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Biomedical subjects

K Sunagawa

Publications and source records attributed to K Sunagawa.

At least 19 recordsLinked to original sources

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

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

Differentiation between aberrant ventricular conduction and ventricular ectopy in atrial fibrillation using RR interval scattergram.

BACKGROUND: Differentiation between aberrant ventricular conduction and ventricular ectopy during atrial fibrillation (AF) is of etiologic, prognostic, and therapeutic importance. We developed a noninvasive technique to diagnose aberrant ventricular conduction and ventricular ectopy in AF. METHODS AND RESULTS: We studied the Holter ECGs of 34 patients with paroxysmal AF and 62 patients with chronic AF. In all the patients, frequent wide QRS complexes were observed, and 32 patients were shown by electrophysiological examination to have ventricular ectopies or aberrant ventricular conductions. We obtained the RR interval scattergrams by plotting sequential pairs of RR intervals. Each point has the (n)th RR interval as its x value and the (n + 1)th RR interval as its y value. The irregularity of the RR intervals in AF resulted in widely scattered points delineated by the envelope along the axes. The y value of the envelope along the x axis indicates the shortest coupling interval to the preceding RR interval. Therefore, this curve defines the functional refractory period of atrioventricular conduction. The scattergram of the RR interval pairs immediately preceding the aberrant conduction (coupling points of aberrant conduction) specifically distributed along the envelope. In contrast, the coupling points of ventricular ectopies showed different distributions that had no relation to the envelope. That is, it included three typical patterns, ie, linear distribution below the envelope, linear distribution partially overlapped in the area of normal AF conduction, and chaotic distribution in the AF area. None of the scattergrams of ventricular ectopies showed curvilinear distribution along the envelope as aberrant conduction did. The specific distribution of the aberrant conduction on the RR interval scattergram suggested that aberrant conduction in AF could result from the difference of refractory periods between the AV node and bundle branch block. CONCLUSIONS: We conclude that the RR interval scattergram makes it possible to differentiate between aberrant ventricular conduction and ventricular ectopy in atrial fibrillation, and thus, it is a useful noninvasive clinical tool.

Atrial Fibrillation

Kaposi sarcoma in Okinawa.

BACKGROUND: The authors encountered six patients with Kaposi sarcoma in Okinawa; one was classic type, two were associated with adult T-cell leukemia (ATL), one was with multiple myeloma, and two were with acquired immune deficiency syndrome (AIDS). In the classic type, many nodular lesions were seen on the skin of the extremities and a few on the trunk, some of which were ulcerated. Most lesions regressed in 1.5 years. In four other patients (three without AIDS and one with AIDS), many plaques and a few nodular lesions were seen on the trunk, face, and extremities. The other patient with AIDS showed Kaposi sarcoma only in the lymph nodes and perineural tissues in the abdomen. METHODS: Immunohistochemical and lectin histochemical studies were done on deparaffinized sections and on cells cultured from small pieces of tumor mass from the classic type Kaposi sarcoma. Isolation of viruses from tumor tissue was also attempted. RESULTS: Large numbers of endothelial cells lining irregular vascular spaces, and some spindle cells showed positive reactions for Factor VIII-related antigen, Ulex europaeus 1 (UEA-1) (E.Y. Labs, Inc., San Mateo, CA), Griffonia simplicifolia (GS-1) (E.Y. Labs, Inc.) lectins, and epidermal growth factor (EGF) receptor antigen. Cytomegalovirus (CMV), hepatitis B, herpes simplex virus (HSV) 1 and 2, papillomavirus antigens, and human immunodeficiency virus (HIV) p24 core antigen were not seen in any patients, except in the patient with AIDS in whom CMV was demonstrated in tissues adjacent to the tumor (Patient 6). In cell culture, elongated spindle cells proliferated in plate and also in three-dimensional cultures. The cells were positive immunohistochemically for Factor VIII-related antigen and EGF receptor. They also stained lectin histochemically with UEA-1 and GS-1. Tube formations were demonstrated by electron microscopic study. CONCLUSIONS: Six cases of Kaposi sarcoma have been diagnosed within a short time span where this condition has previously been said to be rare. The studies suggest a vascular endothelial cell origin and growth factor regulated growth for this tumor.

Adult

Effect of increase in heart rate on interatrial shunt in atrial septal defect.

The effect of increases in heart rate by atrial pacing was investigated in 20 children [mean 9 +/- 4 (SD) years] with atrial septal defect. Systemic blood flow increased by 13 +/- 10 and 27 +/- 22% with a 25 and 50% increase in heart rate, respectively. Pulmonary blood flow, however, remained unaltered. Thus, rapid pacing decreased the pulmonary to systemic blood flow ratio significantly (-15 +/- 10 and -22 +/- 13%, respectively). This hemodynamic alteration was attributed to the difference in diastolic distensibility (compliance) between the left and right ventricles, and the ratio of right ventricular to left ventricular compliance (defined by dV/dP) near the end-diastolic pressure was estimated to be 6.5 +/- 4.2. It is suspected that the increase in heart rate may contribute to the lowering of pulmonary to systemic flow ratio during exercise in children with atrial septal defect.

Adolescent

How to encode arterial pressure into carotid sinus nerve to invoke natural baroreflex.

The purpose of this study was to develop an artificial baroreceptor that was capable of invoking the "natural" baroreflex by electrically stimulating the afferent nerve. In six anesthetized, vagotomized dogs, we first identified, using the white-noise method, the transfer function from carotid sinus pressure to aortic pressure (HCSP.AoP) and that from the electrical carotid sinus nerve stimulation to aortic pressure (HCSN.AoP). We then backcalculated the transfer function required for the artificial baroreceptor (HCSP.CSN) as the ratio of HCSP.AoP to HCSN.AoP. To activate the artificial baroreceptor, we electrically stimulated the carotid sinus nerve with the frequency-modulated pulse train obtained in real time by convolving the impulse response of HCSP.CSN with instantaneous aortic pressure. We tested performance of the artificial baroreceptor by imposing random changes in blood volume. The pressure-stabilizing effects of the artificial baroreceptor were indistinguishable from those of the native one. We conclude that the artificial baroreceptor can invoke the natural baroreflex. The proposed framework generally would be applicable to interface artificial devices with the central nervous system.

Animals

Arterial baroreflex dynamics in normotensive and spontaneously hypertensive rats.

To investigate dynamic or frequency-dependent characteristics of arterial baroreflex control of efferent sympathetic nerve activity in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), we assessed the transfer function from aortic pressure (AP) to renal sympathetic nerve activity (RSNA) using a "white-noise technique." In pentobarbital sodium-anesthetized rats, we recorded RSNA as the output, while AP was randomly perturbed to impose input pressure changes with broad frequencies. We calculated the transfer function from AP to RSNA over the frequency range of 0.01-5 Hz through the spectral analysis of the input and output. The results indicated that the gain, phase shift, and coherence of the transfer function for SHR and for WKY were similar and statistically indistinguishable. The gain was relatively constant below 0.05 Hz but increased steadily by fivefold as frequency increased in the frequency range of 0.05-0.8 Hz. The phase was out of phase where coherence was high. The coherence was high (greater than 0.5) in the frequency range of 0.04-0.8 and 1.00-1.03 Hz but was low in other frequencies. These results suggest that dynamic or frequency-dependent characteristics of arterial baroreflex control of RSNA were not altered in SHR as compared with WKY.

Animals

Dynamic effects of carotid sinus baroreflex on ventriculoarterial coupling studied in anesthetized dogs.

We evaluated dynamic effects of the carotid sinus baroreflex on ventriculoarterial coupling. In seven anesthetized, vagotomized dogs, we bilaterally isolated carotid sinuses and randomly changed carotid sinus pressure while measuring aortic pressure, aortic flow, and left ventricular pressure. Estimating left ventricular end-systolic elastance (Ees) and effective arterial elastance (Ea) on a beat-to-beat basis, we determined transfer functions from the carotid sinus pressure to Ees (HEes) and from the carotid sinus pressure to Ea (HEa) over the frequency range spanning 0.002-0.25 Hz. Both HEes and HEa exhibited characteristics of a second-order low-pass filter. The gains of HEes and HEa were 0.085 +/- 0.065 (mean +/- SD) and 0.081 +/- 0.049 mm Hg/ml/mm Hg, respectively. There were no significant differences in natural frequencies (0.039 +/- 0.013 versus 0.039 +/- 0.007 Hz) or damping ratios (0.65 +/- 0.11 versus 0.64 +/- 0.24). The results indicated that the carotid sinus baroreflex dynamically altered Ees and Ea to the same extent in the process of stabilizing arterial pressure. Because the arterial system extracts maximal external work from a given heart when Ea equals Ees, the carotid sinus baroreflex appeared to be designed to regulate the ventricular and arterial properties to optimize the energy transmission from the left ventricle to the arterial system in anesthetized, vagotomized dogs.

Anesthesia

Mechanical matching of the left ventricle with the arterial system in exercising dogs.

We investigated how changes in ventricular contractility and arterial properties associated with exercise influence the energy transmission from the left ventricle to the arterial system. On six chronically instrumented dogs preconditioned to run on a treadmill, we imposed exercise loads of various degrees by altering the speed and slope of the treadmill (up to 7 km/hr and 20% slope). We evaluated ventricular contractility by end-systolic elastance (Ees) and arterial properties in terms of the effective arterial elastance (Ea). Ea was estimated by the ratio of mean aortic pressure to stroke volume. With exercise, Ees significantly increased from 7.6 +/- 1.7 to 10.9 +/- 2.6 mm Hg/ml (p less than 0.005), and Ea tended to increase from 4.9 +/- 1.4 to 6.7 +/- 1.8 mm Hg/ml (p = 0.068), whereas the ratio of Ea to Ees remained fairly constant (from 0.69 +/- 0.26 to 0.63 +/- 0.21, NS). The mechanical optimality index, defined as the ratio of stroke work to its theoretically derived maximal value, was 0.93 +/- 0.07 at rest and 0.92 +/- 0.08 at peak exercise. Similarly, the metabolic optimality index, defined as the ratio of cardiac oxygen consumption to stroke work conversion efficiency and its theoretical maximal value, was 0.98 +/- 0.02 at rest and 0.99 +/- 0.01 at peak exercise (NS). We conclude that external work of the left ventricle of these dogs was at a near maximal level for a given preload during exercise as well as at rest without compromising the conversion efficiency of metabolic energy to stroke work.

Animals

[Bochdalek diaphragmatic hernia in the elderly: a case report].

We successfully treated surgically an elderly patient, a 80-year-old woman, with Bochdalek diaphragmatic hernia. She had intermittent episodes of intestinal obstruction. A preoperative chest roentgenograph revealed a loop of gas-filled bowel in the left chest and elevation of the left diaphragm. CT scanning of the thorax revealed the bowels filled with gastrografin in the left thoracic cavity. She was treated surgically, through transabdominal and then transthoracic approaches. The herniated large bowel was reduced from the thoracic cavity and the hernial sac was excised. The posterolateral defect of the diaphragm, 5 x 6 cm in size was closed with interrupted mattress sutures. The patient has been well without any symptoms 6 months after the surgery. Bochdalek diaphragmatic hernia is the most common problem in infants with risky respiratory distress and high mortality, however it is preferable to carry out surgical treatment for adult patients because of good postoperative results. As a surgical route in the management of Bochdalek diaphragmatic hernia in adults, a transthoracic approach is preferable since it provides easy separation and reduction of herniated bowels from the thoracic cavity and easy closure of the diaphragmatic defect, furthermore there are no other serious gastrointestinal complications which are required specific repair.

Aged

Identification of the rate-dependent functional refractory period of the atrioventricular node in simulated atrial fibrillation.

We continuously observed successive pairs of R-R intervals during atrial fibrillation and hypothesized that the shortest R-R interval for a given preceding R-R interval in a pair represents the functional refractory period of the atrioventricular node at that preceding interval. To test this hypothesis we simulated atrial fibrillation in 28 isolated cross-perfused canine hearts and obtained an R-R interval scatterplot by plotting the R-R intervals as a function of the immediately preceding R-R interval. This scatterplot enabled us to detect a series of the shortest R-R intervals for a wide range of preceding R-R intervals, and this allowed us to estimate the rate-dependent functional refractory period of the atrioventricular node in simulated atrial fibrillation. The estimated functional refractory periods correlated well with those measured by the conventional method (r = 0.93). We conclude that the proposed method makes it possible to estimate the rate-dependent functional refractory periods of the atrioventricular node in atrial fibrillation.

Animals

Production of 5-methyluridine by immobilized thermostable purine nucleoside phosphorylase and pyrimidine nucleoside phosphorylase from Bacillus stearothermophilus JTS 859.

5-Methyluridine was produced continuously from thymine and inosine by immobilized enzymes, which consisted of thermostable purine nucleoside phosphorylase and thermostable pyrimidine nucleoside phosphorylase obtained from Bacillus stearothermophilus JTS 859. The process was carried out in a column reactor at 60 degrees C for 17 d without any bacterial contamination under non-aseptical conditions. Half-lives of the activity of the immobilized enzymes were 47 d and 4.5 d at 60 degrees C and 70 degrees C, respectively, although half-life of the crude enzyme was only 14 h at 70 degrees C.

Bacterial Proteins

Autoregressive analysis of aortic input impedance: comparison with Fourier transform.

We evaluated the advantages of the autoregressive (AR) model over the conventional Fourier transform in estimating aortic input impedance. In 10 anesthetized open-chest dogs, we digitized aortic pressure and flow at 200 Hz for 51.20 s under random ventricular pacing and subdivided them into five segments. We obtained aortic input impedance over the frequency range of 0.1-20 Hz both by AR model and by Fourier transform for various lengths of data, i.e., from one to four consecutive segments. For any given data length, the impedance spectrum estimated by the AR model was smoother than that obtained by the Fourier transform. To evaluate the accuracy of the estimated impedance, we predicted instantaneous aortic pressure of the fifth segment by convolving corresponding aortic flow with the impulse response of aortic input impedance. The prediction error was less with the AR model than that resulting from Fourier transform as long as the number of the segments was less than four. We conclude that the AR model provides a more accurate estimate of aortic input impedance than does the Fourier transform when data length is limited.

Animals

Arterial baroreflex control of cardiac and renal sympathetic nerve activities is uniform in frequency domain.

To investigate wideband dynamic properties of arterial baroreflex control of cardiac and renal sympathetic nerve activities, we assessed the transfer function using a "white-noise technique." In pentobarbital sodium-anesthetized cats, we simultaneously recorded, as the output, cardiac sympathetic nerve activity (CSNA) and renal sympathetic nerve activity (RSNA), while aortic pressure (AP) was randomly perturbed to impose input pressure changes with broad frequencies. We calculated the transfer function from AP to CSNA or to RSNA over the frequency range of 0.01-5 Hz through the spectral analysis of the input and output. We found that the gain, phase shift, and coherence of those transfer functions were statistically indistinguishable. The gain was rather flat below 0.05 Hz, steadily increased above 0.05 Hz, and plateaued above 0.3 Hz. The phase shift was out of phase up to 0.05 Hz and led by approximately 4 degrees above 0.05 Hz. The coherence was high (above 0.7) below 0.3 Hz and became lower above 0.3 Hz. These results suggest that arterial baroreflex control is uniform and similar between the two activities in the frequency range of 0.01-0.7 Hz.

Animals

Effects of the new cardiotonic phosphodiesterase inhibitor 1,2-dihydro-5- imidazo[1,2-a]pyridin-6-yl-6-methyl-2-oxo-3-pyridine-carbonitrile hydrochloride monohydrate on aortic input impedance.

Beneficial effects of cardiotonic phosphodiesterase inhibitors on congestive heart failure are possibly mediated in part by a reduction of afterload. 1,2-Dihydro-5-imidazo[1,2-a]pyridin-6-yl-6-methyl-2-oxo-3- pyridinecarbonitrile hydrochloride monohydrate (E-1020, CAS 119615-63-3), a new cardiotonic phosphodiesterase inhibitor was evaluated for its effect on aortic input impedance in eight anesthetized open-chest dogs. First instantaneous aortic pressure and flow under random ventricular pacing before and after E-1020 infusions (10, 30, and 100 micrograms/kg i.v.) were measured. Then aortic input impedance over the frequency range of 0.024 to 20 Hz was estimated using a multichannel autoregressive model. With the infusion of E-1020, aortic input impedance was decreased in the low frequency range (below 0.1 Hz) and shifted leftward in the transitional frequency range (from 0.1 to 2 Hz), while it remained unchanged in the high frequency range (above 2 Hz). Parameterization of the aortic input impedance using a three-element Windkessel model indicated that E-1020 (at a dose of 100 micrograms/kg i.v.) decreased arterial resistance by 35% (p less than 0.01) and increased arterial compliance by 12% (p less than 0.01). It is concluded that E-1020 improves cardiac performance by unloading static and dynamic afterload in addition to its cardiotonic effect.

Animals

The effect of extraanatomic bypass on aortic input impedance studied in open chest dogs. Should the vascular prosthesis be compliant to unload the left ventricle?

Left ventricular hypertrophy has been reported after ascending aorta-abdominal aorta bypass, despite seemingly insignificant changes in cardiac output and mean arterial pressure. Such a bypass procedure may be used for the treatment of complex coarctation of the aorta, hypoplastic aortic arch, or thoracoabdominal aortic aneurysm. To investigate the effect of the bypass procedure on left ventricular afterload, we measured aortic input impedance in six open chest dogs by placing a knitted Dacron graft from the ascending aorta to the abdominal aorta and occluding the aortic arch. Cardiac output and mean arterial pressure remained unaltered throughout the experiment, consistent with clinical reports. Systolic pressure increased by 25% of control, and the ratio of diastolic pressure-time index to tension-time index decreased by 27%. The measured input impedance was then approximated with the three-element windkessel model, which consists of resistance, compliance, and characteristic impedance (average of impedance modulus between 5 and 15 Hz). There was no change in resistance and compliance; characteristic impedance increased to 255% of control. Connecting an air chamber to the vascular prosthesis doubled the compliance and decreased the characteristic impedance nearly to the control value without altering resistance. It also reduced the systolic pressure by 14% of the bypass protocol and increased the ratio of diastolic pressure-time index to tension-time index (by 32% of control value and 82% of bypass value). Arterial systolic pressure and pulse pressure were both linearly correlated with the characteristic impedance. Thus we conclude that although ascending aorta-abdominal aorta bypass does not affect cardiac output, mean arterial pressure, resistance, or compliance, it does increase characteristic impedance. Left ventricular systolic load is directly correlated with characteristic impedance. Increased systolic wall stress might be the cause of left ventricular hypertrophy of the previously reported cases. Because decrease in the distensibility of the proximal aorta is one of the factors causing the increase in characteristic impedance, using a compliant graft might help to unload the heart.

Anastomosis, Surgical

Arrhythmia analysis by successive RR plotting.

A successive RR interval plot was developed to analyze arrhythmia. The plot consisted of a set of points with the x-value of (N)th RR interval and the y-value of (N + 1)th RR interval. This method was applied in the arrhythmia analysis of Holter electrocardiograms obtained from 35 patients. In the analysis of ventricular premature contractions (VPCs) this method was useful not only in detecting VPCs but also in demonstrating coupling interval-dependent characteristics of VPCs. In the analysis of atrial fibrillation the successive RR plot enabled the authors to estimate the functional refractory period of the atrioventricular conduction. In conclusion, despite its simplicity, the successive RR plot was found to be powerful in analyzing arrhythmia. Specifically, the potential to analyze integrally the coupling interval-dependent properties of various types of arrhythmia makes it attractive as a clinical tool.

Atrial Fibrillation