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A middle-aged Japanese man who had been on haemodialysis treatment for diabetic nephropathy developed multiple itchy papules and nodules, which were histopathologically diagnosed as acquired perforating dermatosis. Two years later he developed oral lesions and subsequently numerous erosive plaques with necrotic crusts on the trunk and extremities. Histopathology of a papule showed a parakeratotic plug intermingled with basophilic, necrotic debris and collagen bundles, along with penetration of collagen bundles across the epidermis and subepidermal blister. Immunoblotting studies revealed IgG autoantibodies in the patient's serum, which reacted with the C-terminal and the NC16a domains of bullous pemphigoid (BP)180, indicating presence of BP. We searched the literature and found no other cases of an autoimmune blistering disease occurring in association with a perforating disorder. Possible injury to the basement membrane zone induced during the process of transepidermal elimination might be involved in the pathogenesis of the pemphigoid disease.

We have developed the crack-line-update method for two-dimensional piercing simulations by a finite element method. This method is combined with a remeshing process involving an outer line and meshing. By using the crack-line-update method, crack lines, which are derived from a stress and strain analysis of the high-damage regions, are added to the outer line in every remeshing step. In this paper, we compare the simulations between the mesh deletion and crack-line-update methods. The crack-line-update method successfully simulated the arresting of cracks during the piercing process, whereas the mesh deletion method could not express such fracture behavior.

The design variables of both the structural and the control parameters are optimized simultaneously by the sensitivity analyse to minimize the response due to disturbances of both white noise and colored noise subjected to a constraint so that the system is stable corresponding to high-order natural modes. Three kinds of models are adopted in the approach, namely, the original spatial model by finite element method, the reduced modal model for designing the control system, and the original modal model for assuring stability of the system. The validity and the usefulness of the present approach are verified by a vibration control experiment of a steel plate

As local variations in blood flow are implicated in atherogenesis at bifurcations, we measured in vivo blood velocities in different planes within exposed iliofemoral arterial bifurcations in 8 dogs using 20-MHz, 80-channel Doppler ultrasound velocimetry. Cardiac frequency was fixed at 2 Hz by pacing. Local geometry was characterized using 25-MHz, B-mode ultrasound images, photographs, and methacrylate casts. The bifurcations were asymmetrical and planar to within 5 degrees, the diameter ratios of the daughter vessels ranged from 1.47 to 2.00, and the angles between them ranged from 40 to 76 degrees. Measured velocities indicated that just upstream of the bifurcation mean peak Reynolds numbers ranged from 196 to 564 and Womersley (frequency) parameters ranged from 2.00 to 4.1. At the level of the bifurcation, secondary flows were insignificant in the normal plane but strong in the plane of the bifurcation. As a result, two-dimensional velocity fields, reconstructed by vector addition of velocities measured in the plane of the bifurcation, differed markedly from the one-dimensional profiles calculated assuming flow parallel to the vessel axis. In the two-dimensional velocity fields, forward flow was directed toward the flow divider and reversal occurred earliest near the outer wall. Wide spatial and temporal variations in the shear stress at the endothelium are implied by these detailed, in vivo measurements of the bifurcation velocity fields.

The influence of the filling condition of the unstressed volume (UV) of intramyocardial vessels on the diastolic coronary arterial pressure-flow relationship was analyzed. UV is defined as the blood volume at zero transmural pressure. In seven anesthetized, paced dogs with induced heart block, coronary artery inflow was occluded so that blood in the UV was displaced into the coronary vein by myocardial contraction. After pacing was turned off, coronary perfusion pressure was increased stepwise to seven target pressures (20-90 mmHg). After reperfusion, left anterior descending coronary arterial (LAD) flow reached an initial quasi-steady level, but great cardiac venous (GCV) flow was absent (UV-unfilled phase). With reappearance of the GCV flow (UV-filled phase), LAD flow decreased to a final steady level. Pressure-flow relationships during both phases were linear (r = 0.97-0.99). The inverse of the slope of the pressure-flow relationship during the UV-filled phase, 0.69 +/- 0.08 mmHg.min.ml-1, was significantly higher than that during the UV-unfilled phase, 0.55 +/- 0.06 mmHg.min.ml-1 (P less than 0.01), although the zero-flow pressure intercepts were similar (18.9 +/- 1.8 mmHg for UV filled vs. 19.9 +/- 2.2 for UV unfilled). These results indicate that diastolic coronary arterial inflow is impeded by a blood volume within intramyocardial vessels that exceeds the UV.

We examined the effects of brovincamine fumarate, a Ca(2+)-channel blocker, on choroidal blood flow. We measured the choroidal blood volume continuously for 1 hour using laser Doppler flowmetry, as well as systemic blood pressure, heart rate, and intraocular pressure in six urethane-anesthetized rabbits after intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine. As a control, ten rabbits receiving no medication were used. All the data were recorded and analyzed using MacLab on a computer. In both the 0.1 mg/kg and 0.5 mg/kg brovincamine-injected groups, the choroidal blood volume decreased significantly after administration, but showed no significant difference from controls. Vascular resistance in the choroid showed a significant increase over the value before administration and over the control group. The heart rate decreased significantly compared to the value before injection and to the control group. The mean blood pressure in both dose groups and the intraocular pressure in the 0.5 mg/kg injected group were significantly higher than the controls. These results indicate that intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine does not cause an increase in the choroidal blood volume in urethane-anesthetized rabbits.

Digital radiography (100 pixels/mm2) combined with the technique of 3H-labeled desmethylimipramine deposition was employed to visualize regional blood flow distributions in rabbit left ventricular myocardium. A fluctuated pattern of myocardial flow and its dependence on arterial oxygen tension (PaO2) was evaluated with the coefficient of variation (CV) computed at each step of coarse-graining; flow images were revisualized by increasing pixel area (PA) step by step from 0.01 to 1 mm2. The CV values decreased with hypoxia at all resolution levels, suggesting that there is a vascular regulatory mechanism for making myocardial perfusion uniform in response to decreased PaO2. In both perfusion states, Cl/decreased with increasing PA. The relationship between CV and PA fitted the noninteger power law function, implying an apparent fractality of CV.

An approach for integrated optimum design of structure and control system is presented based on modal analysis. This approach consists of two process, namely the process by sensitivity analysis using optimal regulator theory and the process by the complex method in which a control system is composed of a small-order output feedback. In both processes, the design variables of the structural and the control parameters are optimized simultaneously in order to minimize the response due to disturbances of both white noise and colored noise. The integrated optimum design is performed by minimizing the objective function with respect to the response under the constraints of the control cost and the stability of the closed-loop system corresponding to high order natural modes. The validity and the usefulness of the present approach are verified by a vibration control experiment with a steel plate.

An approach for an integrated optimum design of a structure and an H∞ control system is presented. The complex method and the genetic algorithm are adopted in the optimization process in the integrated design. The structural shape and the control system, including the locations of both sensors and actuators, are optimized simultaneously by the proposed approach. The improvement of frequency response shaping under the constraint of the structural mass can be realized by the integrated optimum design presented in this paper. The desired properties with respect to the control performance and the robustness are realized by the frequency shaping ability of H∞ control. Effectiveness of the presented approach is verified by both simulation and experiment by the integrated design of a panel structure and H∞ control system.

The purpose of this study was the visualization of coronary arteries by the diastolic reconstruction method with helical scanning (HES) CT. We chose diastolic phase images from the image data acquired with the HES technique using a continuous nutate-rotate fast CT scanner, because few motion artifacts are induced by cardiac pulsation during the slow filling diastolic phase. We assessed coronary diseases using this method based on HES-CT, and evaluated its clinical effectiveness. We also studied the clinical value of multiplanar reconstruction and three-dimensional surface reconstruction. The subjects consisted of 31 patients with coronary disease, aged 41-77 years. When a diastolic reconstruction HES-CT was employed, the average rate of visualization of the coronary arteries was 72%. An examination can be completed during a 30-second single breath-hold, permitting the acquisition of coronary artery images with excellent continuity. Calcified coronary arteries can be identified.

Helical scanning CT (HES-CT) was applied to multiplanar reconstruction (MPR) and 3-D imaging for the diagnosis of 65 patients with orbital lesions. We employed the the Toshiba TCT-900S, a fourth-generation high-speed CT scanner equipped with a slip-ring system. In HES-CT, scanning was performed with continuous rotation of the X-ray tube for 30 s, while the couch top was simultaneously moved at a constant speed of 1 to 2 mm/s. Images were reconstructed from continuous raw data to obtain a slice pitch of 1 mm in the longitudinal direction. HES-CT was found to have some advantages over conventional thin slice CT: 1) a wide area could be scanned in a short time (30 s) without motion artifact, 2) small lesions could be easily detected because slice images could be generated with a fine pitch at arbitrary positions from continuous raw data, 3) MPR images had good continuity in the longitudinal direction, and 4) high contrast of structures was obtained in the orbital region. HES-CT was considered to be useful for the detection of orbital lesions.

Direct and continuous observation of subendocardial (deep myocardial) microcirculation provides essential information on coronary circulation, since cardiac contraction affects subendocardial vessels most vigorously. To achieve this aim, we developed a portable needle-probe video-microscope with a charge-coupled-device (CCD) camera to visualize the subendocardial microcirculation. Images of the subendocardial microcirculation of a porcine beating heart were successfully observed in all cases. The vascular compression by cardiac contraction decreased the diameter of subendocardial arterioles and venules by about 20%.

We evaluated spatial resolution in the longitudinal axis with helical scanning CT using a fourth-generation fast CT scanner. We made a phantom by stringing acrylic balls (65 mm phi x 8 and 9 mm phi x 6). The acquired images were processed by MPR and assessed visually to evaluate axis resolution. With the conventional scanning method, the partial volume effect varied with the starting position, but helical scanning was able to reconstruct high-resolution images using continuous raw data. During helical scanning, axis resolution varied depending on the slice width and sliding speed of the couch top. Even if the sliding speed was kept constant at 4 mm/sec, axis resolution was superior with a slice width of 2 mm than with one of 5 mm.

We have shown that heat shock does not induce the synthesis of hsp70 in FM3A cells maintained at a low culture temperature of 33 degrees C although it does so in cells maintained at 37 degrees C [T. Hatayama et al. (1991) Biochem. Int. 24, 467-474]. In this paper, we show that FM3A cells maintained at 37 degrees C produced hsp70 mRNA during continuous heating at 42 degrees C or during postincubation at either 37 or 33 degrees C after being heated at 45 degrees C for 15 min, whereas cells maintained at 33 degrees C did not produce hsp70 mRNA during continuous heating at 37, 39, 42, or 45 degrees C, or during postincubation after being heated at any temperature. Thus the lack of hsp70 synthesis in cells maintained at 33 degrees C seemed to be due to the absence of hsp70 mRNA induction. Also, hsp70 was accumulated in cells maintained at 37 degrees C during continuous heating at 42 degrees C and during postincubation at 37 degrees C after heat shock at 45 degrees C, but not during postincubation at 33 degrees C. The cellular level of the constitutive hsp73 as well as the mRNA level were both similar in cells maintained at 33 and 37 degrees C. On the other hand, the cellular level of the constitutive hsp105 in cells maintained at 33 degrees C was only half of that in cells maintained at 37 degrees C. These hsp105 levels increased significantly in both types of cells after continuous heating at 39 degrees C. These findings indicate that the culture temperature affects not only the induction of hsp70 mRNA but also the accumulation of hsp70 and hsp105 in the cells.

Effects of low culture temperature on the induction of heat shock proteins in FM3A cells by a heat shock and on the thermal sensitivity of the cells were examined. FM3A cells maintained at 33 degrees C could not induce hsp70 during continuous heating or after a short heat shock at either 39, 42, or 45 degrees C, although FM3A cells maintained at a normal culture temperature of 37 degrees C can induce the synthesis of hsp70. Furthermore, the cells maintained at 33 degrees C were more sensitive to the subsequent heat shock than the cells maintained at 37 degrees C. Thus, the culture temperature of the mammalian cells may be an important factor for the induction of hsp70, and hsp70 may play an important role to protect or repair the thermal damage of cells.

To clarify the characteristics and possible causes of phasic blood velocity patterns in pressure overload hypertrophy, we measured blood flow velocities in the left anterior descending coronary arteries in 16 patients with left ventricular hypertrophy secondary to systemic hypertension. These measurements were made with a 20MHz Doppler catheter. All patients had normal coronary arteriograms. The blood flow velocity patterns were characterized by the decrease in the rise of early diastolic inflow velocity. Prolongation in the time from the onset of diastole to peak velocity (TDPV) correlated with the degree of left ventricular hypertrophy. TDPV was prolonged in proportion to the increase in the peak left ventricular systolic pressure and left ventricular ejection fraction. The flow reserve calculated from the ratio of the diastolic mean velocity after the intracoronary injection of papaverine to the resting flow showed a trend toward the decrease proportional to the prolongation in TDPV due to an increase of wall thickness. In conclusion, preceding systolic vascular compression and systolic vascular strain can be factors causing early diastolic inflow disturbance in left ventricular hypertrophy secondary to hypertension. The decrease of coronary reserve may partially be attributable to the decrease in the rise of early diastolic inflow velocity.

A new murine cell line, designated F-2, was established from an ultraviolet light-induced tumor which developed on the back skin of a BALB/c x C57BL/6 F1-nu/nu nude mouse. More than 1 x 10(5) F-2 cells injected into nude mouse skin produced rapidly developing hemangiomatous lesions. F-2 had a 14-h doubling time under 10% fetal calf serum-containing Dulbecco's modified Eagle's medium culture conditions without any cell growth factor supplementation, and it showed "cobblestone" appearance at confluency. F-2 was able to rapidly differentiate on Matrigel with resultant fine network structure and tubule formation. Ultrastructural observations of the tubule demonstrated that the F-2 cells were connected to each other by intermediate junctions and arranged to form spaces, but that no Weibel-Palade bodies were found in the cytoplasm. F-2 also showed the active uptake of fluorescent-labeled acetylated low-density lipoprotein at 37 degrees C but not at 4 degrees C, and it showed prominent binding to the lectin, Griffonia simplicifolia I agglutinin. The addition of fibroblast growth factor did not facilitate the growth of F-2 cells. These findings strongly suggest that F-2 is a transformed cell line with tumorigenicity and vascular endothelial cell properties, and it may be useful in the study of vascular tumor biology.

To obtain a smaller sample volume and a suitable sample position for the measurement of blood velocity, we fabricated a laser Doppler velocimeter (LDV) with a dual-fiber pickup. The two fibers (clad: 62.5 micron and core: 50 micron) were placed side by side. An He-Ne laser was introduced into the blood through one fiber and the backscattered light was collected by the other fiber. The Doppler signal was analyzed by a spectrum analyzer. The spectrum of the Doppler shift frequency showed a sharp peaked pattern for both forward and reverse flows and exhibited an excellent correlation with the known blood velocity. The blood velocity in the poststenotic portion of canine coronary artery was successfully measured by the dual-fiber LDV. These results indicate that the dual-fiber LDV is useful for measuring blood velocity accurately with a small sample volume even in disturbed flow fields.

To analyze the origin of the coronary artery inflow and the coronary vein outflow, we measured the intramyocardial artery flow and the epicardial small vein flow by means of a laser Doppler velocimeter with an optical fiber. The functional characteristics of the intramyocardial capacitance vessels were investigated by analyzing the responses of coronary vein flow after stepwise changes in coronary artery pressure during long diastole. Then the effect of the intramyocardial capacitance vessels on coronary artery inflow and vein outflow was evaluated. Intramyocardial artery flow was found to be almost exclusively diastolic with frequent systolic reverse flow, whereas peripheral coronary vein flow was almost systolic exclusively. The intramyocardial capacitance vessels have two functional components, unstressed volume and ordinary capacitance. When the unstressed volume was saturated, the intramyocardial displacable blood volume impeded the coronary artery inflow, but promoted vein outflow.

To elucidate the role of the haemorheological properties of the perfusate in the coronary circulation, the diastolic pressure-flow relation was studied in nine open chest heart blocked dogs with minimal vasomotor tone when blood with various packed cell volumes (12-67%) was used as perfusate. An electrical analogue model with proximal resistance R1, capacitance C, distal resistance R2, and the zero flow pressure intercept Pint was derived from the observation of the pressure-flow relation to support the data analysis. The diastolic pressure decay was then determined after the perfusion line had been clamped to calculate stop flow coronary artery pressure (Psf). The stop flow coronary artery pressure decreased in relation to packed cell volume (r = 0.45, p less than 0.01), and the value for the lowest packed cell volume (10-29%) was slightly higher than the great cardiac vein pressure (about 3 mmHg). The zero flow pressure intercept of the steady state pressure-flow relation showed a close correlation with the stop flow coronary artery pressure (r = 0.87, p less than 0.001). The value of R1 + R2, which reflects the inverse of the steady state pressure-flow slope, decreased simultaneously with the packed cell volume (r = 0.62, p less than 0.001). The resistance ratio R2/(R1 + R2) by our model prediction decreased in relation to packed cell volume (r = 0.5, p less than 0.001). The values of stop flow coronary artery pressure, zero flow pressure intercept, and R1 + R2 for the highest packed cell volume (50-69%) were 17.8(1.1) mmHg, 25.1(1.3) mmHg, and 0.48(0.05) mmHg.ml-1.min.100 g-1 respectively, whereas those for the lowest packed cell volume (10-29%) were 13.4(0.8) mmHg, 19.7(1.0) mmHg, and 0.24(0.02) mmHg.ml-1.min.100 g-1. The pressure difference between the stop flow coronary artery pressure and the zero flow pressure intercept may be due to the non-linearity in the pressure-flow relation at a low perfusion pressure. The left ventricular end diastolic pressure and great cardiac vein pressure did not change in relation to the packed cell volume of the coronary perfusate. Thus it is concluded that packed cell volume is one factor determining the high zero flow pressure.

Characteristics of blood-flow velocities were investigated at different sites in two types of coronary artery bypass grafts, sequential saphenous vein grafts (SSVG) and internal mammary artery grafts (IMAG). The latter appear to have the longest life span. The patency rate of the side-to-side anastomosis of the SSVG is better than that of the end-to-side anastomosis. The SSVG was anastomosed to the major diagonal branch by side-to-side anastomosis and to the left anterior descending coronary artery (LAD) by end-to-side anastomosis in 13 patients who had 75-100% and 75-90% stenoses in the LAD and major diagonal branch, respectively. IMAG anastomoses were performed to the LAD in 10 patients with 75-100% stenoses of the artery. The blood-flow velocities were measured by the 20-MHz, eighty-channel ultrasound pulsed Doppler method during surgery. In six patients in the SSVG group, we investigated the configuration of velocity profiles at the region just proximal to the side-to-side anastomosis and at the bridge portion between the side-to-side and end-to-side anastomosis. In the other seven patients, we measured the blood-flow velocity at several centimeters proximal to the side-to-side anastomosis and compared it with that in the IMAG. At the region just proximal to the side-to-side anastomosis, the velocity profile skewed toward the anastomosis side wall in all patients, and the flow velocity near the wall opposite to the side-to-side anastomosis was reversed in five of six patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Peak rapid filling rate (PRFR) is often used clinically as an index of left ventricular relaxation, i.e., of early diastolic function. This study tests the hypothesis that early filling rate is a function of the atrioventricular pressure difference and hence is influenced by the left atrial pressure as well as by the rate of left ventricular relaxation. As indexes, we chose the left atrial pressure at the atrioventricular pressure crossover (PCO), and the time constant (T) of an assumed exponential decline in left ventricular pressure. We accurately determined the magnitude and timing of filling parameters in conscious dogs by direct measurement of phasic mitral flow (electromagnetically) and high-fidelity chamber pressures. To obtain a diverse hemodynamic data base, loading conditions were changed by infusions of volume and angiotensin II. The latter was administered to produce a change in left ventricular pressure of less than 35% (A-1) or a change in peak left ventricular pressure of greater than 35% (A-2). PRFR increased with volume loading, was unchanged with A-1, and was decreased with A-2; T and PCO increased in all three groups (p less than .005 for all changes). PRFR correlated strongly with the diastolic atrioventricular pressure difference at the time of PRFR (r = .899, p less than .001) and weakly with both T (r = .369, p less than .01) and PCO (r = .601, p less than .001). The correlation improved significantly when T and PCO were both included in the multivariate regression (r = .797, p less than .0001). PRFR is thus determined by both the left atrial pressure and the left ventricular relaxation rate and should be used with caution as an index of left ventricular diastolic function.

Poststenotic blood flow velocities were evaluated in nine patients with 75% to 99% stenosis of the left anterior descending coronary artery (LAD) during coronary artery bypass graft surgery. We used the 20 MHz 80-channel pulsed Doppler velocimeter developed in our laboratory. An operator placed a specially designed probe on the native LAD with his fingers. Before induction of extracorporeal circulation, LAD blood velocities were measured at several locations distal to the stenosis. The poststenotic flow velocities were rich in systolic flow component with reduced diastolic component. The velocity configuration in the poststenotic portions was characterized by the presence of reverse flow velocities and/or irregularity of the velocity pattern near the vessel wall, indicating the existence of flow separation and recirculation in the regions. The broadening of the velocity spectrum observed at central axial regions suggested the occurrence of flow disturbances. After grafting, the velocity waveform in the LAD beyond a vein bypass graft changed to a diastolic-predominant pattern with a relatively small systolic component. A transient bypass graft occlusion caused a marked reduction in diastolic flow velocity. The systolic-to-diastolic velocity ratio increased from 0.27 +/- 0.07 to 1.50 +/- 0.50 (p less than .01) by the graft occlusion.

To clarify the characteristics of the phasic blood velocity pattern in small arteries and veins on the left atrial surface, we used our newly developed fiber-optic laser Doppler velocimeter. We intended particularly to examine the influence of atrial contraction and relaxation on velocity waveforms to obtain some insight into the nature of the mechanical force acting on the atrial intramyocardial vascular beds. In 14 anesthetized open-chest dogs, the left atrial appendage was gently displaced to expose small branches of the artery and vein. Vessels with an outer diameter of about 150-500 microns were chosen for the measurements because their walls are transparent to laser light. The fiber tip (velocity sensor) was fixed on the vessel surface with a drop of cyanoacrylate when good-quality Doppler signals were consistently observed. Additional experiments with three dogs were performed to observe the blood velocities in the atrial artery and vein during arrhythmia. The blood velocity waveform in the artery was similar to the pattern of aortic pressure during ventricular ejection (peak velocity, 18.8 +/- 7.8 cm/sec) but was characterized by a pronounced dip during atrial contraction. The temporal coincidence between the dip formation and atrial contraction was confirmed during atrial flutter with an atrioventricular block. After isoproterenol administration (2 micrograms i.v.), the acceleration rate of the forward flow velocity increased by 176% (p less than 0.05), and reverse flow appeared during atrial contraction in five cases out of eight (p = 0.013). The blood flow velocity in atrial small veins, on the other hand, was predominant during atrial contraction (peak velocity, 15.6 +/- 5.8 cm/sec). Isoproterenol increased the acceleration rate of this forward flow velocity by 121% (p less than 0.01). Nitroglycerin did not change the blood velocity waveform significantly in atrial arteries or in veins. The phase opposition between arterial inflow into and venous outflow from the atrial myocardium indicates that a large portion of the coronary inflow to the atrial myocardium may be stored due to the presence of atrial myocardial vascular capacitance. We conclude that atrial myocardial contraction impedes atrial inflow and promotes venous outflow from atrial capacitance vessels.

Isometric relaxation in cardiac sarcomeres is characterised by an early, very slow phase of tension fall which is terminated by a 'give' in tension. A 'give' which occurs during relaxation in cardiac muscle can not be attributed to decrease in myofilament overlap. After the 'give' asynchronous motion occurs between sarcomeres, but the duration and extent of their displacement is limited. Intriguingly, the effect of isotonic displacements on the early fall in the velocity of sarcomere shortening indicates that an internal resistance increases near the peak of contraction. The complex shape of the sarcomere's complete force-velocity relation, with lengthening motions in particular, was consistent with an idealized model of cross-bridge cycling. The sarcomere's resistance to stretch is high at low velocity, but it diminishes to reveal yielding at larger velocities. Relative to tension, the resistance to yielding does not decrease during relaxation, and it may actually increase. The decay of isometric tension after a controlled stretch also slows during relaxation. Consequently, cycling slows in those cross-bridges which form (or persist but produce less force) later in contraction. Changes in cross-bridge properties may restrict sarcomere shortening, prolong activation, but promote a disequilibrium which favors rapid relaxation in cardiac muscle.

A case of cutaneous leiomyoma of the male nipple is reported. This is the second case reported by dermatologists to the best of our knowledge.

In this paper we describe a laser Doppler velocimeter (LDV) with an optical fiber that measures blood flow velocities accurately in a small sample volume. The principle, optical arrangement, spatial and the temporal resolutions and accuracy for blood flow measurements are delineated, followed by a report of the results of measurements of coronary artery and vein blood flow velocities in dogs. Finally, we touch upon some recent progress made in the LDV with an optical fiber pickup.

We investigated the characteristics of blood velocities in different types of coronary bypass grafts, i.e., the saphenous vein graft (SVG; 6 cases) vs the internal mammary artery graft (IMAG; 6 cases) and for different positioning of the sequential saphenous vein bypass graft (SSVG), i.e., the side-to-side anastomosis (SSA) vs the end-to-side anastomosis (ESA), the life span of which are known to be different. The blood velocities were measured by the dual mode (zerocross and FFT), multichannel, high frequency ultrasound Doppler method during bypass graft surgery. Comparing the blood velocities in the SVG with those in the IMAG (longer life span), the velocity profile was much more parabolic and the velocity spectrum was narrower in the IMAG. Regarding the velocities in the SSVG (the SSA has longer life span), the skew of the velocity profile and the reverse flow at the position just proximal to the SSA were always recognized near the probe-side wall (the opposite side of the SSA), indicating the existence of flow separation and recirculation in this region. The direction of skew changed between the SSA and the ESA in almost all cases. These patterns of blood flow seem to be a contributory factor in determining the fate of the graft.

To evaluate local blood flow velocities accurately at many sampling points in small vessels, especially in human coronary arteries, we have developed an 80 channel 20 MHz pulsed Doppler velocimeter. Doppler signals from 80 channels are detected by a zero-cross method and a signal from an optional channel is analyzed by a fast-Fourier transform method, both in real time. Basic experiments using a model and animals have demonstrated the accuracy and utility of our method of measurement of blood flow velocity for both nondisturbed and disturbed flow. Velocity waveforms in a native coronary artery beyond a vein bypass graft insertion were measured during cardiac surgery. They showed a diastolic-predominant pattern with a small systolic component. During transient graft occlusion, the waveforms changed to a systolic-predominant pattern in a patient with severe stenosis and to a to-and-fro pattern in a patient with total occlusion. In a patient with severe aortic regurgitation, the coronary arterial velocity waveforms exhibited a systolic-predominant pattern with a broad velocity spectrum. After aortic valve replacement, however, a diastolic-predominant pattern with a narrow spectrum was observed.

The effects of 5-isopropyl 3-methyl 2-cyano-1,4-dihydro-6-methyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate (nilvadipine, FR 34235, FK 235) on the cardiovascular system were investigated in isolated organs and whole animals. 1. Nilvadipine inhibited Ca2+-induced contractions of isolated dog coronary artery in high-K+, Ca2+-free medium, and the pA2 value was 10.64. In this effect, nilvadipine was 18 times more potent than nifedipine and 525 times more potent than diltiazem. In contrast, its inhibitory effect on Ca2+-induced contractions of isolated guinea pig atria was weaker (pA2:8.2): only twice that of nifedipine and 25 times that of diltiazem. 2. Nilvadipine also inhibited K+-induced 45Ca2+ uptake in isolated dog coronary arteries and isolated guinea pig atria. In the coronary arteries, the IC50 value of nilvadipine was 2.7 x 10(-10) mol/l, which was, respectively 17, 8, and 589 times lower than that of nifedipine, nicardipine and diltiazem. In the atria, on the other hand, the IC50 value of nilvadipine was 4.4 x 10(-9) mol/l, almost the same as that of nifedipine or nicardipine, and 47 times lower than that of diltiazem. These 45Ca2+ uptake inhibitory effects of the drugs were consistent with their effects on mechanical response in both tissues. 3. Nilvadipine (2.6 x 10(-10) mol/l and higher) dose-dependently inhibited ergometrine (ergonovine)-, serotonin-, and norepinephrine-induced contractions of isolated dog coronary artery, and its effects were 2 to 450 times more potent than those of nifedipine, nicardipine and diltiazem. 4. Nilvadipine (2.6 x 10(-8) mol/l or more, 32 micrograms/heart or more), like nifedipine, produced negative inotropic and chronotropic effects in isolated guinea pig atria and in dog heart-lung preparation, and was more potent than nifedipine in the negative chronotropic effect. 5. Nilvadipine in intravenous doses of 1-32 micrograms/kg decreased total peripheral resistance and systemic blood pressure, and slightly increased cardiac output, pulmonary arterial blood flow and stroke volume, but had no significant effects on pulmonary vascular resistance or pulmonary arterial blood pressure. Heart rate decreased at doses of 32 micrograms/kg or more. Nifedipine had almost the same effects as nilvadipine on total peripheral resistance and blood pressure, but was more potent than nilvadipine in increasing effects on cardiac output, stroke volume and pulmonary arterial blood flow.(ABSTRACT TRUNCATED AT 400 WORDS)

In this paper we describe a laser Doppler velocimeter (LDV) with an optical fiber that measures blood flow velocities accurately in a small sample volume. The principle, optical arrangement, spatial and the temporal resolutions and accuracy for blood flow measurements are delineated, followed by a report of the results of measurements of coronary artery and vein blood flow velocities in dogs. Finally, we touch upon some recent progress made in the LDV with an optical fiber pickup.

We have developed an 80 + 1 channel high resolution pulsed Doppler velocimeter for measuring in detail the blood flow velocities in relatively small human vessels (1-5 mm in diameter). Real time velocity measurements were performed at 80 sample points using a multigated zero-cross method. The Doppler signal in the desired channel was subjected to real time Fourier analysis. This facilitated analyzing in detail the blood flow velocity profile across vessel, as well as the velocity distribution in a sample volume. The sampling volume was pi X 0.5(2) X 0.2 mm3 and the maximum depth was 1.5 cm. When the incidence angle was selected as 60 degrees, the velocity resolution and maximum velocity were 1.5 and 1.9 m/sec, respectively. Blood flow velocities were measured in the coronary artery and in the aorto-coronary bypass graft in patients during cardiac surgery. The blood flow velocities in the normal coronary artery had a predominantly diastolic pattern which is characteristic of coronary artery flow. Comparing with the systolic forward velocities in the left coronary artery, those of the right coronary artery were more prominent. The velocity wave forms in the graft and in the coronary artery distal to the insertion of the graft had a predominantly diastolic pattern when there was sufficient coronary blood flow through the graft. In contrast, during the occlusion of the graft, the blood velocity wave form in the distal coronary artery became predominantly systolic, indicating insufficient myocardial inflow before the bypass graft. Intravenous dipyridamole administration increased the bypass flow by 50% in a patient who had 100% occlusion before the bypass operation. This indicates that the coronary reserve can still be preserved in some cases of total coronary occlusion. With an intra-aortic balloon pumping (IABP) assist (2:1), the velocity wave form in the graft had predominantly diastolic in both IABP-on and -off beats. However, diastolic augmentation and systolic reduction of the velocity wave form were clearly observed in beats with IABP-on. The velocity wave forms in the anterior descending coronary artery in a patient with aortic regurgitation showed a predominantly systolic pattern with a broad velocity spectrum. After aortic valve replacement, the blood velocity pattern became predominantly diastolic, indicating improvement of the coronary perfusion into the myocardium. In conclusion, our velocimeter proved effective for evaluating coronary blood flow velocities in patients during cardiac surgery.

The sympathetic inhibitory mechanism in dog urinary bladder studied. The bladder contractions induced by electrical stimulation of the pelvic nerve both proximal and distal to the pelvic plexus and by intraarterial administration of tetramethylammonium (TMA) were inhibited by stimulation of the hypogastric nerve and intraarterial injection of catecholamines. The inhibition by hypogastric nerve stimulation was more potent at the low frequency of pelvic nerve stimulation than at the high frequency. The inhibition of contraction induced by stimulation of the pre-plexal pelvic nerve was antagonized by phentolamine and propranolol, whereas the inhibition of contraction induced by stimulation of the post-plexal pelvic nerve and by TMA treatment were antagonized only by propranolol. It is concluded that inhibition by hypogastric nerve stimulation of bladder contraction induced by pelvic nerve stimulation is composed of two different components. One occurs at the ganglia in the pelvic plexus and is mediated by alpha-adrenoceptors. The other occurs at the post-plexal pelvic pathway, probably at the ganglia in the bladder wall or on the muscle cells, and is mediated by beta-adrenoceptors. Moreover, the alpha-adrenergic action facilitated the pelvic nerve excitation in its pathway from the ganglionic cell bodies to the muscle cells.