Kenji Sunagawa

Chronic vagal stimulation decreased vasopressin secretion and sodium ingestion in heart failure rats after myocardial infarction

Chronic vagal stimulation (VS) markedly improved long-term survival in the heart failure rats. We examined the effects of VS on arginine vasopressin (AVP) secretion and salt ingestion in heart failure rats after myocardial infarction (MI). Surviving rats after MI were randomly assigned to two groups. One group was treated with sham stimulation (SS), and the other group was treated with VS. All rats could access water and 1.8% NaCl solution ad libitum. Treatment started at 2 weeks after MI, and continued for 6 weeks. We monitored drinking behavior during treatment. At the end of treatment, we measured hemodynamics and plasma levels of AVP and brain natriuretic peptide (BNP). The plasma AVP and BNP levels were significantly lower in the VS group than the SS group. VS significantly inhibited the ingestion of 1.8% NaCl solution. The normalized biventricular weight of the VS group was significantly lower than that of the SS group. The VS group had significantly lower left ventricular end-diastolic pressure, and higher cardiac index than the SS group. In conclusion, these results suggest that chronic VS regulates the water balance by suppression of plasma AVP level and salt ingestion in the heart failure rats after MI

Development of an algorithm for detection of fatal cardiac arrhythmia for implantable cardioverter-defibrillator using a self-organizing map.

In this study, we have introduced the pattern classifier using the self-organizing map (SOM) for detecting fatal cardiac arrhythmia in implantable cardioverter-defibrillators (ICDs). The SOM has learned patterns of sinus rhythm, ventricular fibrillation and ventricular tachycardia with the feature vectors extracted from electrocardiogram and right ventricular volume measured during an arrhythmia induction experiment of a dog. After learning, neurons of the SOM were labeled by using the k-Nearest Neighbor method. It was shown that the accuracy of the proposed method was higher than other competitive methods applied to the same test data

Neural loop of baroreflex optimizes dynamic arterial pressure regulation

The baroreflex loop consists of both a fast neural arc and a slow mechanical arc. We hypothesized that the neural arc of the baroreflex compensates the slow mechanical response and thereby substantially improves the quality of blood pressure regulation. In 12 anesthetized, vagotomized rabbits, we isolated carotid sinuses and randomly changed intrasinus pressure while measuring intrasinus pressure (P/sub s/), cardiac sympathetic nerve activity (SNA) and systemic arterial pressure (P/sub a/) using a white noise technique. We estimated the open-loop transfer characteristics of the neural arc (Hn) of the baroreflex, that is, from P/sub s/ to SNA, that of the peripheral mechanical arc (Hp), from SNA to P/sub a/, and that of the total baroreflex loop (Ht). The gain of Hn was constant below 0.12/spl plusmn/0.057 Hz and increased with a slope of about 6 dB/octave above it, suggesting that the response was increasingly faster with frequency. In contrast, the gain of Hp was constant below 0.071/spl plusmn/0.030 Hz and decreased with a slope of about -12dB/octave above it, suggesting the response progressively slowed with increasing frequency. Although too much acceleration in the high frequency range could result in instability of the system, numerical analysis of the closed loop baroreflex response indicated that the neural arc optimized arterial pressure regulation in achieving both stability and quickness.

Chapter 139 – Bionic Baroreflex

Publisher Summary nThis chapter focuses on bionic baroreflex system (BBS) and implementation of algorithm of artificial vasomotor center in it. The arterial baroreflex is the most important negative feedback system to suppress rapid daily disturbances in arterial pressure. It is of critical importance to identify the algorithm of the artificial vasomotor center, i.e., how to determine the stimulation frequency (STM) of the vasomotor sympathetic nerves in response to a change in arterial pressure (AP). To operate in real time as the artificial vasomotor center, the computer was programmed to automatically calculate instantaneous STM in response to instantaneous AP changes according to a convolution algorithm. In a prototype of the BBS for rats with central baroreflex failure, the celiac ganglion was selected as the sympathetic vasomotor interface. Without the activation of the BBS, HUT produced a rapid progressive fall in AP by 40 mmHg in 2 seconds. To apply BIONIC technology to patients, one needs a neural interface with quick and effective controllability of AP in humans.

Estimation of total baroreflex gain using an equilibrium diagram between sympathetic nerve activity and arterial pressure

The arterial baroreflex system may be divided into the mechano-neural arc from pressure input to sympathetic nerve activity (SNA) and the neuro-mechanical arc from SNA to arterial pressure (AP). We explored a new strategy to estimate total baroreflex gain (G/sub baro/) using an equilibrium diagram between the mechano-neural and neuro-mechanical arcs. In 8 anesthetized rabbits, a neck suction procedure (NS) was simulated by shifting isolated carotid sinus pressure above AP by 30 mmHg. NS shifted the mechano-neural arc alone, yielding the slope of the neuro-mechanical arc around the operating point. A lower body negative pressure procedure (LBNP) was simulated by 5 ml/kg hemorrhage. LBNP shifted the neuro-mechanical arc alone, yielding the slope of the mechano-neural arc around the operating point. By multiplying the slopes of the neuro-mechanical and mechano-neural arcs, we obtained G/sub baro/ under baroreflex closed-loop conditions. We also estimated G/sub baro/ from the relationship between isolated carotid sinus pressure and AP under baroreflex open-loop conditions. G.. estimated by the equilibrium diagram matched reasonably well with that estimated by the open-loop method (y=1.06/spl times/-0.09, r/sup 2/=0.96, SEE=0.15). In conclusion, G/sub baro/ could be estimated using the equilibrium diagram without opening the baroreflex negative feedback loop when data obtained from NS and LBNP were combined in a given subject.

Development of online monitoring of myocardiac elastance by imposing dual-frequency minute vibration

It is necessary to determine both ventricular and myocardial mechanical properties for the assessment of cardiac contractility in patients with heart disease. It is important to establish a framework to integrate myocardial properties into ventricular time-varying elastance for understanding the pathophysiology of heart failure. We measured myocardial mechanical properties by imposing minute sinusoidal vibration of different frequencies. Analysis between the amplitude and phase of force relative to those of displacement of at least two frequencies yielded elastance, viscosity, and inertia. Of these, elastance and viscosity were time varying, while inertia was constant during cardiac cycle. Applications of vibration of two different frequencies simultaneously have realized the online monitoring of myocardial properties continuously.

Development of a large-scale computer heart model for supporting clinical studies of arrhythmias

Although a large number of studies on cardiac electrical properties have been conducted, it remains difficult to integrate all fragmented data into one unified framework. As an approach to this, we developed a large-scale (6 /spl times/ 10/sup 6/ elements) three-dimensional simulator of cardiac electrical activity based on human ventricular geometry and experimentally derived ionic channel models. This simulator has the advantages over previous simulators in that ventricular fibrillation can be induced with clinical programmed extrastimulation, fibrillation can be induced more easily by extrastimulation at right ventricular outflow tract as in a clinical situation, and it is possible to examine the contribution of early afterdepolarization to arrhythmogenecity in patients with e.g., long QT syndrome. These advantages indicate that our simulator is useful in supporting a wide range of clinical studies of arrhythmias.

Attenuation of a pulsatile pressure component in the neural arc of the arterial baroreflex

A transfer function from baroreceptor pressure input to sympathetic nerve activity (SNA) shows high-pass characteristics in the frequency range from 0.01 to 1 Hz in anesthetized rabbits. The high-pass characteristics of the neural arc contribute to a quick and stable arterial pressure (AP) regulation. However, if the high-pass characteristics hold up to the frequency of heart rate (3-5 Hz), a pulsatile pressure component in AP would yield an extremely large amplitude of pulsatility in SNA. Such a large amplitude in SNA would hit the nonlinearities in baroreflex pathways, thereby disable the baroreflex regulation of AP. We hypothesized therefore that the transfer gain at the frequency of heart rate would-be much smaller than that predicted from the high-pass characteristics of the neural arc. In anesthetized rabbits (n=6), we perturbed carotid sinus pressure (CSP) according to a binary white noise with a switching interval of 50 ms. The transfer function from CSP to cardiac SNA was then estimated in the range from 0.012 to 10 Hz. The neural arc transfer function showed high-pass characteristics in the frequencies below 0.7 Hz, while losing the transfer gain above the frequency at -20 dB/decade. A simulation study indicated that the attenuation of the pulsatile pressure component in the neural arc was effective to retain the reflex regulation of AP.

A bionic approach to cardiovascular regulation: bionic arterial baroreflex system

A bionic system is an artificial device, integrated into natural human physiology by communicating with the native regulatory system. This can functionally operate as if it were a part of the body. Bionic systems can be realized only with the knowledge of detailed characteristics of the native system. We made use of a white-noise approach and have succeeded in functionally identifying the native arterial baroreflex. Using thus identified characteristics, we developed a bionic baroreflex system. Animal experiments in rats revealed that the bionic baroreflex system can stabilize pressure against hypotensive stimuli such as head-up tilt even without the native baroreflex system.

The significance of dynamic nonlinearities in the autonomic regulation of heart rate

The beat-to-beat regulation of heart rate (HR) is achieved through a beautifully elaborate but not well-understood system of dynamic interactions between sympathetic and parasympathetic (vagal) components of the autonomic nervous system. While numerous investigators consistently have reported dramatic nonlinearities in the HR response to concurrent activation of sympathetic and vagal nerves, a quantitative characterization of such dynamic nonlinearities has been lacking. Therefore, in the present study performed in 8 anesthetized Japanese white rabbits, we surgically isolated vagal and cardiac sympathetic efferent nerves such that we were able to stimulate them simultaneously according to mutually independent, band-limited Gaussian white-noise stimuli as we measured the HR response. Under two-input, single-output system assumptions we took advantage of LYSIS 6.2 software to compute first- and second-order nonlinear self kernels relating input nerve stimulation to HR response, as well as compute the nonlinear cross-kernel that quantified the dynamic interaction between concurrent sympathetic and vagal stimulation on HR response. Our results demonstrated nonlinear kernels that significantly enhanced the predictive validity of our model to predict HR response over results obtained using linear kernels alone. We conclude that dynamic nonlinearities play a quantitatively significant role in mediating the HR response to autonomic activation.