Ichiro Hidaka

Structural Heterogeneity in the Ventricular Wall Plays a Significant Role in the Initiation of Stretch-Induced Arrhythmias in Perfused Rabbit Right Ventricular Tissues and Whole Heart Preparations

Rationale: Mechanical stress is known to alter the electrophysiological properties of the myocardium and may trigger fatal arrhythmias when an abnormal load is applied to the heart. Objective: We tested the hypothesis that the structural heterogeneity of the ventricular wall modulates globally applied stretches to create heterogeneous strain distributions that lead to the initiation of arrhythmias. Methods and Results: We applied global stretches to arterially perfused rabbit right ventricular tissue preparations. The distribution of strain (determined by marker tracking) and the transmembrane potential (measured by optical mapping) were simultaneously recorded while accounting for motion artifacts. The 3D structure of the preparations was also examined using a laser displacement meter. To examine whether such observations can be translated to the physiological condition, we performed similar measurements in whole heart preparations while applying volume pulses to the right ventricle. At the tissue level, larger stretches (≥20%) caused synchronous excitation of the entire preparation, whereas medium stretches (10% and 15%) induced focal excitation. We found a significant correlation between the local strain and the local thickness, and the probability for focal excitation was highest for medium stretches. In the whole heart preparations, we observed that such focal excitations developed into reentrant arrhythmias. Conclusions: Global stretches of intermediate strength, rather than intense stretches, created heterogeneous strain (excitation) distributions in the ventricular wall, which can trigger fatal arrhythmias.

Noise-induced compensation for postural hypotension in primary autonomic failure.

Noise can have a beneficial effect on sensory neurological systems, enhancing detection of small afferent signals and thereby improve efferent neural responses. We hypothesized whether a similar mechanism would facilitate impaired neural transmission associated with neurological disease, and tested whether addition of external noise to baroreceptor signaling could improve blunted autonomic efferent responses to a postural challenge in patients with primary autonomic failure (PAF). Five PAF patients were tested, one in duplicate and another triplicate, for their transient responses of heart rate (measured from electrocardiographic RR intervals; RRIs) and systolic (SBP) and diastolic (DBP) blood pressures to either 30 degrees or 60 degrees head-up tilt, with and without continuous application of beat-to-beat Gaussian white noise to the carotid sinus baroreceptors. Also, the effects of noise were compared with those by a continuous positive pressure applied to the carotid sinus baroreceptors. The data were fit to a first order model to evaluate the speed (by the time constant; tau) and the magnitudes (by the steady state gains; Gs) of RRI and blood pressure responses. The PAF patients exhibited marked drops in SBP and DBP and a blunted increase in heart rate upon transition from a supine to a head-up position. Addition of noise, not the continuous positive pressure, to the arterial baroreceptors significantly (P<0.05) increased the G in RRI and diminished the Gs in SBP and DBP, though the time courses (taus) of both the RRI and blood pressure responses were unaffected. The addition of external noise to baroreceptor signaling ameliorated the marked postural hypotension seen in patients with PAF.

Relevance of cardiomyocyte mechano-electric coupling to stretch-induced arrhythmias: Optical voltage/calcium measurement in mechanically stimulated cells, tissues and organs

Stretch-induced arrhythmias are multi-scale phenomena in which alterations in channel activities and/or calcium handling lead to the organ level derangement of the heart rhythm. To understand how cellular mechano-electric coupling (MEC) leads to stretch-induced arrhythmias at the organ level, we developed stretching devices and optical voltage/calcium measurement techniques optimized to each cardiac level. This review introduces these experimental techniques of (1) optical voltage measurement coupled with a carbon-fiber technique for single isolated cardiomyocytes, (2) optical voltage mapping combined with motion tracking technique for myocardial tissue/whole heart preparations and (3) real-time calcium imaging coupled with a laser optical trap technique for cardiomyocytes. Following the overview of each methodology, results are presented. We conclude that individual MEC in cardiomyocytes can be heterogeneous at the ventricular level, especially when moderate amplitude mechanical stretches are applied to the heart, and that this heterogeneous MEC can evoke focal excitation that develops into re-entrant arrhythmias.

Noise-induced sensitization of human brain

In the past decade, it has been recognized that noise can enhance the response of nonlinear systems to weak signals, via a mechanism known as stochastic resonance (SR). Particularly, the concept of SR has generated considerable interest in sensory biology, because it has been shown in several experimental studies that noise can assist neural systems in detecting weak signals which could not be detected in its absence. Recently, we have shown a similar type of noise-induced sensitization of human brain; externally added noise to the brain stem baroreflex centers sensitized their responses in maintaining adequate blood perfusion to the brain itself. Furthermore, the addition of noise has also shown to be useful in compensating for dysfunctions of the baroreflex centers in certain neurological diseases. It is concluded that the statistical physics concept of SR could be useful in sensitizing human brain in health and disease.

Effects of nicardipine and diltiazem on fractal features of short-term heart rate variability—application of coarse graining spectral analysis

AbstractPurpose. This study was designed to investigate the effects of nicardipine and diltiazem on the fractal features of short-term heart rate variability (HRV), using coarse graining spectral analysis (CGSA). Methods. Eighteen healthy volunteers participated in this study; they were divided into two groups according to the drug administered. Five-minute electrocardiogram and arterial pressure recordings were made during stepwise infusions of either nicardipine (0.4, 0.8, 1.6, and 3.2 μg·kg−1·min−1) or diltiazem (2, 4, 8, and 16 μg·kg−1·min−1) under rate-controlled breathing at 0.25 Hz. CGSA broke down the total power of the time series into harmonic (low frequency [0.0–0.15 Hz; LF] and high frequency [0.15–0.5 Hz; HF]) and nonharmonic (fractal) components. Cardiac sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activity indicators were evaluated as the ratios LF/HF and HF/TP (total spectral power), respectively. Fractal components were evaluated as %fractal and the spectral exponent β of 1/fβ. Results. Compared with control measurements, the maximum dose of nicardipine infusion caused a significant decrease in systolic arterial pressure, a significant increase in the mean heart rate, and a significant increase in plasma norepinephrine level, findings that were associated with significant increases in %fractal and β values (54.2 ± 13.3 vs 75.6 ± 9.8, and 0.86 ± 0.22 vs 1.32 ± 0.46, respectively; P < 0.05). PNS and SNS indicators showed decreased and increased values, respectively. Diltiazem caused a reduction in arterial pressure; however, no other parameters, including the nonharmonic components of HRV, were affected by this drug. Conclusions. These findings strongly suggest that nicardipine suppresses vagal cardiac neural outflow and activate the SNS, an action which, subsequently, causes changes in the fractal features of HRV. Although diltiazem reduces arterial pressure, it preserves the basic neural balance of the autonomic nervous system in regard to heart rate control.

Functional Roles of Noise and Fluctuations in the Human Brain

In the past decade, it has been recognized that noise can enhance the response of nonlinear systems to weak signals, via a mechanism known as stochastic resonance (SR). In this short review, we introduce our experimental demonstration of SR‐type behavior in the human brain, and medical (neurological) applications and a possible mechanism of such phenomenon.

Noise‐Induced Sensitization of Human Brain: Toward the Neurological Application of Stochastic Resonance

In the past decade, it has been recognized that noise can enhance the response of nonlinear systems to weak signals, via a mechanism known as stochastic resonance (SR). Particularly, the concept of SR has generated considerable interest in sensory biology, because it has been shown in several experimental studies that noise can assist neural systems in detecting weak signals which could not be detected in its absence. Recently, we have shown a similar type of noise‐induced sensitization of human brain; externally added noise to the brain stem baroreflex centers sensitized their responses in maintaining adequate blood perfusion to the brain itself. Furthermore, the addition of noise has also shown to be useful in compensating for dysfunctions of the baroreflex centers in certain neurological diseases. It is concluded that the statistical physics concept of SR could be useful in sensitizing human brain in health and disease.

Biological fluctuations and neuronal dynamics

「確率共振 (Stochastic Resonance; SR) とは, 非線形なシステムに, あるレベルのノイズを加えたとき, 微少な入力信号に対する応答が最適化されるという現象であり, 近年, 物理学, 工学, 生理学等の広範な自然科学の分野で非常に注目されている. とりわけ神経系におけるSRは, 閾値以下の信号を検出可能にするという点で極めて画期的であり, 1個のニューロンやニューラル・ネットワークの数理モデルにSRを見いだす理論研究, あるいは, 実験動物の神経素子に実際にノイズを加えたり, ヒトの視覚-認知系, 皮膚感覚-認知系におけるSRを調べる実証的研究が行われてきた. また, 生体には1/fβ型 (特にβ=1) のスペクトル構造を持つ信号が遍在していることが知られているが, SRのノイズ項にさまざまなβをもつノイズを適用してシミュレートしたところ, 実際の生体信号と同様の有色雑音 (β=1) を負荷した方が, スペクトルが一様で時間相関のない白色雑音 (β=0) を用いるよりも低いノイズ強度で至適応答に達したという研究結果が報告されており, このことは生体1/fゆらぎの機能的意義をSRによって説明できる可能性を示唆するものである. SRにおいては, ノイズは信号を攪乱するものではなく, 逆に信号の検出力を高める媒体であるとみなせることから, 適切なノイズを外部から人工的に負荷することによって, 加齢や疾病によって低下した感覚機能を回復/向上できるかもしれない.