Search PubMed⌕ Search

Biomedical subjects

K Sunagawa

Publications and source records attributed to K Sunagawa.

At least 91 records · Page 5Linked to original sources

Vagal stimulation decreases left ventricular contractility mainly through negative chronotropic effect.

Although an increase in vagal tone is known to slow heart rate (HR), whether it also depresses left ventricular contractility through mechanisms independent of the bradycardic effect remains unknown. The chief aim of this investigation, therefore, was the separation of the observed vagally mediated depression of ventricular contractility into direct and indirect vagal effects, the latter resulting via negative chronotropism. In 12 anesthetized, sympathectomized open-chest rabbits, we measured left ventricular contractility through determination of the end-systolic elastance (Ees). We found that tonic vagal stimulation administered at 0, 5, and 10 Hz decreased both HR (226.9 +/- 39.7, 201.9 +/- 25.7, and 171.3 +/- 18.5 beats/min, respectively; P = 0.0003) and Ees (109.5 +/- 25.7, 85.1 +/- 34.1, and 71.9 +/- 33.1 mmHg/ml, respectively; P = 5 x 10(-6)) in a frequency-dependent fashion. However, we observed that as long as HR was kept constant through fixed-rate atrial pacing, vagal stimulation resulted in little or no change in Ees. Thus we conclude that the negative inotropic effect of vagal stimulation is attributable primarily to its negative chronotropic effect when sympathetic tone is minimal.

Animals↗

Interstitial norepinephrine level by cardiac microdialysis correlates with ventricular contractility.

Although a cardiac microdialysis technique has made it possible to estimate myocardial interstitial norepinephrine (NE) levels, whether such levels reflect the local NE concentration that would regulate ventricular contractility remains unknown. If such levels indicate locally regulating NE concentration, then ventricular contractility should be a unique function of the interstitial NE level regardless of how the latter is altered. To examine this hypothesis, we altered the interstitial NE level endogenously by stimulating the cardiac sympathetic nerves at 1 and 2 Hz while monitoring ventricular contractility. We also altered the interstitial NE level exogenously by means of intravenous NE infusions at 10 and 40 micrograms.kg-1.h-1. The basal NE levels did not differ between the stimulation and the infusion experiments (42.9 +/- 11.2 vs. 40.1 +/- 6.2 pg/ml, means +/- SE). The slopes of regression lines relating ventricular contractility and interstitial NE level were also not different between the two experiments [1.13 +/- 0.20 vs. 1.17 +/- 0.20%/(pg/ml), means +/- SE]. We conclude that the interstitial NE level estimated by cardiac microdialysis reflects the local NE concentration regulating ventricular contractility.

Animals↗

Estimation of arterial mechanical properties from aortic and tonometric arterial pressure waveforms.

Although arterial mechanical properties have been evaluated using arterial input impedance, the relative difficulty in accurate flow measurement made the value of impedance somewhat limited. To develop an alternative method to evaluate arterial mechanical properties, we analyzed the aortic pressure (AoP)-radial arterial pressure (RAP) relationship because of relative ease in obtaining peripheral pressure waveform by tonometry. In 8 patients we simultaneously recorded aortic root and radial arterial pressure waveforms. We calculated the transfer function from AoP to RAP. We then fitted the transfer function to a model of a lossless uniform elastic tube terminated with a modified Windkessel model. The fact that the model transfer function predicted AoP from RAP waveform with considerable accuracy indicated that the model represented the arterial mechanical properties well. We conclude that we can estimate the arterial mechanical properties by the pressure-pressure transfer function analysis.

Adolescent↗

Inhaled nitric oxide: diameter response patterns in feline small pulmonary arteries and veins.

Using an X-ray television system on the in vivo cat lung, we directly measured internal diameter (ID) changes in the small pulmonary arteries and veins (100-1,100 microns ID) in response to 5, 15, and 40 ppm nitric oxide (NO) inhalations. We also measured to what extent 40 ppm NO inhalation can attenuate large ID constrictions at the different serial segments of the small vessels due to unilobar anoxic (0% O2) exposure. Under normoxic conditions, 5-40 ppm NO inhalations significantly increased the ID of both arteries and veins less than approximately 900 microns dose dependently but caused no significant, or only slight, ID increases in the vessels larger than this, if any at all. The ID increase in the serially connected arteries was nonuniform (4-18, 8-28, and 7-35% with 5, 15, and 40 ppm NO inhalations, respectively), whereas that for the veins was relatively uniform (4-9, 6-17, and 7-18% with 5, 15, and 40 ppm NO, respectively). The maximum ID increase occurred in the 200- to 500- and 200- to 700-microns arteries in response to 5-15 and 40 ppm NO, respectively. Unilobar anoxic exposure significantly decreased the ID of the 100- to 700-microns arteries and veins, but not the ID of the other-sized vessels. The ID decrease in the serially connected arteries was nonuniform (13-29%) but relatively uniform in the veins (8-12%). The maximum ID decrease occurred in the 200- to 300-microns arteries. However, adding 40 ppm NO to the lobe completely eradicated the ID decreases at all segments of the arteries and veins and, instead, caused significant ID increase (11-21%) in the arteries and (10-12%) in the veins. The data indicate that, according to dosage, 5-40 ppm NO inhalations cause selective dilation of approximately 100- to 900-microns pulmonary arteries and veins, particularly the 200- to 700-microns arteries. During anoxic exposure, the vasodilator effect of NO is preserved and can completely reverse the marked pulmonary vasoconstriction.

Administration, Inhalation↗

Bidirectional augmentation of heart rate regulation by autonomic nervous system in rabbits.

Although the characteristics of the static interaction between the sympathetic and parasympathetic nervous systems in regulating heart rate (HR) have been well established, how the dynamic interaction modulates the HR response remains unknown. We therefore investigated dynamic interaction by estimating the transfer function from nerve stimulation to HR using a band-limited Gaussian white-noise technique. The transfer function relating dynamic sympathetic stimulation to HR had characteristics of a second-order low-pass filter. Simultaneous tonic vagal stimulation at 5 and 10 Hz increased gain of the transfer function by 55.0 +/- 40.1 and 80.7 +/- 50.5%, respectively (P < 0.05). The transfer function from dynamic vagal stimulation to HR had characteristics of a first-order low-pass filter. Simultaneous tonic sympathetic stimulation at 5 and 10 Hz increased the gain by 18.2 +/- 17.9 and 24.1 +/- 18.0%, respectively (P < 0.05). Thus interaction augmented dynamic gain bidirectionally, even though it affected mean HR antagonistically. By virtue of this interaction, the autonomic nervous system appears to extend its dynamic range of operation.

Animals↗

Neural arc of baroreflex optimizes dynamic pressure regulation in achieving both stability and quickness.

The baroreflex loop consists of a fast neural arc and a slow mechanical arc. We hypothesized that the neural baroreflex arc compensates the slow mechanical response and thus improves the quality of blood pressure regulation. We estimated the open-loop transfer characteristics of the neural baroreflex arc (HP), i.e., from carotid sinus pressure to sympathetic nerve activity (SNA), and that of the effective peripheral baroreflex arc (Hp), i.e., from SNA to arterial pressure, in anesthetized rabbits. The gain of Hn was constant below 0.12 +/- 0.057 Hz and increased with a slope of 6.1 +/- 0.06 dB/octave above its frequency up to 1 Hz. In contrast, the gain of Hp was constant below 0.071 +/- 0.03 Hz and decreased with a slope of -11.0 +/- 1.48 dB/octave above the frequency. These data indicate that Hn accelerates slow peripheral responses in the frequency range of 0.1-1 Hz. Although too much acceleration in the high-frequency range could result in instability of the system, numerical analysis of the closed-loop baroreflex response indicated that the neural arc optimized arterial pressure regulation in achieving both stability and quickness.

Animals↗

[Questionnaire survey of AIDS examination recipients at government-run public health center regarding AIDS awareness promotion and HIV examinations].

An anonymous questionnaire survey was conducted among persons who had undergone screening for AIDS at public health centers under the auspices of 7 local government bodies (Hokkaido, Metropolitan Tokyo, Aichi Prefecture, Osaka Prefecture, Kobe City, Saga Prefecture, Okinawa Prefecture). There were 1,230 replies, for a response rate of 46.8%. Questions in the survey pertained to general knowledge of AIDS, information desired by the recipients, desired ways to foster awareness, and a desirable examination system. A comparison was made in terms of gender, marriage status (married, single) and age (less than 40 years of age, more than 40 years of age), respectively. The survey results were as follows. 1. Concerning the infection route, accurate response rate was low with regard to the mother-child infection, mosquito transmission, and use of contaminated needles. 2. Desired methods to promote AIDS awareness expressed among replies were given in the following order or frequency: "information via radio and TV," "spread of knowledge through telephone consultation," and "holding an AIDS Week or similar kinds of campaigns." 3. Information sought by respondents frequently included AIDS treatment, pathology, and spread. This trend was most obvious among those under 40 years of age. 4. As for the AIDS examination system, replies most often reflected the hope that the examination site would be the Public Health Center, the charge would be gratis, and that one could be examined at night during the week, and on days off. 5. For those undergoing examination where there was no actual concern of possibility of HIV infection, single persons, accounted for around 80% of the overall. 6. More than half of those who had been examined mentioned having experienced concerns about maintaining confidentiality at the time they were examined.

Acquired Immunodeficiency Syndrome↗

[Estimation of right ventricular contractility by continuous-wave Doppler echocardiography].

The right ventricular dP/dtmax and relatively load-independent index, dP/dtmax/IP (IP: instantaneous pressure difference between the right ventricle and right atrium) can be measured from the tricuspid regurgitant velocity by continuous-wave Doppler echocardiography. The present study investigated these indices as measures of right ventricular contractility. Thirty-one patients were classified into three groups: 11 patients without right ventricular disease (control group), 9 with dilated cardiomyopathy and 1 with hypertrophic cardiomyopathy in the dilated phase (DCM group), and 10 with pulmonary hypertension (PH group). Right ventricular contractility was impaired in both the PH group and DCM group, but dP/dtmax was significantly larger in the PH group compared with the control group and DCM group (519 +/- 113 vs 249 +/- 66 and 234 +/- 78 mmHg/sec, p < 0.01). There was no significant difference between dP/dtmax in the control group and DCM group. dP/dtmax/IP in the PH group was smaller than the control group (31 +/- 8 vs 39 +/- 7/sec, p < 0.05) and larger than the DCM group (22 +/- 12/sec, p < 0.05). Mean New York Heart Association grading was 1.0 in the control group, 3.1 in the DCM group, and 2.8 in the PH group, respectively. Thus, dP/dtmax/IP, noninvasively obtained by continuous-wave Doppler echocardiography, may be a better index for evaluating right ventricular contractility than dP/dtmax.

Adult↗

Continuous measurement of left ventricular volume in rabbit, using a two-electrode catheter.

We developed a device for monitoring instantaneous left ventricular (LV) volume using an alternating-current excitation two-electrode conductance catheter. Instantaneous conductance between a pair of electrodes was amplified by a non-inverting circuit. The level of conductance was linearly related to changes in blood volume from 0.8 to 2.0 ml in a latex balloon (r2 = 0.95), and to changes in blood volume from 0.4 to 2.2 ml in a post-mortem rabbit left ventricle (r2 = 0.99). The difference between the maximal and minimal conductance of the LV in situ during a cardiac cycle was closely correlated with changes in stroke volume, measured by an electromagnetic flow probe (r2 = 0.97). The endsystolic pressure-conductance relation (ESPCR) was highly linear (r2 = 0.92). Changes of the slope (Ees) of the ESPCR correlated directionally with changes of the time derivative of LV pressure (LVdP/dt) during intravenous infusions of dobutamine and propranolol. Accordingly, the two-electrode conductance catheter was useful in vivo in rabbits for continuously assessing changes in the LV volume.

Animals↗

Percutaneous transvenous mitral commissurotomy immediately restores quick response of VO2 to mild exercise despite insignificant increases in peak VO2.

Percutaneous transvenous mitral commissurotomy (PTMC) increases peak oxygen uptake (VO2) chronically, but not acutely, despite early symptomatic improvements. Analysis of transient VO2 responses to submaximal exercise (an exercise regimen more comparable to the patients' daily activities than that provided by maximal exercise testing), may be sensitive in detecting the acute hemodynamic benefits of PTMC. Since no methods are available to accurately estimate the transient response of VO2, we developed a new technique, using random exercise. In 15 patients who underwent successful PTMC, we repeated the conventional maximal exercise test and the random exercise test before and within a few days after PTMC. For the random exercise test, we intermittently imposed upright bicycle exercise at 50 W, according to a random binary sequence, while measuring breath-by-breath VO2. After determining the transfer function relating workload to VO2, we computed the high resolution VO2 response to a hypothetical step increase in exercise. Despite improvements in resting hemodynamics and New York Heart Association (NYHA) Class, peak VO2 improved insignificantly (952 +/- 271 vs 1,029 +/- 342 ml/min, P = 0.063) shortly after successful PTMC. In contrast, the amplitude of the VO2 step response increased significantly in the early-to-mid portion (28-76s; P < 0.01-0.05). The remaining portion was unchanged. Consequently, the time constant shortened from 64 +/- 26 to 48 +/- 22s (P < 0.05). The maximal Borg scale value during random exercise decreased significantly (13.1 +/- 1.8 vs 11.4 +/- 1.1; P < 0.01). We conclude that the VO2 step response, using the random exercise test, is more sensitive than peak VO2 in detecting the functional improvement that is coupled with the hemodynamic improvement immediately after PTMC.

Adult↗

Explorations into development of a neurally regulated cardiac pacemaker.

Although the artificial cardiac pacemaker has contributed to the management of patients with serious arrhythmias, its rate-responsive function is not sufficient to provide physiological regulation of heart rate (HR). To achieve truly physiological rate response in any given patient, we propose a framework to develop a pacemaker directly regulated by sympathetic nerve activity (SNA). In eight anesthetized rabbits, we quantified the dynamic transduction characteristics from SNA to HR as a transfer function. We then characterized the decoding rule as an impulse response, that is the transfer characteristics in the time domain. The transfer function was approximated by a first-order, low-pass filter with lag time (corner frequency: 0.024 +/- 0.013 Hz, lag time: 0.98 +/- 0.09 s). Predicted HR correlated well with measured HR (r = 0.80-0.98). The standard error of the prediction relative to mean HR was only 1.2 +/- 0.7%, indicating that the prediction was reasonably accurate. Direct decoding of SNA to predict instantaneous HR is possible through this analysis. This framework should enable development of a neurally regulated artificial pacemaker.

Animals↗

Pathologic studies and comparison of the virulence of herpes simplex virus type 2 from Okinawa, Japan and Chiang Mai, Thailand.

The virulence of four herpes simplex virus type 2 (HSV 2) strains (K1-K4) isolated in Okinawa, Japan was investigated, and compared with four strains (C1-C4) from Chiang Mai, Thailand and a standard laboratory strain SAV. Virulence was tested on BALB/c and C57/black mice. After viral inoculation intraperitoneally, the distribution with the passage of time of the virus in the brain and other organs was also studied using the polymerase chain reaction (PCR) method and immunohistochemistry. Generally, Okinawan HSV 2 (K1, K3 and K4) were less virulent than Chiang Mai strains (C1-C4). Among the Okinawan strains, K2 was the most virulent, but slightly less so than C3 and C4. All four Chiang Mai strains (C1-C4) and one Okinawan strain (K2) were more virulent than SAV strain. The virulence of K3 was very weak and no animals died from the intraperitoneal inoculation. In the brain, viral DNA from each strain was demonstrated at 1-9 days after inoculation by the PCR method. However, K3 strain was detected in the brain only between one day and 3 days after virus inoculation, and not after day 5. Immunohistochemically, the virus antigen was first demonstrated around the 3rd ventricle at one day after viral inoculation, then strongly at the ventral hypothalamus and the temporal lobe at 3 days after viral inoculation, and slightly in the frontal lobe, hippocampus, pons and cerebellum (on day 5 after inoculation). Furthermore, in Kupffer cells in the liver and macrophages in the spleen, numerous viral antigens were demonstrated from one to 9 days after viral inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Restriction endonuclease cleavage analysis of herpes simplex virus type 2 from Chiang Mai, Thailand and Okinawa, Japan.

Genomic variations of herpes simplex viruses type 2 (HSV 2) isolated from Chiang Mai, Thailand and Okinawa, southernmost part of Japan were studied. The genomic polymorphism of 40 HSV 2 Chiang Mai strains and 10 HSV 2 Okinawan strains was analyzed by means of the variations of cleavage sites and electrophoretic mobilities of DNA fragments after digestion with 4 restriction endonucleases (RE (BamH I, Kpn I, EcoR I, and Bgl II)). Using the main 6 variable RE cleavage sites, HSV 2 strains were classified into 10 major groups. The strains categorized into group 1 and 9 were predominant in Chiang Mai. Groups 1, 3, 4, 5, 6 and 7 were found only in Chiang Mai, but contained only a few strains each. Groups 2 and 10 were found only in Okinawa, whereas groups 8 and 9 were found in both Chiang Mai and Okinawa.

DNA Restriction Enzymes↗

Postganglionic sympathetic nerve discharges can contain both central and pulse-related oscillations simultaneously in rabbits.

We examined whether modulation of sympathetic nerve discharges (SND) by changes in carotid sinus pressure (CSP) is influenced by the pattern of the rhythm of central sympathetic neurons and whether the rhythm of the sympathetic nerve derived from central sympathetic neurons and that from the inputs from baroreceptors can coexist in postganglionic renal SND. In alpha-chloralose-anesthetized rabbits with aortic denervation and vagotomy, firing of central sympathetic neurons was at first left spontaneous and then driven artificially at 3 Hz by peroneal nerve stimulation. Under these conditions, renal SND were recorded and compared while CSP was altered at low frequencies. When central sympathetic neurons were firing spontaneously and low frequency oscillation was applied to CSP, two kinds of oscillation were noted in SND; first oscillation at the same frequency as that of central sympathetic neurons, and second oscillation of CSP changes. Power spectra of SND also showed two peaks at these two oscillations. When central sympathetic neurons regularly discharged at 3 Hz by electrical stimulation and CSP was kept constant, the power spectra of SND had a discrete single peak at 3 Hz. When a regular oscillation was applied to CSP at 1 Hz, the amplitude of central sympathetic outflow at 3 Hz was modulated at 1 Hz without disturbance of the frequency of the central 3 Hz rhythm. In other words, two apparently different rhythms coexisted in SND. In the power spectra, two discrete peaks were noted at the frequency of CSP changes and at the central sympathetic oscillation. When SND were averaged by CSP-triggered summation during spontaneous or artificial 3 Hz central firing, it was revealed that the shape of these two averaged SND were completely same in spite of obviously different central firing patterns. Nadir of SND occurred about 400 ms after the peak of CSP during changes in CSP at several frequencies in these two conditions. Thus, these results indicated two points; (1) CSP changes modulate the amplitude of SND in the same manner irrespective of the frequency or pattern of discharge of central sympathetic neurons; (2) both of frequency components of SND induced by oscillatory changes in central sympathetic neurons and oscillatory inhibitory input from baroreceptors can coexist even if their frequencies were different.

Action Potentials↗

Role of carotid sinus baroreflex in attenuating systemic arterial pressure variability studied in anesthetized dogs.

Attenuation of systemic arterial pressure (SAP) variability by the carotid sinus baroreflex (CSBR) was quantified in nine anesthetized, vagotomized dogs. SAP amplitude spectrum was compared between open-loop [SAPo(f)] and closed-loop [SAPc(f)] operation of the CSBR. At 0.002 Hz, SAPc amplitude was 3.5 +/- 2.2 (SD) mmHg, and SAPo was 9.6 +/- 3.5 mmHg (P < 0.01). At 0.02 Hz, SAP(c) amplitude was 2.8 +/- 1.2 mmHg, and SAPo was 4.3 +/- 1.2 mmHg (P < 0.05). At higher frequencies, SAPo(f) was indistinguishable from SAPc(f). With the opened CSBR, intracarotid sinus pressure (CSP) was pseudorandomly varied, and the resulting SAP responses were recorded to determine the transfer function from CSP to SAP [HCSP.SAP(f)]. From SAPo(f) and the determined HCSP.SAP(f), we estimated SAP(f) if the CSBR was closed [SAPc,est(f)] and compared it with SAPc(f). These two spectra were similar in each dog over a frequency range of 0.002-0.15 Hz, the differences between SAPo(f) and SAPc(f) being reconcilable with HCSP.SAP(f). Although the anesthetized state and vagotomy may have distorted the transfer characteristics of the CSBR from those in conscious (with the intact vagi) states, the results of the present study indicate that the CSBR attenuated SAP variability mainly in a low-frequency range below 0.02 Hz and that this attenuation was attributable to the transfer properties of the CSBR.

Anesthesia, General↗

Contribution of wall mechanics to the dynamic properties of aortic baroreceptors.

To examine the contribution of wall mechanics to dynamic properties of baroreceptors, we subdivided the transfer function of baroreceptors into two subsystems [aortic pressure to diameter and diameter to aortic depressor nerve activity (ANA)]. In six alpha-chloralose-anesthetized rabbits, we measured pressure, diameter, and ANA while randomly perturbing pressure. We obtained transfer functions (pressure to ANA, diameter to ANA, and pressure to diameter) by taking the ratio of crosspower spectrum to the input power spectrum (0.005-5 Hz). Below 3 Hz, the transfer function from pressure to ANA was nearly identical to that from diameter to ANA, whereas that from pressure to diameter was flat. Using transfer functions we could reproduce adaptation and hysteresis that were quantitatively similar between pressure-ANA transduction and diameter-ANA transduction. The pressure-diameter relationship was almost instantaneous and thus showed no hysteresis. In a second group of rabbits, the ratio of the shift of the hysteresis loop was unchanged by ouabain (40 micrograms/kg iv, n = 7). We conclude that the dynamic properties of baroreceptors may not be related to the wall mechanics or the Na(+)-K(+)-adenosinetriphosphatase activity.

Animals↗