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K Sunagawa

Publications and source records attributed to K Sunagawa.

At least 73 records · Page 4Linked to original sources
PubMed1998

A new method to measure regional myocardial time-varying elastance using minute vibration.

We developed a new technique to evaluate regional myocardial elastance using minute vibration. In 13 isolated cross-circulated canine hearts, we applied small sinusoidal vibrations of displacement to the left ventricular surface at various frequencies (50-100 Hz). Using the measured displacement and force between the vibrator head and myocardium, we derived myocardial elastance on the basis of the equation of motion for a given moment of the cardiac cycle. Simultaneous solution of the equations of motion at different frequencies yielded a unique value of elastance. Time-varying myocardial elastance increased from diastole (0.028 +/- 0.211 x 10(6) dyn/cm) to systole (0.833 +/- 0.391 x 10(6) dyn/cm). The end-systolic elastance (ees) linearly correlated with end-systolic left ventricular elastance (r = 0.717, P < 0.001) and also with the end-systolic Young's modulus (r = 0.874, P < 0.0001). We also measured ees at both ischemic and nonischemic regions during coronary occlusion. Young's modulus, estimated by normalizing ees by the wall thickness and by the estimated mass, did not change significantly at the nonischemic regions, whereas it decreased significantly from 2.303 +/- 0.556 to 1.173 +/- 0.370 x 10(6) dyn/cm2 at the ischemic region after coronary occlusion (P < 0.005). We conclude that this technique is useful for the quantitative assessment of regional myocardial elastance.

Animals↗
PubMed1998

ESPVR of in situ rat left ventricle shows contractility-dependent curvilinearity.

We developed a miniaturized conductance catheter for in situ rat left ventricular (LV) volumetry. After the validation study of the conductance volumetry in 11 rats, we characterized the end-systolic pressure-volume relationship (ESPVR) in 24 sinoaortic-denervated, vagotomized and urethan-anesthetized rats. Stroke volume (SV) measured with the conductance catheter correlated closely with that measured by electromagnetic flowmetry (r > 0.95). No significant difference was found between the in situ LV end-diastolic volumes measured by conductance volumetry and postmortem morphometry; a linear regression analysis indicated that the correlation coefficient was 0.934, that the slope was not significantly different from 1, and that the intercept was not significantly different from 0. During cardiac sympathotonic conditions, the ESPVR was curvilinear. The estimated slope of ESPVR (end-systolic elastance, Ees) by quadratic curve fitting at end-systolic pressure of 100 mmHg was 2,647 +/- 846 mmHg/ml. Bilateral cervical and stellate ganglionectomy depressed contractility and made the ESPVR linear; a quadratic equation did not improve the fit. Ees was 946 +/- 55 mmHg/ml with the volume-axis (V0) intercept of 0.076 +/- 0.007 ml. Administration of propranolol (1 mg/kg) further reduced Ees (573 +/- 61 mmHg/ml, P < 0.001) and increased V0 slightly (0.091 +/- 0.011 ml). We conclude that the conductance catheter method is useful for the assessment of the ESPVR of the in situ rat left ventricle and that the ESPVR displays contractility-dependent curvilinearity.

Animals↗
PubMed1998

Dynamic sympathetic regulation of left ventricular contractility studied in the isolated canine heart.

We investigated the dynamic sympathetic regulation of left ventricular end-systolic elastance (Ees) using an isolated canine ventricular preparation with functioning sympathetic nerves intact. We estimated the transfer function from both stellate ganglion stimulation to Ees and ganglion stimulation to heart rate (HR) for both left and right ganglia by means of the white noise approach and transformed those transfer functions into corresponding step responses. The HR response was much larger with right sympathetic stimulation than with left sympathetic stimulation (4.3 +/- 1.4 vs. 0.7 +/- 0.6 beats . min-1 . Hz-1, P < 0.01). In contrast, the Ees responses without pacing were not significantly different between left and right sympathetic stimulation (0.72 +/- 0.34 vs. 0.76 +/- 0. 42 mmHg . ml-1 . Hz-1). Fixed-rate pacing significantly decreased the Ees response to right sympathetic stimulation (0.53 +/- 0.43 mmHg . ml-1 . Hz-1, P < 0.01), but not to left sympathetic stimulation (0.67 +/- 0.32 mmHg . ml-1 . Hz-1, not significant). Although the mechanism by which the sympathetic nervous system regulates cardiac contractility is different depending on whether the left or right sympathetic nerves are activated, this difference does not affect the apparent response of Ees to dynamic sympathetic stimulation.

Animals↗
PubMed1998

Accumulation of cAMP augments dynamic vagal control of heart rate.

Recent investigations in our laboratory using a Gaussian white noise perturbation technique have shown that simultaneous sympathetic stimulation augmented the gain of the transfer function from vagal stimulation frequency to heart rate response. However, the mechanism of that augmentation remains to be elucidated. In this study, we examined in anesthetized rabbits how three pharmacological interventions known to cause intracellular accumulation of cAMP affected the transfer function. Isoproterenol (0.3 microg . kg-1 . min-1 iv) increased the dynamic gain of transfer function from 7.12 +/- 0.67 to 12.4 +/- 1.21 beats . min-1 . Hz-1 (P < 0.05) without changing the corner frequency or the lag time. Similar augmentations were observed when forskolin (5 microg . kg-1 . min-1 iv) or theophylline (20 mg/kg iv) was administered under conditions of beta-adrenergic blockade. These results suggest that the accumulation of cAMP at postjunctional effector sites contributes, at least in part, to the sympathetic augmentation of the dynamic vagal control of heart rate.

Animals↗
PubMed1998

Cholinesterase affects dynamic transduction properties from vagal stimulation to heart rate.

Recent investigations in our laboratory using a Gaussian white noise technique showed that the transfer function representing the dynamic properties of transduction from vagus nerve activity to heart rate had characteristics of a first-order low-pass filter. However, the physiological determinants of those characteristics remain to be elucidated. In this study, we stimulated the vagus nerve according to a Gaussian white noise pattern to estimate the transfer function from vagal stimulation to the heart rate response in anesthetized rabbits and examined how changes in acetylcholine kinetics affected the transfer function. We found that although increases in the mean frequency of vagal stimulation from 5 to 10 Hz did not change the characteristics of the transfer function, administration of neostigmine (30 microg . kg-1 . h-1 iv), a cholinesterase inhibitor, increased the dynamic gain from 8.19 +/- 3.66 to 11.7 +/- 4.88 beats . min-1 . Hz-1 (P < 0.05), decreased the corner frequency from 0.12 +/- 0.05 to 0.04 +/- 0.01 Hz (P < 0.01), and increased the lag time from 0.17 +/- 0.12 to 0.27 +/- 0.08 s (P < 0.05). These results suggest that the rate of acetylcholine degradation at the neuroeffector junction, rather than the amount of available acetylcholine, plays a key role in determining the dynamic properties of transduction from vagus nerve activity to heart rate.

Acetylcholine↗
PubMed1998

Preload and incident angle independent index of left ventricular contractility determined by continuous wave Doppler echocardiography.

Although left ventricular dP/dtmax can be accurately assessed using Doppler echocardiography, the fact that Doppler-derived dP/dtmax depends both on preload and Doppler incident angle limits its clinical value. We investigated the clinical usefulness of Doppler-derived (dP/dtmax)/IP (IP, isovolumic pressure), which is known to be relatively insensitive to preload and theoretically independent of the incident angle in 9 subjects. We conclude that Doppler-derived (dP/dtmax)/IP is relatively insensitive to both the incident angle and preload. In addition to its noninvasiveness, these unique features makes it very attractive as a clinical index of ventricular contractility.

Echocardiography, Doppler↗
PubMed1997

Negative inotropic effect of basic fibroblast growth factor on adult rat cardiac myocyte.

BACKGROUND: Basic fibroblast growth factor (bFGF) is highly expressed in the myocardium in some cardiac disorders, such as ischemia-reperfusion and cardiac allograft rejection. However, whether bFGF has any effects on myocardial contraction is unknown. METHODS AND RESULTS: We examined the effects of bFGF on myocardial contractility using isolated adult rat cardiac myocyte preparations. bFGF exerted a direct negative inotropic effect that was concentration and time dependent. The pretreatment of myocytes with a neutralizing anti-bFGF antibody (100 ng/mL) abolished the negative inotropic effects of bFGF (100 ng/mL). Platelet-derived growth factor (12.5 ng/mL) and transforming growth factor-beta (1 ng/mL) did not exert such effects, which indicated that bFGF-induced negative inotropism was considered to be specific for this growth factor. bFGF decreased the peak intracellular Ca2+ transient by 46% during systole. The enhanced production of nitric oxide was unlikely to be responsible for the bFGF-induced negative inotropic effect. CONCLUSIONS: bFGF, primarily a potent growth promoter, produced acute negative inotropic effects in the adult cardiac myocyte that could have resulted from alterations in intracellular Ca2+ homeostasis. The negative inotropic effect of bFGF may contribute to myocardial dysfunction associated with ischemia-reperfusion injury and heart transplant rejection.

Animals↗
PubMed1997

omega-Conotoxin GVIA and desipramine insensitive norepinephrine efflux from cardiac sympathetic nerve terminal.

Using dialysis technique, prominent accumulation of norepinephrine (NE) in the myocardial interstitial space was observed under local administration of a monoamine oxidase inhibitor (pargyline, 10 mM), and a vesicle uptake inhibitor (reserpine, 10 microM). Accumulation of NE in the myocardial interstitial space was associated with a reduction of dihydroxyphenylglycol levels. Pretreatment with omega-conotoxin GVIA (10 microM) or desipramine (10 microM) did not suppress this response. A brisk increase in dialysate NE levels might occur as a consequence of exocytotic or neurotransporter insensitive efflux of NE.

Adrenergic Fibers↗
PubMed1997

Aortic blood momentum--the more the better for the ejecting heart in vivo?

OBJECTIVES: The aim of the present study was to test two hypotheses: (1) the momentum of the blood flowing out of the left ventricle toward the aorta (inertia force) plays an important role in the initiation of decay and the maximum rate of decay (peak (-dP/dt)) of left ventricular pressure (P); (2) a normal heart itself generates the inertia force which enhances its function. METHODS: The contribution of the inertia force to (-dP/dt) was theoretically given as rho c alpha, where rho is the blood density, c the pulse wave velocity, and alpha the deceleration rate of aortic blood flow. The correlations of peak (-dP/dt) with rho c alpha and with the time constant (tau) of the pressure decay during isovolumic relaxation, which was considered to represent myocardial relaxation characteristics, were compared in seven dogs. We developed a method of grading the strength of the inertia force, using the phase loop of left ventricular pressure (dP/dt vs. P relation). The method was applied to the records of 25 patients with ischemic heart disease, from which high fidelity left ventricular pressure recordings were available. RESULTS: The correlation of peak (-dP/dt) with rho c alpha was much higher than with tau (0.75 vs. -0.46). 16 of the 25 patients showed evidence of the inertia force. However, other patients showed no inertia force. The strength of the inertia force showed a significant (P < 0.05) correlation with left ventricular end-diastolic pressure (r = -0.46), cardiac index (r = 0.62), stroke volume index (r = 0.69), ejection fraction (r = 0.46), and peak (-dP/dt) (r = 0.56). CONCLUSION: The inertia force of late systolic aortic flow contributed to ventricular relaxation in the normal heart.

Aged↗
PubMed1997

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↗
PubMed1997

Vasodilator effects of adrenomedullin on small pulmonary arteries and veins in anaesthetized cats.

1. This study was conducted to determine adrenomedullin (AM) action sites in the pulmonary vascular bed and the relation between its vasodilator effects and vascular tone. Moreover, an examination was made into whether calcitonin gene-related peptide (CGRP) receptors mediate pulmonary vasodilatations induced by AM. To this end, we directly measured internal diameter (i.d.) changes in small pulmonary arteries and veins (100-1100 microns i.d.) by use of an X-ray television system on the in vivo cat lung. 2. Under control (resting vascular tone) conditions, AM injections into the left main pulmonary artery caused dose-related i.d. increases in both small arteries and veins. The mean i.d. increase of the 100-1100 microns arteries (4 +/- 1, 11 +/- 2, and 17 +/- 2% with 0.01, 0.1, and 1 nmol kg-1 AM, respectively) was significantly larger than that for the veins (1 +/- 1, 5 +/- 2, and 7 +/- 2% with 0.01, 0.1 and 1 nmol kg-1 AM, respectively) whatever the injected dose of AM. 3. When unilobar hypoxia (5% O2) had decreased the i.d. of the 100-1100 microns arteries and veins by 16 +/- 3 and 6 +/- 3%, respectively, AM (0.1 nmol kg-1) was able to induce significantly larger i.d. increases in the arteries (28 +/- 3%) and veins (11 +/- 3%) than those under control conditions. 4. The AM-induced i.d. response pattern in the serially connected pulmonary arteries was quite different from that induced by CGRP; AM caused a greater increase in smaller vessels (100-500 microns) than in larger vessels (500-1100 microns). In the case of CGRP, a greater increase was observed in the larger vessels. 5. CGRP8-37 (100 nmol kg-1, i.v., followed by a continuous infusion of 0.2 nmol kg-1 min-1) had no significant effect on the i.d. increase induced by AM (0.1 nmol kg-1) in any serial segments of the arteries and veins. 6. The results indicate that, in the cat, AM induces greater vasodilatation in small pulmonary arteries and lesser vasodilatation in small veins, the maximum dilatation being in the more peripheral arterial segment (100-500 microns). The vasodilator effect of AM was enhanced when vascular tone was elevated. The data suggest that the AM-induced pulmonary vasodilatation is not mediated by CGRP receptors but by its own specific receptor.

Adrenomedullin↗
PubMed1997

Experimental myelitis caused by herpes simplex virus type 2 in C57BL/6N and BALB/cN mice.

Intraperitoneal and intracranial inoculation of herpes simplex virus type 2 (HSV 2) into BALB/cN and C57BL/6N mice was carried out to induce experimental myelitis. The myelitis was clearly observed in C57BL/6N mice following intraperitoneal inoculation. Within 24 hours before death, the mice showed urinary and rectal incontinence and paraplegia of the hind legs. Randomly distributed, severe necrosis was demonstrated in the spinal cord, mainly at the lower cord. In BALB/cN mice the clinical symptoms were not clearly observed, as the mice died shortly after their onset. Although spinal cord necrosis was more prominent in C57BL/6N mice than BALB/cN mice, brain necrosis was only found in the latter, and not in the former. Both strains of mouse showed marked nuclear pyknosis of the nerve cells and slight nuclear pyknosis of the astrocytes in the brain where HSV 2 antigen was demonstrated immunohistochemically. The antigen was also detected in the necrotic spinal cord. In contrast, intracranial inoculation of the virus into both strains did not cause myelitis. Spinal cord necrosis was not demonstrated and virus DNA was not detected, by PCR, in spinal cord samples. In the brain, however, the virus was demonstrated by both PCR and immunohistochemistry.

Animals↗
PubMed1997

A new, concise dialysis approach to assessment of cardiac sympathetic nerve terminal abnormalities.

We applied a dialysis technique to the hearts of anesthetized cats and examined whether the concentration of dialysate norepinephrine (NE) reflected NE disposition at the cardiac sympathetic nerve terminals. Dialysis probes were implanted in the left ventricular wall, and dialysate NE concentrations were measured as an index of myocardial interstitial NE levels. Stimulation of stellate ganglia significantly increased dialysate NE responses that were suppressed by local administration of an NE-releasing inhibitor (omega-conotoxin GVIA, 10 microM). Increments in basal dialysate NE levels were correlated with concentrations of a locally administered neuronal uptake blocker (desipramine; 1, 10, and 100 microM). Desipramine (100 microM) augmented stimulation-induced dialysate NE responses. Local administration of a neuronal vesicle uptake blocker (reserpine, 1 and 10 microM) did not alter dialysate NE levels but increased dialysate dihydroxyphenylglycol levels. An NE-releasing amine (tyramine, 100 microg/ml) was locally administered to examine NE storage capacity at the nerve terminal. The tyramine-induced NE-releasing response was completely abolished by pretreatment with reserpine (1 mg/kg i.p.). Thus cardiac dialysis with local administration of a pharmacological tool offers a new, concise approach to assessment of neuronal NE release, uptake, vesicle uptake, and storage capacity by cardiac sympathetic nerve terminals.

Animals↗
PubMed1997

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↗
PubMed1997

Inhibition of NO synthesis minimally affects the dynamic baroreflex regulation of sympathetic nerve activity.

The purpose of this investigation was to examine the role of nitric oxide (NO) in the dynamic baroreflex regulation of cardiac sympathetic nerve activity. In anesthetized rabbits, we imposed random pressure perturbations on the isolated carotid sinuses before and after the intravenous administration of NG-monomethyl-L-arginine. We characterized the dynamic properties relating carotid sinus pressure input to sympathetic nerve activity by means of a transfer function analysis. NG-monomethyl-L-arginine decreased the corner frequency of the transfer function (0.100 +/- 0.054 vs. 0.074 +/- 0.035 Hz; P < 0.05), whereas other parameters such as the steady-state gain and transmission lag time remained unchanged. Although cursory examination of these findings would suggest a possible contribution of NO in the dynamic baroreflex regulation of sympathetic nerve activity, quantitative assessment of the transfer function reveals only a minimal effect on the baroreflex regulation of arterial pressure, particularly under closed-loop conditions. We conclude that NO noticeably affects the dynamic baroreflex regulation of sympathetic nerve activity. However, it may not significantly affect arterial pressure regulation through central modulation of the carotid sinus baroreflex.

Animals↗
PubMed1997

Inhibition of NO synthesis does not potentiate dynamic cardiovascular response to sympathetic nerve activity.

We examined whether the inhibition of nitric oxide (NO) synthesis potentiates the dynamic sympathetic regulation of the cardiovascular system through the baroreflex. In anesthetized rabbits, we imposed random pressure perturbations on the isolated carotid sinuses to evoke random changes in sympathetic nerve activity (SNA). We estimated the transfer functions from SNA to both aortic pressure (AoP) and heart rate (HR). The inhibition of NO synthesis by NG-monomethyl-L-arginine (L-NMMA, 40 mg/ kg) altered neither the transfer function from SNA to AoP nor that from SNA to HR. In contrast, sodium nitroprusside (3-6 micrograms.kg-1.min-1) significantly decreased the steady-state gain (40.3 +/- 11.7% of the control, P < 0.05) of the transfer function from SNA to AoP without affecting the HR responses. We conclude that the basal release of NO may have a role in the tonic blood pressure regulation, whereas it may not be involved in the dynamic sympathetic regulation of AoP or HR through the baroreflex.

Animals↗
PubMed1997

Closed-loop identification of carotid sinus baroreflex open-loop transfer characteristics in rabbits.

In the circulatory system, a change in blood pressure operates through the baroreflex to alter sympathetic efferent nerve activity, which in turn affects blood pressure. Existence of this closed feedback loop makes it difficult to identify the baroreflex open-loop transfer characteristics by means of conventional frequency domain approaches. Although several investigators have demonstrated the advantages of the time domain approach using parametric models such as the autoregressive moving average model, specification of the model structure critically affects their results. Thus we investigated the applicability of a nonparametric closed-loop identification technique to the carotid sinus baroreflex system by using an exogenous perturbation according to a binary white-noise sequence. To validate the identification method, we compared the transfer functions estimated by the closed-loop identification with those estimated by open-loop identification. The transfer functions determined by the two identification methods did not differ statistically in their fitted parameters. We conclude that exogenous perturbation to the baroreflex system enables us to estimate the open-loop baroreflex transfer characteristics under closed-loop conditions.

Animals↗