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Biomedical subjects

T Kawada

Publications and source records attributed to T Kawada.

At least 91 records · Page 5Linked to original sources

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↗

Summation of dynamic transfer characteristics of left and right carotid sinus baroreflexes in rabbits.

Although interactions among parallel negative-feedback baroreflex systems have been extensively investigated with respect to their steady-state responses, the dynamic interactions remain unknown. In anesthetized, vagotomized, and aortic-denervated rabbits, we perturbed isolated intracarotid sinus pressure (CSP) unilaterally or bilaterally around the physiological operating pressure according to binary white noise. The neural arc transfer function from CSP to cardiac sympathetic nerve activity (SNA) and the peripheral arc transfer function from SNA to aortic pressure were estimated. The gain values of the neural arc at 0.01 Hz estimated by the left (L) and right (R) CSP perturbations were 0.94 +/- 0.31 and 0.96 +/- 0.25, respectively. The gain value increased to 2.17 +/- 0.97 during the bilateral identical CSP perturbation and was not significantly different from L + R. The phase values of the neural arc did not differ among protocols. No significant differences were observed in the peripheral arc transfer functions among protocols. We conclude that summation of the dynamic transfer characteristics of the bilateral carotid sinus baroreflexes around the physiological operating pressure approximates simple addition.

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↗

Novel method to estimate ventricular contractility using intraventricular pulse wave velocity.

We developed a novel technique for estimating ventricular contractility using intraventricular pulse wave velocity (PWV). In eight isolated, cross-circulated canine hearts, we used a fast servo pump to inject a volume pulse into the base of the left ventricular chamber at late diastole and at late systole. We measured the transit time of the volume pulse wave as it traversed the distance from base to apex and calculated the intraventricular PWV. The intraventricular PWV increased from diastole (2.3 +/- 0.4 m/s) to systole (11.7 +/- 2.4 m/s, P < 0.0001 vs. diastole). The square of the intraventricular PWV at late systole correlated linearly with the left ventricular end-systolic elastance (r = 0.939, P < 0.0001) and with the end-systolic Young's modulus (r = 0.901, P < 0.0001). Moreover, the intraventricular PWV was insensitive to preload. We conclude that the intraventricular PWV at late systole reflects left ventricular end-systolic elastance reasonably well. The fact that estimation of PWV does not require volume measurement or load manipulation makes this technique an attractive means of assessing ventricular contractility.

Animals↗

Simultaneous identification of static and dynamic vagosympathetic interactions in regulating heart rate.

We earlier reported that stimulation of either one of the sympathetic and vagal nerves augments the dynamic heart rate (HR) response to concurrent stimulation of its counterpart. We explained this phenomenon by assuming a sigmoidal static relationship between nerve activity and HR. To confirm this assumption, we stimulated the sympathetic and/or vagal nerve in anesthetized rabbits using large-amplitude Gaussian white noise and determined the static and dynamic characteristics of HR regulation by a neural network analysis. The static characteristics approximated a sigmoidal relationship between the linearly predicted and the measured HRs (response range: 212.4 +/- 46.3 beats/min, minimum HR: 96.0 +/- 28.4 beats/min, midpoint of operation: 196.7 +/- 31.3 beats/min, maximum slope: 1.65 +/- 0.51). The maximum step responses determined from the dynamic characteristics were 7.9 +/- 2.9 and -14.0 +/- 4.9 beats. min-1. Hz-1 for the sympathetic and the vagal system, respectively. Because of these characteristics, changes in sympathetic or vagal tone alone can alter the dynamic HR response to stimulation of the other nerve.

Acoustic Stimulation↗

Neuronal uptake affects dynamic characteristics of heart rate response to sympathetic stimulation.

Recently, studies in our laboratory involving the use of a Gaussian white noise technique demonstrated that the transfer function from sympathetic stimulation frequency to heart rate (HR) response showed dynamic characteristics of a second-order low-pass filter. However, determinants for the characteristics remain to be established. We examined the effect of an increase in mean sympathetic stimulation frequency and that of a blockade of the neuronal uptake mechanism on the transfer function in anesthetized rabbits. We found that increasing mean sympathetic stimulation frequency from 1 to 4 Hz significantly (P < 0.01) decreased the dynamic gain of the transfer function without affecting other parameters, such as the natural frequency, lag time, or damping coefficient. In contrast, the administration of desipramine (0.3 mg/kg iv), a neuronal uptake blocking agent, significantly (P < 0.01) decreased both the dynamic gain and the natural frequency and prolonged the lag time. These results suggest that the removal rate of norepinephrine at the neuroeffector junction, rather than the amount of available norepinephrine, plays an important role in determining the low-pass filter characteristics of the HR response to sympathetic stimulation.

Adrenergic Uptake Inhibitors↗

Thermoregulatory responses of the inbred heat-tolerant FOK rat to cold.

The responses of inbred heat-tolerant FOK rats to cold were compared with those of Wistar King A/H (WKAH) and Std:Wistar (WSTR) strains. The fall of colonic temperature during cold exposure was unexpectedly smaller in FOK than in other groups, but the onset of shivering was delayed in FOK. Norepinephrine (NE)-induced in vivo oxygen consumption and the mitochondrial uncoupling protein 1 level of brown adipose tissue (BAT) were not different among the groups, but the cold-induced increases in in vivo oxygen consumption as well as plasma glycerol and free fatty acids were higher in FOK than in other groups. In vitro NE-induced oxygen consumption of BAT was less in FOK than WSTR, but not WKAH. The magnitude of the NE-induced increase in blood flow through BAT was higher in FOK than in other groups. These results suggest that FOK paradoxically have a high capacity for nonshivering thermogenesis in spite of their high capacity for heat tolerance, probably due to an increased lipid utilization and improved circulation of BAT.

Adaptation, Physiological↗

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↗

Ultrasonography evaluation of abdominal fat in live rats.

We have developed a new noninvasive method of estimating abdominal fat volume in live rats using ultrasonography. By this method, cross sections of perirenal (retroperitoneal) fat tissue, which is an abdominal fat, at the renal vein level could be identified and the area determined. The perirenal fat in Wistar rats (wide body weight range, 111.4 to 497.3 g; limited range, 300.1 to 337.9 g) measured by ultrasonography was compared with the actual fat tissue weight. The cross-sectional area of perirenal fat tissue was significantly correlated to the actual whole tissue weight. Using this procedure, we examined the changes of perirenal fat stores during fasting. Consequently, the cross-sectional area of perirenal fat and its actual weight decreased in parallel. Total body electrical conductivity (TOBEC) is currently used to measure fat-free mass (FFM) and indirectly predicts total body fat mass of live laboratory animals. The body fat distribution, that is, the location of adipose tissue in the abdominal region, is closely associated with obesity-related diseases. Therefore, it is important to focus not only on the accumulation of total body fat, but also on that of abdominal fat. The present ultrasonographic method is considered to be useful for repeated noninvasive measurement of abdominal fat in the live rat.

Abdomen↗

Five cases of asymptomatic spontaneous pneumothorax.

Asymptomatic spontaneous pneumothorax (ASPT) is an uncommon condition. Between January 1, 1989 and December 31, 1997, 269 patients were admitted to our department with spontaneous pneumothorax. Of the 269 patients, 5 had no symptoms at the time of discovery. Their ages ranged from 15 to 61 years (mean, 37.8 years), and all of them were male. Of the 5 patients with no complaints, 2 had bilateral metachronous pneumothoraces and 3 had hemilateral pneumothorax. All of these ASPTs were revealed by chest roentgenographs taken during medical examinations or follow-up studies relating to other diseases. The mean value of body mass index (BMI) was 19.96 +/- 1.4 (range 18.7 - 22.1). Two of the 5 patients underwent bilateral partial lung resection. Histopathological examination of the resected specimens showed elastofibrosis, scar formation, and an interruption of the elastic fiber of the pleura. In these 5 cases, clinical courses were uneventful, and relapse of the pneumothorax did not occur. Clinical physicians should be aware of the possibility of asymptomatic pneumothorax, as well as the optimal radiographic techniques for revealing small pneumothoraces.

Adolescent↗

[Risk assessment in urgent or emergent coronary artery bypass grafting for acute coronary syndrome].

Emergent coronary artery bypass grafting (CABG) for the treatment of acute coronary syndrome has increased the operative mortality. Forty-nine patients underwent urgent or emergent CABG for the treatment of medically refractory unstable angina in 10 patients, and for acute myocardial infarction (AMI) in 39 patients. Ten operative deaths were occurred in the AMI patients, and the mortality was 20 percent. The preoperative risk factors were evaluated in 10 patients who died in the operative period. Cardiopulmonary resuscitation before operation, intra aortic balloon pumping, the use of catecholamine, and intubation with or without percutaneous cardiopulmonary support revealed operative risk factor. Because the patients who have preoperatively shock, it seemed to be needed that the rescue of the patients should improve the clinical results for urgent or emergent CABG.

Adult↗

[Lung resection affects the postoperative arrhythmia and electrocardiographic axis deviation].

After lung lobectomy or pneumonectomy, the mediastinal shift and diaphragmatic elevation are occurred. Because this phenomenon may affect the heart positional change, we studied the electrocardiographic QRS axis in the frontal plane (from leads I and III) and the postoperative arrhythmia. Seventy three patients who had no heart disease including arrhythmia before the surgery were recorded their electrocardiogram (ECG) before their surgery and after their discharge. When the postoperative ECG was recorded, they had no respiratory failure nor cancer recurrence, and their lungs were fully expanded in their thoracic cages. After right upper lobectomy (19 cases), the axis was twisted rightward slightly (2.1 degrees). Right middle lobectomy (2 cases, 9.5 degrees) and right upper and middle lobectomies (3 cases, 7.3 degrees) twisted the heart axes more rightwards. Right lower lobectomy (12 cases, -1.0 degree) and right middle and lower lobectomies (3 cases, -17.7 degrees) contorted their axes leftwards and right pneumonectomy (5 cases, 31.4 degrees) rightwards. The axes were turned rightwards after the left upper lobectomy (18 cases, 2.8 degrees) and the left lower lobectomy (7 cases, 3.9 degrees). Left pneumonectomy (4 cases, -4.0 degrees) twisted the axis leftwards. After the surgery, arrhythmias were recorded in 14 cases and, among these patients, 5 cases were required the oral anti-arrhythmic medication. Most of these cases changed their heart axes after the surgery and it is suggested that the axial deviation may contribute to their postoperative arrhythmia.

Arrhythmias, Cardiac↗

Liquid chromatographic determination of myocardial interstitial epinephrine.

This study describes a high-performance liquid chromatographic method with electrochemical detection (HPLC-ED) for monitoring of epinephrine (Epi) in the myocardial interstitial space. The in vitro detection limit for Epi was 200 fg in a 50-microl injection. Using a cardiac dialysis technique, 60-microl dialysates were sampled from the myocardial interstitial space (6-min fractions). After an alumina procedure, the dialysate Epi concentration was measured using the HPLC-ED system. Although the basal Epi concentration was undetectable, local administration of desipramine increased Epi concentration of the dialysate to 38.1+/-18.5 pg/ml. This system affords a new possibility for estimating myocardial interstitial Epi level.

Animals↗

Norepinephrine efflux evoked by potassium chloride in cat sympathetic nerves: dual mechanism of action.

Using a dialysis technique, prominent efflux of norepinephrine (NE) from cardiac sympathetic nerve endings was observed under local administration of potassium chloride (KCl, 100 mM). KCl induced NE efflux was suppressed by omega-conotoxin GVIA or desipramine but residual efflux of NE was still detectable. In the presence of omega-conotoxin GVIA, KCl induced efflux of NE was augmented by pretreatment with reserpine, indicating that this efflux of NE was derived from axoplasma with neurotransporter. These data suggest that a KCl induced brisk increase in dialysate NE levels might occur as a consequence of exocytotic NE release and carrier mediated outward NE transport from nerve endings.

Adrenergic Uptake Inhibitors↗

Thiazolidinedione induces the adipose differentiation of fibroblast-like cells resident within bovine skeletal muscle.

To investigate the role of peroxisome proliferator-activated receptor gamma (PPARgamma) in adipocyte formation within the skeletal muscle of beef cattle, fibroblast-like cells were isolated from the longissimus muscle of cattle and cultured with activators of murine PPARgammaA thiazolidinedione T-174, which is a specific ligand for PPARgamma, stimulated adipose differentiation (evaluated by counting differentiated adipocytes under microscopic observation) in a dose-dependent fashion. A peroxisome proliferator Wy14,643 which strongly activates the alpha isoform of murine PPAR also stimulated differentiation but its potency was weaker than that of T-174. Unexpectedly, 15-deoxy-Delta12,14-prostaglandin J2, which is believed to be an endogenous ligand for PPARgamma, could not induce adipose differentiation in doses which have been found to be effective on rodent cells. Immunoblotting analysis confirmed the significant expression of PPARgamma protein in fibroblast-like cell cultures prepared from bovine skeletal muscle. In conclusion, bovine skeletal muscle contains adipose precursor cells expressing functionally active PPARgamma.

Adipocytes↗

Dynamic nonlinear vago-sympathetic interaction in regulating heart rate.

Although the characteristics of the static interactions between the sympathetic and parasympathetic nervous systems in regulating heart rate have been well established, how the dynamic interaction modulates the heart rate response remains unknown. Thus, we investigated the dynamic interaction by estimating the transfer function from nerve stimulation to heart rate, using band-limited Gaussian white noise, in anesthetized rabbits. Concomitant tonic vagal stimulation at 5 and 10 Hz increased the gain of the transfer function relating dynamic sympathetic stimulation to heart rate by 55.0%+/-40.1% and 80.7%+/-50.5%, respectively (P < 0.05). Concomitant tonic sympathetic stimulation at 5 and 10 Hz increased the gain of the transfer function relating dynamic vagal stimulation to heart rate by 18.2%+/-17.9% and 24.1%+/-18.0%, respectively (P < 0.05). Such bidirectional augmentation was also observed during simultaneous dynamic stimulation of the sympathetic and vagal nerves independent of their stimulation patterns. Because of these characteristics, changes in sympathetic or vagal tone alone can alter the dynamic heart rate response to stimulation of the other nerve. We explained this phenomenon by assuming a sigmoidal static relationship between autonomic nerve activity and heart rate. To confirm this assumption, we identified the static and dynamic characteristics of heart rate regulation by a neural network analysis, using large-amplitude Gaussian white noise input. To examine the mechanism involved in the bidirectional augmentation, we increased cytosolic adenosine 3',5'-cyclic monophosphate (cAMP) at the postjunctional effector site by applying pharmacological interventions. The cAMP accumulation increased the gain of the transfer function relating dynamic vagal stimulation to heart rate. Thus, accumulation of cAMP contributes, at least in part, to the sympathetic augmentation of the dynamic vagal control of heart rate.

Animals↗

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↗