Kazunori Uemura

High-frequency dominant depression of peripheral vagal control of heart rate in rats with chronic heart failure.

To examine whether dynamic characteristics of the peripheral vagal control of heart rate (HR) are altered in chronic heart failure (CHF).

Chronic vagal nerve stimulation improves baroreflex neural arc function in heart failure rats.

We tested whether 6-wk 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-wk 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.

Adding the acetylcholinesterase inhibitor, donepezil, to losartan treatment markedly improves long‐term survival in rats with chronic heart failure

Modulation of vagal tone using electrical vagal nerve stimulation or pharmacological acetylcholinesterase inhibition by donepezil exerts beneficial effects in an animal model of chronic heart failure (CHF). Considering different treatment mechanisms underlying renin–angiotensin system (RAS) suppression and parasympathetic activation, we hypothesized that parasympathetic activation together with RAS inhibition could attenuate CHF progression. To test this hypothesis, we investigated the therapeutic effects of a combination of donepezil and losartan in CHF rats with extensive myocardial infarction (MI).

A minimally invasive monitoring system of cardiac output using aortic flow velocity and peripheral arterial pressure profile.

BACKGROUND:In managing patients with unstable hemodynamics, monitoring cardiac output (CO) can provide critical diagnostic data. However, conventional CO measurements are invasive, intermittent, and/or inaccurate. The purpose of this study was to validate our newly developed CO monitoring system. METHODS:This system automatically determines peak velocity of the ascending aortic flow using continuous-wave Doppler transthoracic echocardiography and estimates cardiac ejection time and aortic cross-sectional area using the pulse contour of the radial arterial pressure. These parameters are continuously processed to estimate CO (COest). In 10 anesthetized closed-chest dogs instrumented with an aortic flowprobe to measure reference CO (COref), hemodynamic conditions were varied over wide ranges by infusing cardiovascular drugs or by random atrial pacing. Under each condition, COref and COest were determined. Absolute changes of COref (&Dgr;COref) and COest (&Dgr;COest), and relative changes of COref (%&Dgr;COref) and COest (%&Dgr;COest) from the corresponding baseline values were determined in each animal. We calibrated COest against COref to obtain proportionally scaled COest (COestN). RESULTS:A total of 1335 datasets of COref and COest were obtained, in which COref ranged from 0.17 to 5.34 L/min. Bland–Altman analysis between COref and COest indicated that the limits of agreement (the bias ± 1.96 × SD of the difference) and the percentage error (1.96 × [SD of the difference]/[mean CO] × 100) were from −1.01 to 1.13 L/min (95% confidence interval, −1.76 to 1.88 L/min) and 43%, respectively. The agreement between COref and COestN was improved, with limits of agreement from −0.53 to 0.49 L/min (95% confidence interval, −0.62 to 0.59 L/min) and the percentage error of 20%. Polar plot analysis between &Dgr;COref and &Dgr;COest indicated that mean ± 1.96 × SD of polar angle was −2° ± 22°. Four quadrant plot analysis indicated that %&Dgr;COest correlated tightly with %&Dgr;COref (R2 = 0.93). The %&Dgr;COest and %&Dgr;COref changed in the same direction in 95% of the datasets. Reliability of this system was well preserved under conditions of random atrial pacing and also in a continuous manner. CONCLUSION:Over a wide range of hemodynamic conditions, irrespective of cardiac beat irregularity, this system may allow minimally invasive monitoring of CO with a good trending ability. The present results warrant further research and development of this system for future clinical application.

Consideration on parameter determination of a new model describing dynamic vagal heart rate control in rats

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.

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

P2738Development of closed-loop drug infusion system for automated hemodynamic resuscitation in septic shock

上村 和紀 Kazunori Uemura (国立循環器病研究センター循環動態制御部 Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center) 川田 徹 Toru Kawada (国立循環器病研究センター循環動態制御部 Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center) 鄭 燦 Zheng Can (国立循環器病研究センター循環動態制御部 Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center) 李 梅花 Meihua Li (国立循環器病研究センター循環動態制御部 Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center) 杉町 勝 Masaru Sugimachi (国立循環器病研究センター循環動態制御部 Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center)