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Biomedical subjects

K Sunagawa

Publications and source records attributed to K Sunagawa.

At least 55 records · Page 3Linked to original sources
PubMed1999

Acute effect of tumor necrosis factor-alpha is minimal on mechanics but significant on energetics in blood-perfused canine left ventricles.

OBJECTIVES: We hypothesized that tumor necrosis factor-alpha (TNF-alpha) acutely alters left ventricular mechanoenergetics in blood-perfused hearts. To test this hypothesis, we examined the relation between left ventricular mechanics and energetics, both before and after infusion of TNF-alpha. DESIGN: Prospective, experimental study. SETTING: Research laboratory. SUBJECTS: Nine isolated, blood-perfused canine hearts. INTERVENTIONS: Recombinant human TNF-alpha (90 microg/min) was infused into the coronary circulation of the isolated hearts for 20 mins. MEASUREMENTS AND MAIN RESULTS: In the isolated, cross-circulated, blood-perfused canine left ventricles, left ventricular contractility was assessed through measurement of end-systolic elastance (Ees). Energetics were examined in terms of the end-systolic pressure-volume area-myocardial oxygen consumption (MVo2) relation. TNF-alpha concentration in coronary venous blood was >1000 ng/mL throughout the experiments. Nevertheless, infusion of TNF-alpha barely affected contractility acutely, i.e., there was a minimal decrease during the infusion (8.1+/-2.8% at 10 mins, p < .01) and a minimal increase after the infusion (11.2+/-2.5% at 10 mins, p< .01). Neither did the TNF-alpha infusion affect the slope of the end-systolic pressure-volume area-MVo2 relation. This finding indicated that the chemomechanical conversion efficiency remained unchanged. However, TNF-alpha infusion significantly increased the oxygen cost of contractility by 40% (1.25+/-0.13 vs. 1.75+/-0.24 mL oxygen.mL/mm Hg/beat, p< .05), indicating that MVo2 for the excitation-contraction coupling increased. CONCLUSIONS: TNF-alpha minimally alters left ventricular mechanics, but significantly changes energetics. The latter effect may result from changes in intracellular calcium handling.

Animals↗
PubMed1999

New simple methods for isolating baroreceptor regions of carotid sinus and aortic depressor nerves in rats.

We developed new methods for isolating in situ baroreceptor regions of carotid sinus and aortic depressor nerves in halothane-anesthetized rats. After ligation of the root of the external carotid artery, the internal carotid and pterygopalatine arteries were embolized with two ball bearings of 0.8 mm in diameter. Bilateral carotid sinus pressures were changed between 60 and 180 mmHg in 20-mmHg steps lasting 1 min each. The sigmoidal steady-state relationship between aortic and carotid sinus pressures in 11 rats indicated the maximum gain of the carotid sinus baroreflex to be -2. 99 +/- 0.75 at 120 +/- 5 mmHg. An in situ isolation of the baroreceptor area of the right aortic depressor nerve could be made by ligation of the innominate, common carotid, and subclavian arteries in 9 rats. Pressure imposed on the subclavian baroreceptor was altered between 40 and 180 mmHg in 20-mmHg steps lasting 1 min each. The sigmoidal steady-state relationship between the aortic depressor nerve activity and imposed pressure showed that the baroreceptor gain peaked at 118 +/- 4 mmHg. We established an easy approach to the rat baroreflex and baroreceptor research.

Animals↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

Regional cerebral blood flow during rewarming of cardiopulmonary bypass correlates with posthypothermic regional glucose use.

BACKGROUND AND OBJECTIVES: Although global measurements of cerebral blood flow and metabolism during and after profoundly hypothermic cardiopulmonary bypass have been performed both in experimental animals and in human beings, little is known about their regional changes. The purpose of this study was to investigate the changes in regional cerebral blood flow during profoundly hypothermic cardiopulmonary bypass and regional cerebral glucose use after cardiopulmonary bypass. METHODS: We measured regional cerebral blood flow with positron emission tomography during both the cooling (n=5) and rewarming (n=5) of hypothermic cardiopulmonary bypass in anesthetized dogs by continuously infusing 15O-labeled water. We altered the core temperature between 20 degrees and 37 degrees C. To assess the integrity of brain metabolism, we measured the regional cerebral glucose use by bolus injections of 18F-labeled 2-fluoro-2-deoxy-D-glucose. RESULTS: Regional cerebral blood flow decreased homogeneously during cooling. The regional cerebral blood flow at 20 degrees C was about one fourth of that at 37 degrees C. In contrast, at 24 degrees, 28 degrees , and 32 degrees C during rewarming, there were significant interregional differences in the regional cerebral blood flow for given temperatures (p=0.0075, 0.034, and 0.048, respectively). These interregional differences disappeared after rewarming. Although the regional cerebral blood flow significantly correlated with the regional cerebral glucose use in the control condition at 37 degrees C without cardiopulmonary bypass (r=0.75; p=0.00012), this correlation disappeared after profoundly hypothermic cardiopulmonary bypass (r=0.204; p=0.388). Regional cerebral blood flow at 32 degrees C during rewarming positively correlated with the regional cerebral glucose use after cardiopulmonary bypass (r=0.655; p=0.0017). CONCLUSION: The altered regional cerebral blood flow during rewarming of profoundly hypothermic cardiopulmonary bypass might affect regional brain metabolism.

Animals↗
PubMed1998

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↗
PubMed1998

The brain is a possible target for an angiotensin-converting enzyme inhibitor in the treatment of chronic heart failure.

BACKGROUND: Although many lines of evidence have shown beneficial effects of angiotensin-converting enzyme (ACE) inhibitors on patients with chronic heart failure (CHF) after myocardial infarction (MI), the target of ACE inhibitors still remains unclear. The objectives of the present study were to evaluate the dipsogenic response to centrally administered angiotensin and to examine the effect of central administration of an ACE inhibitor on cardiac remodeling in rats with CHF after large MI. METHODS AND RESULTS: The drinking responses to intracerebroventricular (i.c.v.) injections of saline and angiotensin I (100 ng) were measured in 22 male Sprague-Dawley rats with or without CHF at 2-5 weeks after the ligation of the left coronary artery. The dipsogenic responses to i.c.v. angiotensin I were significantly larger in rats with CHF and large MI (infarct size > 30%) than in sham-operated rats. Pretreatment with losartan abolished the significant difference between the two groups. Left ventricular (LV) weights of 32 surviving rats with CHF were measured after the 3-week subcutaneous infusions of vehicle (s.c.-VEH) and captopril (1 mg x kg(-1) x h(-1), s.c.-CAP) or the 3-week i.c.v. infusions of vehicle (i.c.v.-VEH) and captopril (50 microg x kg(-1) x h(-1), i.c.v.-CAP). The LV weights normalized by body weights of s.c.-CAP rats were significantly smaller than those of s.c.-VEH rats (1.73 +/- 0.04 vs 2.08 +/- 0.09 g x kg(-1); P < .01); those of i.c.v.-CAP rats were also significantly smaller than those of i.c.v.-VEH rats (1.84 +/- 0.08 vs 2.1 +/- 0.10 g x kg(-1); P < .05). CONCLUSIONS: These results suggest that the brain is a possible target for ACE inhibitors in the treatment of CHF after MI.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Dynamic transduction properties of in situ baroreceptors of rabbit aortic depressor nerve.

We developed a new method for isolating in situ baroreceptor regions of the rabbit aortic depressor nerve (ADN) and estimated the transfer function from pressure to afferent nerve activity in the frequency range of 0.01-5 Hz by a white noise technique. Complete isolation of the baroreceptor area of the right ADN was made in situ by ligation of the innominate artery and the right subclavian and common carotid arteries. We altered the pressure in the isolated baroreceptor area according to a binary quasi-white noise between 80 and 100 mmHg in 12 urethan-anesthetized rabbits. The gain increased two to three times as the frequency of pressure perturbation increased from 0.01 to 2 Hz and then decreased at higher frequencies. The phase slightly led below 0.2 Hz. The squared coherence value was > 0.8 in the frequency range of 0.01-4 Hz. The step responses estimated from the transfer function were indistinguishable from those actually observed. We conclude that the baroreceptor transduction of the ADN is governed by linear dynamics under the physiological operating pressure range.

Afferent Pathways↗