical stimulation of the left cervical vagal nerve increased dialysate ACh concentration in proportion to the frequency of stimulation. Intravenous administration of hexamethonium, prevented the increase in dialysate ACh concentration during vagal nerve stimulation, indicating that ACh in the dialysate primarily reflects ACh released from post-ganglionic cardiac vagal nerves. Microdialysis permits monitoring of ACh release from post-ganglionic cardiac vagal nerves that are most likely to be innervating the left ventricle in mice.
    Autonomic neuroscience: basic & clinical 03/2013; · 1.82 Impact Factor
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    ABSTRACT: AIM: To examine whether dynamic characteristics of the peripheral vagal control of heart rate (HR) are altered in chronic heart failure (CHF). METHODS: The right vagal nerve was electrically stimulated according to a binary white noise signal, and the transfer function from vagal nerve stimulation (VNS) to HR was estimated in the frequency range from 0.01 to 1 Hz in five control rats and five CHF rats under anesthetized conditions. The rate of VNS was changed among 10, 20, and 40 Hz. RESULTS: A multiple linear regression analysis indicated that the increase in the VNS rate augmented the ratio of the high-frequency gain to the steady-state gain in the control group but not in the CHF group. As a result, the dynamic gain of the transfer function in the frequencies near 1 Hz decreased more in the CHF group than in the control group. CONCLUSION: Changes in the dynamic characteristics of the peripheral vagal control of HR may contribute to the manifestation of decreased high-frequency components of HR variability observed in CHF. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.
    Acta Physiologica 12/2012; · 4.38 Impact Factor
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    ABSTRACT: The dynamic characteristics of vagal heart rate control can be approximated by a first-order low-pass filter with pure dead time in rabbits. However, this model may not necessarily be the best approximation of the vagal transfer function of the heart rate control in rats, because a flatter portion exists in the gain plot above approximately 0.3 Hz. We developed a new model that includes a frequency-independent gain term to reproduce the flatter portion of the gain plot seen in the vagal transfer function in rats. The inclusion of the new term increased the coefficient of determination in an external validation of the linear regression relationship between measured and predicted heart rate responses to vagal stimulation, and made the slope of the regression line closer to unity. The parameters of mathematical transfer functions were determined in both the frequency and time domains. The frequency-domain fitting provided a set of parameters that was also able to reproduce the time-domain step response reasonably well. In contrast, the time-domain fitting provided a set of parameters that reproduced the frequency-domain transfer function only up to 0.2 Hz. Determination of proper model parameters was crucial for the development of a new model to describe the dynamic heart rate response to vagal stimulation in rats.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2012; 2012:3809-12.
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    ABSTRACT: Intravenous leiomyomatosis is a benign smooth muscle tumor that sometimes spreads to the right heart via the inferior vena cava. A complete surgical resection is necessary to ensure its successful treatment. Surgical removal has been performed safely in middle-aged patients. Here we report a case of successful surgical removal in an elderly woman (age 81 years). The woman was admitted with palpitation and diagnosed as having an intravenous leiomyomatosis with cardiac extension. She underwent a one-stage surgical removal with cardiopulmonary bypass and circulatory arrest. We therefore recommend a one-stage operation, if possible, even in elderly patients.
    General Thoracic and Cardiovascular Surgery 03/2012; 60(3):153-6.
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    ABSTRACT: Although α(2)-adrenergic agonists have been reported to induce a vagal-dominant condition through suppression of sympathetic nerve activity, there is little direct evidence that they directly increase cardiac vagal nerve activity. Using a cardiac microdialysis technique, we investigated the effects of medetomidine, an α(2)-adrenergic agonist, on norepinephrine (NE) and acetylcholine (ACh) release from cardiac nerve endings. A microdialysis probe was implanted into the right atrial wall near the sinoatrial node in anesthetized rabbits and perfused with Ringer's solution containing eserine. Dialysate NE and ACh concentrations were measured using high-performance liquid chromatography. Both 10 and 100µg/kg of intravenous medetomidine significantly decreased mean blood pressure (BP) and the dialysate NE concentration, but only 100µg/kg of medetomidine enhanced ACh release. Combined administration of medetomidine and phenylephrine maintained mean BP at baseline level, and augmented the medetomidine-induced ACh release. When we varied the mean BP using intravenous administration of phenylephrine, treatment with medetomidine significantly steepened the slope of the regression line between mean BP and log ACh concentration. Medetomidine increased ACh release from cardiac vagal nerve endings and augmented baroreflex control of vagal nerve activity.
    Circulation Journal 01/2012; 76(1):152-9. · 3.58 Impact Factor
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    ABSTRACT: When the Norwood procedure is conducted for the hypoplastic left heart syndrome using a non-valved right ventricle (RV) to pulmonary artery (PA) shunt, diastolic regurgitation from PA to RV may have an adverse effect on postoperative hemodynamics. In this study, we examined the impact of the diastolic regurgitation on ventricular energetics by computational analysis using a combination of a time-varying elastance chamber model and a modified three-element Windkessel vascular model. This study revealed that use of the valved or non-valved RV-PA shunt eliminated pulmonary over-circulation which was observed when using the systemic to pulmonary artery shunt (modified Blalock-Taussig shunt). Although the valved RV-PA shunt improved pulmonary blood supply and consequently increased pulmonary artery flow and oxygen saturation compared to the non-valved RV-PA shunt, the non-valved RV-PA shunt improved ventricular energetics in spite of the presence of PA to RV regurgitation.
    The Journal of Physiological Sciences 08/2011; 61(6):457-65. · 1.09 Impact Factor
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    ABSTRACT: To examine whether moderate efferent vagal nerve stimulation (VNS) attenuates the carotid sinus baroreflex-mediated arterial pressure (AP) regulation via its antagonism to the sympathetic system. Carotid sinus baroreceptor regions were isolated from the systemic circulation in eight anesthetized and vagotomized rats. A staircase-wise input was imposed on carotid sinus pressure (CSP) with or without efferent VNS (20Hz, 2ms, 1-4V), while the responses in AP, heart rate (HR), and splanchnic sympathetic nerve activity (SNA) were measured. A multiple linear regression analysis indicated that VNS decreased the minimum HR in the CSP-HR relationship by 58.2±4.9 beats/min (P<0.01) from its reference value of 387.0±5.8 beats/min. Although VNS significantly decreased an intercept of the SNA-AP relationship, it did not affect parameters of the CSP-AP relationship or the CSP-SNA relationship significantly. The operating-point AP of the baroreflex was decreased by 2.8±1.0mmHg (P<0.01) during VNS, which was less than 3% of the reference value of 117.7±1.2mmHg. VNS, at an intensity of decreasing HR by approximately 13%, does not acutely attenuate the baroreflex-mediated sympathetic AP regulation.
    Life sciences 08/2011; 89(13-14):498-503. · 2.56 Impact Factor
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    ABSTRACT: The carotid sinus baroreflex is one of the most important negative feedback systems to stabilize arterial pressure. Although static characteristics of the carotid sinus baroreflex can be assessed by using a stepwise input protocol under baroreflex open-loop conditions, the step duration has been determined empirically. In the present study, we examined the effects of different time windows (5-10, 15-20, 25-30, 35-40, 45-50, and 55-60 s) on the static characteristics estimated by using a 60-s stepwise input protocol in 10 anesthetized rats. Based on the results, we compared the static characteristics between actual 60-s and 20-s stepwise input protocols. Most of the parameters of the static characteristics did not differ significantly between the 60-s and 20-s stepwise input protocols, suggesting that the open-loop baroreflex static characteristics can be estimated by using a stepwise input with the step duration as short as 20 s in normal rats.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2011; 2011:689-92.
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    ABSTRACT: Although central ghrelin has cardioprotective effect through inhibiting sympathetic nerve activity, the effects of central ghrelin on cardiac vagal nerve remain unknown. We investigated the effects of centrally administered ghrelin on cardiac autonomic nerve activities using microdialysis technique. A microdialysis probe was implanted in the right atrial wall adjacent to the sinoatrial node of an anesthetized rabbit and was perfused with Ringer's solution containing a cholinesterase inhibitor, eserine. After injection of ghrelin (1 nmol) into the right lateral cerebral ventricle, norepinephrine (NE) and acetylcholine (ACh) concentrations in the dialysate samples were measured as indices of NE and ACh release from nerve endings to the sinoatrial node using high-performance liquid chromatography. Heart rate was 270±4 bpm at baseline and decreased gradually after ghrelin injection to 234±9 bpm (P<0.01) at 60-80 min, followed by gradual recovery. Dialysate ACh concentration was 5.5±0.8 nM at baseline and increased gradually after ghrelin injection to 8.8±1.2 nM (P<0.01) at 60-80 min; the concentration started to decrease gradually from 100 to 120 min after injection reaching 5.6±0.8 nM at 160-180 min. Central ghrelin did not change mean arterial pressure or dialysate NE concentration. The elevated dialysate ACh concentration declined rapidly after transection of cervical vagal nerves. These results indicate that centrally administered ghrelin activates cardiac vagal nerve.
    Autonomic neuroscience: basic & clinical 07/2011; 162(1-2):60-5. · 1.82 Impact Factor
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    ABSTRACT: Although the dynamic characteristics of the baroreflex system have been described by baroreflex transfer functions obtained from open-loop analysis, the predictability of time-series output dynamics from input signals, which should confirm the accuracy of system identification, remains to be elucidated. Moreover, despite theoretical concerns over closed-loop system identification, the accuracy and the predictability of the closed-loop spontaneous baroreflex transfer function have not been evaluated compared with the open-loop transfer function. Using urethane and α-chloralose anaesthetized, vagotomized and aortic-denervated rabbits (n = 10), we identified open-loop baroreflex transfer functions by recording renal sympathetic nerve activity (SNA) while varying the vascularly isolated intracarotid sinus pressure (CSP) according to a binary random (white-noise) sequence (operating pressure ± 20 mmHg), and using a simplified equation to calculate closed-loop-spontaneous baroreflex transfer function while matching CSP with systemic arterial pressure (AP). Our results showed that the open-loop baroreflex transfer functions for the neural and peripheral arcs predicted the time-series SNA and AP outputs from measured CSP and SNA inputs, with r2 of 0.8 ± 0.1 and 0.8 ± 0.1, respectively. In contrast, the closed-loop-spontaneous baroreflex transfer function for the neural arc was markedly different from the open-loop transfer function (enhanced gain increase and a phase lead), and did not predict the time-series SNA dynamics (r2; 0.1 ± 0.1). However, the closed-loop-spontaneous baroreflex transfer function of the peripheral arc partially matched the open-loop transfer function in gain and phase functions, and had limited but reasonable predictability of the time-series AP dynamics (r2, 0.7 ± 0.1). A numerical simulation suggested that a noise predominantly in the neural arc under resting conditions might be a possible mechanism responsible for our findings. Furthermore, the predictabilities of the neural arc transfer functions obtained in open-loop and closed-loop conditions were validated by closed-loop pharmacological (phenylephrine and nitroprusside infusions) pressure interventions. Time-series SNA responses to drug-induced AP changes predicted by the open-loop transfer function matched closely the measured responses (r2, 0.9 ± 0.1), whereas SNA responses predicted by closed-loop-spontaneous transfer function deviated greatly and were the inverse of measured responses (r, −0.8 ± 0.2). These results indicate that although the spontaneous baroreflex transfer function obtained by closed-loop analysis has been believed to represent the neural arc function, it is inappropriate for system identification of the neural arc but is essentially appropriate for the peripheral arc under resting conditions, when compared with open-loop analysis.
    The Journal of Physiology 04/2011; 589(Pt 7):1769-90. · 4.38 Impact Factor

Publication Stats

136 Citations
106.90 Total Impact Points

Institutions

  • 2007–2014
    • National Cerebral and Cardiovascular Center
      • Department of Cardiovascular Medicine
      Ōsaka, Ōsaka, Japan
  • 2013
    • Kinki University
      • Department of Cardiology
      Ōsaka, Ōsaka, Japan
  • 2010–2011
    • University of Texas Southwestern Medical Center
      • Department of Physical Therapy
      Dallas, TX, United States