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Background Etelcalcetide is the first intravenously administered calcimimetic agent used to manage secondary hyperparathyroidism (SHPT) in hemodialysis (HD) patients. We evaluated the safety and efficacy of replacing cinacalcet with etelcalcetide in HD patients. Methods One hundred and thirty-three patients HD on cinacalcet were screened, and 93 patients with serum-intact parathyroid hormone (iPTH) level of ≥ 60 pg/mL and serum albumin-corrected calcium (cCa) level of ≥ 8.4 mg/dL were enrolled. The patients were divided into three groups based on the dose of cinacalcet (i.e., 25, 50, and ≥ 75 mg) and switched to etelcalcetide. Etelcalcetide was administered three times per week for 24 weeks. The primary and secondary endpoints were etelcalcetide conversion dose and etelcalcetide effectiveness for iPTH levels (target range: 60–240 pg/mL), respectively. Results Of the 68 patients whose iPTH level was within the management target at screening, 60 patients maintained the target level at the end of the study. Among patients whose iPTH level exceeded 240 pg/mL at screening, it decreased from 401 ± 246 pg/mL to 220 ± 209 pg/mL (p < 0.001) at the end of the study. Among 22 patients with the iPTH level of ≥ 240 pg/mL, 17 achieved the target level. The mean dose of cinacalcet was 41.4 ± 22.2 mg/day and that of etelcalcetide at the end of the study was 6.4 ± 3.7 mg/session in all patients. In 45 patients whose iPTH level was within the management target throughout the study and active vitamin D agent and calcium-based phosphate binder doses were constant, the mean dose of cinacalcet was 45.0 ± 22.4 mg/day and that of etelcalcetide at the end of the study was 6.1 ± 3.1 mg/session. The spKt/V might affect the ratio of etelcalcetide per session to oral cinacalcet per day (45 patients, p = 0.087; 90 patients, p < 0.05) in the generalized linear model. Etelcalcetide-induced severe adverse events were not observed. Conclusions This study reports the conversion dose of etelcalcetide and demonstrates its safety and efficacy in HD patients with SHPT previously treated with cinacalcet. Trial registration UMIN, UMIN000027637; Registered on June 5, 2017.

In many countries, 40–60% of the traffic accidents occur at junctions, making the reduction of junction accidents paramount to achieving UN Sustainable Development Goals. In Japan, the road safety guidelines specify the proximity between junctions and non-perpendicular angles at junctions as the two main risk factors behind junction accidents, yet their impact remains understudied. Using binomial logistic regression models, this study investigates the impact of junction intervals and junction angles on the severity of traffic accidents. The study found that, in general, (1) shorter intervals between adjacent junctions helps reduce the risk of serious accidents, which is the opposite of the current road safety guidelines in Japan, and (2) results from the junction angle analysis were mixed but there was no evidence that the roads should meet at a right angle to reduce traffic accidents. Some types of accidents also returned a non-linear curve, e.g., vehicle-to-vehicle collisions at four-armed junctions involving a driver aged 65 years and over have the highest risk of fatal/serious accidents when adjacent junctions were 32 m apart, and the risk reduces at a shorter or longer interval. These results suggest that the current road safety guidelines require updating to improve road safety around junctions.

L-carnitine (LC) supplementation improves cardiac function in hemodialysis (HD) patients. However, whether reducing LC supplementation affects carnitine kinetics and cardiac function in HD patients treated with LC remains unclear. Fifty-nine HD patients previously treated with intravenous LC 1000 mg per HD session (three times weekly) were allocated to three groups: LC injection three times weekly, once weekly, and placebo, and prospectively followed up for six months. Carnitine fractions were assessed by enzyme cycling methods. Plasma and red blood cell (RBC) acylcarnitines were profiled using tandem mass spectrometry. Cardiac function was evaluated using echocardiography and plasma B-type natriuretic peptide (BNP) levels. Reducing LC administration to once weekly significantly decreased plasma carnitine fractions and RBC-free carnitine levels during the study period, which were further decreased in the placebo group (p &lt, 0.001). Plasma BNP levels were significantly elevated in the placebo group (p = 0.03). Furthermore, changes in RBC (C16 + C18:1)/C2 acylcarnitine ratio were positively correlated with changes in plasma BNP levels (β = 0.389, p = 0.005). Reducing LC administration for six months significantly decreased both plasma and RBC carnitine levels, while the full termination of LC increased plasma BNP levels, however, it did not influence cardiac function in HD patients.

Late-onset hypogonadism (LOH) and depression contribute to cardiovascular disease (CVD) in male hemodialysis (HD) patients. Carnitine deficiency is frequently observed in HD patients, playing a role in CVD. We examined whether carnitine deficiency was independently associated with LOH and depression in these patients. Twenty-six male HD patients underwent determinations of serum levels of free carnitine and testosterone. Status of LOH and depression were evaluated by questionnaires using aging male symptoms' (AMS) scale and self-rating depression scale (SDS), respectively. Free carnitine and testosterone levels in male HD patients were significantly lower than those in age-matched healthy male subjects. Linear regression analysis showed that AMS scale was positively associated with SDS. Univariate regression analysis revealed that total carnitine (inversely), free carnitine (inversely) and HD duration were correlated with AMS scale. Multiple stepwise regression analysis revealed that free carnitine was an independent determinant of AMS scale. Furthermore, free carnitine was also independently correlated with SDS in male HD patients. This study demonstrated that decreased free carnitine levels were independently associated with AMS scale and SDS in male HD patients. The observations suggest that decreased free carnitine levels could be a marker and therapeutic target of LOH and depression in uremic men with HD.

Phosphate binders are useful for the treatment of hyperphosphatemia in hemodialysis (HD) patients. This study was performed to examine the effects of switching from calcium carbonate (CC) to lanthanum carbonate (LC) on bone mineral metabolism and inflammatory markers in HD patients. We conducted 29 stable HD patients receiving CC, which was replaced by LC and followed-up for 12 weeks. Patients underwent determinants of blood chemistries such as serum calcium (Ca), phosphorus, parathyroid hormone (PTH) and vitamin D status, and interleukin-6 (IL-6) mRNA levels in whole blood cells were evaluated by real-time PCR just before and after the treatment with LC. Corrected Ca [corrected] levels were significantly reduced, but serum phosphorus levels (P levels) were unchanged after LC treatment. Switching to LC increased whole-PTH, osteocalcin, 1,25(OH)(2) D(3) levels and 1,25(OH)(2) D(3)/25(OH)D(3) ratio. 1,25(OH)(2) D(3)/25(OH)D(3) ratio was negatively correlated with HD duration. Furthermore, whole blood cell IL-6 mRNA levels were significantly reduced by LC treatment. We provided that the switching from CC to LC improved Ca overload and ameliorated vitamin D and inflammatory status in HD patients. These observations suggest that LC may play a protective role for the progression of atherosclerosis and vascular calcification in these patients.

Organic materials with diverse molecular designs show multifunctional properties such as coupled ferroelectric, optical, ferromagnetic, and transport properties. We report the design of an alkylamide-substituted pyrene derivative displaying fluorescent ferroelectric properties coupled with electron transport properties. In solution phase, this compound displayed concentration-dependent fluorescence, whereas in xerogels, a fluorescent green organogel (>0.1 mM) and entangled nanofibers were observed. A discotic hexagonal columnar liquid crystalline phase was observed above 295 K due to intermolecular hydrogen bonding and π-stacking interactions. The direction of the hydrogen-bonded chains could be inverted by the application of an external electric field along the π-stacked column, resulting in ferroelectric polarization-electric field (P-E) hysteresis. The local electric field arising from the ferroelectric macrodipole moment arrangement along the π-stacking direction affected the electron transport properties on the π-stack of pyrenes, thus confirming the current-switching phenomena according to P-E hysteresis. We report that multifunctional properties such as ferroelectricity, fluorescence, and electron transport switching were successfully achieved in hydrogen-bonded dynamic π-molecular assemblies.

Food or supplement-derived L-carnitine is changed to trimethylamine (TMA) by interstinal microbiota, which is further metabolized to trimethylamine-N-oxide (TMAO), being involved in the promotion of atherosclerosis in animal models. Meanwhile, carnitine deficiency has played a role in accelerated atherosclerosis in hemodialysis (HD) patients. However, effects of oral L-carnitine supplementation on circulating levels of TMAO and markers of vascular injury and oxidative stress in patients on HD remain unclear. In this study, we addressed the issue.Thirty-one HD patients with carnitine deficiency were treated with oral L-carnitine (900 mg/d) for 6 months. At baseline and after treatment, clinical variables including circulating levels of carnitine fractions, TMA, TMAO, advanced glycation end products (AGE), soluble forms of intracellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and malondialdehyde (MDA) were measured.Oral L-carnitine supplementation significantly increased total, free, acyl carnitine, and plasma TMA and TMAO levels, whereas it decreased markers of vascular injury and oxidative stress such as sICAM-1, sVCAM-1, and MDA levels. TMA and TMAO levels at baseline were correlated with each other, and free carnitine was independently associated with TMAO levels. Furthermore, change in AGE values from baseline ([INCREMENT]AGE) was positively correlated with [INCREMENT]sICAM-1 (P = 0.043) and was a sole independent determinant of [INCREMENT]sICAM-1 (R = 0.133, P = 0.043).This study demonstrated that although oral L-carnitine supplementation was associated with increased TMAO levels, it might be beneficial on vascular injury in patients on HD. Vasculoprotective properties of L-carnitine supplementation in HD patients might be ascribed partly to its inhibitory actions on AGE.

Hypertension is a major complication of recombinant human erythropoietin therapy in patients with end-stage renal disease. Although the mechanisms for this pressor effect remain unknown, in vitro and ex vivo experiments suggest that erythropoietin stimulates release of cyclooxygenase-dependent endothelium-derived contracting factors (EDCFs) and attenuates endothelium-dependent vasorelaxation. To investigate the effect of erythropoietin on human endothelial function, we measured forearm blood flow by strain gauge plethysmography before and after intraarterial incremental administration of erythropoietin (10 to 300 IU/min, total 3000 U), while infusing acetylcholine (4 to 24 microg/min) and sodium nitroprusside (0.2 to 1.2 microg/min) in healthy male volunteers (n = 12). To examine a possible role of EDCFs, we repeated the same protocol under the pretreatment with oral indomethacin (50 mg), a cyclooxygenase inhibitor (n = 8). Infusion of erythropoietin into the brachial artery increased the erythropoietin blood concentration of venous effluents significantly (P < .0001) without changes in blood pressure and basal forearm blood flow. Acetylcholine and sodium nitroprusside increased forearm blood flow dose dependently before and after erythropoietin administration. However, acetylcholine-induced vasodilation (endothelium dependent) was significantly attenuated (P < .001) after erythropoietin administration, whereas vasodilation to sodium nitroprusside (endothelium independent) was unchanged. After indomethacin pretreatment, erythropoietin no longer attenuated endothelium-dependent vasorelaxation. Our results indicate that erythropoietin may impair endothelial function acutely, probably through cyclooxygenase-dependent EDCFs in humans. Long-term effects of erythropoietin on endothelial function in uremic patients remain to be elucidated.

Acute inhibition of nitric oxide (NO) synthase in the brain causes elevation of blood pressure and sympathetic excitation under anesthetized conditions. To investigate chronic effects of NO synthase inhibition in the central nervous system on blood pressure regulation in conscious unrestrained animals, we administered NG-monomethyl-L-arginine (L-NMMA), a potent NO synthase inhibitor, at low (22.5 μmol/kg) and high (67.5μmol/kg) doses for 1wk into the cisterna magna with an osmotic pump and measured mean arterial pressure (MAP) and heart rate (HR) by a telemetry method. The same dose of NG-monomethyl-D-arginine (D-NMMA), an inactive isomer of L-NMMA, was administered to control rats. Chronic intracisternal administration of low-dose L-NMMA significantly decreased the brain nitrite/nitrate and NO metabolite contents as compared with D-NMMA (p

N G , N G -dimethyl- l -arginine (ADMA) is an endogenously synthesized nitric oxide (NO) synthase inhibitor which has potent pressor/vasoconstrictor effects. Dimethylargininase metabolizes ADMA to l -citrulline and plays a key role in determining the in vivo levels of ADMA. To investigate the role of ADMA in the pathogenesis of hypertension, we measured 24-hour urinary excretion of ADMA (UADMA) and nitrate/nitrite (NOx) in Dahl salt-sensitive hypertensive rats and spontaneously hypertensive rats (SHR). In Dahl salt-resistant rats, high-salt diet (8% NaCl) did not increase blood pressure and increased urinary NOx ( P P P r =.65, P P P r =.64, P

Transition metal dichalcogenide (TMDC) monolayers have attracted much attention due to their strong light absorption and excellent electronic properties. These advantages make this type of two-dimensional crystal a promising one for optoelectronic device applications. In the case of photoelectric conversion devices such as photodetectors and photovoltaic cells, p-n junctions are one of the most important devices. Here, we demonstrate photodetection with WSe2 monolayer films. We prepare the electrolyte-gated ambipolar transistors and electrostatic p-n junctions are formed by the electrolyte-gating technique at 270 K. These p-n junctions are cooled down to fix the ion motion (and p-n junctions) and we observed the reasonable photocurrent spectra without the external bias, indicating the formation of p-n junctions. Very interestingly, two-terminal devices exhibit higher photoresponsivity than that of three-terminal ones, suggesting the formation of highly balanced anion and cation layers. The maximum photoresponsivity reaches 5 mA/W in resonance with the first excitonic peak. Our technique provides important evidence for optoelectronics in atomically thin crystals., Accepted in Applied Physics Letters (2016)

著明な出血傾向を伴う腎不全患者の血液透析導入時に, 内シャント, 外シャントを同時に, かつ同側に作成し, その外シャントを用いて導入を行った1例を報告する.症例は38歳の男性, 慢性腎炎にて外来加療を受けていたが, 腎不全の急性増悪にて入院となる. 血小板凝集能の低下を含め著明な出血傾向を認め, 穿刺によるカテーテル留置は危険と思われ手術的に確実に止血を行い得る外シャントを作成し, その早期抜去を可能とするため内シャントも同時に作成した. 外シャントにて導入を行ったが透析効率, 内シャント発達ともに良好であり術後10日で内シャント使用可能となり, 外シャントも抜去した.外シャントは感染, シャント閉塞, 動脈狭窄等の問題で最近はあまり使用されていない方法であるが, 内シャントと同側, 同時に作成する場合には有用と考えられた.

Phosphate binders are useful for the treatment of hyperphosphatemia in hemodialysis (HD) patients. This study was performed to examine the effects of switching from calcium carbonate (CC) to lanthanum carbonate (LC) on bone mineral metabolism and inflammatory markers in HD patients. We conducted 29 stable HD patients receiving CC, which was replaced by LC and followed-up for 12 weeks. Patients underwent determinants of blood chemistries such as serum calcium (Ca), phosphorus, parathyroid hormone (PTH) and vitamin D status, and interleukin-6 (IL-6) mRNA levels in whole blood cells were evaluated by real-time PCR just before and after the treatment with LC. Corrected Ca [corrected] levels were significantly reduced, but serum phosphorus levels (P levels) were unchanged after LC treatment. Switching to LC increased whole-PTH, osteocalcin, 1,25(OH)(2) D(3) levels and 1,25(OH)(2) D(3)/25(OH)D(3) ratio. 1,25(OH)(2) D(3)/25(OH)D(3) ratio was negatively correlated with HD duration. Furthermore, whole blood cell IL-6 mRNA levels were significantly reduced by LC treatment. We provided that the switching from CC to LC improved Ca overload and ameliorated vitamin D and inflammatory status in HD patients. These observations suggest that LC may play a protective role for the progression of atherosclerosis and vascular calcification in these patients.

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.

The purpose of this study was to simulate postoperative radiographs by preoperative radiographs using a personal computer. METHOD: Preoperative radiograph was scanned by image scanner and full color frame memory, and simulations of the osteotomies were carried out using a personal computer. RESULT: The quality of the pictures on the computer display was equal to the plane radiograph. More intensive calculation of the osteotomy was possible with our method than with a diagram method using the tracing paper. Furthermore, the pictures could be saved on the floppy disk.

We propose a strategy for improving the response speed of electric double-layer capacitors (EDLCs) and electric double-layer transistors (EDLTs), based on an asymmetric structure with differently sized active materials and gate electrodes. We validate the strategy analytically by a classical calculation and experimentally by fabricating EDLCs with asymmetric Au electrodes (1:50 area ratio and 7.5 μm gap distance). The performance of the EDLCs is compared with that of conventional symmetric EDLCs. Our strategy dramatically improved the cut-off frequency from 14 to 93 kHz and this improvement is explained by fast charging of smaller electrodes. Therefore, this approach is particularly suitable to EDLTs, potentially expanding the applicability to medium speed (kHz–MHz) devices.

Caveolae in mesangial cells and caveolin expression in mesangial proliferative glomerulonephritis. Background Caveolae are plasma membrane invaginations that have a diameter of 40 to 60 nm. Recent evidences have demonstrated that caveolae contain a variety of signal transduction molecules. Caveolin is a marker protein of caveolae and has been proposed to play a negative regulatory role in signal transduction. The aim of this study was to investigate the behavior of caveolae and caveolin in experimental glomerulonephritis, the localization of both platelet-derived growth factor (PDGF) and transforming growth factor-βbgr; (TGF-βbgr;) receptors in the caveolae membrane, and the regulation of caveolin expression in cultured mesangial cells. Methods The expression of caveolin-1 was examined by immunoblotting and immunohistology using anti-caveolin antibody in anti-Thy-1 nephritis. The caveolae membrane fraction of mesangial cells was isolated by sucrose gradient method and expression of PDGF receptor and TGF-βbgr; receptor were detected by immunoblotting. The effects of mitogens such as phorbol 12-myristate 13-acetate (PMA) and PDGF on the expression of caveolin-1 protein and mRNA were also examined in cultured mesangial cells. Results Caveolin-1 was mainly expressed in glomeruli and was significantly up-regulated in anti-Thy-1 nephritis rat kidney. In cultured mesangial cells, the membrane invaginations of caveolae were revealed by electron microscopy. PDGF receptors abounded in the caveolae membrane and rapidly changed their subcellular distribution after ligand stimulation. In contrast, TGF-βbgr; receptors abounded in the non-caveolae membrane and did not change after ligand stimulation. Decreases in caveolin-1 protein, which were associated with increases in mRNA expression after the exposure of PMA or PDGF-BB, suggested an increased turnover of caveolin-1 in mesangial cells stimulated by mitogens. Conclusion To our knowledge, this electron microscopical study is the first to demonstrate the presence of caveolae in cultured mesangial cells. Caveolae integrate PDGF receptors, and caveolin-1 may play a role in the pathogenesis of the mesangial proliferative glomerular diseases through PDGF signaling.

Background Although long-term lipid-lowering therapy improves endothelium-dependent vasodilatation in humans, it remains unknown whether the short-term removal of LDL per se ameliorates endothelial dysfunction. Methods and Results To examine the effects of a single session of LDL apheresis on endothelial function in patients with hypercholesterolemia, we measured forearm blood flow (FBF) by strain-gauge plethysmography before and after single LDL apheresis while infusing acetylcholine (ACh; 4 to 24 μg/min) and sodium nitroprusside (SNP; 0.2 to 1.2 μg/min). The single session of LDL apheresis reduced total LDL (from 142.2±15.0 to 32.6±5.0 mg/mL, P P P P r =.99, P Conclusions We demonstrated that even a single session of LDL apheresis with the reduction of total LDL and oxidized LDL improved endothelial function. Our results suggest that total LDL and/or oxidized LDL may directly impair endothelial function in the human forearm vessel.

We fabricated stretchable molybdenum disulfide thin-film transistors (MoS2 TFTs) on poly(dimethylsiloxane) substrates using ion gels as elastic gate dielectrics. The TFTs exhibited an electron mobility of 1.40 cm2/(V·s) and an on/off current ratio of 104 with a notably low threshold voltage (∼1 V). Furthermore, our MoS2 TFTs operated at a mechanical strain of 5% without significant degradation of their electrical properties. These results demonstrate the potential for using MoS2 films for stretchable electronics.

We prepared string like assemblies of aligned single-wall carbon nanotubes (SWCNTs) in a (6,5) nearly single-chiral state. We observed that by simply adjusting the temperature and incubation time of SWCNT monodispersed solutions, string-like assemblies of aligned SWCNTs could be generated. Polarized Raman and scanning electron microscopy measurements clearly indicated that the SWCNTs were aligned parallel to the string axis. These assemblies exhibited good field-effect performances, exhibiting an on/off ratio of 6.8×103 and a maximum mobility of 106.5 cm2 V-1 s-1.

Idiopathic chondrolysis of the hip is characterized by pain, limping and a progressive restriction in the range of motion of the hip. The paper describes the case of two female patients, age 28 and 37, who were referred to our hospital in October 1985 and May 1991 for pain and limitation of movement in the right hip. Neither patient had a previous history of systemic illness or trauma or medication such as steroids. On admission they underwent clinical and X-ray examinations. Both required an open biopsy to confirm the diagnosis. They have been followed for 4 years and 8 years, respectively.

The aim was to evaluate the relative contribution of atrial muscle contraction and atrial pressure to the phasic patterns of left atrial arterial and venous flows. Methods: Using a laser Doppler velocimeter, blood velocities were measured in the atrial small arteries and veins (outer diameter: 150-500 μm) in anaesthetised open chest dogs (n=21). The velocity sensor was fixed on the vessel surface with a drop of cyanoacrylate glue when good quality Doppler signals were consistently observed. Left atrial pressure and the contractility of the left atrium were changed by premature ventricular contraction and by intracoronary injection of isoprenaline (0.5 μg), respectively. Results: Premature ventricular contraction increased left atrial pressure significantly during arterial velocity measurements from 8.1(SD 2.7) to 16.4(1.3) mm Hg and during venous measurements from 8.2(1.2) to 14.3(3.7) mm Hg. However, premature ventricular contraction did not change the blood velocity patterns, the maximum deceleration rate of the systolic velocity wave in arteries, or the maximum acceleration rate of the systolic velocity wave in veins. Although isoprenaline did not change the left atrial pressure, it decreased minimum arterial blood velocity during atrial systole, from 3.3(3.4) to -2.5(3.2) cm·s−1, and increased maximum venous blood velocity from 15.9(5.5) to 19.2(7.4) cm·s−1. Isoprenaline also increased both the maximum arterial systolic velocity deceleration rate, from 90(45) to 234(143) cm·s−2, and the maximum venous systolic velocity acceleration rate from 356(230) to 763(366) cm·s−2. Conclusions: (1) Left atrial pressure is not a major determinant of the blood flow patterns of the atrial arteries and veins, and therefore it may not closely reflect pressure around mural vessels. (2) Atrial contractility affects the blood flow patterns of the atrial arteries and veins. Cardiovascular Research 1992; 26 :1219-1225

Study objective — The aim was to clarify the characteristics of the phasic blood velocity pattern and their possible causes in left ventricular hypertrophy secondary to systemic hypertension. Design — Measurements of blood velocities in the left anterior descending coronary artery were made with a 20 MHz Doppler catheter with a top mounted annular crystal. All patients had normal coronary arteriograms. Patients — 23 hypertensive patients [systolic/diastolic pressure: 181(SD 15)/100(4) mm Hg)] with left ventricular hypertrophy, and 13 atypical chest pain patients without left ventricular hypertrophy or any abnormal haemodynamic findings (normal controls) entered the study. Measurements and main results — The left anterior descending coronary artery blood velocity waveform in pressure overloaded left ventricular hypertrophy was characterised by delayed early diastolic inflow. The diastolic rise time of coronary flow (TDR), ie, the time from the beginning of diastole to peak velocity, was higher in patients with hypertensive left ventricular hypertrophy than in normal controls, at 145(56) v 66(15) ms, p

The accuracy of 20-MHz Doppler catheter coronary artery velocimetry (Millar Instruments) was evaluated by model experiments using a turntable and a flow tube. In the turntable experiments, the flow away from the catheter tip (away flow) was significantly lower than that toward the catheter (toward flow), but the measured velocities for both away and toward flows were always lower than the known velocities. Nevertheless, the blood velocities measured at a sampling point 4 mm from the catheter tip showed excellent correlation with the known velocities irrespective of flow direction. The shape of the FFT spectra of the Doppler shift frequency from blood was broadened, and the frequency corresponding to the known velocity was always close to the maximum Doppler shift frequency. We concluded that zero-cross detection of blood velocity by the 20-MHz pulsed Doppler catheter provides a reliable measure for evaluating relative velocity changes, although it underestimates the blood velocity.

The intramyocardial capacitance vessels have two functional components, unstressed volume and ordinary capacitance. The estimated value of unstressed volume was about 5% of the left ventricular mass, and the time constant in relation to ordinary capacitance was about 1 s, although both are pressure-dependent. The coronary venous outflow was closely related to the total displaceable blood volume stored in the intramyocardial capacitance vessels, i.e., the more intramyocardial blood volume, the more coronary venous outflow. On the other hand, the diastolic coronary arterial inflow was decreased when the blood volume in the intramyocardial vessels increased above the unstressed volume. This may be important as a mechanical control of the coronary circulation system.

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.

In order to evaluate the functional characteristics of the intramyocardial capacitance vessels during prolonged diastole, we analyzed the response of coronary vein flow after stepwise changes of coronary artery pressure in anesthetized open-chest dogs by using our newly developed laser Doppler velocimeter with an optical fiber. The peripheral portion of the great cardiac vein was isolated and the optical fiber tip was inserted into the vessel. The left anterior descending coronary artery was cannulated and connected to a reservoir to regulate coronary perfusion pressure. Intracoronary adenosine administration was carried out to avoid any change in coronary vasomotor tone. After 15 seconds of occlusion of the perfusion route, the heart was arrested by pacing-off. Two seconds later, coronary perfusion pressure was increased stepwise to a preset target pressure. This procedure was repeated by changing target pressure at 4 (or 5) different pressure levels (31-105 mm Hg). The great cardiac vein flow became zero due to the cardiac arrest and remained at zero for a moment (dead time) after the initiation of reperfusion. Then the flow reappeared and increased with first order time delay. The presence of dead time indicates the existence of unstressed volume, and the first order time delay represents the product of resistance and capacitance. The unstressed volume with a minimal vasomotor tone for perfusion pressure of 60-90 mm Hg was 5.2 +/- 2.2 ml per 100 g left ventricle, which is comparable to coronary blood flow for several beats. The capacitance at perfusion pressure of 60-90 mm Hg was 0.08 +/- 0.04 ml/mm Hg per 100 g left ventricle, while that at low perfusion pressure (30-50 mm Hg) was 0.14 +/- 0.09 ml/mm Hg per 100 g left ventricle. These results indicate that the intramyocardial capacitance vessels have two functional components, and that the phasic nature of coronary vein flow is solely the result of the myocardial squeezing of the blood in the capacitance vessels.

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)

To evaluate regional myocardial function, we developed a curvature sensor for direct and instantaneous measurement of the regional curvature radius of the LV wall. The sensor is a bimorph of two sheets of thin piezoelectric polymer film. The relation between output voltage of the sensor and the reciprocal of the known curvature radius has been shown to be linear. In anesthetized dogs, we inserted the curvature sensor into the subepimyocardium with a specially designed introducer. Special care was taken to insert it parallel to the epicardial surface. Circumferential regional curvature radius, which is defined as the reciprocal of regional curvature, showed the same phasic changes as the short-axis diameter under control conditions. Under regional ischemia caused by transient occlusion of the coronary artery, amplitude of the phasic change in regional curvature radius decreased, whereas that of the short-axis diameter did not change or slightly increased. Phasic changes in regional curvature radius cannot be estimated from short-axis diameter during regional ischemia. We calculated regional wall tension from the directly measured regional curvature radius and LV pressure and found that tension-length loop clearly differentiates between regional myocardial function under control and ischemic conditions. We have concluded that our newly developed curvature sensor is accurate, that its practical use is feasible, and that measurement of the regional curvature radius of the LV wall provides detailed and accurate information on regional shape and function of the left ventricle.

In the present study, characteristics of the phasic flow pattern in the great cardiac vein and the mechanism of such pattern formation were investigated using a laser Doppler velocimeter with an optic fiber probe. The laser Doppler velocimeter allowed measurements of venous blood velocity under more physiological conditions than were possible with previous methods. Moreover, venous blood flow measurement in the great cardiac vein mirrors the effects of myocardial contraction on the venous flow more directly than does measurement in the coronary sinus. Thus, our method is considered very useful. Results obtained from the present study are as follows: 1) Measurement of the phasic flow in the great cardiac vein was made in 11 anesthetized dogs using our laser Doppler method. The blood velocity curve obtained in the great cardiac vein was always characterized by a prominent systolic flow wave (SFW). The mean value for the maximum velocities under control conditions in 11 cases was 40±13 cm/s. The blood velocity increased with the onset of left ventricular ejection and decreased gradually after the peak formation at mid- or late systole. — 2) Besides the above SFW, one or two small wave components were frequently observed during the atrial contraction period and/or during the isovolumic contraction phase. On the waveform during the atrial contraction period, two cases showed forward flow, while one case showed reverse flow. The small reverse flow waves during the isovolumic contraction phase were found in seven cases. — 3) Pharmacological interventions of dipyridamole and isoproterenol increased the maximum velocity. Compared with dipyridamole, isoproterenol accelerated the rate of rise in the SFW. — 4) No significant coronary venous flow was observed during the diastolic period prolonged by vagal nerve stimulation. However, after coronary vasodilator drugs were administered, there was a transient significant coronary venous flow during the prolonged diastole. This may be the overflow from the coronary capacitance vessels. — 5) During a reactive hyperemic response, the flow velocity of the great cardiac vein increased with the increment of the blood flow volume of the left anterior descending artery. However, its phasic change did not always correspond to that of intramyocardial pressure.

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.

A detailed assessment of flow dynamics in coronary stenosis is essential for better understanding of the pathophysiology of the obstructive coronary artery disease. However, measurements of phasic blood flow velocity and velocity distribution in a native human coronary artery have been hampered by methodological limitations. The ultrasound pulsed Doppler method is useful for measuring local blood flow velocity in vessels noninvasively. However, a conventional single-channel pulsed Doppler velocimeter with low carrier frequencies cannot obtain detailed blood velocity profiles of small vessels like the coronary artery. Recently, we have developed an 80-channel 20-MHz pulsed Doppler velocimeter [1-3], which detects Doppler signals from 80 channels by a zero-cross method and analyzes Doppler signals from one optional channel by a fast Fourier transform method, both in real time.

患者は64才,男性.健康診断で心室期外収縮を指摘されて来院.側壁領域に心室瘤類似のドーム状ST上昇を伴う異常Q波があり,精査目的で入院した. 201Tl心筋シンチグラムでは心尖部を中心に広範囲の欠損像を,左室造影では内腔の拡大, diffuse hypokinesis, apical dyskinesisを認め駆出率は16%と著明に低下していた.冠動脈造影では,有意狭窄はなく,持続性ST上昇を示す拡張型心筋症と診断した.本例のドーム状ST上昇の成因は,重症の貫壁性心筋障害とそれに基づく左窒asynergyによるものと推測された.以上より,心室瘤と類似する心電図の鑑別診断に拡張型心筋症も考慮する必要があると思われた.

It is well established that the part of the left ventricle at greatest risk to ischemia is the subendocardium. Both in myocardial infarction in humans and experimental myocardial infarction in dogs, the subendocardial muscle shows the most extensive necrosis and the subepicardium is spared. Thus, it is important to evaluate phasic blood flow in deeper intramyocardial layers. Measurements, however, have been restricted in the region of epimyocardium because of the methodological limitations [1–3].

The anatomical characteristics of the coronary circulation are summarized (Gregg and Fisher 1963; Berne and Rubio 1979; Marcus 1983) as follows: Two major coronary arteries (Fig. 6.1), a right and left, arise respectively from the right anterior and left anterior aortic sinuses of Valsalva. The left main coronary artery in adult humans is about 4–5 mm in diameter, and the mean length of this artery is 1.3 cm. The right coronary artery as its origin is about 3–4 mm in diameter. The left anterior descending coronary artery and its diagonal branches in humans perfuse most of the left ventricular myocardium. The septal perforating branches from the left anterior descending artery supply the interventricular septum. The left circumflex coronary artery follows the respective auriculoventricular groove to the left and terminates at a variable distance from the posterior longitudinal sulcus. In contrast to humans, the circumflex coronary artery in the dog supplies the largest area of cardiac muscle. The right coronary artery follows the respective auriculoventricular groove to the right. In man it usually (in about 80%) reaches the posterior sulcus and becomes the posterior descending artery.