Exercise Physiology and Pulmonary Hemodynamic Abnormality in PH Patients with Exercise Induced Venous-To-Systemic Shunt

Objectives

To identify the pulmonary hypertension (PH) patients who develop an exercise induced venous-to-systemic shunt (EIS) by performing the cardiopulmonary exercise test (CPET), analyse the changes of CPET measurements during exercise and compare the exercise physiology and resting pulmonary hemodynamics between shunt-PH and no-shunt-PH patients.

Methods

Retrospectively, resting pulmonary function test (PFT), right heart catheterization (RHC), and CPET for clinical evaluation of 104 PH patients were studied.

Results

Considering all 104 PH patients by three investigators, 37 were early EIS+, 61 were EIS-, 3 were late EIS+, and 3 others were placed in the discordant group. PeakVO₂, AT and OUES were all reduced in the shunt-PH patients compared with the no-shunt-PH subjects, whereas VE/VCO₂ slope and the lowest VE/VCO₂ increased. Besides, the changes and the response characteristics of the key CPET parameters at the beginning of exercise in the shunt group were notably different from those of the no shunt one. At cardiac catheterization, the shunt patients had significantly increased mean pulmonary artery pressure (mPAP), mean right atrial pressure (mRAP) and pulmonary vascular resistance (PVR), reduced cardiac output (CO) and cardiac index (CI) compared with the no shunt ones (P<0.05). Resting CO was significantly correlated with exercise parameters of AT (r = 0.527, P<0.001), OUES (r = 0.410, P<0.001) and Peak VO₂ (r = 0.405, P<0.001). PVR was significantly, but weakly, correlated with the above mentioned CPET parameters.

In Conclusions

CPET may allow a non-invasive method for detecting an EIS and assessing the severity of the disease in PH patients.     

Dynamic hyperinflation is associated with a poor cardiovascular response to exercise in COPD patients

Background

Pulmonary hyperinflation has the potential for significant adverse effects on cardiovascular function in COPD. The aim of this study was to investigate the relationship between dynamic hyperinflation and cardiovascular response to maximal exercise in COPD patients.

Methods

We studied 48 patients (16F; age 68 yrs ± 8; BMI 26 ± 4) with COPD. All patients performed spirometry, plethysmography, lung diffusion capacity for carbon monoxide (TLco) measurement, and symptom-limited cardiopulmonary exercise test (CPET). The end-expiratory lung volume (EELV) was evaluated during the CPET. Cardiovascular response was assessed by change during exercise in oxygen pulse (ΔO₂Pulse) and double product, i.e. the product of systolic blood pressure and heart rate (DP reserve), and by the oxygen uptake efficiency slope (OUES), i.e. the relation between oxygen uptake and ventilation.

Results

Patients with a peak exercise EELV (%TLC) ≥ 75% had a significantly lower resting FEV₁/VC, FEF₅₀/FIF₅₀ ratio and IC/TLC ratio, when compared to patients with a peak exercise EELV (%TLC) < 75%. Dynamic hyperinflation was strictly associated to a poor cardiovascular response to exercise: EELV (%TLC) showed a negative correlation with ΔO₂Pulse (r = - 0.476, p = 0.001), OUES (r = - 0.452, p = 0.001) and DP reserve (r = - 0.425, p = 0.004). Furthermore, according to the ROC curve method, ΔO₂Pulse and DP reserve cut-off points which maximized sensitivity and specificity, with respect to a EELV (% TLC) value ≥ 75% as a threshold value, were ≤ 5.5 mL/bpm (0.640 sensitivity and 0.696 specificity) and ≤ 10,000 Hg · bpm (0.720 sensitivity and 0.783 specificity), respectively.

Conclusion

The present study shows that COPD patients with dynamic hyperinflation have a poor cardiovascular response to exercise. This finding supports the view that in COPD patients, dynamic hyperinflation may affect exercise performance not only by affecting ventilation, but also cardiac function.     

Effects of Blood Transfusion on Exercise Capacity in Thalassemia Major Patients

Anemia has an important role in exercise performance. However, the direct link between rapid changes of hemoglobin and exercise performance is still unknown.To find out more on this topic, we studied 18 beta-thalassemia major patients free of relevant cardiac dysfunction (age 33.5±7.2 years,males = 10). Patients performed a maximal cardiopulmolmonary exercise test (cycloergometer, personalized ramp protocol, breath-by-breath measurements of expired gases) before and the day after blood transfusion (500 cc of red cell concentrates). After blood transfusion, hemoglobin increased from 10.5±0.8 g/dL to 12.1±1.2 (p<0.001), peak VO₂ from 1408 to 1546mL/min (p<0.05), and VO₂ at anaerobic threshold from 965 to 1024mL/min (p<0.05). No major changes were observed as regards heart and respiratory rates either at peak exercise or at anaerobic threshold. Similarly, no relevant changes were observed in ventilation efficiency, as evaluated by the ventilation vs. carbon dioxide production relationship, or in O₂ delivery to the periphery as analyzed by the VO₂ vs. workload relationship. The relationship between hemoglobin and VO₂ changes showed, for each g/dL of hemoglobin increase, a VO₂ increase = 82.5 mL/min and 35 mL/min, at peak exercise and at anaerobic threshold, respectively. In beta-thalassemia major patients, an acute albeit partial anemia correction by blood transfusion determinates a relevant increase of exercise performance, observed both at peak exercise and at anaerobic threshold.     

新理论CPET指导个体化精准运动整体方案有效改善“虚弱症”的整体功能状态*

目的: 探讨整体整合生理学医学新理论指导下,根据心肺运动试验（CPET）制定个体化精准运动整体方案对整体功能状态的影响。方法: 李xx,女,31岁,自幼心率快（90~100 bpm）,平时手脚冰凉,秋冬季为甚,既往体健。2019年9月底在阜外医院签署知情同意书后行CPET,峰值摄氧量、无氧阈（AT）和峰值心排量分别为（69~72）%pred,摄氧通气效率和二氧化碳排出通气效率基本正常（96~100）%pred。静息心率快、血压偏低,运动过程中血压反应弱,以心率升高为主。整体整合生理学医学理论认为其自身虚弱,且以心脏弱为主。以CPET指导个体化精准运动强度进行滴定,结合连续逐搏血压、心电、脉搏和血糖动态监测制定个体化定量运动整体方案,实施8周强化管理后复查CPET等。结果: 经整体强化管理8周后四肢温暖,发凉症状消失。复查CPET峰值摄氧量、无氧阈和峰值心排量分别为（90~98）%pred,分别提高30%~36%,虚弱的整体功能状态得到显著提升;基本正常的摄氧通气效率和二氧化碳排出通气效率也分别提高10%~37%;静息心率和血压基本恢复正常,运动中血压和心率反应均正常。连续动态血糖监测提示血糖平均水平略下降,更趋于平稳,连续心电、逐搏血压等的重复测定结果也提示静息、运动全程和睡眠期间的心率降低、血压提升,桡动脉脉搏波的重搏波幅度加大,变得更加明显。结论: 新理论体系指导CPET制定个体化精准运动整体方案可以安全有效增强心肌收缩力、增加每搏输出量,提升血压、降低心率,稳定并略降低血糖,提高整体功能状态。     

心肺运动试验用于冠心病诊断价值的临床研究*

目的: 评估心肺运动试验（CPET）相关指标对于冠心病的诊断价值。方法: 选择156例疑诊为冠心病的患者（病情相对稳定,年龄在18~80岁）行CPET、运动负荷心电图及冠状动脉造影,以冠状动脉造影结果为标准,分析CPET相关指标（峰值摄氧量％预计值Peak VO₂%pred、峰值氧脉搏％预计值Peak O₂ pulse%pred、摄氧量对应功率的做功效率（ΔVO₂/ΔWR）诊断冠心病的敏感度、特异度及其诊断价值。结果: Peak VO₂%pred的最佳截断点是≤69%pred,其诊断冠心病的敏感度为55.1%,特异度为77.0%,AUC为0.698。Peak O₂ pulse%pred最佳截断点诊断冠心病的敏感度为50.7%,特异度为72.4%,AUC为 0.58。ΔVO₂/ΔWR最佳截断点处其诊断冠心病的敏感度为44.9%,特异度为87.4%,AUC为0.647。Peak VO₂%pred及ΔVO₂/ΔWR敏感度远高于负荷心电图,差异有统计学意义（P<0.01）。结论: CPET部分指标诊断冠心病的敏感度优于运动负荷心电图,最佳截断点处特异度及诊断价值均较高,而且CPET本身也包括连续动态全程心电图分析,不建议各自分割使用,主张所有指标整体整合分析使用。CPET相关指标对冠心病诊断有预测价值,可以早期、较准确的诊断冠心病。     

代谢、血液碱化和纯氧影响呼吸调控的人体实验研究I:运动试验*

目的: 在整体整合生理学医学理论的指导下,通过分析正常人运动期间心肺代谢等多系统功能整体整合的连续动态变化,探讨正常环境运动状态下呼吸反应模式的调控机理。方法: 选正常志愿者5名,在美国洛杉矶加州大学Harbor-UCLA医学中心分别进行动脉置管,在常温室内空气状态下完成症状限制性最大极限心肺运动试验(CPET)。在运动过程中,连续测定肺通气指标及每分钟动脉取样的血气分析指标的变化,对CPET期间呼吸气体交换和血气指标的动态变化进行统计分析。结果: 在CPET期间,随着运动功率逐步递增,分钟摄氧量(每呼吸摄氧量×呼吸频率=每搏摄氧量×心率）和分钟通气量(潮气量×呼吸频率)均呈现近于线性渐进性递增(与静息状态比较,P<0.05~0.001);在运动超过无氧阈和呼吸代偿点后,分钟通气量的上升反应更加显著。结论: 人体在运动过程中,为了克服自行车功率计的阻力而发生代谢率改变,呼吸随代谢改变而变化,高强度运动时酸性代谢产物堆积更加加剧呼吸反应。     

The Prognostic Value of Peak Cardiac Power Output in Chinese Patients with Chronic Heart Failure

Background

Cardiopulmonary exercise testing has been widely used to risk stratify patients with chronic heart failure (CHF). Peak oxygen consumption (peakVO₂) was regarded as a powerful predictor of survival, as it is a surrogate for peak cardiac output (CO), which by most is considered the “true” measure of heart failure. Therefore, it is reasonable to hypothesize that CO is an even stronger predictor than peak VO₂. The present study is aimed to investigate the prognostic value of peak cardiac power output (peak CPO) in comparison with peakVO₂ in Chinese patients with CHF.

Methods

Participants provided written informed consent to participate in this study. Totally 129 patients with CHF underwent symptom-limited cardiopulmonary exercise testing (CPET), with mean age 59.1±11.4 years, 87.6% male, 57.4% ischemic etiology, body mass index (BMI) 24.7±3.7 kg/m² and LVEF 38±9%. CO was measured using an inert gas rebreathing method. The primary endpoints are cardiac deaths.

Results

Over median 33.7-month follow-up, 19 cardiac deaths were reported. Among peak VO₂,VE/VCO₂ slope and Peak CPO, their area under ROC were 0.64, 0.67, 0.68, respectively (Ρ<0.05).The optimal thresholds for predicting cardiac deaths were peak VO₂≤13.4 ml.kg^-1.min^-1, and VE/VCO₂ slope≥39.3 and peak CPO≤ 1.1 respectively by ROC analysis. Finally, in patients with a peak VO2≤13.4 ml.kg^-1.min^-1 those with peak CPO>1.1W had better survival than those with peak CPO ≤ 1.1W. However, by multivariate analysis adjusted for age, sex, BMI, resting heart rate, LVMI, LVEF, Peak CPO was not an independent predictor of cardiac deaths (P> 0.05).

Conclusions

Peak CPO was not a predictor of cardiac death in Chinese CHF patients.     

Response of left ventricular diastolic filling to graded exercise relative to the lactate threshold

During incremental exercise, the left ventricular ejection fraction increases up to the intensity of the anaerobic threshold and tends to level off at higher exercise intensities. Since there is a correlation between the response of peak filling rate and ejection fraction to exercise, this study was conducted to determine whether the response of left ventricular diastolic function is similar to the response of systolic function relative to lactate threshold. Twelve healthy men performed two exercise tests on a cycle ergometer. In the first test, lactate threshold and maximal power output were determined. In the second exercise test, gated radionuclide ventriculography was performed at rest, at the lactate threshold intensity, and at peak exercise to measure ejection fraction and peak filling rate. Ejection fraction increased significantly from rest [mean (SD): 62 (5)%] to lactate threshold [76 (7) %] and did not change significantly from lactate threshold to peak exercise [77 (7)%]. Likewise, peak filling rate (normalized for stroke counts) increased from resting [6.1 (0.9)V _s · s^–1] to lactate threshold [9.4 (1.8)V _s · s^–1] and did not change significantly from lactate threshold to peak exercise [9.6 (2.9)V _s · s^–1]. There was no correlation between the change in peak filling rate and the change in ejection fraction from rest to lactate threshold. Thus, during incremental exercise, left ventricular diastolic function responds qualitatively similar to systolic function.     

Reduced Oxygen Uptake Efficiency Slope in Patients with Cardiac Sarcoidosis

Background

The non-invasive diagnosis of cardiac sarcoidosis (CS) is difficult. Cardiovascular magnetic resonance (CMR) has become a very valuable diagnostic tool in patients with suspected CS, but usually a combination of different tests is used. Oxygen uptake efficiency slope (OUES) is a parameter of cardiopulmonary exercise testing (CPET), which is used as an indicator for cardiovascular impairment. We investigated the predictive value of OUES for the diagnosis of myocardial involvement in sarcoid patients.

Methods

Retrospectively 37 consecutive patients (44.9±13.8 years) with histologically confirmed sarcoidosis and clinical suspicion of heart involvement underwent noninvasive diagnostic testing including CMR. CS was diagnosed according to the guidelines from the Japanese Society of Sarcoidosis and other Granulomatous Disorders with additional consideration of CMR findings. Furthermore, CPET with calculation of predicted OUES according to equations by Hollenberg et al. was carried out.

Results

Patients with CS (11/37; 30%) had a worse cardiovascular response to exercise. OUES was significantly lower in CS-group compared to non-CS-group (59.3±19.1 vs 88.0±15.4%pred., p<0.0001). ROC curve method identified 70%pred. as the OUES cut-off point, which maximized sensitivity and specificity for detection of CS (96% sensitivity, 82% specificity, 89% overall accuracy). OUES <70%pred. was the single best predictor of CS (Odds ratio: 100.43, 95% CI: 1.99 to 5064, p<0.001) even in multivariate analyses.

Conclusion

OUES assessed in CPET may be helpful in identifying patient with cardiac involvement of sarcoidosis. Patient selection for CMR may be assisted by CPET findings in patients with sarcoidosis.     

心肺运动试验（CPET）评价个体化精准运动整体方案强化管控心脑血管慢病疗效的临床研究*

目的: 探讨研究症状限制性极限运动心肺运动试验（CPET）评价个体化精准运动整体方案强化管控3月后（简称强化管控）的长期慢病患者整体功能的改善。方法: 选取2014年至2016年由我们团队强化管控的长期心脑血管代谢慢病为主的患者20例,签署知情同意书后完成CPET,根据CPET及连续功能学检测结果制定以个体化适度运动强度为核心的整体管理方案,强化管控3月后再行CPET,个体化分析每例患者强化管控前后CPET指标的变化、计算差值和百分差值。结果: 本研究心脑血管代谢性慢病为主的患者20例（18男2女）,年龄（55.75±10.80,26~73）岁,身高（172.20±8.63,153~190）cm,体重（76.35±15.63,53~105）kg,所有患者CPET和强化管控期间均无任何危险事件发生。①强化管控后患者静态肺功能指标及静息收缩压、心率收缩压乘积和空腹血糖等均显著改善（P<0.05）。②强化管控前峰值摄氧量为（55.60±15.69,34.37~77.45）%pred和无氧阈为（60.11±12.26,43.29~80.63）%pred;强化管控后峰值耗氧量为（71.85±21.04,42.40~102.00）%pred和无氧阈为（74.95±17.03,51.90~99.47）%pred;管控后较管控前峰值摄氧量和无氧阈显著提高分别达（29.09±7.38,17.78~41.80）%和（25.16±18.38,1.77~81.86）%（P均<0.01）;其他核心指标峰值氧脉搏、峰值负荷功率、摄氧通气效率平台和递增功率运动持续时间均显著升高（P均<0.01）,二氧化碳排出通气效率最低值及二氧化碳排出通气斜率也显著好转（P<0.01）。③个体化分析而言,强化管控后15例上述8项CPET核心指标全部改善,另5例7项指标改善;全部病例峰值摄氧量（%pred）提高>15%以上,16例>20%,13例>25%,10例>30%。结论: CPET能安全客观定量地评估人体整体功能状态和治疗效果、指导制定个体化精准运动强度。个体化精准运动整体方案强化管控三个月能安全有效逆转长期心脑血管代谢等慢病患者的整体功能状态和异常指标。     

经皮冠状动脉腔内血管成形术改变稳定性冠心病患者整体功能的临床研究*

目的: 应用症状限制极限负荷心肺运动试验（CPET）评估稳定性冠心病患者经皮冠状动脉腔内血管成形术（PCI）治疗前后的整体心肺功能变化。方法: 入选2014年8月至12月在本院经冠脉造影和心脏超声等检查诊断为稳定性冠心病患者59例,择期行PCI治疗31例（PCI组）,另单纯药物保守治疗28例为对照组。患者治疗前、后均进行CPET。结果: 所有患者均安全完成CPET,无任何并发症。药物对照组治疗前后所有功能指标均无明显变化（P>0.05）。PCI组治疗后仅无氧阈、峰值摄氧量和峰值氧脉搏比治疗前明显提高（P<0.05）,其他指标变化不显著（P>0.05）。CPET评估个体化分析发现PCI组治疗后升高（≥10%）峰值摄氧量和峰值氧脉搏比例明显高于对照组（P<0.05）。结论: PCI通过冠状动脉血运重建可明显改善患者心肺功能,提高运动能力。CPET是客观定量评估冠心病治疗效果的一种客观、定量、安全、有效方法。     

不同功率递增速率对正常人心肺运动试验整体功能的影响Ⅱ—亚极限运动相关指标的影响*

目的: 观察健康志愿者不同功率递增速率完成症状限制性极限心肺运动试验（CPET）对CPET亚极限运动相关核心指标的影响。方法: 选择12名健康志愿者在一周内不同工作天随机完成中等适度程度（30 W/min）及比较低（10 W/min）和比较高（60 W/min）3种不同功率递增速率CPET。按标准方法比较12名志愿者CPET亚极限运动相关核心指标：无氧阈（AT）、单位功率摄氧量（ΔVO₂/ΔWR）、摄氧通气有效性峰值平台（OUEP）、二氧化碳通气当量平均90 s最低值（Lowest VE/ VCO₂）、二氧化碳通气当量斜率（VE/ VCO₂ Slope）及截距（intercept）和无氧阈时的摄氧通气效率值（VO₂/ VE@AT）和无氧阈时的二氧化碳通气当量值（VE/ VCO₂@AT）。对三组不同功率递增速率下各个指标的差异组间两两比较。结果: 中等适度功率递增速率组与比较低和比较高功率递增速率组相比摄氧通气有效性峰值平台（42.22±4.76 vs 39.54±3.30 vs 39.29±4.29）和二氧化碳通气当量平均90 s最小值（24.13±2.88 vs 25.60±2.08 vs 26.06±3.05）明显好,差异有统计学意义（P<0.05）;比较低、比较高功率递增速率组与中等适度功率递增速率组相比,单位功率摄氧量显著升高和降低（（8.45±0.66 vs 10.04±0.58 vs 7.16±0.60）ml/（min·kg））,差异有统计学意义（P<0.05）;无氧阈值没有发生明显改变（（0.87±0.19 vs 0.87±0.19 vs 0.89±0.19）L/min）,差异无统计学意义（P>0.05）;结论: 比较低、比较高功率递增速率可以明显改变摄氧通气有效性、二氧化碳排出通气有效性、单位功率摄氧量等CPET亚极限运动相关指标;选择比较低和比较高的功率递增速率和适度功率递增速率CPET相比明显降低了健康个体的摄氧通气有效性和二氧化碳排出通气有效性。CPET规范化操作要求选择适合受试者的功率递增速率,这样得到的CPET亚极限相关指标才最能反应受试者的真实功能状态。     

Change in the peripheral CO2 chemoreflex from rest to exercise

A single-breath CO₂ test of peripheral chemosensitivity has recently been described, and elaborated based on model simulations. This study was designed to measure the peripheral CO₂ chemoreflex at rest and during heavy exercise to see if carotid chemosensitivity to CO₂ increased. Ten healthy, adult males performed an incremental exercise test to determine their ventilatory anaerobic threshold (VAT), and 20 minutes of steady-state exercise at a pre-determined power output above VAT. Arterialized venous blood was obtained during each minute of incremental exercise to verify development of metabolic acidosis. Carotid chemosensitivity was tested repeatedly at rest and in steady-state exercise by the ventilatory response to a single breath of 13% CO₂ in air. The peripheral chemoreflex for CO₂ for the group of subjects doubled from rest to exercise (mean 0.0961 · s^–1 · kPa^–1) with all subjects showing an increase. We conclude that the gain of the carotid CO₂ chemoreflex increases from rest to exercise at work above the VAT.     

Max试验验证症状限制心肺运动试验为最大极限运动进一步临床研究*

目的: 验证临床受试者所完成的心肺运动试验（CPET）为最大极限运动,进一步设计完善Max试验验证CPET结果客观定量功能评估的准确性及以某特定指标的特定数值作为停止运动的标准是否可行。方法: 选择2017年9月至2019年1月在阜外医院签署知情同意书后进行CPET和Max试验受试者216例。其中正常受试者41例,因CPET峰值呼吸交换率（RER）≤1.10,或运动中心率和血压不上升,对CPET极限运动结果存在质疑的临床患者175例进行研究。其中60例已初步报告,本研究进一步扩大研究。Max试验方法：完成CPET测试后,先蹬车≥60 r/min,再施加130%峰值功率的恒定功率,鼓励受试者运动至不能坚持的极限状态。计算分析Max试验30 s的最大心率和最大摄氧量、及其与峰值心率和峰值摄氧量之间的差值和百分差值。百分差值=（Max值-峰值值）/Max值× 100%。评测标准：①若心率和摄氧量任一指标的差值百分比≤-10%（Max测试的数值低于CPET峰值数据）则定义Max试验操作失败,否则为成功;2若心率和摄氧量的差值百分比均在-10%~10%,则Max试验操作成功,证明CPET数据为极限运动,CPET 峰值相关数据较为准确;③若心率和摄氧量差值任一指标差值百分比≥10%时,则Max试验操作成功,证明CPET结果为非极限运动。结果: 病例组峰值摄氧量（L/min、ml/（min·kg）、%pred）、无氧阈（L/min、ml/（min·kg）、%pred）、峰值氧脉搏（ml/beat、%pred）、峰值RER、峰值收缩压（mmHg）、峰值运动负荷（W/min）、峰值心率（bpm）、摄氧有效性峰值平台（OUEP）（比值、%pred）低于正常组,二氧化碳通气有效性平均90 s最低值（Lowest Ve/VCO₂）（比值、%pred）、二氧化碳通气效率斜率（Ve/VCO₂ Slope）（比值、%pred）高于正常组（P<0.05）。所有正常组与病例组均安全无任何事件完成CPET和Max试验。216例受试者中,Max试验成功198例（91.7%）,其中证明CPET为极限运动182例,为非极限运动16例;失败18例（8.3%）。结论: 在临床检查中,若对CPET结果是否为最大极限存在质疑,利用Max试验可验证CPET是否为极限运动。Max试验方法安全可行,值得进一步深入研究和临床推广应用。     

Skeletal Muscle Abnormalities in Pulmonary Arterial Hypertension

Background

Pulmonary arterial hypertension is a progressive disease that is characterized by dyspnea and exercise intolerance. Impairment in skeletal muscle has recently been described in PAH, although the degree to which this impairment is solely determined by the hemodynamic profile remains uncertain. The aim of this study was to verify the association of structural and functional skeletal muscle characteristics with maximum exercise in PAH.

Methods

The exercise capacity, body composition, CT area of limb muscle, quality of life, quadriceps biopsy and hemodynamics of 16 PAH patients were compared with those of 10 controls.

Results

PAH patients had a significantly poorer quality of life, reduced percentage of lean body mass, reduced respiratory muscle strength, reduced resistance and strength of quadriceps and increased functional limitation at 6MWT and CPET. VO₂ max was correlated with muscular variables and cardiac output. Bivariate linear regression models showed that the association between muscular structural and functional variables remained significant even after correcting for cardiac output.

Conclusion

Our study showed the coexistence of ventilatory and quadriceps weakness in face of exercise intolerance in the same group of PAH patients. More interestingly, it is the first time that the independent association between muscular pattern and maximum exercise capacity is evidenced in PAH, independently of cardiac index highlighting the importance of considering rehabilitation in the treatment strategy for PAH.     

The use of muscle near-infrared spectroscopy (NIRS) to assess the aerobic training loads of world-class rowers

The objectives of this study were (1) to characterize the changes in oxygenation derived from muscle near-infrared spectroscopy (NIRS) during aerobic constant-load exercise with intensities close to Maximal Lactate Steady-State (MLSS) and (2) to establish reference values in the world-class rowers, for such workload often included in rowing training programs. Eight senior world-class rowers performed an incremental progressive submaximal exercise test and a 30-minute test on a rowing ergometer. The power corresponding to intensive aerobic training (84±1% of the anaerobic threshold) was adopted as an exercise load in the 30-minute test. The NIRS device was fixed on the vastus lateralis muscle which was active during rowing to record muscle O₂ saturation (SmO₂) and total hemoglobin concentration (THb) at rest and during exercise. Statistically significant increments in blood lactate (LA) and heart rate (HR) were observed, with 1.18±0.61 mmol/l and 10±5 beats/min, respectively, in 30th minute compared to 10th minute in 30-minute test. SmO₂ decreased significantly by 2.9±1.4%, whereas THb did not change. The examinations may suggested the low diagnostic value of THb in constant-load exercise. In each subject, SmO₂ was gradually reduced during the intense aerobic exercise. During workload close to MLSS, the SmO₂ of the vastus lateralis ranged from 14.0±3.13 to 11.1±2.81% in 10 and 30 minutes respectively, with a reduction in muscle oxygenation (ΔSmO₂) exceeding 50%. The non-invasive nature of the NIRS measurement and the continuous monitoring of SmO₂ values are useful in the practice of monitoring training in terms of aerobic training loads.     

Impaired cardiac and peripheral hemodynamic responses to inhaled β2-agonist in cystic fibrosis

Background

Pulmonary system dysfunction is a hallmark of cystic fibrosis (CF) disease. In addition to impaired cystic fibrosis transmembrane conductance regulator protein, dysfunctional β₂-adrenergic receptors (β₂AR) contribute to low airway function in CF. Recent observations suggest CF may also be associated with impaired cardiac function that is demonstrated by attenuated cardiac output (Q), stroke volume (SV), and cardiac power (CP) at both rest and during exercise. However, β₂AR regulation of cardiac and peripheral vascular tissue, in-vivo, is unknown in CF. We have previously demonstrated that the administration of an inhaled β-agonist increases SV and Q while also decreasing SVR in healthy individuals. Therefore, we aimed to assess cardiac and peripheral hemodynamic responses to the selective β₂AR agonist albuterol in individuals with CF.

Methods

18 CF and 30 control (CTL) subjects participated (ages 22 ± 2 versus 27 ± 2 and BSA = 1.7 ± 0.1 versus 1.8 ± 0.0 m², both p < 0.05). We assessed the following at baseline and at 30- and 60-minutes following nebulized albuterol (2.5mg diluted in 3.0mL of normal saline) inhalation: 12-lead ECG for HR, manual sphygmomanometry for systolic and diastolic blood pressure (SBP and DBP, respectively), acetylene rebreathe for Q and SV. We calculated MAP = DBP + 1/3(SBP–DBP); systemic vascular resistance (SVR) = (MAP/Q)•80; CP = Q•MAP; stroke work (SW) = SV•MAP; reserve (%change baseline to 30- or 60-minutes). Hemodynamics were indexed to BSA (Q_I, SV_I, SW_I, CP_I, SVR_I).

Results

At baseline, CF demonstrated lower SV, SV_I, SW, and SW_I but higher HR than CTL (p < 0.05); other measures did not differ. At 30-minutes, CF demonstrated higher HR and SVR_I, but lower Q, SV, SV_I, CP, CP_I, SW, and SW_I versus CTL (p < 0.05). At 60-minutes, CF demonstrated higher HR, SVR, and SVR_I, whereas all cardiac hemodynamics were lower than CTL (p < 0.05). Reserves of CP, SW, and SVR were lower in CF versus CTL at both 30 and 60-minutes (p < 0.05).

Conclusions

Cardiac and peripheral hemodynamic responsiveness to acute β₂AR stimulation via albuterol is attenuated in individuals with CF, suggesting β₂AR located in cardiac and peripheral vascular tissue may be dysfunctional in this population.     

Developing pulmonary vasculopathy in systemic sclerosis, detected with non-invasive cardiopulmonary exercise testing

Background

Patients with systemic sclerosis (SSc) may develop exercise intolerance due to musculoskeletal involvement, restrictive lung disease, left ventricular dysfunction, or pulmonary vasculopathy (PV). The latter is particularly important since it may lead to lethal pulmonary arterial hypertension (PAH). We hypothesized that abnormalities during cardiopulmonary exercise testing (CPET) in patients with SSc can identify PV leading to overt PAH.

Methods

Thirty SSc patients from the Harbor-UCLA Rheumatology clinic, not clinically suspected of having significant pulmonary vascular disease, were referred for this prospective study. Resting pulmonary function and exercise gas exchange were assessed, including peakVO₂, anaerobic threshold (AT), heart rate- VO₂ relationship (O₂-pulse), exercise breathing reserve and parameters of ventilation-perfusion mismatching, as evidenced by elevated ventilatory equivalent for CO₂ (VE/VCO₂) and reduced end-tidal pCO₂ (P_ETCO₂) at the AT.

Results

Gas exchange patterns were abnormal in 16 pts with specific cardiopulmonary disease physiology: Eleven patients had findings consistent with PV, while five had findings consistent with left-ventricular dysfunction (LVD). Although both groups had low peak VO₂ and AT, a higher VE/VCO₂ at AT and decreasing P_ETCO₂ during early exercise distinguished PV from LVD.

Conclusions

Previously undiagnosed exercise impairments due to LVD or PV were common in our SSc patients. Cardiopulmonary exercise testing may help to differentiate and detect these disorders early in patients with SSc.     

Leg vasoconstriction during dynamic exercise with reduced cardiac output.

We evaluated whether a reduction in cardiac output during dynamic exercise results in vasoconstriction of active skeletal muscle vasculature. Nine subjects performed four 8-min bouts of cycling exercise at 71 +/- 12 to 145 +/- 13 W (40-84% maximal oxygen uptake). Exercise was repeated after cardioselective (beta 1) adrenergic blockade (0.2 mg/kg metoprolol iv). Leg blood flow and cardiac output were determined with bolus injections of indocyanine green. Femoral arterial and venous pressures were monitored for measurement of heart rate, mean arterial pressure, and calculation of systemic and leg vascular conductance. Leg norepinephrine spillover was used as an index of regional sympathetic activity. During control, the highest heart rate and cardiac output were 171 +/- 3 beats/min and 18.9 +/- 0.9 l/min, respectively. beta 1-Blockade reduced these values to 147 +/- 6 beats/min and 15.3 +/- 0.9 l/min, respectively (P < 0.001). Mean arterial pressure was lower than control during light exercise with beta 1-blockade but did not differ from control with greater exercise intensities. At the highest work rate in the control condition, leg blood flow and vascular conductance were 5.4 +/- 0.3 l/min and 5.2 +/- 0.3 cl.min-1.mmHg-1, respectively, and were reduced during beta 1-blockade to 4.8 +/- 0.4 l/min (P < 0.01) and 4.6 +/- 0.4 cl.min-1.mmHg-1 (P < 0.05). During the same exercise condition leg norepinephrine spillover increased from a control value of 2.64 +/- 1.16 to 5.62 +/- 2.13 nM/min with beta 1-blockade (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)