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OBJECTIVES The present study was conducted to investigate the decrease in left ventricular stroke volume index (LVSVI) that is caused by pulmonary regurgitation-induced right heart dysfunction and its clinical implications before and after pulmonary valve replacement (PVR). METHODS Between January 2010 and December 2019, 30 adults who underwent surgical PVR for chronic pulmonary regurgitation with right ventricular dilation late after tetralogy of Fallot (TOF) repair were included. All patients were evaluated using cardiac magnetic resonance before PVR. The median interval from TOF repair to PVR was 29 [25th, 75th percentile: 25, 37] years. The median pulmonary regurgitation fraction and right ventricular end-diastolic volume index were 56 [48, 66] % and 203 [187, 239] ml/m2. Twenty-three patients (76.7%) were re-evaluated 1 year after PVR. RESULTS Before PVR, the median LVSVI was 40 [35, 46] ml/beat/m2. A lower LVSVI was associated with a longer interval from TOF repair to PVR (r = −0.40, P = 0.029) and a lower right ventricular ejection fraction (r = 0.52, P = 0.004). A lower LVSVI was not associated with a higher right ventricular end-diastolic volume index. LVSVI remained unchanged after PVR. The patients were subdivided into Normal-stroke volume index (SVI) and Subnormal-SVI groups using the preoperative LVSVI cut-off value of 35 mL/beat/m2. Compared with the Normal-SVI group, the Subnormal-SVI group had a higher incidence of ablation therapy before PVR (4.7 vs 2.3 patient-years, P = 0.044). After PVR, LVSVI in the Subnormal-SVI group was still lower (40 [34, 42] vs 44 [42, 47] ml/beat/m2, P = 0.038) despite the right ventricular end-diastolic volume index normalization. There was no difference in the clinical event incidence between the 2 groups during the follow-up period. Brain natriuretic peptide level in the Subnormal-SVI group was higher within 3 years after PVR (P = 0.046). CONCLUSIONS Reduced left ventricular stroke volume did not fully recover after PVR. PVR for patients with repaired TOF should be performed before the left ventricular stroke volume begins to decrease.

Modular stems are useful for total hip arthroplasty (THA) in anatomically difficult dysplasia. Here, we present mean 6.8-year outcomes of cementless primary THA using S-ROM-A (modified modular stem for Asian patients) femoral prosthesis in anatomically difficult cases.Charts of 373 patients (461 hips) undergoing THA (mean age, 58 years) were reviewed for clinical evaluation of modified Merle d'Aubigné-Postel score and Kaplan-Meier survivorship with revision for any reason as the end point. For radiographic analysis, 331 patients (412 hips) followed up for ≥5 years were included. Bearing couples were metal-on-metal (n = 145), metal-on-polyethylene (n = 120), and ceramic-on-polyethylene (n = 147). Radiography and multiplanar computed tomography were performed.No postoperative dislocation or deep infection occurred. Mean modified Merle d'Aubigné-Postel score improved significantly (10.9 points preoperatively, 16.7 points at last follow-up; P.001). Cumulative 5- and 10-year stem survival rates were 100% and 84%, respectively (95% confidence interval, 75%-93%). All stems were classified as bone ingrown fixation. Osteolysis occurred in metal-on-metal (42.8%) and metal-on-polyethylene (15.8%) groups. Mean time to osteolysis was ~3 years, with no significant difference between 3 groups (P = .264). In logistic regression, lower cup inclination angle was significantly associated with osteolysis (odds ratio, 0.914; 95% confidence interval, 0.84-0.99; P = .029).S-ROM-A femoral prosthesis achieved excellent midterm fixation, and the modular system was useful in primary THA with severe deformity. Bearing couples are potentially associated with adverse reactions to metal debris. S-ROM-A with ceramic-on-polyethylene bearing couples may be an option for anatomically difficult THA.

In children with dilated cardiomyopathy, heart transplantation is the last treatment option. However, new regenerative treatments, such as cell therapy, have attracted scientific attention. We have previously demonstrated the efficacy of autologous skeletal myoblast sheet implantation for treatment of ischemic and dilated cardiomyopathy in adults. Because of the mechanism underlying this cell therapy, a similar effectiveness is expected for patients with pediatric dilated cardiomyopathy. Herein, we describe the case of a child with dilated cardiomyopathy who underwent an autologous skeletal myoblast sheet implantation, which proved to be safe, and led to sustained maintenance and improvements in cardiac function and clinical status.

Berlin Heart EXCOR® (BHE) ventricular assist device (VAD) (Berlin Heart, Berlin Heart AG, Berlin, Germany) implantation is prevalent in patients with severe heart failure. However, clinical outcomes of pediatric patients on long-term BHE support remain mainly unknown. This study aimed to report our clinical experience with long-term support of pediatric patients with severe heart failure supported by BHE VAD. Clinical outcomes of 11 patients (median age 8.4 months; two male), who underwent LVAD implantation of the Berlin Heart EXCO® (BHE) VAD (Berlin Heart, Berlin Heart AG, Berlin, Germany) between 2013 and 2017 at our institution were reviewed. The median support period was 312 (range 45-661) days and five patients were supported for more than 1 year. The longest support duration was 661 days. No mortality occurred, and six patients were successfully bridged to heart transplantation, while three patients were successfully weaned off the device. Two patients are currently on BHE support while they await heart transplantation. Four patients had cerebral bleeding or infarction, but only one case of persistent neurological deficit occurred. No fatal device-related infection occurred during LVAD support. BHE VAD can provide long-term support for pediatric patients with severe heart failure with acceptable mortality and morbidity rates with long-term support.

OBJECTIVES The aim of this study was to identify the impact of bilateral bidirectional Glenn (BBDG) anastomosis on staged Fontan strategy and late Fontan circulation. METHODS Of 267 patients who underwent bidirectional Glenn prior to Fontan completion between 1989 and 2013, 62 patients (23%) who underwent BBDG were enrolled in this study. Age at operation was 0.84 years (25th–75th percentile: 0.58–1.39). Thirty-three patients had heterotaxy syndrome (53%). The mean follow-up period was 12.7 ± 8.1 (max. 30.6) years. RESULTS The overall survival rate at 15 years was 73%. Although 49 patients (79.0%) went on to Fontan completion, 12 patients (19.4%) died without achieving it. Thrombus formation and poor development in a central pulmonary artery were not observed, but obstruction of the superior vena cava (SVC) occurred in 8 patients (13%), mainly those with right atrial isomerism (P = 0.037). SVC obstruction was not, however, a risk factor for mortality (P = 0.097) or Fontan completion (P = 0.41). The shape of BBDG anastomosis, symmetricity of pulmonary blood flow, impingement of caval blood flow returning from the superior and inferior vena cavae or coexisting interrupted inferior vena cava with azygos or hemi-azygos continuation did not affect late Fontan outcomes, such as overall survival, freedom from protein-losing enteropathy or pulmonary arterio-venous malformation rates. CONCLUSIONS SVC obstruction after BBDG frequently occurred, mainly in patients with right atrial isomerism; however, its direct impact on prognosis or achieving Fontan completion was not identified. Once Fontan circulation was established, the arrangement of the Fontan pathway did not affect late Fontan outcomes.

OBJECTIVES Atrial arrhythmia and right ventricular (RV) diastolic dysfunction are associated with increased morbidity and mortality in patients with repaired tetralogy of Fallot (TOF). This study was performed to determine whether the preoperative right atrial (RA) volume can predict the development of atrial arrhythmia after pulmonary valve replacement (PVR) in patients with TOF. METHODS Forty-seven consecutive adult patients with repaired TOF underwent PVR from 2003 to 2018. Seventeen patients showed preoperative atrial arrhythmia and underwent the Maze procedure concomitantly. The preoperative RA volume was evaluated with computed tomography and image analysis software. RESULTS The median follow-up period after PVR was 6.8 years. Among 17 patients who underwent the Maze procedure, recurrent atrial arrhythmia developed in 8 patients. Among 30 patients without preoperative atrial arrhythmia, novel atrial arrhythmia developed in 2 patients. The RA volume index was a significant predictor according to the multivariate analysis (P = 0.003). The RA volume index showed a significant positive correlation with the RV end-diastolic pressure (P CONCLUSIONS The RA volume predicts the development of atrial arrhythmia after PVR in patients with repaired TOF. RA volume measurement is strongly recommended in the management of this patient population. Clinical trial registration number Institutional review board of Osaka University Hospital, number 16105.

It has been suggested that breakfast omission, as opposed to breakfast consumption, has the detrimental effects on cognitive function. However, the effects of acute exercise following breakfast omission on cognitive function are poorly understood, particularly during exercise. The purpose of this study was to examine the interactive effects of breakfast and exercise on cognitive function. Ten participants completed cognitive tasks at rest and during exercise in the breakfast consumption or omission conditions. Blood glucose concentration was measured immediately after each cognitive task. We used cognitive tasks to assess working memory [Spatial Delayed Response (DR) task] and executive function [Go/No-Go (GNG) task]. The participants cycled ergometer for 30 min while keeping their heart rate at 140 beats·min(-1). Accuracy of the GNG task was lower at rest in the breakfast omission condition than that in the breakfast consumption condition (Go trial: P=0.012; No-Go trial: P=0.028). However, exercise improved accuracy of the Go trial in the breakfast omission condition (P=0.013). Reaction time in the Go trial decreased during exercise relative to rest in both conditions (P=0.002), and the degree of decreases in reaction time was not different between conditions (P=0.448). Exercise and breakfast did not affect the accuracy of the Spatial DR task. The present results indicate that breakfast omission impairs executive function, but acute exercise improved executive function even after breakfast omission. It appears that beneficial effects of acute exercise on cognitive function are intact following breakfast omission.

The seismic demand of a structure could be reduced by isolating the floors using laminated visco-elastic materials (LVEM). Such a LVEM-isolated floor system exhibits many advantages, such as the embedded large mass-isolation ratio, the mitigation of floor acceleration, the easy-to-demolish characteristic, etc. This paper focuses on the elastic seismic performance of single-story steel structures equipped with the LVEM-isolated floor system, wherein the LVEM-isolators are made of acrylic visco-elastic materials. The numerical simulating approach and the dynamic analysis procedure are developed for the structural system. In the procedure, the LVEM isolators are simulated by the Kelvin-Voigt model. The numerical simulating approach is validated by shaking table tests. Based on the results of an extensive response history analysis, the effects of several key parameters on the elastic structural seismic demand are quantified. The considered parameters include the structural natural period (T), the mass-isolation ratio, and the stiffness of the LVEM isolators. The displacement response spectra for both the substructure and the LVEM isolators, namely, the λS−T spectra and the λVEM−T spectra, are developed corresponding to the ambient temperature θ = 20 °C. In the structural design, λS is used for checking the seismic capacity of the substructure, while λVEM is used for determining an appropriate deforming space for the LVEM isolators. The seismic demand of the substructure generally decreases as the LVEM isolators become more flexible and the mass-isolation ratio becomes larger. The effect of ambient temperature-changing on the proposed elastic design spectra is analyzed. Generally, such effect is more pronounced when the mass-isolation ratio increases and the stiffness of the LVEM isolator decreases. Analysis data is provided for quantifying the effect of ambient-temperature-changing on the λS−T spectra and the λVEM−T spectra. Based on the data, the structural design and evaluation could be carried out efficiently.

Background: Intrapulmonary tunnel repair, called the Takeuchi technique, is a unique procedure for repairing anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). Since 1986, we have clearly defined the indication for the Takeuchi technique based on the location of the left coronary artery (LCA) orifice. Methods and Results: From 1986 to 2011, 19 consecutive patients with ALCAPA underwent surgical repair; the dual-coronary system was reconstructed in 16 of these patients with either Takeuchi (n=9: 1 male; median age 14.7 years; median weight 42.7kg) or a translocation procedure (n=7, 3 males; 0.4 years old, 5.6kg). Takeuchi was performed in patients whose LCA arose far from the aorta (middle of posterior facing sinus in 3 patients, left side of posterior facing sinus in 2, non-facing sinus in 4). The mean postoperative follow-up period was 7.4±6.1 years in the Takeuchi group and 9.3±8.5 years in the Translocation group. Actuarial survival rate at 10 years was 87.5% and 71.4%, respectively, and the freedom from either reoperation or re-intervention rate at 10 years was 67.7% and 85.7%, respectively. All the patients who died had a preoperative left ventricular ejection fraction ≤30%. Conclusions: The long-term outcome of the Takeuchi technique was acceptable. Although late reoperation and/or re-intervention cannot be disregarded, Takeuchi can be recommended when the LCA arises far from the aorta. (Circ J 2013; 77: 1202–1207)

Background This study aimed to identify the prognostic value of the preoperative stroke volume ratio (right ventricular stroke volume/left ventricular stroke volume) for redilatation of the right ventricle after pulmonary valve replacement in patients with repaired tetralogy of Fallot. Methods From April 2004 to November 2013, 20 patients with repaired tetralogy of Fallot underwent pulmonary valve replacement for pulmonary valve regurgitation and right ventricular dilatation. Serial changes in ventricular volume were examined by cardiac magnetic resonance or computed tomography imaging. The redilatation ratio was calculated for right ventricular end-diastolic and end-systolic volume indices by dividing the increment in right ventricular volume from the first (median, 1.1 years) to the second (median, 3.2 years) evaluations after pulmonary valve replacement by the first evaluation. The relationships between the stroke volume ratio and redilatation ratio were assessed. The degree of right ventricular myocardial fibrosis was examined in 13 patients and compared with the stroke volume ratio. Results Right ventricular volume (redilatation) significantly increased from a median of 1.1 to 3.2 years after pulmonary valve replacement. Significant positive correlations were detected between the stroke volume ratio and redilatation ratio of the right ventricular end-diastolic ( r = 0.50. p = 0.02) and end-systolic volume indices ( r = 0.49, p = 0.03). The stroke volume ratio also showed a significant positive correlation with the degree of right ventricular myocardial fibrosis ( r = 0.73, p = 0.005). Conclusions The preoperative stroke volume ratio can predict redilatation of the right ventricle after pulmonary valve replacement and the degree of right ventricular myocardial fibrosis.

ED-71, a novel analog of 1alpha,25-(OH)2 D3, increases bone mass to a greater extent than alfacalcidol, an 1alpha,25-(OH)2 D3 prodrug. In this study, we used a murine bone marrow ablation model to compare the effect of ED-71 on bone formation and resorption in vivo with that of 1alpha,25-(OH)2 D3. We discovered that bone matrix remodeling occurring within the first week after bone marrow ablation was enhanced by a single injection of ED-71, but not by 1alpha,25-(OH)2 D3. This enhancement was associated with an increase in bone surface. Trabecular bone resorption occurring from 1 to 2 weeks after the procedure was suppressed by a single injection of ED-71, but not 1alpha,25-(OH)2 D3, with treated mice exhibiting a reduction in osteoclast numbers, despite increases in osteoblast surface. As seen with the single injection, daily administration of ED-71 also enhanced bone modeling. Bone marrow osteoblast differentiation was also augmented by ED-71 pretreatment. Furthermore, ED-71 treatment immediately after bone marrow ablation enhanced angiogenesis within the bone marrow cavity via enhancement of VEGF(120) expression. In this paper, we clearly demonstrate that ED-71 is an orally administered small molecular weight compound with an anabolic effect on bone metabolism.

Cross-sectional studies have shown that home blood pressure (BP) correlates with hypertensive target organ damage better than clinic BP. However, there have been few longitudinal studies regarding the predictive value of home BP on the changes in organ damage in treated hypertensive patients. Clinic and home BP over a 12-month period, antihypertensive medication use, echocardiographic and electrocardiographic results, and serum creatinine and urinary protein levels were examined in 209 treated hypertensive patients in 1993. These patients were prospectively followed for 5 years. The patients were divided into 4 subgroups according to hypertension control as follows: good control (

The cause of residual hypertension after adrenalectomy for primary aldosteronism (PA) is unknown. The purpose of this study is to investigate the characteristic pathological kidney features associated with PA. Between 1977 and 1999 at our hospital, 26 patients with PA caused by a unilateral adrenal cortical adenoma (Conn's syndrome) underwent unilateral adrenalectomy with concurrent open-wedge renal biopsy. Patients were categorized into two groups: (1) those with normotension with diastolic blood pressure less than 90 mm Hg who were not administered antihypertensive drugs, and (2) those with residual hypertension with diastolic blood pressure of 90 mm Hg or greater who were administered medication for 6 months after surgery. Thirteen patients were cured of hypertension postoperatively, and 12 patients were administered antihypertensive medications. Glomerulosclerosis, renal arteriolosclerosis, and preoperative left ventricular mass (LVM) index were worse in the group with residual hypertension than in that with normotension (17.8% +/- 7.8% versus 9.6% +/- 3.8%; P = 0.01; 2.5 +/- 0.5 versus 1.6 +/- 0.4, Bader's grade; P = 0.005; and 165 +/- 31 versus 139 +/- 24 g/m(2); P = 0.02, respectively). Severity of tubulointerstitial injury, preoperative duration of hypertension, preoperative severity of proteinuria, plasma aldosterone level, and serum potassium concentration were not significantly different between the two groups. In conclusion, severity of glomerulosclerosis and arteriolosclerosis and LVM are related to blood pressure after adrenalectomy in patients with PA.

OBJECTIVE To clarify the role of insulin resistance and hyperinsulinaemia in the pathogenesis of obesity-related hypertension. DESIGN An open study comparing the effects of weight reduction by low-energy diet and treatment with troglitazone, an insulin-sensitizing agent. SETTING A tertiary teaching hospital. PATIENTS Thirty overweight hypertensive patients (15 men and 15 women, mean age 61 years, mean body mass index 29.1 kg/m2). INTERVENTIONS Fifteen patients were assigned to a weight-reduction programme by low-energy diet (3360 kJ/day) for 3 weeks; the remaining 15 patients were treated with troglitazone (400 mg/day) for 8 weeks. MAIN OUTCOME MEASURES Casual and ambulatory blood pressures, glucose and lipid metabolism, and insulin sensitivity. RESULTS The baseline values of body mass index, fasting and post-glucose plasma insulin, and casual and ambulatory blood pressures were comparable between the two groups. Weight reduction (4.1 +/- 0.3 kg, mean +/- SEM) was associated with significant decreases in plasma insulin, blood glucose, homeostasis model assessment (HOMA) insulin resistance index, serum triglyceride, casual blood pressure (7.7 +/- 2.3/ 3.9 +/- 1.4 mmHg) and 24 h blood pressure (8.3 +/- 1.9/ 4.3 +/- 1.1 mmHg). Treatment with troglitazone caused comparable decreases in the metabolic parameters and HOMA index, but did not change casual or 24 h blood pressure (0.8 +/- 3.4/0.8 +/- 2.1 and 1.5 +/- 2.4/ 1.0 +/- 1.9 mmHg, respectively). CONCLUSIONS Insulin resistance/hyperinsulinaemia may not have an important role in the pathogenesis of obesity-related hypertension. The antihypertensive effect of weight reduction seems to be mediated mainly by other mechanisms.

Background Dihydropyridine calcium antagonists increase heart rate due to reflex activation of the sympathetic nervous system, although these effects are less obvious for long-acting agents. Objective To study the effects of diltiazem retard, a long-acting nondihydropyridine calcium antagonist, on 24h blood pressure, heart rate and autonomic nerve activity in patients with essential hypertension. Design Randomized crossover design. Methods Thirteen patients [five men and eight women, aged 64+/-2 years (mean+/-SEM)] were administered placebo or diltiazem retard (100-200mg once daily) for 4 weeks each. Ambulatory monitoring of blood pressure and heart rate, and electrocardiography were carried out at the end of each period using a multibiomedical recorder (TM-2425). Autonomic nerve activity was evaluated by power spectral analysis of variability of heart rate using the high-frequency component as an index of parasympathetic nerve activity and the ratio of the low-frequency component and the high-frequency component as an index of sympathovagal balance. Results Treatment with diltiazem retard significantly decreased 24h average blood pressure and heart rate by 11.6+/-3.6/5.7+/-1.8mmHg and 5.0+/-1.1 beats/min, respectively. The changes in daytime and night-time values were comparable. Diltiazem retard also significantly decreased daytime and 24h low:high-frequency-component ratio (2.0+/-0.2 versus 1.7+/-0.2 and 1. 8+/-0.2 versus 1.6+/-0.2, respectively). Conclusions These results indicate that diltiazem retard is effective as a once-daily antihypertensive agent and has favorable effects on heart rate and the autonomic nervous system.

Pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) is still challenging. The outcome of patients with proximal pulmonary artery disease is generally better than that of a distal lesion. However, we experienced poor results in two difficult cases having predominant proximal lesions even after effective PEA. Both of them had a long-time history of CTEPH and preoperative condition was critical. Although relatively large amount of thickened intima with massive thrombi were extracted from the proximal pulmonary arteries, they required postoperative percutaneous cardiopulmonary support due to residual pulmonary hypertension. Both of them finally died from pulmonary bleeding and adult respiratory distress syndrome.

In the present study, we evaluated the hemodynamic and metabolic profiles derived from oral administration of the angiotensin converting enzyme inhibitor, delapril 50mg/kg/day, and the non-peptide angiotensin II type I (AT1) receptor antagonist, TCV-116 1mg/kg/day, for five days, to try to discriminate AT1 receptor-related responses from the depressor properties of chronic treatment with delapril in spontaneously hypertensive rats (SHRs). Both TCV-116 and delapril oral administrations significantly decreased blood pressure without any changes in heart rate. Delapril induced dipsogenic response and natriuresis associated with augmentation of urinary catecholamine excretion, while TCV-116 did not cause any changes in these variables. Neither delapril nor TCV-116 changed urinary excretion of prostaglandin (PG) E2 and 6-keto PG F1α. We also examined the effects of centrally administered angiotensin converting enzyme inhibitor and AT1 receptor antagonist to determine the central role of these drugs.Either the active metabolite of delapril, delapril-M1 1 mg/kg/day, or the active form of TCV-116, CV-11974 0.1mg/kg/day, were administered intracerebroventricularly for five days. Both treatments significantly decreased the blood pressure, in association with augmentation of the baroreceptor reflex control of heart rate, in response to phenylephrine injection. These findings suggest that the depressor properties of orally administered delapril are more complex than those of TCV-116, while central blockade by both angiotensin converting enzyme and AT1 receptor decreases blood pressure in part through baroreceptor sensitization. (Hypertens Res;1993 16: 239-246)

Objective To investigate the molecular mechanisms underlying particle-induced osteolysis, we focused on osteopontin (OPN), a cytokine and cell-attachment protein that is associated with macrophage chemoattractant and osteoclast activation. Methods We compared OPN protein levels in human periprosthetic osteolysis tissues with those in osteoarthritis (OA) synovial tissues. To investigate the functions of OPN during particle-induced osteolysis in vivo, titanium particles were implanted onto the calvaria of OPN-deficient mice and their wild-type (WT) littermates. Mice were killed on day 10 and evaluated immunohistologically. The effects of OPN deficiency on the secretion of inflammatory cytokines were examined using cultured bone marrow–derived macrophages (BMMs). BMMs from OPN-deficient and WT mice were cultured with titanium particles for 12 hours, and the concentrations of inflammatory cytokines in the conditioned media were measured by enzyme-linked immunosorbent assay. Results Expression of OPN protein was enhanced in human periprosthetic osteolysis tissues as compared with OA synovial tissues. In the particle-induced model of osteolysis of the calvaria, bone resorption was significantly suppressed by OPN deficiency via inhibition of osteoclastogenesis, whereas an inflammatory reaction was observed regardless of the genotype. Results of immunostaining indicated that OPN protein was highly expressed in the membrane and bone surface at the area of bone resorption in WT mice. When BMMs were exposed to titanium particles, the concentration of proinflammatory cytokines, such as tumor necrosis factor α, interleukin-1α (IL-1α), IL-1β, and IL-6, as well as chemotactic factors, such as monocyte chemoattractant protein 1 and macrophage inflammatory protein 1α, in the conditioned medium were significantly reduced by OPN deficiency. Whereas phagocytic activity of BMMs was not attenuated by OPN deficiency, phagocytosis-mediated NF-κB activation was impaired in OPN-deficient BMMs. These data indicated that OPN was implicated in the development of particle-induced osteolysis via the orchestration of pro-/antiinflammatory cytokines secreted from macrophages. Conclusion OPN plays critical roles in wear debris–induced osteolysis, suggesting that OPN is a candidate therapeutic target for periprosthetic osteolysis.

To assist in the development of better treatments for elderly hypertensive patients, we studied the degree to which the baseline values of urinary albumin excretion (UAE) and other cardiovascular risk factors were predictive of cardiovascular complications in a cohort of elderly hypertensive patients. In 1994, we adopted 144 elderly hypertensive patients, who had been treated for more than 6 years at various clinics and more than 1 year at the National Cardiovascular Center, Osaka, Japan. They were divided into 2 groups: a NA group (n=111) with normoalbuminuria (UAE

1. The effect of propranolol on amino acid neurotransmitter release in the rostral ventrolateral medulla (RVLM) was examined in urethane-anaesthetized male Wistar rats. 2. Amino acids released in the RVLM in response to intravenous administration of propranolol (0.4 mg/kg per min; n = 6) or nitroglycerin (0.02 mg/kg per min; n = 5) were determined by the brain microdialysis method. 3. Amino acids in dialysates were analysed by high- performance liquid chromatography and were quantified by ultraviolet absorbance. 4. Administration of both intravenous propranolol and nitroglycerin significantly decreased arterial blood pressure. Heart rate was decreased only by propranolol. 5. The reduction in arterial blood pressure produced by intravenous propranolol was accompanied by a decrease in the release of the excitatory amino acid glutamate in the RVLM. 6. The reduction in arterial blood pressure following intravenous nitroglycerin was not accompanied by a release of glutamate. 7. There were no significant changes in the levels of other amino acids (glycine, taurine, GABA) following either propranolol or nitroglycerin. 8. The decrease in glutamate release in the RVLM may account, in part, for the central depressor mechanism of propranolol.

To assess the relation between salt sensitivity and autonomic nervous function by power spectral analysis of heart rate variability in normotensive subjects, low and high salt diets were given to 13 normotensive men (aged 25 to 39 years) for 4 days each. Autonomic function was assessed by power spectral analysis of R-R intervals based on an autoregressive algorithm from 24-h Holter electrocardiogram. Subjects whose mean blood pressure was increased more than 3 mm Hg by high salt diet were defined as salt sensitive (SS, n = 5), and the remainder as salt resistant (SR, n = 8). Using the low frequency (LF, 0.1 Hz) and high frequency (HF, 0.25 Hz) components, the LF to total power ratio (%LF) was used as a marker of sympathetic activity, and the HF to total power ratio (%HF) as a marker of parasympathetic activity. Compared to the daytime, SR revealed a decrease in %LF and an increase in %HF during the night on both diets. In SS, these circadian changes were observed only during low-salt diet. During the night, SS showed a higher %LF and a lower %HF than SR. Plasma catecholamines tended to be decreased by the high sodium diet in SR but not in SS subjects. These results suggest that the persistent nocturnal predominance of sympathetic nervous activity in a salt-sensitive men may contribute to the subsequent increase of blood pressure in these subjects.

SUMMARY 1. To test the hypothesis that a central mechanism may play a role in the minimal reflex tachycardia noted in response to peripheral converting enzyme inhibition, we compared the effects of intravenous (i.v.) ceronapril (CER) with nitroglycerin (NTG) on neurotransmitter release in the rostral ventrolateral medulla (RVLM), using an in vivo microdialysis method in pentobarbital anaesthetized rats. 2. CER (0.1 mg/kg, i.v.) caused a progressive decrease in glutamate (GLU) release (CER 65 ± 7%vs NTG 83 ± 3% of each baseline at 140 min, P

Objective : To investigate the effects of central amino acid neurons on the antihypertensive action of a newly developed angiotensin II type 1 receptor (AT1) antagonist, CV 11974. Materials and methods : We measured the release of various amino acids in the rostral ventrolateral medulla using the brain microdialysis technique. A microdialysis probe was inserted into the exposed rostral ventrolateral medulla in male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats anaesthetized with urethane. Mean arterial pressure and the release of amino acids (glutamate, glycine, glutamine, taurine and y-aminobutyric acid) were monitored before and after intravenous administration of CV 11974 (5 mg/kg), nitroglycerin (5 μg/kg per min) or vehicle. Results : In SHR, CV11974 decreased mean arterial pressure (-40 ± 6 mmHg) accompanied by significant increases in the release of inhibitory amino acids, glycine (411 ± 83%) and γ-aminobutyric acid (363 ± 71%) in the rostral ventrolateral medulla, whereas intravenous nitroglycerin produced a decrease in mean arterial pressure (-35 ± 4 mmHg) without changes in amino acid release. In WKY rats, both intravenous CV 11974 and intravenous nitroglycerin produced smaller but significant decreases in mean arterial pressure (CV 11974, -18 ± 5 mm Hg ; nitroglycerin, -20 ± 7 mmHg) without change in the release of amino acids in the rostral ventrolateral medulla. Selective perfusion of glycine or γ-aminobutyric acid into the rostral ventrolateral medulla caused a larger mean arterial pressure reduction in SHR than in WKY rats. Furthermore, the use of a specific antagonist of glycine or of the γ-aminobutyric acid receptor in the rostral ventrolateral medulla attenuated the antihypertensive response induced by the intravenous AT 1 antagonist in SHR. Conclusion : The present results suggest that the release of the inhibitory amino acids glycine and γ-aminobutyric acid in the rostral ventrolateral medulla contributes to the depressor action of this AT 1 receptor antagonist in the genetic hypertensive rat model.