Can Zheng - Academia.edu (original) (raw)

Papers by Can Zheng

Circulation, 2006

Background— We proposed a novel therapeutic strategy against central baroreflex failure: implemen... more Background— We proposed a novel therapeutic strategy against central baroreflex failure: implementation of an artificial baroreflex system to automatically regulate sympathetic vasomotor tone, ie, a bionic baroreflex system (BBS), and we tested its efficacy in a model of sudden hypotension during surgery. Methods and Results— The BBS consisted of a computer-controlled negative-feedback circuit that sensed arterial pressure (AP) and automatically computed the frequency (STM) of a pulse train required to stimulate sympathetic nerves via an epidural catheter placed at the level of the lower thoracic spinal cord. An operation rule was subsequently designed for the BBS using a feedback correction with proportional and integral gain factors. The transfer function from STM to AP was identified by a white noise system identification method in 12 sevoflurane-anesthetized patients undergoing orthopedic surgery involving the cervical vertebrae, and the feedback correction factors were determin...

Circulation Journal Official Journal of the Japanese Circulation Society, Mar 1, 2008

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2007

Contribution of abnormal cardiovascular regulation to the maintenance and progression of heart fa... more Contribution of abnormal cardiovascular regulation to the maintenance and progression of heart failure has been repeatedly demonstrated. Besides the current therapeutic modalities, development of an additional therapeutic strategy is needed. We have been developing a bionic system, an artificial device designed for integration into native physiological systems. By communicating with the physiological regulatory system, we tried to not only restore lost function but also correct abnormal function. We have already shown that modification of autonomic balance by direct electrical vagal stimulation has inhibited cardiac remodeling, and improved survival in rats. Because the benefit of the correction of autonomic balance would be greatly enhanced if available by a less invasive method, we examined the possibility of modifying the autonomic balance by electrical acupuncture. The results indicated that electrical acupuncture resets the neural arc of the arterial baroreflex (SNA response ra...

The Journal of Physiology, 2005

Since humans are under ceaseless orthostatic stress, the mechanism to maintain arterial pressure ... more Since humans are under ceaseless orthostatic stress, the mechanism to maintain arterial pressure (AP) under orthostatic stress against gravitational fluid shift is of great importance. We hypothesized that (1) orthostatic stress resets the arterial baroreflex control of sympathetic nerve activity (SNA) to a higher SNA, and (2) resetting of the arterial baroreflex contributes to preventing postural hypotension. Renal SNA and AP were recorded in eight anaesthetized, vagotomized and aortic-denervated rabbits. Isolated intracarotid sinus pressure (CSP) was increased stepwise from 40 to 160 mmHg with increments of 20 mmHg (60 s for each CSP level) while the animal was placed supine and at 60 deg upright tilt. Upright tilt shifted the CSP-SNA relationship (the baroreflex neural arc) to a higher SNA, shifted the SNA-AP relationship (the baroreflex peripheral arc) to a lower AP, and consequently moved the operating point to marked high SNA while maintaining AP. A simulation study suggests that resetting in the neural arc would double the orthostatic activation of SNA and increase the operating AP in upright tilt by 10 mmHg, compared with the absence of resetting. In addition, upright tilt did not change the CSP-AP relationship (the baroreflex total arc). A simulation study suggests that although a downward shift of the peripheral arc could shift the total arc downward, resetting in the neural arc would compensate this fall and prevent the total arc from shifting downward to a lower AP. In conclusion, upright tilt increases SNA by resetting the baroreflex neural arc. This resetting may compensate for the reduced pressor responses to SNA in the peripheral cardiovascular system and contribute to preventing postural hypotension.

The Japanese Journal of Physiology, 2002

The conductance catheter technique, a real-time ventricular volumetry method, is essential in the... more The conductance catheter technique, a real-time ventricular volumetry method, is essential in the experimental and clinical application of the ventricular pressure-volume relationship framework [1-7]. The principles of conductance volumetry are described extensively elsewhere [1, 2]. The sum (G) of ventricular conductance signals between electrode pairs can be converted to the absolute ventricular volume (V) by the formula where ␣ is a volume calibration factor, L is the distance between the recording electrodes, is the blood conductivity, and G p is the conductance resulting from the surrounding structures (i.e., parallel conductance). Although the volume calibration factor is reported to be relatively constant [8], excessive changes in plasma electrolyte concentration, hematocrit, or tissue fluid contents, which are often observed during cardiac surgery, can alter blood conductivity and parallel conductance. This is also the case with the progression of chronic heart failure. Therefore, for the accurate estimation of ventricular volume, it is necessary to repeat calibrations for these quantities by blood V L

The Japanese Journal of Physiology, 2002

The arterial baroreflex is a negative feedback system essential to maintaining arterial pressure ... more The arterial baroreflex is a negative feedback system essential to maintaining arterial pressure (AP) against exogenous pressure perturbations. The total buffering capacity of the arterial baroreflex can be most precisely evaluated by the baroreflex open-loop gain (G Baro). In animal experiments, G Baro can be estimated over the entire operating range by imposing desired pressure inputs on isolated baroreceptor regions and observing the AP responses [1-10]. Although this open-loop analysis is theoretically straightforward, it has the practical drawback that the isolation of baroreceptor regions is difficult, if not impossible, in conscious animals [11]. Furthermore, the invasive technique is not applicable to clinical settings. When G Baro is evaluated around a physiological operating point, the problem associated with the open-loop analysis may be resolved by estimating G Baro from closed-loop perturbations. These perturbations are classified into two types, depending on the site at which the disturbance is introduced [12]. The first type of pressure disturbance (P D1) is applied to the baroreceptors without a direct effect on AP (Fig. 1A). The neck suction procedure is an example of P D1. The second type (P D2) initially affects AP, then changes in AP induce reflex compensatory responses (Fig. 1B). P D2 includes hemorrhage, lower body negative pressure (LBNP), and body tilting. Both P D1 and P D2 are equally effective as inputs to estimate G Baro if the absolute magnitudes of P D1 and P D2 are known (see APPENDIX, Eqs. A1b and A2b). In reality, P D1 and P D2 are not always measurable. For instance, P D1 during neck suction depends not only on the negative pressure around the neck, but also on the pressure transduction from the neck to the perivascu

Journal of Cardiac Failure, 2010

Vagal nerve stimulation (VS) has been suggested to be an effective adjunct to reperfusion therapy... more Vagal nerve stimulation (VS) has been suggested to be an effective adjunct to reperfusion therapy in myocardial infarction (MI). However, the effect of VS on left ventricular (LV) remodeling after reperfused MI has not been examined. We investigated the effects of early, brief VS on acute inflammatory reactions (study 1) and chronic LV remodeling (study 2) in a rabbit model of reperfused MI. In study 1, rabbits were subjected to 60-minute coronary artery occlusion followed by reperfusion alone (MI, n = 8) or treated with 24-hour VS (MI-VS, n = 8). At 24 hours after ischemia-reperfusion, MI-VS rabbits showed significantly decreased myocardial infiltration of neutrophils and reduced myocardial expressions of tumor necrosis factor-alpha and matrix metalloproteinase-8 and -9, compared with MI rabbits. Myocardial expression of interleukin-6 was not affected by VS. In study 2, rabbits were subjected to coronary occlusion and reperfusion alone (n = 16) or treated with VS for 3 days (n = 14). At 8 weeks after ischemia-reperfusion, MI-VS rabbits showed significantly improved LV dysfunction and dilatation, and significantly reduced infarct size, infarct wall thinning, and LV weight compared with MI rabbits. Early, short-term VS attenuates LV remodeling after reperfused MI, which may be associated with suppression of acute inflammatory reactions.

Journal of Applied Physiology, 2004

A bionic baroreflex system (BBS) is a computer-assisted intelligent feedback system to control ar... more A bionic baroreflex system (BBS) is a computer-assisted intelligent feedback system to control arterial pressure (AP) for the treatment of baroreflex failure. To apply this system clinically, an appropriate efferent neural (sympathetic vasomotor) interface has to be explored. We examined whether the spinal cord is a candidate site for such interface. In six anesthetized and baroreflex-deafferentiated cats, a multielectrode catheter was inserted into the epidural space to deliver epidural spinal cord stimulation (ESCS). Stepwise changes in ESCS rate revealed a linear correlation between ESCS rate and AP for ESCS rates of 2 pulses/s and above ( r2, 0.876–0.979; slope, 14.3 ± 5.8 mmHg·pulses−1·s; pressure axis intercept, 35.7 ± 25.9 mmHg). Random changes in ESCS rate with a white noise sequence revealed dynamic transfer function of peripheral effectors. The transfer function resembled a second-order, low-pass filter with a lag time (gain, 16.7 ± 8.3 mmHg·pulses−1·s; natural frequency, ...

AJP: Heart and Circulatory Physiology, 2007

Although ANG II exerts a variety of effects on the cardiovascular system, its effects on the peri... more Although ANG II exerts a variety of effects on the cardiovascular system, its effects on the peripheral parasympathetic neurotransmission have only been evaluated by changes in heart rate (an effect on the sinus node). To elucidate the effect of ANG II on the parasympathetic neurotransmission in the left ventricle, we measured myocardial interstitial ACh release in response to vagal stimulation (1 ms, 10 V, 20 Hz) using cardiac microdialysis in anesthetized cats. In a control group ( n = 6), vagal stimulation increased the ACh level from 0.85 ± 0.03 to 10.7 ± 1.0 (SE) nM. Intravenous administration of ANG II at 10 μg·kg−1·h−1 suppressed the stimulation-induced ACh release to 7.5 ± 0.6 nM ( P < 0.01). In a group with pretreatment of intravenous ANG II receptor subtype 1 (AT1 receptor) blocker losartan (10 mg/kg, n = 6), ANG II was unable to inhibit the stimulation-induced ACh release (8.6 ± 1.5 vs. 8.4 ± 1.7 nM). In contrast, in a group with local administration of losartan (10 mM...

The Journal of Physiological Sciences, 2009

In an earlier study we demonstrated the beneficial effect of direct vagal electrical stimulation ... more In an earlier study we demonstrated the beneficial effect of direct vagal electrical stimulation on cardiac remodeling and survival. In the study reported here, we attempted to reproduce the effect of vagal enhancement through the administration of an acetylcholinesterase inhibitor, donepezil. A rat model of heart failure following extensive healed myocardial infarction was used. Compared to their nontreated counterparts, rats given donepezil (5 mg/kg/day) in their drinking water had a smaller biventricular weight (3.40 ± 0.13 vs. 3.02 ± 0.21 g/kg body weight, P \ 0.05), and maximal rate of rise (3256 ± 955 vs. 3822 ± 389 mmHg/s, P \ 0.05) and the end-diastolic value (30.1 ± 5.6 vs. 23.2 ± 5.7 mmHg, P \ 0.05) of left ventricular pressure were improved. Neurohumoral factors were suppressed in donepezil-treated rats (norepinephrine 1885 ± 1423 vs. 316 ± 248 pg/ml, P \ 0.01; brain natriuretic peptide 457 ± 68 vs. 362 ± 80 ng/ml, P \ 0.05), and the high-frequency component of heart rate variability showed a nocturnal increase. These findings indicated that donepezil reproduced the anti-remodeling effect of electrical vagal stimulation. Further studies are warranted to evaluate the clinical usefulness of donepezil in heart failure.

Physiological Reports

Fluid retention is the main reason for the high hospitalization rate among patients with chronic ... more Fluid retention is the main reason for the high hospitalization rate among patients with chronic heart failure (CHF). Given the lack of knowledge about fluid intake regulation and its consequences in patients with CHF, current guidelines do not provide clear direction for fluid management. Using a rat model of CHF, we investigated altering drinking behaviors and explored fluid management strategies. CHF was induced by ligating the left anterior descending coronary arteries in 8-week-old, male, Sprague-Dawley rats. A customdesigned drop counting and feedback control system was used to record and modulate drinking behaviors. During the first month after an induced myocardial infarction (MI), we observed that the spontaneous per drinking volume (PDV) was significantly increased in animals with prolonged intervals between drinking episodes. In addition, there was a significant inverse correlation between the early PDV and the post-MI lifespan (r = À0.907; P < 0.001). Moreover, modulating the drinking behavior of rats with CHF to involve frequent drinking of small PDVs significantly enhanced hemodynamics and prevented cardiac remodeling, with a significant improvement in the 180-day survival rate, compared with animals allowed to drink freely (50% vs. 36%; P < 0.01). The results of dynamic PDV changes, after MI, suggest that an impaired thirst mechanism is associated with the sensing and regulating of fluid balance in rats with CHF. These results suggest that increasing the drinking frequency, with small PDVs, may be beneficial to preventing progression of cardiac dysfunction in CHF.

The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society

 We examined the applicability of a sieve electrode to the autonomic nervous system as a potenti... more  We examined the applicability of a sieve electrode to the autonomic nervous system as a potential neural interface for bionic medicine. We developed, using a Sisemiconductor process, a sieve electrode having a square diaphragm (1 mm in one side, 12 µm in thickness) with 30-81 penetrating square holes (50-100 µm in one side). In the first protocol, we implanted the sieve electrode to the vagal nerve in rats. One hundred and twenty days after the implantation, cuff electrodes were attached to the vagal nerve proximal and distal to the sieve electrode under halothane anesthesia. The evoked action potential was recorded from the sieve electrode by nerve stimulation via the cuff electrodes. The evoked action potential was also recorded from the cuff electrodes by nerve stimulation via the sieve electrode. In the second protocol, we implanted the sieve electrode to the renal sympathetic nerve in rabbits. Forty days after the implantation, the spontaneous action potential or sympathetic nerve activity was recorded under pentobarbital anesthesia. In conclusion, we were able to record the evoked and spontaneous action potentials using the sieve electrode. The sieve electrode will provide a useful neural interface for recording and stimulating the autonomic nervous system.

報告番号: 甲14455 ; 学位授与年月日: 1999-03-29 ; 学位の種別: 課程博士 ; 学位の種類: 博士(獣医学) ; 学位記番号: 博農第2063号 ; 研究科・専攻: 農学生... more 報告番号: 甲14455 ; 学位授与年月日: 1999-03-29 ; 学位の種別: 課程博士 ; 学位の種類: 博士(獣医学) ; 学位記番号: 博農第2063号 ; 研究科・専攻: 農学生命科学研究科獣医学専攻

The arterial baroreflex system may be divided into the neural arc (from pressure input to efferen... more The arterial baroreflex system may be divided into the neural arc (from pressure input to efferent sympathetic nerve activity) and the peripheral arc (from sympathetic nerve activity to arterial pressure). In rabbits, the baroreflex neural arc reveals derivative characteristics in the frequency range below 0.8 Hz and high-cut characteristics above 0.8 Hz. To examine such high-cut characteristics are also present in rats, we isolated the carotid sinus regions in anesthetized rats (n = 5) and imposed a Gaussian white noise input with a switching interval of 50 ms. The transfer function of the baroreflex neural arc showed derivative characteristics in the frequency range from 0.1 to 1.3 Hz and high-cut characteristics above 1.3 Hz in rats. These results indicate that the baroreflex neural arc possesses high-cut characteristics in rats as well as in rabbits, which may contribute to preserving baroreflex gain against pulsatile pressure.

Japanese Circulation Journal-english Edition, 2007

Japanese Circulation Journal-english Edition, 2008

Our previous study indicated that intravenously administered ivabradine (IVA) augmented the dynam... more Our previous study indicated that intravenously administered ivabradine (IVA) augmented the dynamic heart rate (HR) response to moderate-intensity vagal nerve stimulation (VNS). Considering an accentuated antagonism, the results were somewhat paradoxical; i.e., the accentuated antagonism indicates that an activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels via the accumulation of intracellular cyclic adenosine monophosphate (cAMP) augments the HR response to VNS, whereas the inhibition of HCN channels by IVA also augmented the HR response to VNS. To remove the possible influence from the accentuated antagonism, we examined the effects of IVA on the dynamic vagal control of HR under beta-blockade. In anesthetized rats (n = 7), the right vagal nerve was stimulated for 10 min according to binary white noise signals between 0 and 10 Hz (V0-10), between 0 and 20 Hz (V0-20), and between 0 and 40 Hz (V0-40). The transfer function from VNS to HR was estimated. U...

Circulation, 2006

Background— We proposed a novel therapeutic strategy against central baroreflex failure: implemen... more Background— We proposed a novel therapeutic strategy against central baroreflex failure: implementation of an artificial baroreflex system to automatically regulate sympathetic vasomotor tone, ie, a bionic baroreflex system (BBS), and we tested its efficacy in a model of sudden hypotension during surgery. Methods and Results— The BBS consisted of a computer-controlled negative-feedback circuit that sensed arterial pressure (AP) and automatically computed the frequency (STM) of a pulse train required to stimulate sympathetic nerves via an epidural catheter placed at the level of the lower thoracic spinal cord. An operation rule was subsequently designed for the BBS using a feedback correction with proportional and integral gain factors. The transfer function from STM to AP was identified by a white noise system identification method in 12 sevoflurane-anesthetized patients undergoing orthopedic surgery involving the cervical vertebrae, and the feedback correction factors were determin...

Circulation Journal Official Journal of the Japanese Circulation Society, Mar 1, 2008

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2007

Contribution of abnormal cardiovascular regulation to the maintenance and progression of heart fa... more Contribution of abnormal cardiovascular regulation to the maintenance and progression of heart failure has been repeatedly demonstrated. Besides the current therapeutic modalities, development of an additional therapeutic strategy is needed. We have been developing a bionic system, an artificial device designed for integration into native physiological systems. By communicating with the physiological regulatory system, we tried to not only restore lost function but also correct abnormal function. We have already shown that modification of autonomic balance by direct electrical vagal stimulation has inhibited cardiac remodeling, and improved survival in rats. Because the benefit of the correction of autonomic balance would be greatly enhanced if available by a less invasive method, we examined the possibility of modifying the autonomic balance by electrical acupuncture. The results indicated that electrical acupuncture resets the neural arc of the arterial baroreflex (SNA response ra...

The Journal of Physiology, 2005

Since humans are under ceaseless orthostatic stress, the mechanism to maintain arterial pressure ... more Since humans are under ceaseless orthostatic stress, the mechanism to maintain arterial pressure (AP) under orthostatic stress against gravitational fluid shift is of great importance. We hypothesized that (1) orthostatic stress resets the arterial baroreflex control of sympathetic nerve activity (SNA) to a higher SNA, and (2) resetting of the arterial baroreflex contributes to preventing postural hypotension. Renal SNA and AP were recorded in eight anaesthetized, vagotomized and aortic-denervated rabbits. Isolated intracarotid sinus pressure (CSP) was increased stepwise from 40 to 160 mmHg with increments of 20 mmHg (60 s for each CSP level) while the animal was placed supine and at 60 deg upright tilt. Upright tilt shifted the CSP-SNA relationship (the baroreflex neural arc) to a higher SNA, shifted the SNA-AP relationship (the baroreflex peripheral arc) to a lower AP, and consequently moved the operating point to marked high SNA while maintaining AP. A simulation study suggests that resetting in the neural arc would double the orthostatic activation of SNA and increase the operating AP in upright tilt by 10 mmHg, compared with the absence of resetting. In addition, upright tilt did not change the CSP-AP relationship (the baroreflex total arc). A simulation study suggests that although a downward shift of the peripheral arc could shift the total arc downward, resetting in the neural arc would compensate this fall and prevent the total arc from shifting downward to a lower AP. In conclusion, upright tilt increases SNA by resetting the baroreflex neural arc. This resetting may compensate for the reduced pressor responses to SNA in the peripheral cardiovascular system and contribute to preventing postural hypotension.

The Japanese Journal of Physiology, 2002

The conductance catheter technique, a real-time ventricular volumetry method, is essential in the... more The conductance catheter technique, a real-time ventricular volumetry method, is essential in the experimental and clinical application of the ventricular pressure-volume relationship framework [1-7]. The principles of conductance volumetry are described extensively elsewhere [1, 2]. The sum (G) of ventricular conductance signals between electrode pairs can be converted to the absolute ventricular volume (V) by the formula where ␣ is a volume calibration factor, L is the distance between the recording electrodes, is the blood conductivity, and G p is the conductance resulting from the surrounding structures (i.e., parallel conductance). Although the volume calibration factor is reported to be relatively constant [8], excessive changes in plasma electrolyte concentration, hematocrit, or tissue fluid contents, which are often observed during cardiac surgery, can alter blood conductivity and parallel conductance. This is also the case with the progression of chronic heart failure. Therefore, for the accurate estimation of ventricular volume, it is necessary to repeat calibrations for these quantities by blood V L

The Japanese Journal of Physiology, 2002

The arterial baroreflex is a negative feedback system essential to maintaining arterial pressure ... more The arterial baroreflex is a negative feedback system essential to maintaining arterial pressure (AP) against exogenous pressure perturbations. The total buffering capacity of the arterial baroreflex can be most precisely evaluated by the baroreflex open-loop gain (G Baro). In animal experiments, G Baro can be estimated over the entire operating range by imposing desired pressure inputs on isolated baroreceptor regions and observing the AP responses [1-10]. Although this open-loop analysis is theoretically straightforward, it has the practical drawback that the isolation of baroreceptor regions is difficult, if not impossible, in conscious animals [11]. Furthermore, the invasive technique is not applicable to clinical settings. When G Baro is evaluated around a physiological operating point, the problem associated with the open-loop analysis may be resolved by estimating G Baro from closed-loop perturbations. These perturbations are classified into two types, depending on the site at which the disturbance is introduced [12]. The first type of pressure disturbance (P D1) is applied to the baroreceptors without a direct effect on AP (Fig. 1A). The neck suction procedure is an example of P D1. The second type (P D2) initially affects AP, then changes in AP induce reflex compensatory responses (Fig. 1B). P D2 includes hemorrhage, lower body negative pressure (LBNP), and body tilting. Both P D1 and P D2 are equally effective as inputs to estimate G Baro if the absolute magnitudes of P D1 and P D2 are known (see APPENDIX, Eqs. A1b and A2b). In reality, P D1 and P D2 are not always measurable. For instance, P D1 during neck suction depends not only on the negative pressure around the neck, but also on the pressure transduction from the neck to the perivascu

Journal of Cardiac Failure, 2010

Vagal nerve stimulation (VS) has been suggested to be an effective adjunct to reperfusion therapy... more Vagal nerve stimulation (VS) has been suggested to be an effective adjunct to reperfusion therapy in myocardial infarction (MI). However, the effect of VS on left ventricular (LV) remodeling after reperfused MI has not been examined. We investigated the effects of early, brief VS on acute inflammatory reactions (study 1) and chronic LV remodeling (study 2) in a rabbit model of reperfused MI. In study 1, rabbits were subjected to 60-minute coronary artery occlusion followed by reperfusion alone (MI, n = 8) or treated with 24-hour VS (MI-VS, n = 8). At 24 hours after ischemia-reperfusion, MI-VS rabbits showed significantly decreased myocardial infiltration of neutrophils and reduced myocardial expressions of tumor necrosis factor-alpha and matrix metalloproteinase-8 and -9, compared with MI rabbits. Myocardial expression of interleukin-6 was not affected by VS. In study 2, rabbits were subjected to coronary occlusion and reperfusion alone (n = 16) or treated with VS for 3 days (n = 14). At 8 weeks after ischemia-reperfusion, MI-VS rabbits showed significantly improved LV dysfunction and dilatation, and significantly reduced infarct size, infarct wall thinning, and LV weight compared with MI rabbits. Early, short-term VS attenuates LV remodeling after reperfused MI, which may be associated with suppression of acute inflammatory reactions.

Journal of Applied Physiology, 2004

A bionic baroreflex system (BBS) is a computer-assisted intelligent feedback system to control ar... more A bionic baroreflex system (BBS) is a computer-assisted intelligent feedback system to control arterial pressure (AP) for the treatment of baroreflex failure. To apply this system clinically, an appropriate efferent neural (sympathetic vasomotor) interface has to be explored. We examined whether the spinal cord is a candidate site for such interface. In six anesthetized and baroreflex-deafferentiated cats, a multielectrode catheter was inserted into the epidural space to deliver epidural spinal cord stimulation (ESCS). Stepwise changes in ESCS rate revealed a linear correlation between ESCS rate and AP for ESCS rates of 2 pulses/s and above ( r2, 0.876–0.979; slope, 14.3 ± 5.8 mmHg·pulses−1·s; pressure axis intercept, 35.7 ± 25.9 mmHg). Random changes in ESCS rate with a white noise sequence revealed dynamic transfer function of peripheral effectors. The transfer function resembled a second-order, low-pass filter with a lag time (gain, 16.7 ± 8.3 mmHg·pulses−1·s; natural frequency, ...

AJP: Heart and Circulatory Physiology, 2007

Although ANG II exerts a variety of effects on the cardiovascular system, its effects on the peri... more Although ANG II exerts a variety of effects on the cardiovascular system, its effects on the peripheral parasympathetic neurotransmission have only been evaluated by changes in heart rate (an effect on the sinus node). To elucidate the effect of ANG II on the parasympathetic neurotransmission in the left ventricle, we measured myocardial interstitial ACh release in response to vagal stimulation (1 ms, 10 V, 20 Hz) using cardiac microdialysis in anesthetized cats. In a control group ( n = 6), vagal stimulation increased the ACh level from 0.85 ± 0.03 to 10.7 ± 1.0 (SE) nM. Intravenous administration of ANG II at 10 μg·kg−1·h−1 suppressed the stimulation-induced ACh release to 7.5 ± 0.6 nM ( P < 0.01). In a group with pretreatment of intravenous ANG II receptor subtype 1 (AT1 receptor) blocker losartan (10 mg/kg, n = 6), ANG II was unable to inhibit the stimulation-induced ACh release (8.6 ± 1.5 vs. 8.4 ± 1.7 nM). In contrast, in a group with local administration of losartan (10 mM...

The Journal of Physiological Sciences, 2009

In an earlier study we demonstrated the beneficial effect of direct vagal electrical stimulation ... more In an earlier study we demonstrated the beneficial effect of direct vagal electrical stimulation on cardiac remodeling and survival. In the study reported here, we attempted to reproduce the effect of vagal enhancement through the administration of an acetylcholinesterase inhibitor, donepezil. A rat model of heart failure following extensive healed myocardial infarction was used. Compared to their nontreated counterparts, rats given donepezil (5 mg/kg/day) in their drinking water had a smaller biventricular weight (3.40 ± 0.13 vs. 3.02 ± 0.21 g/kg body weight, P \ 0.05), and maximal rate of rise (3256 ± 955 vs. 3822 ± 389 mmHg/s, P \ 0.05) and the end-diastolic value (30.1 ± 5.6 vs. 23.2 ± 5.7 mmHg, P \ 0.05) of left ventricular pressure were improved. Neurohumoral factors were suppressed in donepezil-treated rats (norepinephrine 1885 ± 1423 vs. 316 ± 248 pg/ml, P \ 0.01; brain natriuretic peptide 457 ± 68 vs. 362 ± 80 ng/ml, P \ 0.05), and the high-frequency component of heart rate variability showed a nocturnal increase. These findings indicated that donepezil reproduced the anti-remodeling effect of electrical vagal stimulation. Further studies are warranted to evaluate the clinical usefulness of donepezil in heart failure.

Physiological Reports

Fluid retention is the main reason for the high hospitalization rate among patients with chronic ... more Fluid retention is the main reason for the high hospitalization rate among patients with chronic heart failure (CHF). Given the lack of knowledge about fluid intake regulation and its consequences in patients with CHF, current guidelines do not provide clear direction for fluid management. Using a rat model of CHF, we investigated altering drinking behaviors and explored fluid management strategies. CHF was induced by ligating the left anterior descending coronary arteries in 8-week-old, male, Sprague-Dawley rats. A customdesigned drop counting and feedback control system was used to record and modulate drinking behaviors. During the first month after an induced myocardial infarction (MI), we observed that the spontaneous per drinking volume (PDV) was significantly increased in animals with prolonged intervals between drinking episodes. In addition, there was a significant inverse correlation between the early PDV and the post-MI lifespan (r = À0.907; P < 0.001). Moreover, modulating the drinking behavior of rats with CHF to involve frequent drinking of small PDVs significantly enhanced hemodynamics and prevented cardiac remodeling, with a significant improvement in the 180-day survival rate, compared with animals allowed to drink freely (50% vs. 36%; P < 0.01). The results of dynamic PDV changes, after MI, suggest that an impaired thirst mechanism is associated with the sensing and regulating of fluid balance in rats with CHF. These results suggest that increasing the drinking frequency, with small PDVs, may be beneficial to preventing progression of cardiac dysfunction in CHF.

The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society

 We examined the applicability of a sieve electrode to the autonomic nervous system as a potenti... more  We examined the applicability of a sieve electrode to the autonomic nervous system as a potential neural interface for bionic medicine. We developed, using a Sisemiconductor process, a sieve electrode having a square diaphragm (1 mm in one side, 12 µm in thickness) with 30-81 penetrating square holes (50-100 µm in one side). In the first protocol, we implanted the sieve electrode to the vagal nerve in rats. One hundred and twenty days after the implantation, cuff electrodes were attached to the vagal nerve proximal and distal to the sieve electrode under halothane anesthesia. The evoked action potential was recorded from the sieve electrode by nerve stimulation via the cuff electrodes. The evoked action potential was also recorded from the cuff electrodes by nerve stimulation via the sieve electrode. In the second protocol, we implanted the sieve electrode to the renal sympathetic nerve in rabbits. Forty days after the implantation, the spontaneous action potential or sympathetic nerve activity was recorded under pentobarbital anesthesia. In conclusion, we were able to record the evoked and spontaneous action potentials using the sieve electrode. The sieve electrode will provide a useful neural interface for recording and stimulating the autonomic nervous system.

報告番号: 甲14455 ; 学位授与年月日: 1999-03-29 ; 学位の種別: 課程博士 ; 学位の種類: 博士(獣医学) ; 学位記番号: 博農第2063号 ; 研究科・専攻: 農学生... more 報告番号: 甲14455 ; 学位授与年月日: 1999-03-29 ; 学位の種別: 課程博士 ; 学位の種類: 博士(獣医学) ; 学位記番号: 博農第2063号 ; 研究科・専攻: 農学生命科学研究科獣医学専攻

The arterial baroreflex system may be divided into the neural arc (from pressure input to efferen... more The arterial baroreflex system may be divided into the neural arc (from pressure input to efferent sympathetic nerve activity) and the peripheral arc (from sympathetic nerve activity to arterial pressure). In rabbits, the baroreflex neural arc reveals derivative characteristics in the frequency range below 0.8 Hz and high-cut characteristics above 0.8 Hz. To examine such high-cut characteristics are also present in rats, we isolated the carotid sinus regions in anesthetized rats (n = 5) and imposed a Gaussian white noise input with a switching interval of 50 ms. The transfer function of the baroreflex neural arc showed derivative characteristics in the frequency range from 0.1 to 1.3 Hz and high-cut characteristics above 1.3 Hz in rats. These results indicate that the baroreflex neural arc possesses high-cut characteristics in rats as well as in rabbits, which may contribute to preserving baroreflex gain against pulsatile pressure.

Japanese Circulation Journal-english Edition, 2007

Japanese Circulation Journal-english Edition, 2008

Our previous study indicated that intravenously administered ivabradine (IVA) augmented the dynam... more Our previous study indicated that intravenously administered ivabradine (IVA) augmented the dynamic heart rate (HR) response to moderate-intensity vagal nerve stimulation (VNS). Considering an accentuated antagonism, the results were somewhat paradoxical; i.e., the accentuated antagonism indicates that an activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels via the accumulation of intracellular cyclic adenosine monophosphate (cAMP) augments the HR response to VNS, whereas the inhibition of HCN channels by IVA also augmented the HR response to VNS. To remove the possible influence from the accentuated antagonism, we examined the effects of IVA on the dynamic vagal control of HR under beta-blockade. In anesthetized rats (n = 7), the right vagal nerve was stimulated for 10 min according to binary white noise signals between 0 and 10 Hz (V0-10), between 0 and 20 Hz (V0-20), and between 0 and 40 Hz (V0-40). The transfer function from VNS to HR was estimated. U...