plethysmography

体积描记术
  • 文章类型: Journal Article
    血液乳酸是组织缺氧的标志,而毛细血管再充盈时间(CRT)是组织灌注的替代指标。建议测量这些参数以评估循环状态和指导复苏。然而,血乳酸在非洲急诊科并不广泛使用.此外,CRT评估面临着与其准确性和可重复性相关的挑战。这项研究旨在评估视觉CRT(V-CRT)与体积描记术CRT(P-CRT)在预测败血症患者乳酸水平方面的准确性。
    这项前瞻性观察性研究纳入了马拉喀什三级医院连续6个月的脓毒症或脓毒性休克患者,Morroco.入院时对V-CRT和P-CRT进行评估,并同时测量动脉乳酸水平。使用ROC曲线分析评估V-CRT和P-CRT预测动脉乳酸的准确性。
    43名年龄为64±15岁的患者,其中70%是男性,包括在研究中。其中,23例患者(53%)有败血症,和20例患者(47%)经历了脓毒性休克。V-CRT和P-CRT均与动脉乳酸具有统计学意义,相关系数为0.529(p<0.0001)和0.517(p=0.001),分别。ROC曲线分析显示,V-CRT在预测动脉乳酸水平>2mmol/l方面表现出令人满意的准确性,曲线下面积(AUC)为0.8(95%CI=0.65-0.93;p<0.0001)。P-CRT的预测能力低于V-CRT,AUC为0.73(95%CI:0.57-0.89;p=0.043)。V-CRT的最佳阈值确定为3.4s(灵敏度=90%,特异性=58%)和P-CRT的4.1s(灵敏度=85%,特异性=62%)。
    这些研究结果表明,体积描记评估并没有提高CRT预测乳酸水平的准确性。然而,在低收入环境中,V-CRT仍可作为脓毒症患者乳酸的可行替代品。
    UNASSIGNED: Blood lactate is a marker of tissue hypoxia while capillary refill time (CRT) is a surrogate of tissue perfusion. Measuring these parameters is recommended for assessing circulatory status and guiding resuscitation. However, blood lactate is not widely available in African emergency departments. Additionally, CRT assessment faces challenges related to its precision and reproducibility. This study aims to evaluate the accuracy of visual CRT(V-CRT) compared to plethysmographic CRT (P-CRT) in predicting lactate levels among septic patients.
    UNASSIGNED: This prospective observational study enrolled consecutive patients with sepsis or septic shock over a 6-month period from a tertiary hospital in Marrakech, Morroco. V-CRT and P-CRT were evaluated upon admission, and simultaneous measurements of arterial lactate levels were obtained. The precision of V-CRT and P-CRT in predicting arterial lactate was assessed using ROC curve analysis.
    UNASSIGNED: Forty-three patients aged of 64±15 years, of whom 70 % were male, were included in the study. Of these, 23 patients (53 %) had sepsis, and 20 patients (47 %) experienced septic shock. Both V-CRT and P-CRT demonstrated statistically significant correlations with arterial lactate, with correlation coefficients of 0.529 (p < 0.0001) and 0.517 (p = 0.001), respectively. ROC curve analysis revealed that V-CRT exhibited satisfactory accuracy in predicting arterial lactate levels >2 mmol/l, with an area under the curve (AUC) of 0.8 (95 % CI=0.65 - 0.93; p < 0.0001). The prediction ability of P-CRT was lower than V-CRT with an AUC of 0.73 (95 % CI: 0.57-0.89; p = 0.043). The optimal thresholds were determined as 3.4 s for V-CRT (sensitivity = 90 %, specificity = 58 %) and 4.1 s for P-CRT (sensitivity = 85 %, specificity = 62 %).
    UNASSIGNED: These findings suggest that the plethysmographic evaluation did not improve the accuracy of CRT for predicting lactate level. However, V-CRT may still serve as a viable surrogate for lactate in septic patients in low-income settings.
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  • 文章类型: Journal Article
    从临床实践(2021年1月至9月)对没有呼吸支持的早产儿和足月儿进行每周重复PEAPOD®身体成分测量的质量主动分析。统计分析,包括回归分析,Bland-Altman地块和cv-均方根检验,已执行。从119名婴儿(88名早产儿,31学期)。对于无脂质量(FFM),重复之间的中值绝对差为31.5g。FFM的线性相关分析显示R2=0.97。FFM和脂肪量的绝对差异与年龄增长没有显着相关。FFM%在体重为1kg3kg(0.9%;IQR:0.3,2.1)的组中存在差异(p=0.02)。体重的中值绝对差异为1g(IQR:0.4,3.1),体体积为5.6mL(IQR:2.1,11.8)。身体体积估算带有恒定的绝对误差,这是重复身体成分评估之间差异的主要因素。这种错误在体重较低的婴儿中变得更加突出。然而,每周PEAPOD测试的可重复性足以监测身体隔室的变化,为早产儿和足月婴儿的营养决策提供基础。
    The quality-initiative analysis of weekly duplicate PEAPOD® body composition measurements was conducted from clinical practice (January to September 2021) on preterm and term infants without respiratory support. Statistical analysis, including regression analysis, Bland-Altman plots and cv-root-mean-square tests, was performed. A total of 188 duplicate (376 individual) measurements were collected from 119 infants (88 preterm, 31 term). The median absolute difference between duplicates was 31.5 g for fat-free mass (FFM). Linear correlation analysis showed R2 = 0.97 for FFM. The absolute differences in FFM and fat mass did not significantly correlate with increasing age. The %FFM differed (p = 0.02) across body weight groups of 1 kg < BW ≤ 2 kg (1.8%; IQR: 0.8, 3.6) and BW > 3 kg (0.9%; IQR: 0.3, 2.1). The median absolute differences were 1 g (IQR: 0.4, 3.1) for body weight and 5.6 mL (IQR: 2.1, 11.8) for body volume. Body volume estimation is charged with a constant absolute error, which is the main factor for differences between repeated body composition assessments. This error becomes more prominent in infants with lower body weights. Nevertheless, reproducibility of weekly PEAPOD testing is sufficient to monitor body compartment changes, offering a foundation for nutritional decisions in both preterm and term infants.
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  • 文章类型: Journal Article
    身体成分是与坐式排球(SV)运动员的表现有关的身体素质的基本组成部分。此外,建立最佳的方法来评估这些准运动员的身体成分对于这个领域是非常必要的。这项研究的目的是(1)描述男性和女性训练有素的SV运动员的身体成分,(2)比较通过两种不同方法从该人群中获得的值,以及(3)建立这些方法之一的有效性。13名巴西SV国家队球员(5名男性和8名女性)参加了这项研究。对每个运动员进行了以空气置换体积描记术(ADP)方法作为评估标准和皮肤褶皱(SF)方法。结果表明,所有球员的价值观之间没有显着差异,其中ADP和SF测量体脂百分比(BF%)和体密度(BD)(p>0.05)。我们发现,按SF计算的BF%(p=0.04)和按SF计算的BD(p=0.04)的男女球员之间的值存在显着差异。在BF%和BD的ADP和SF测量之间发现了高度的可靠性。两种方法的所有值的BF%和BD之间均存在统计学上的显著正相关(p<0.01)。这项初步研究表明,考虑到空间的大小,费用,以及与ADP方法相对于SF方法的其他限制,我们建议使用SF方法,这是一个有效的,在优秀的SV运动员中测量身体成分的可行和可靠的方法。
    Body composition is a fundamental component of physical fitness related to the performance of Sitting volleyball (SV) players. Also, establishing the best method for evaluating the body composition of these para-athletes would be highly necessary for this field. The purpose of this study was (1) to describe the body composition of male and female highly trained SV players, (2) to compare the values obtained from this population by two different methods and (3) to establish validity on one of these methods. Thirteen Brazilian SV national team players (five males and eight females) participated in this study. The air-displacement plethysmography (ADP) method as the criterion assessment and the skinfolds (SF) method were conducted for each player. Results showed that there were no significant differences between the values of all players, which ADP and SF measured for body fat percentage (BF%) and body density (BD) (p > 0.05). We found significantly different values between male and female players for BF% by SF (p = 0.04) and BD by SF (p = 0.04). A high degree of reliability was found between ADP and SF measures for BF% and BD. There were statistically significant positive correlations between BF% and BD in all values for both methods (p < 0.01). This pilot study suggests that considering the magnitude of space, expense, and other limitations related to the ADP method against the SF method, we recommend using the SF method, which is a valid, viable and reliable method for measuring body composition in elite SV players.
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  • 文章类型: Journal Article
    这项前瞻性临床研究的目的是评估手术指数(SPI)的疗效,人体麻醉中经过验证的伤害感受监测器,在狗。该技术使用来自特定脉搏血氧测量探头的体积描记信号来分析脉搏波振幅和心跳间隔。包括26只麻醉去势的健康狗。SPI,连续监测有创平均动脉压(MAP)和心率(HR)。血液动力学反应(HDR)的发生或消退,定义为HR和/或MAP增加>20%,在预定时间进行评估:皮肤切口,睾丸外化,皮肤缝合,和芬太尼给药。在伤害性事件之后,表现出HDR的狗在3和5分钟时SPI分别显着增加了8%和10%,而芬太尼给药后,观察到SPI显著下降13%和16%.接收器操作特征曲线分析表明,SPI在1分钟内的动态变化具有中等性能,可以预测3分钟内芬太尼给药后的HDR(AUC:0.68,阈值:+15%)或其分辨率(AUC为0.72,阈值:-15%)。SPI根据围手术期的伤害性事件和镇痛治疗而变化;然而,其预测HDR的性能受到限制,特异性高,但灵敏度低.可能需要改进算法以专门适应犬类。需要进一步研究以评估其他因素对该指标性能的影响。
    The aim of this prospective clinical study was to evaluate the efficacy of the Surgical Pleth Index (SPI), a validated nociception monitor in human anaesthesia, in dogs. The technology uses a plethysmographic signal from a specific pulse oximetry probe to analyse pulse wave amplitudes and heartbeat intervals. Twenty-six healthy dogs anaesthetised for castration were included. SPI, invasive mean arterial pressure (MAP) and heart rate (HR) were continuously monitored. The occurrence or resolution of a haemodynamic reaction (HDR), defined as a > 20% increase in HR and/or MAP, was assessed at predefined times: cutaneous incision, testicles\' exteriorization, cutaneous suture, and fentanyl administration. Following nociceptive events, the dogs presenting a HDR showed a significant 8% and 10% increase in SPI at 3 and 5 min respectively, whereas after fentanyl administration, a 13% and 16% significant decrease in SPI were noted. Receiver operating characteristic curves analysis indicated a moderate performance for the dynamic variations of SPI over 1 min to predict a HDR (AUC: 0.68, threshold value: +15%) or its resolution after fentanyl administration (AUC of 0.72, threshold value: -15%) within 3 min. The SPI varied according to perioperative nociceptive events and analgesic treatment; however, its performance to anticipate a HDR was limited with high specificity but low sensivity. Refinement of the algorithm to specifically accommodate for the canine species may be warranted. Further studies are required to evaluate the influence of other factors on the performance of this index.
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  • 文章类型: Journal Article
    与足月婴儿相比,早产儿在出生后的头几个月有无脂质量赤字,这增加了未来代谢性疾病的风险。在这个出生在32周胎龄以下或小于1500克的儿童队列中,我们的目的是评估足月等效年龄时和出生后前3个月时的身体成分与4~7岁时的无脂肪量和脂肪量百分比之间的关系.在足月进行了通过空气置换体积描记术和人体测量术进行的身体成分评估,在矫正年龄3个月时,4至7岁。使用多元线性回归分析来观察这些年龄的身体成分之间的关联。在学期,4~7年时,脂肪质量百分比呈负相关,无脂肪质量与无脂肪质量呈正相关.3个月时的无脂质量和足月至3个月之间的无脂质量增加与4至7年的无脂质量呈正相关。结论:学龄前的身体成分与生命最初3个月的无脂肪量有关,代谢疾病风险的敏感期。已知:•与足月婴儿相比,早产儿在足月等效年龄时具有无脂肪质量的不足和高肥胖。•无脂质量反映了整个生命的代谢能力,因此被认为是预防代谢综合征风险的保护因素。新增内容:•校正年龄的前3个月的无脂质量增加与学龄前和学龄期的无脂质量有关。•生命的前3个月是代谢疾病风险的敏感期。
    Compared with full-term infants, preterm infants have fat-free mass deficit in the first months of life, which increases the risk of metabolic diseases in the future. In this cohort of children born under 32-week gestational age or less than 1500 g, we aimed to evaluate the associations of body composition at term equivalent age and in the first 3 months of life with fat-free mass and fat mass percentage at 4 to 7 years of life. Body composition assessments by air displacement plethysmography and anthropometry were performed at term, at 3 months of corrected age, and at 4 to 7 years of age. Multiple linear regression analysis was used to observe the associations between body composition at these ages. At term, fat mass percentage showed a negative association and fat-free mass a positive association with fat-free mass at 4 to 7 years. The fat-free mass at 3 months and the gain in fat-free mass between term and 3 months showed positive associations with fat-free mass at 4 to 7 years.   Conclusion: Body composition at preschool age is associated with fat-free mass in the first 3 months of life, a sensitive period for the risk of metabolic diseases. What is Known: • Preterm infants have a deficit in fat-free mass and high adiposity at term equivalent age compared to full-term infants. • Fat-free mass reflects metabolic capacity throughout life and therefore is considered a protective factor against the risk of metabolic syndrome. What is New: •Fat-free mass gain in the first 3 months of corrected age is associated with fat-free mass at preschool and school ages. •The first 3 months of life is a sensitive period to the risk of metabolic diseases.
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  • 文章类型: Journal Article
    目的:我们研究了吸气肌训练(IMT)对吸气肌力的影响,健康老年人运动期间的功能能力和呼吸肌运动学。
    方法:24名成人随机分为IMT或SHAM-IMT组。两组都进行了30次呼吸,每天两次,八个星期,在~50%最大吸气压力(PImax;IMT)或<15%PImax(SHAM-IMT)的强度下。测量PImax,在一次IMT期间呼吸不适,步行六分钟,身体活动水平,并在干预前后进行平衡评估.在恒定工作速率循环期间,通过光电体积描记术(OEP)评估呼吸肌运动学。
    结果:仅IMT组PImax显著改善(20.0±11.9cmH2O;p=0.001)。IMT期间的呼吸不适等级显着降低(从3.5±0.9降至1.7±0.8)。每日久坐时间减少(28.0±39.8分钟;p=0.042),仅在IMT组中,反应平衡显着改善(1.2±0.8;p<0.001)。OEP测量显示,肺和腹部肋骨室对IMT后总潮气量扩张的贡献明显更大。
    结论:IMT显著改善了该人群的吸气肌肉力量和呼吸不适。运动期间IMT引起更大的肋骨扩张和膈肌下降,从而表明对胸部扩张的限制作用较小,膈肌发电增加。
    OBJECTIVE: We investigated the effect of inspiratory muscle training (IMT) on inspiratory muscle strength, functional capacity and respiratory muscle kinematics during exercise in healthy older adults.
    METHODS: 24 adults were randomised into an IMT or SHAM-IMT group. Both groups performed 30 breaths, twice daily, for 8 weeks, at intensities of ∼50 % maximal inspiratory pressure (PImax; IMT) or <15 % PImax (SHAM-IMT). Measurements of PImax, breathing discomfort during a bout of IMT, six-minute walk distance, physical activity levels, and balance were assessed pre- and post-intervention. Respiratory muscle kinematics were assessed via optoelectronic plethysmography (OEP) during constant work rate cycling.
    RESULTS: PImax was significantly improved (by 20.0±11.9 cmH2O; p=0.001) in the IMT group only. Breathing discomfort ratings during IMT significantly decreased (from 3.5±0.9-1.7±0.8). Daily sedentary time was decreased (by 28.0±39.8 min; p=0.042), and reactive balance significantly improved (by 1.2±0.8; p<0.001) in the IMT group only. OEP measures showed a significantly greater contribution of the pulmonary and abdominal rib cage compartments to total tidal volume expansion post-IMT.
    CONCLUSIONS: IMT significantly improves inspiratory muscle strength and breathing discomfort in this population. IMT induces greater rib cage expansion and diaphragm descent during exercise, thereby suggesting a less restrictive effect on thoracic expansion and increased diaphragmatic power generation.
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  • 文章类型: Journal Article
    目的:腹胀导致腹肌协同失调(即,the肌收缩和腹壁松弛)患有肠-脑相互作用障碍的患者。本研究旨在验证一个简单的生物反馈程序,由腹胸壁运动引导,用于治疗腹胀.
    方法:在本随机分组中,平行,安慰剂对照试验,招募了42名连续患者(36名女性和6名男性;年龄17-64岁),这些患者均患有膳食引发的明显腹胀。通过自适应带使用电感体积描记术获得腹部和胸壁运动的记录。该信号显示给生物反馈组的患者,他们被教导动员隔膜。相比之下,安慰剂组的患者没有得到信号,给他们服用了安慰剂胶囊。在为期4周的干预期内进行了三次会议,指示进行锻炼(生物反馈组)或每天服用安慰剂3次(对照组)在家。通过对不良膳食的反应(腹胸电活动和周长的变化)和使用每日量表测量的临床症状持续7天,来评估结果。
    结果:生物反馈组(n=19)的患者学会了纠正由进餐引起的腹肌协同失调(肋间活动平均降低了82%±10%,前壁活动增加了97%±6%的平均±SE,周长的增加平均±SE减少了108%±4%),并且临床症状得到改善(腹胀评分降低了66%±5%的平均±SE)。在安慰剂组中未观察到这些效果(所有,P<.002)。
    结论:腹胸壁运动可作为一种有效的生物反馈信号,用于纠正肠-脑相互作用障碍患者的腹肌协同失调和腹胀。ClincialTrials.gov,编号:NCT04043208。
    OBJECTIVE: Abdominal distention results from abdominophrenic dyssynergia (ie, diaphragmatic contraction and abdominal wall relaxation) in patients with disorders of gut-brain interaction. This study aimed to validate a simple biofeedback procedure, guided by abdominothoracic wall motion, for treating abdominal distention.
    METHODS: In this randomized, parallel, placebo-controlled trial, 42 consecutive patients (36 women and 6 men; ages 17-64 years) with meal-triggered visible abdominal distention were recruited. Recordings of abdominal and thoracic wall motion were obtained using inductance plethysmography via adaptable belts. The signal was shown to patients in the biofeedback group, who were taught to mobilize the diaphragm. In contrast, the signal was not shown to the patients in the placebo group, who were given a placebo capsule. Three sessions were performed over a 4-week intervention period, with instructions to perform exercises (biofeedback group) or to take placebo 3 times per day (control group) at home. Outcomes were assessed through response to an offending meal (changes in abdominothoracic electromyographic activity and girth) and clinical symptoms measured using daily scales for 7 days.
    RESULTS: Patients in the biofeedback group (n = 19) learned to correct abdominophrenic dyssynergia triggered by the offending meal (intercostal activity decreased by a mean ± SE of 82% ± 10%, anterior wall activity increased by a mean ± SE of 97% ± 6%, and increase in girth was a mean ± SE of 108% ± 4% smaller) and experienced improved clinical symptoms (abdominal distention scores decreased by a mean ± SE of 66% ± 5%). These effects were not observed in the placebo group (all, P < .002).
    CONCLUSIONS: Abdominothoracic wall movements serve as an effective biofeedback signal for correcting abdominophrenic dyssynergia and abdominal distention in patients with disorders of gut-brain interaction. ClincialTrials.gov, Number: NCT04043208.
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  • 文章类型: Journal Article
    背景:术中液体治疗维持血容量正常,正常组织灌注,正常的代谢功能,正常电解质,和酸碱状态。体积描记变异性指数已被证明可以预测液体反应性,但其在指导术中液体治疗中的作用仍然难以捉摸。
    目的:本研究的目的是比较在接受腹部手术的足月新生儿中,基于体积描记变异性指数的术中目标导向液体治疗与自由液体治疗。
    方法:在三级护理中心进行了一项前瞻性随机对照研究,为期18个月。在筛查的132名新生儿中,共有30名新生儿完成了这项研究。新生儿气管食管瘘,先天性膈疝,先天性心脏病,呼吸系统疾病,肌酐清除率<90mL/min和血流动力学不稳定者被排除.新生儿被随机分为目标导向的液体治疗组,其中体积描记变异性指数的目标为<18或自由液体治疗组。主要结果是比较两组术中输注的液体总量。次要结果包括术中和术后动脉血气参数,生化参数,使用血管升压药,流体推注的数量,并发症和住院时间。
    结果:术中注入的液体总量[90(84-117.5mL)在目标导向液体治疗中与105(85.5-144.5mL)在自由液体治疗组中没有显着差异(p=.406)],中位数差异(95%CI)-15(-49.1至19.1)。从术前到术后24h,两组的血清乳酸水平均下降。与目标定向液体治疗组(36[22-44mL]相比,自由液体治疗组(58[50.25-65mL])在多巴胺给药前输注的液体量明显更高,p=.008),中位数差异(95%CI)-22(-46至2)。在术后期间,两组24小时内的液体摄入总量相当(目标导向液体治疗组222[204-253mL]和自由液体治疗组224[179.5-289.5mL],p=.917)中位数差异(95%CI)截止-2(-65.3至61.2)。
    结论:术中体积描记变异性指数指导的目标导向液体治疗在围手术期新生儿注入的液体总量方面与自由液体治疗相当。需要更多具有更高样本量的随机对照试验。
    背景:印度中央审判登记处(CTRI/2020/02/023561)。
    Intraoperative fluid therapy maintains normovolemia, normal tissue perfusion, normal metabolic function, normal electrolytes, and acid-base status. Plethysmographic variability index has been shown to predict fluid responsiveness but its role in guiding intraoperative fluid therapy is still elusive.
    The aim of the present study was to compare intraoperative goal-directed fluid therapy based on plethysmographic variability index with liberal fluid therapy in term neonates undergoing abdominal surgeries.
    A prospective randomized controlled study was conducted in a tertiary care centre, over a period of 18 months. A total of 30 neonates completed the study out of 132 neonates screened. Neonates with tracheoesophageal fistula, congenital diaphragmatic hernia, congenital heart disease, respiratory disorders, creatinine clearance <90 mL/min and who were hemodynamically unstable were excluded. Neonates were randomized to goal-directed fluid therapy group where the plethysmographic variability index was targeted at <18 or liberal fluid therapy group. Primary outcome was comparison of total amount of fluid infused intraoperatively in both the groups. Secondary outcomes included intraoperative and postoperative arterial blood gas parameters, biochemical parameters, use of vasopressors, number of fluid boluses, complications and duration of hospital stay.
    There was no significant difference in total intraoperative fluid infused [90 (84-117.5 mL) in goal-directed fluid therapy and 105 (85.5-144.5 mL) in liberal fluid therapy group (p = .406)], median difference (95% CI) -15 (-49.1 to 19.1). There was a decrease in serum lactate levels in both groups from preoperative to postoperative 24 h. The amount of fluid infused before dopamine administration was significantly higher in liberal fluid therapy group (58 [50.25-65 mL]) compared to goal-directed fluid therapy group (36 [22-44 mL], p = .008), median difference (95% CI) -22 (-46 to 2). In postoperative period, the total amount of fluid intake over 24 h was comparable in two groups (222 [204-253 mL] in goal-directed fluid therapy group and 224 [179.5-289.5 mL] in liberal fluid therapy group, p = .917) median difference (95% CI) cutoff -2 (-65.3 to 61.2).
    Intraoperative plethysmographic variability index-guided goal-directed fluid therapy was comparable to liberal fluid therapy in terms of total volume of fluid infused in neonates during perioperative period. More randomized controlled trials with higher sample size are required.
    Central Trial Registry of India (CTRI/2020/02/023561).
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  • 文章类型: Journal Article
    丁硫酮(也称为C21)是一种有效的选择性血管紧张素II2型受体(AT2R)激动剂,开发用于口服治疗纤维化肺病。这个阶段I,开放标签,药效学研究在5名健康男性志愿者中研究了丁氯西丁的血管效应。受试者以3、10、30、100和200μg/min的递增剂量动脉内输注巴洛西丁5分钟,依次注入前臂。以0.8-3.2μg/min的剂量输注硝普钠(SNP)溶液作为阳性对照。通过静脉闭塞体积描记术测量前臂血流量(FBF)。评估了动脉内给药的安全性和耐受性。在以3-200μg/min的剂量输注丁氯西丁后,FBF的增加幅度为27.8%,17.2%,37.0%,28.5%,60.5%,与各自的基线相比。在最高剂量组中观察到最大的增加。输入SNP作为阳性对照,与基线相比,FBF增加230-320%。三个轻度不良事件(AE),与丁氧布丁或SNP无关,报告了两名受试者。这些AE中的两个与研究程序有关。在研究期间动脉血压没有临床相关的变化。低动脉内输注丁氯西丁,递增剂量增加FBF,表明丁氯西丁在与内皮功能障碍相关的疾病中可能有效。发现静脉闭塞体积描记术是探索新型AT2R激动剂的药效学血管效应的有用方法。同时避免全身不良反应。
    Buloxibutid (also known as C21) is a potent and selective angiotensin II type 2 receptor (AT2R) agonist, in development for oral treatment of fibrotic lung disease. This phase I, open-label, pharmacodynamic study investigated vascular effects of buloxibutid in five healthy male volunteers. Subjects were administered intra-arterial infusions of buloxibutid for 5 min in ascending doses of 3, 10, 30, 100, and 200 μg/min, infused sequentially in the forearm. Infusions of sodium nitroprusside (SNP) solution in doses of 0.8-3.2 μg/min were administered as a positive control. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Safety and tolerability of intra-arterial administrations of buloxibutid were evaluated. Following infusion of buloxibutid in doses of 3-200 μg/min, the range of increase in FBF was 27.8%, 17.2%, 37.0%, 28.5%, and 60.5%, compared to the respective baseline. The largest increase was observed in the highest dose group. Infusions of SNP as a positive control, increased FBF 230-320% compared to baseline. Three adverse events (AEs) of mild intensity, not related to buloxibutid or SNP, were reported for two subjects. Two of these AEs were related to study procedures. There were no clinically relevant changes in arterial blood pressure during the study period. Intra-arterial infusion of buloxibutid in low, ascending doses increased FBF, indicating that buloxibutid may be effective in conditions associated with endothelial dysfunction. Venous occlusion plethysmography was found to be a useful method to explore pharmacodynamic vascular effects of novel AT2R agonists, while avoiding systemic adverse effects.
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  • 文章类型: Journal Article
    背景:呼吸困难是慢性阻塞性肺疾病(COPD)的复杂症状,与肺功能指标无明显相关性。长效支气管扩张剂(LAB)可以减少这种呼吸困难,但一些患者报告尽管接受了这种治疗,但仍有持续的慢性呼吸困难。这项研究旨在评估已接受LAB治疗并报告持续呼吸困难的COPD患者在使用短效支气管扩张剂(SAB)后的残留可逆性和临床反应。
    方法:纳入尽管目前使用至少一种LAB进行稳定治疗,但伴有持续性呼吸困难(改良医学研究委员会量表(mMRC)≥1)的COPD患者。肺活量测定,体积描记术和脉冲振荡(IOS)在其LAB的峰值效应下进行,并在摄入两种SAB(400µg沙丁胺醇和80µg异丙托溴铵)后45分钟重复。在SAB后45分钟通过比较双侧VAS评估呼吸困难改善(-100mm用于最大改善;+100mm用于最大降解)。
    结果:分析了22例COPD患者,主要为男性(59.1%),平均年龄为60.6岁,FEV1中位数为预测值的54%.50%的患者报告严重的基础呼吸困难(mMRC≥2)。在SAB之后,肺活量和体积描记测量结果在统计学上有所改善。对于IOS测量,5Hz的电抗(X5)和电抗面积(AX)也得到了改善。50%的患者报告其静息呼吸困难的临床相关改善。然而,在呼吸困难改善和功能措施之间没有发现相关性.
    结论:50%的定期接受一种或两种LAB治疗的COPD患者在辅助摄入双效短效支气管扩张剂后仍报告静息性呼吸困难的相关改善。与这种改善相关的生理机制仍有待确定。
    背景:NCT02928744。
    BACKGROUND: Dyspnea is a complex symptom of chronic obstructive pulmonary disease (COPD) which is not strongly correlated with lung function measures. Long-acting bronchodilators (LAB) may reduce this dyspnea, but some patients report persistent chronic dyspnea despite this treatment. This study aims to assess residual reversibility and clinical response after short-acting bronchodilator (SAB) in COPD patients already treated by LAB and reporting persistent dyspnea.
    METHODS: COPD patients with a persistent dyspnea (modified Medical Research Council scale (mMRC) ≥1) despite current stable treatment with at least one LAB were included. Spirometry, plethysmography and impulse oscillometry (IOS) were performed at peak effect of their LAB and repeat 45 min after the intake of two SAB (400 µg of salbutamol and 80 µg of ipratropium). Dyspnea improvement was assessed at 45 min after SAB through a comparative two-sided VAS (-100 mm for maximal improvement; +100 mm for maximal degradation).
    RESULTS: Twenty-two COPD patients were analyzed, mainly men (59.1 %) with a mean age of 60.6 years and a median FEV1 of 54 % of predicted values. Fifty percent of patients reported a severe basal dyspnea (mMRC ≥2). After SAB, spirometric and plethysmographic measurements were statistically improved. For IOS measurement, reactance at 5 Hz (X5) and area of reactance (AX) were also improved. Fifty percent of patients reported a clinically relevant improvement of their resting dyspnea. However, no correlation was found between dyspnea improvement and functional measures.
    CONCLUSIONS: Fifty percent of COPD patients regularly treated with one or two LAB still report a relevant improvement of resting dyspnea after the adjunctive intake of double short-acting bronchodilators. Physiological mechanisms associated with this improvement remain to be determined.
    BACKGROUND: NCT02928744.
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