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Biomedical subjects

H Takaki

Publications and source records attributed to H Takaki.

At least 37 records · Page 2Linked to original sources

Development of a servo-controller of heart rate using a cycle ergometer.

In exercise training, precise control of exercise intensity would maximize the training efficacy while minimizing risks. To adjust work rate, heart rate (HR) has been used as a measure of exercise intensity. Thus, we developed a servo-controller of HR using a cycle ergometer. After estimating the transfer function from work rate to HR, we optimized feedback parameters for achieving a quick and stable HR response by means of a computer simulation. We then examined the performance of the servo-controller of HR in 55 healthy volunteers. We set the target HR at 60% and 75% of the age-predicted maximum HR. Times required for HR to reach 90% of the target HR were 136 +/- 33 and 137 +/-22s in the respective protocols. Standard deviations of the steady-state difference between the target and measured HRs were 2.5 +/- 0.6 and 3.8 +/- 1.1 beats/min. We conclude that the developed servo-controller makes it possible to precisely regulate HR and, thereby, exercise intensity.

Adult↗

Exercise-induced ST elevation in patients with arrhythmogenic right ventricular dysplasia.

To test the hypothesis that local or diffuse wall motion abnormalities in the right ventricle in patients with arrhythmogenic right ventricular dysplasia (ARVD) may induce the ST-segment elevation in response to exercise, we examined exercise electrocardiograms in patients with ARVD. In 17 patients with ARVD, who demonstrated right ventricular wall motion abnormalities without organic coronary lesions, we conducted a treadmill exercise test. Significant exercise-induced ST-segment elevation (ESTE) was defined as a 0.1 mV or more ST-segment elevation at J point. ESTE was observed in 11 patients (65%). It manifested most frequently in right-sided precordial leads. Severe right ventricular asynergy was seen in all but one (91%) among 11 with ESTE, whereas it was seen only in two (33%) among six without ESTE (P<.05). The maximal magnitude of ESTE inversely correlated with right ventricular ejection fraction (r = -0.58, P<.05). ESTE was seen in two thirds of ARVD patients, helping us noninvasively diagnose ARVD. The fact that ventricular wall motion abnormalities could cause ESTE in the absence of organic coronary lesions suggested the critical role of mechanical factors in the genesis of ESTE.

Adolescent↗

Exercise-induced QRS prolongation in patients with mild coronary artery disease: computer analysis of the digitized multilead ECGs.

Although exercise-induced QRS prolongation has been reported as a possible marker for inducible ischemia, subtleness of the prolongation makes it unidentifiable from standard, chart-recorded electrocardiograms (ECGs). To overcome such a limitation, we measured the QRS width using high-resolution ECGs and examined the diagnostic value of the exercise-induced QRS prolongation in patients before and after percutaneous transluminal coronary angioplasty (PTCA). In 16 patients with single- (n = 12) or double-vessel disease (n = 4), treadmill exercise ECG tests were performed before and after PTCA, while continuously recording 8-lead ECGs at 500 Hz. The onset of the QRS complexes was defined by the earliest deflection, and the end was defined as the latest deflection among 8 leads with the use of algebraic sum of the absolute voltage and their time derivatives (dV/dt) from all 8 leads. We compared QRS complexes before and 1 minute after exercise. Before PTCA, exercise prolonged the QRS width in all but 3 patients (unchanged in 2, decreased in 1) (84 +/- 7 to 87 +/- 8 ms, P < .005). After PTCA, it decreased in 4, was unchanged in 5, and increased in 7 (83 +/- 7 to 83 +/- 6 ms, not significant). PTCA shortened postexercise QRS width in all but 3 (unchanged in 2, increased in 1: 83 +/- 6 to 87 +/- 8 ms, P < .001). High-resolution ECGs enabled us to measure subtle QRS prolongation induced by mild ischemia. Because the QRS prolongation and ST-segment changes would reflect different aspects of myocardial ischemia, incorporating this measure into ST segment criteria might significantly improve the diagnostic accuracy for coronary artery disease.

Adult↗

New analytic framework for understanding sympathetic baroreflex control of arterial pressure.

The sympathetic baroreflex is an important feedback system in stabilization of arterial pressure. This system can be decomposed into the controlling element (mechanoneural arc) and the controlled element (neuromechanical arc). We hypothesized that the intersection of the two operational curves representing their respective functions on an equilibrium diagram should define the operating point of the arterial baroreflex. Both carotid sinuses were isolated in 16 halothane-anesthetized rats. The vagi and aortic depressor nerves were cut bilaterally. Carotid sinus pressure (CSP) was sequentially altered in 10-mmHg increments from 80 to 160 mmHg while sympathetic efferent nerve activity (SNA) and systemic arterial pressure (SAP) were recorded simultaneously under various hemorrhagic conditions. The mechanoneural arc was characterized by the response of SNA to CSP and the neuromechanical arc by the response of SAP to SNA. We parametrically analyzed the relationship between input and output for each arc using a four-parameter logistic equation model. In baseline states, the two arcs intersected each other at the point at which the instantaneous gain of each arc attained its maximum. Severe hemorrhage lowered the gain and offset of the neuromechanical arc and moved the operating point, whereas the mechanoneural arc remained unchanged. The operating points measured under the closed-loop conditions were indistinguishable from those estimated from the intersections of the two arc curves on the equilibrium diagram. The average root mean square errors of estimate for arterial pressure and SNA were 2 and 3%, respectively. Such an analytic approach could explain a mechanism for the determination of the operating point of the sympathetic baroreflex system and thus helps us integratively understand its function.

Animals↗

Dynamic counterbalance between direct and indirect vagal controls of atrioventricular conduction in cats.

The vagal system regulates the atrioventricular conduction time (TAV) via two opposing mechanisms: a direct effect on the atrioventricular node and an indirect effect through changes in heart period (TAA). To evaluate how dynamic vagal activation affects TAV, we stimulated the vagal nerve with frequency-modulated Gaussian white noise and estimated the transfer function from vagal stimulation to the TAV response under conditions of no pacing and constant pacing in anesthetized cats. The effect of changes in TAA on TAV was estimated by a random-pacing protocol. The transfer function from vagal stimulation to TAV has low-pass filter characteristics. Constant pacing increased the maximum step response in TAV (2.4 +/- 1.2 vs. 6.3 +/- 2.2 ms/Hz, P < 0.01). The time constant did not differ between the vagal effect on TAV and that on TAA (2.9 +/- 1.2 vs. 2.3 +/- 0.5 s). Because changes in TAA reciprocally affected TAV without significant delay, the direct and indirect effects were dynamically counterbalanced and exerted stable TAV transient response during vagal stimulation under normal sinus rhythm.

Acoustic Stimulation↗

Development of a servo-controller of heart rate using a treadmill.

Although treadmill exercise involves a more familiar range of motions and is thus more physiological in terms of daily activity than cycle ergometer exercise, difficulties in controlling the exercise intensity have limited its utility. As heart rate (HR) has been used as a measure of exercise intensity, controlling HR should allow for the proper control of exercise intensity during treadmill exercise. Thus, a servo-controller framework was applied to regulate HR during treadmill exercise. After estimating an averaged transfer function from speed command to HR, feedback parameters were optimized via a computer simulation in order to achieve a quick and stable HR response. The performance of the servo-controller of HR was then examined in 10 healthy subjects. Standard deviations of the steady-state difference between the target and measured HRs were 2.7+/-0.9 and 5.0+/-1.4 beats/min in the stepwise and ramp target HR protocols, respectively. The rise time to reach 90% of the target HR was 93+/-20 s in the stepwise protocol. It was concluded that a treadmill implemented with a negative feedback mechanism made it possible to precisely regulate HR and thus exercise intensity.

Adult↗

Diagnosis of lung cancer in a patient with pneumoconiosis and progressive massive fibrosis using MRI.

We report the MRI features and correlative pathologic findings of a lung cancer in a patient with progressive massive fibrosis (PMF). In this case, MRI was able to distinguish the lung cancer as a high signal intensity area, and the fibrotic mass as a low signal intensity area, on both T1-weighted and T2-weighted images when compared with muscle. MRI is potentially useful in distinguishing cancer tissue from PMF in patients with pneumoconiosis.

Aged↗

Transient oxygen uptake response to exercise characterizes functional capacity of the cardiocirculatory system in patients with chronic heart failure: a random stimulus approach.

The transient response of oxygen uptake (VO2) to submaximal exercise, known to be abnormal in patients with cardiovascular disorders, can be useful in assessing the functional status of the cardiocirculatory system, however, a method for evaluating it accurately has not yet been established. As an alternative approach to the conventional test at constant exercise intensity, we applied a random stimulus technique that has been shown to provide relatively noise immune responses of system being investigated. In 27 patients with heart failure and 24 age-matched control subjects, we imposed cycle exercise at 50 W intermittently according to a pseudo-random binary (exercise-rest) sequence, while measuring breath-by-breath VO2. After determining the transfer function relating exercise intensity (W) to VO2 and attenuating the high frequency ranges (> 6 exercise-rest cycles x min(-1)), we computed the high resolution band-limited (0-6 cycles x min(-1)) VO2 response (0-120 s) to a hypothetical step exercise. The VO2 response showed a longer time constant in the patients than in the control subjects [47 (SD 37) and 31 (SD 8) s, respectively, P < 0.05]. Furthermore, the amplitude of the VO2 response after the initial response was shown to be significantly smaller in the patients than in the control subjects [176 (SD 50) and 267 (SD 54) ml x min(-1) at 120 s]. The average amplitude over 120 s correlated well with peak VO2 (r = 0.73) and deltaVO2/deltaW (r = 0.70), both of which are well-established indexes of exercise tolerance. The data indicated that our band-limited VO2 step response using random exercise was more markedly attenuated and delayed in the patients with heart failure than in the normal controls and that it could be useful in quantifying the overall functional status of the cardiocirculatory system.

Adult↗

Noninvasive differential diagnosis between chronic pulmonary thromboembolism and primary pulmonary hypertension by means of Doppler ultrasound measurement.

OBJECTIVES: The purpose of this investigation was to differentiate chronic pulmonary thromboembolism (CPTE) from primary pulmonary hypertension (PPH) by using noninvasive Doppler ultrasound techniques. BACKGROUND: A recent investigation in our laboratory has indicated that the pulmonary artery (PA) pressure waveform conveys significant information that can be used to differentiate CPTE from PPH. Pulse pressure was markedly larger in CPTE than in PPH, indicating that the major occlusive site is central in CPTE and peripheral in PPH. METHODS: In 19 patients with CPTE and 16 patients with PPH, we estimated PA systolic pressure and diastolic pressure from the velocities of tricuspid regurgitation and pulmonary regurgitation, respectively. RESULTS: Estimated systolic pressure was not significantly different between CPTE and PPH (mean [+/-SD] 81+/-20 and 79+/-21 mm Hg, respectively, p=NS). Pulse pressure normalized by systolic pressure was higher in CPTE than in PPH (0.82+/-0.05 vs. 0.63+/-0.10, respectively, p < 0.01). Pulse pressure normalized by mean pressure was also higher in CPTE than in PPH (1.65+/-0.30 vs. 0.94+/-0.25, respectively, p < 0.01). Receiver operating characteristic analysis indicated that pulse pressure normalized by systolic pressure separated CPTE from PPH, with a sensitivity of 0.95 and a specificity of 1.00. Pulse pressure normalized by mean pressure also separated them, with a sensitivity of 0.95 and a specificity of 1.00. CONCLUSIONS: Normalized pulse pressures estimated from Doppler ultrasound measurements enable us to noninvasively differentiate between CPTE and PPH.

Adult↗

Local disappearance of epiphyseal growth plates in rats with hypervitaminosis A.

Epiphyseal growth plates of proximal tibiae in rats with high doses of vitamin A (V-A) were observed. Of 4 groups, each consisting of 5 rats, three groups were given V-A at doses, IU/100 g by body weight/day, of 50,000, 100,000, and 150,000, respectively. The other group rats were given no V-A (control). Rats were administered V-A for the 5 days from 4 weeks after birth and sacrificed at 12 weeks after birth. Three rats of the 150,000 IU group died during the period of observation. The decalcified sections were stained with hematoxylin-eosin or toluidine blue. In the ground sections, microradiography, backscattered electron imaging, and energy-dispersive X-ray microanalysis were performed. These observations suggest that the local disappearance of epiphyseal growth plates under high doses of V-A goes in the order of the increased doses through the process of (1) calcified cartilage areae appearing in the resting cell zone, (2) some of the calcified areae extending in the growth plate towards the diaphysial side, (3) bone tissue replacing the calcified areae, and (4) the local disappearing of the growth plate. Such a local disappearance may be formed in the stressed proximal regions of tibiae.

Animals↗

Usefulness of low doses of atropine to quantify the vagal stimulus-response relation in patients with congestive heart failure.

The response of low doses of atropine is reported to be attenuated in patients with congestive heart failure (CHF). Judging from the main site of action of low doses of atropine, we may be able to assess the functional state of the vagal center in the central nervous system. This study examines the clinical significance of heart rate (HR) response to a low dose of atropine in patients with CHF. Low and high doses of atropine were administered intravenously in 72 patients with CHF. HR after a low (parasympathomimetic) dose injection was assessed by the ratio Rm (minimal HR/basal HR), and after a high (parasympatholytic) dose by the ratio R1 (augmented HR/basal HR). Rm and R1 were related to indexes of CHF. Rm increased with progression of CHF (0.92 +/- 0.03 in New York Heart Association functional class I, 0.98 +/- 0.05 in class II, and 1.00 +/- 0.04 in class III). It also correlated with ejection fraction (r = -0.48, p <0.01) and more importantly, with peak oxygen uptake (r = -0.59, p <0.01). R1 exhibited weak correlation with basal HR (r = -0.33, p <0.05) and ejection fraction (r = 0.31, p <0.05), but had no correlation with other indexes. The vagal center may be already blunted in New York Heart Association class II with respect to increased Rm, which may be related to depressed exercise capacity. A low dose of atropine injection offers a simple and safe method for providing important information on the functional state of the vagal center in the central nervous system in patients with CHF.

Adult↗

Mild mitral regurgitation reduces exercise capacity in patients with idiopathic dilated cardiomyopathy.

We evaluated 30 patients with dilated cardiomyopathy (New York Heart Association functional Class II or III with medical treatment) to assess the effect of mild mitral regurgitation (MR) on exercise capacity in patients with congestive heart failure. They were classified into two groups based on results of left ventriculography: MR present (n = 10) and MR absent (n = 20). The severity of the MR by left ventriculography was grade I (mild) in all patients with MR. Steady-state hemodynamic data and angiographic data did not differ significantly between the two groups. Heart rate and systolic blood pressure at rest and in response to symptom-limited exercise testing did not differ between the groups. However, the peak work load was significantly lower in the group with MR than that in the group without MR (101 +/- 32 vs. 142 +/- 29 W, respectively; p < 0.005). Peak oxygen uptake and peak oxygen pulse were also significantly lower in the group with MR than in that without MR (peak oxygen uptake: 18 +/- 23 +/- 5 ml/min/kg; p < 0.05, peak oxygen pulse: 6.6 +/- 2.6 vs. 9.5 +/- 2.7 ml/min/beat: p < 0.01, respectively). Thus, mild MR had a detrimental effect on the exercise capacity in patients with dilated cardiomyopathy.

Adult↗

Characteristics of pulmonary artery pressure waveform for differential diagnosis of chronic pulmonary thromboembolism and primary pulmonary hypertension.

OBJECTIVES: The accurate diagnosis of chronic pulmonary thromboembolism (CPTE) is a prerequisite for life-saving surgical interventions. To help in the differential diagnosis of CPTE and primary pulmonary hypertension (PPH), we characterized the configuration of the pulmonary artery pressure waveform. BACKGROUND: Because CPTE predominantly involves the proximal arteries, whereas PPH involves the peripheral arteries, we hypothesized that patients with CPTE would have stiff or high resistance proximal arteries, whereas those affected by PPH would have high resistance peripheral arteries. These differences in the primary lesions would make arterial pulsatility relative to mean pressure larger in CPTE than in PPH. METHODS: In 34 patients with either CPTE (n = 22) or PPH (n = 12) whose pulmonary systolic pressure was > or = 50 mm Hg, we measured pulmonary artery pressure using a fluid-filled system that included a balloon-tipped flow-directed catheter. RESULTS: To quantify the magnitude of pulsatility relative to mean pressure, we normalized pulse pressure by mean pressure, hereinafter referred to as fractional pulse pressure (PPf). PPf was markedly higher in CPTE than in PPH (mean [+/-SD] 1.41 +/- 0.20 and 0.80 +/- 0.18, respectively, p < 0.001) and was diagnostic in separating the two groups without overlap. Similarly, the coefficient of variation of pulmonary artery pressure also separated the two groups without overlap (0.45 +/- 0.06 and 0.25 +/- 0.06, respectively, p < 0.001). Fractional time to half the area under the pressure curve separated the two groups reasonably well (0.35 +/- 0.02 and 0.43 +/- 0.03, respectively, p < 0.001). CONCLUSIONS: The analysis of pulsatility of pulmonary artery pressure is useful in the differential diagnosis of CPTE and PPH.

Adult↗

Effect of exercise on plasma adrenomedullin and natriuretic peptide levels in myocardial infarction.

1. We investigated the effect of exercise on plasma adrenomedullin, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations and studied the relationship between these peptides and haemodynamic parameters in nine patients with old myocardial infarction (MI) and in eight normal subjects. 2. The exercise protocol consisted of two fixed work loads (40 and 80 W) for 4 min each and venous blood samples were taken at rest, during each exercise stage and after exercise while monitoring the mean arterial pressure (MAP) and heart rate (HR). In MI, pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), left ventricular end-diastolic pressure (LVEDP) and cardiac output (CO) were measured throughout exercise. 3. Adrenomedullin levels did not significantly increase with exercise. Adrenomedullin levels correlated with PAP and PCWP at rest (P < 0.05). Atrial natriuretic peptide levels correlated with PAP, PCWP and LVEDP throughout exercise (P < 0.05) but, on multiple regression analysis, PCWP correlated only with ANP (P < 0.01). Brain natriuretic peptide levels correlated with LVEDP throughout exercise (P < 0.01) and its increment correlated closely with basal BNP levels at rest (P < 0.01). 4. These results suggest that adrenomedullin does not respond to the acute haemodynamic changes of exercise, whereas ANP responds to it and PCWP is the major stimulus factor. Brain natriuretic peptide responds to exercise in proportion to the basal synthesis of BNP in patients with left ventricular dysfunction and LVEDP may play a role in increasing BNP during exercise.

Adrenomedullin↗

Early afterdepolarizationlike activity in patients with class IA induced long QT syndrome and torsades de pointes.

Early afterdepolarizations (EADs) have been linked to the mechanism of torsades de pointes in long QT syndrome. The purpose of this study was to investigate the role of EADs in Class IA induced torsades de pointes. We studied nine patients with Class IA induced torsades de pointes at the time this arrhythmia was present (acute period, n = 7) and after Class IA therapy was discontinued (chronic period, n = 6). ECGs and monophasic action potentials were recorded in both periods. In the chronic period, electrophysiological studies were performed before and after disopyramide infusion. In the acute period, QTc interval was markedly prolonged (655 +/- 32 ms1/2), and EAD-like activity was recorded in all patients. QTc interval returned to normal (428 +/- 45 ms1/2) and EAD-like activity disappeared after discontinuation of IA drug. Although, in the chronic period, disopyramide infusion prolonged QTc interval from 428 +/- 48 ms1/2 to 479 +/- 31 ms1/2 and induced EAD in three of six patients, the degree was not as marked as observed in the acute period. EADs may play an important role in the genesis of long QT and torsades de pointes. Disopyramide infusion in the chronic period could not reproduce marked repolarization abnormalities and torsades de pointes.

Action Potentials↗

Dynamic vagosympathetic interaction augments heart rate response irrespective of stimulation patterns.

We previously demonstrated that tonic stimulation of either the sympathetic or the vagal nervous system augmented the dynamic heart rate response to the other of the two systems. We characterized the phenomenon as bidirectional augmentation of heart rate regulation. The question remained unanswered, however, as to whether such augmentation could occur under simultaneous dynamic stimulation of the two systems. The transfer characteristics from nerve stimulation to heart rate were well described by linear systems analysis, although no attention was paid to the aphasic nature of the stimuli in relation to each R-R interval. When we stimulated the two nerves with statistically independent Gaussian white noises, gain of the transfer function increased by 63.2 +/- 47.4% relative to individual stimulation (P < 0.05). When we stimulated the two nerves with mutually reciprocal Gaussian white noises, gain of the transfer function increased by 54.9 +/- 49.1% (P < 0.05). Thus simultaneous dynamic stimulation of the sympathetic and vagal systems bidirectionally augmented heart rate regulation irrespective of the pattern of the stimulation signals.

Animals↗