Hideyuki Honda

Modification of Human Left Ventricular Relaxation by Small-Amplitude, Phase-Controlled Mechanical Vibration on the Chest Wall

BACKGROUND Direct clinical manipulation to improve an impairment of left ventricular (LV) relaxation has not been reported. We investigated whether the LV relaxation rate in humans could be modulated by phase-controlled mechanical vibration applied to the patients anterior chest wall and whether there are some quantitative differences in the responses of normal (N), hypertrophied (H), and failing (F) ventricle. METHODS AND RESULTS In 46 patients (N, 10; H, 18 [hypertrophic cardiomyopathy]; F, 18 [heart failure]), the vibrator was attached to the precordium and a 50-Hz, 2-mm sinusoidal mechanical vibration was applied, with the timing restricted from the onset of isovolumic relaxation to end-diastole during cardiac catheterization. Heart rate and peak LV pressure showed no difference with vibration. However, in all patients, precordial vibration caused an acceleration of the LV pressure fall. The magnitude of the induced reduction of the time constant of LV pressure decay (delta T) was larger (P < .01) in H and F than in N (4.6 +/- 2.3, 4.0 +/- 1.6, and 0.6 +/- 1.5 ms for H, F, and N, respectively). Delta T correlated strongly with the magnitude of impaired relaxation and the magnitude of transmitted vibration to the ventricle. CONCLUSIONS Phase-controlled, small-amplitude vibration on the chest wall can directly modulate LV relaxation rate, especially in those with hypertrophy or failing ventricle.

Diastolic vibration improves systolic function in cases of incomplete relaxation.

BackgroundIncomplete relaxation of the left ventricle (LV) affects LV filling, but the subsequent effect on LV systolic function remains unclear. We attempted to improve relaxation by applying oscillatory mechanical perturbation during diastole (diastolic vibration) and examined the extent to which systolic function improved. Methods and ResultsUsing 10 open-chest canine preparations, pacing tachycardia and administration of propranolol were imposed to induce various levels of incomplete relaxation. Myocardial length perturbation was induced with an oscillator attached to the LV surface (50 Hz, 1-mm amplitude) and was restricted to the period from the beginning of isovolumic relaxation to end diastole. At resting heart rates, diastolic vibration caused an immediate decrease in the time constant (T) of LV pressure fall without any influence on heart rate, LV peak systolic pressure (peak LVP), stroke volume (SV), LV peak positive dP/dt, and total systemic vascular resistance. With pacing tachycardia, diastolic vibration increased both peak LVP and SV at 160 beats per minute (before) and 120 beats per minute (after propranolol), simultaneously decreasing both T and LV diastolic pressures and increasing end-diastolic segment length. The increase in peak LVP and SV caused by diastolic vibration correlated with the T/diastolic interval (r=0.82), the assumed index of severity of incomplete relaxation. ConclusionsThese results suggest that diastolic vibration accelerates the LV relaxation rate and that this increased relaxation improves systolic function through the Frank-Starling mechanism.

Non-invasive estimation of human left ventricular end-diastolic pressure

Sato et al. (Electronic Letters 32, 949-950, 1996) reported that one can obtain a non-invasive estimate of left ventricular (LV) pressure at around end-diastole in an isolated canine preparation. In this study we examined whether this method can be applied to humans. Using the method proposed by Kanai et al. (IEEE. Trans. UFFC, 43, 791-810,1996), we detected small amplitude LV vibration from an ultrasonic pulse Doppler signal reflected from the interventricular septum in five patients (44-63 y.o., male;4, female;1). We measured the oscillation frequency of the LV wall through the wavelet transform of small amplitude LV vibration, and calculated LV pressure at around end-diastole from the values of oscillation frequency, internal radius and wall thickness using Mirskys equation. The estimated LV pressures at around end-diastole were similar to end-diastolic pressure measured directly by cardiac catheterization. These results show the possibility that this method allows for the non-invasive estimate of LV pressure at around end-diastole, and furthermore provides the basis for future clinical applicability of this technique.

The effect of applied mechanical vibration on two different phases of rat papillary muscle relaxation

Abstract Applying external mechanical vibration during the relaxation phase of rat papillary muscle decreases the duration of the first part of the relaxation phase. To elucidate the basic mechanism responsible for this shortening of the relaxation period, we applied a controlled vibration to isolated twitching rat papillary muscles during various phases in the relaxation of a twitch. The first part of the relaxation phase was accelerated when length perturbations were applied in the first part of the relaxation of a twitch, dependent on both amplitude and frequency of the perturbation. When vibrations were applied in the first half of the relaxation, the second phase of relaxation was slightly slower (about 20%), but when no vibrations were applied in the first phase, relaxation could be accelerated by applying vibration in the latter half of the relaxation phase. Thus, in the latter half of relaxation, the acceleration of relaxation depended upon perturbation events earlier during that twitch. This study indicates that vibration-induced acceleration of relaxation is due (at least in part) to an apparent increase in detachment rate of attached cross-bridges from the thin filament without substantial reattachment.

Simulation study on the effect of external vibration on left ventricular function: potential indicator of LV tolerance to the sudden reduction of myocardial contractility

In a previous study the authors reported that external mechanical vibration applied to the left ventricular (LV) epicardium induces contractility-dependent depression in LV pressure, stroke volume and stroke work. It was suggested that this depression may be caused by the direct effect of external vibration on contractile protein. In another paper in this issue, it is proved that LV function with various myocardial contractilities and the actual process of deterioration in heart failure are well simulated in the model proposed by Beyar and Sideman, after some modifications have been made. In the study reported here it is assumed that an external mechanical vibration induces sudden reduction in myocardial active stress in the model of Beyar and Sideman; in this way the contractility-dependent effect of external vibration on LV function has been simulated. The results of this simulation support the suggestion that external mechanical vibration directly affects contractile protein and reduces LV function, and it is further suggested that the reduction of LV function induced by external vibration reflects the reserve or tolerance capacity of LV to a sudden reduction of myocardial contractility.

Precordial or Epicardial Input of Phase-Controlled Minute Vibration: Effect on Coronary Flow Rate in Regional Ischemia

Phase-controlled vibration at diastole (diastolic vibration) induces a millisecond time scale response in in situ heart, and the magnitude of the induced response (the improvement of the ventricular relaxation) is related to the severity of the impairment of relaxation as well as the amplitude of the vibration applied. However, it is still unknown whether diastolic vibration increases the coronary flow rate in the heart with impaired relaxation. We examined in experimental and clinical studies if external diastolic vibration to the heart with impaired relaxation could result in an improvement of the coronary flow rate and, if so, how to interpret the underlying mechanism of the response observed in the heart with regional ischemia. In an experimental study using an open-chest canine preparation with regional ischemia, the diastolic vibration applied to the ventricular surface increased coronary flow rate without increasing the coronary perfusion pressure and simultaneously shortened the time constant of the ventricular pressure decay. The diastolic vibration improved the nonuniformity of the relaxation by accelerating myocardial relaxation in the ischemic region. In clinical studies the response of the coronary flow velocity was measured by the transesophageal Doppler method in 10 healthy volunteers (8 men, 2 women; 50.6 ± 12.8 years old, mean ± SD) and 10 patients with coronary artery disease (8 men, 2 women; 66.4 ± 8.0 years old). The intracoronary Doppler catheter method was used in three patients with coronary artery disease (two men, one woman; 60.3 ± 10.5 years old). Mechanical diastolic vibration on the precordium has been demonstrated to transmit effectively to the ventricle and cause an increase in coronary flow velocity with no change in the coronary arterial diameter, blood pressure, or heart rate. We concluded that diastolic vibration increased the coronary flow rate in the clinical situation as well as in an experimental preparation. This increase mainly resulted from an acceleration of the ventricular relaxation rate caused by crossbridge detachment, normalization of the nonuniformity of the relaxation, or both.

Theoretical treatment of striated muscle: Dynamic extension of four-state model

SummaryWe constructed a muscle model, based on the model first proposed by Gray and Gonda [6,7], that simulates the twitch contraction of striated muscle. Their original model postulated four basic states in the contraction cycle and predicted the properties of steady state contraction in striated muscle. Using the relationship between steady state tension and calcium concentration, we described several rate constants as functions of calcium concentration and calculated the number of attached crossbridges at various calcium concentration values. The results for both skeletal and cardiac muscle were approximately consistent with those of X-ray studies. Assuming that rate constants change immediately with the phasic alteration of intracellular calcium concentration, we estimated the time course of crossbridge distribution during twitch contraction; these findings were also consistent with those of X-ray studies. We also simulated the effects of calcium concentration and sarcomere length on the magnitude of twitch tension. These simulations suggest that the major determinants of crossbridge distribution during twitch contraction are the time courses of calcium transients and the rate constants of crossbridge kinetics. Our findings suggest that the model used in this study provides a theoretical basis for interpreting the characteristics of cardiac muscle encountered in the clinical setting.

Estimation of left ventricular myocardial elasticity and viscosity by a thick-walled spherical model

The authors measured the transfer function (TF) of the left ventricle (LV) in an isolated canine preparation. Here TF indicates the ratio of induced vibration in LV to input vibration when an external mechanical oscillation is applied. TF had a single peak the frequency of which changed from 40 Hz to 80 Hz when LV pressure (LVP) increased from 6 mm Hg to 96 mm Hg. A mathematical model was formulated to estimate the viscoelasticity of the spherical shell. This model was constructed of the material points, elastic components which connected all the material points, and viscous components placed in series with elastic components. Theoretical TF can be computed if the viscoelastic values are given. The value of viscoelasticity at which the theoretical TF best fitted the experimental TF was considered to be the viscoelasticity of the model. The validity of this approach was verified using a silicone spherical shell. The estimated myocardial elasticity was 40 kPa when LVP was 6 mm Hg, 160–170 kPa when LVP was 96 mm Hg and was approximately proportional to LVP, whereas viscosity showed small change. The inclination of elasticity was consistent with previous reports. These results proved that myocardial elasticity can be estimated by analysing the transfer function of the left ventricle.

Regional myocardial layer function in Doxorubicin cardiomyopathy; clinical evaluation using novel ultrasonic Doppler method

We examined whether the novel Doppler technique could be a sensitive diagnostic method for the histological deterioration of Doxorubicin cardiomyopathy (DoxCM). 25 patients with acute lymphoblastic leukaemia were examined for six years. Moreover, in Doxorubicin injected rabbits, histological damage was compared to the myocardial layer function by the Doppler technique. In normal subjects, myocardial layer thickening occurred in a synchronized fashion during the cardiac cycle. However, in patients, it was characterized by the appearance of a non-functioning layer in the septum. The conventional echocardiography could not be sensitive enough to demonstrate the change in DoxCM. In contrast, the myocardial layer function by this novel method obviates subclinical change in the myocardium. The histological examination in rabbits verified the linear relationship between the myocardial damage and the myocardial layer function. We concluded that the novel Doppler technique could be a useful modality for the histological change in DoxCM.

Cross-bridge movement in rat slow skeletal muscle as a function of calcium concentration

A single fibre bundle from rat soleus muscle was chemically skinned with saponin and the transfer of myosin heads from the thick filaments to the thin filaments at a sarcomere length of 2.4 μm was measured as a function of Ca2+ concentration using an x-ray diffraction method at 4–7 °C. In the relaxed state, the 1,0 spacing was 42.08 nm. The spacing showed no significant decrease when the Ca2+ concentration was below the threshold (−log10 [Ca2+] or pCa 5.8). No significant transfer of the myosin heads occurred when the Ca2+ concentration was below the threshold (pCa 5.8). When the muscle was maximally activated at pCa 4.4, the spacing decreased to 40.35 nm. During the maximum isometric contraction at pCa 4.4, 54.9 ± 6.5% (±SE of the mean) of the myosin heads were transferred to the thin filaments. The transfer of the myosin heads was approximately proportional to relative tension. These results suggest that myosin heads of both fast-twitch and slow-twitch skeletal muscles transferred on the common movement as a function of Ca2+ concentration.