Cardiopulmonary exercise testing in congenital heart disease: equipment and test protocols

Cardiopulmonary exercise testing (CPET) in paediatric cardiology differs in many aspects from the tests as performed in adult cardiology. Children's cardiovascular responses during exercise testing present different characteristics, particularly oxygen uptake, heart rate and blood pressure response, which are essential in interpreting haemodynamic data. Diseases that are associated with myocardial ischaemia are very rare in children. The main indications for CPET in children are evaluation of exercise capacity and the identification of exercise-induced arrhythmias. In this article we will review exercise equipment and test protocols for CPET in children with congenital heart disease. (Neth Heart J 2009;17:339–44.)     

Control approach for high sensitivity cardiopulmonary exercise testing during stimulated cycle ergometry in spinal cord injured subjects

AimPeople with complete lower-limb paralysis resulting from spinal cord injury (SCI) can perform cycle ergometry by means of functional electrical stimulation. Here, we propose and evaluate new exercise testing methods for estimation of cardiopulmonary performance parameters during this form of exercise.MethodsWe utilised a customised ergometer incorporating feedback control of stimulated exercise workrate and cycling cadence. This allowed the imposition of arbitrary workrate profiles with high precision with the potential for improved sensitivity in exercise testing. New incremental exercise test (IET) and step exercise test (SET) protocols for determination of peak and steady-state performance parameters were assessed.ResultsThe IET protocol allowed reliable determination of the ventilatory threshold, peak workrate and oxygen uptake-workrate relationship, but gave unrepresentative peak oxygen uptake values and highly variable measures of oxygen uptake kinetics. The SET protocol gave reliable estimation of steady-state oxygen uptake and metabolic efficiency of constant load exercise, but high variability in the estimation of oxygen uptake kinetics.ConclusionThe feedback-controlled testbed and the new IET and SET protocols have the potential for estimation of cardiopulmonary performance parameters with improved sensitivity during stimulated cycle ergometry in subjects with SCI.     

Development and testing of protocols for computer-aided design of peptide drugs, using oxytocin

Considerable clinical interest in neuropeptides and peptide hormones has stimulated recent research and development of peptide-based drugs. This process differs from most classical drug discovery procedures because peptide molecules have considerable inherent flexibility. In the present paper, to identify lowest energy and metastable conformers for drug design, and to develop protocols for such studies, conformational search algorithms, incorporating empirical energy calculations, have been applied in the analysis of the peptide oxytocin. Energy minimization in torsion angle space was carried out from a variety of starting conformations, including published structures, in all-atom mode and all with distance constraints for disulphide bond formation. The energy-minimized conformations have been further optimized by a mapping method. Complementary simulations have been performed in united-atom mode and a model representing the effects of water using dummy sites has been developed and tested for this representation. Several of the preferred conformers together with de novo conformations have been used as starting points in molecular dynamics simulations; 28 low potential energy conformations were located at a temperature of 4 K. Conformations are analysed to identify hydrogen bonds, phi-psi angle distributions and the RMS values relative to the X-ray structure of deamino-oxytocin. The modelled structure of lowest energy in the molecular mechanics calculations was also that of least RMS deviation from the crystal structure; whilst structures of lower energy but larger deviation were identified by molecular dynamics techniques. A metastable structure has been identified which satisfies existing criteria for the "active form", and this model is tested by a theoretical residue-substitution technique, to provide clues on the agonist/antagonist relationship at the atomic level.     

Habitual Functional Electrical Stimulation Therapy Improves Gait Kinematics and Walking Performance,but Not Patient-Reported Functional Outcomes,of People with Multiple Sclerosis who Present with Foot-Drop

Background

People with Multiple Sclerosis (pwMS) often experience a disturbed gait function such as foot-drop. The objective of this pilot study was to investigate the medium term effects of using Functional Electrical Stimulation (FES) to treat foot-drop over a period 12 weeks on gait and patient reported outcomes of pwMS.

Methods and Findings

Nine pwMS aged 35 to 64 (2 males, 7 females) were assessed on four occasions; four weeks before baseline, at baseline and after six weeks and twelve weeks of FES use. Joint kinematics and performance on the 10 meter and 2 minute walk tests (10WT, 2 minWT) were assessed with and without FES. Participants also completed the MS walking Scale (MSWS), MS impact scale (MSIS29), Fatigue Severity Score (FSS) and wore an activity monitor for seven days after each assessment. Compared to unassisted walking, FES resulted in statistically significant improvements in peak dorsiflexion in swing (p = 0.006), 10MWT (p = 0.006) and 2 minWT (p = 0.002). Effect sizes for the training effect, defined as the change from unassisted walking at baseline to that at 12 weeks, indicated improved ankle angle at initial contact (2.6°, 95% CI −1° to 4°, d = 0.78), and a decrease in perceived exertion over the 2 min walking tests (−1.2 points, 95% CI −5.7 to 3.4, d = −0.86). Five participants exceeded the Minimally Detectable Change (MDC) for a training effect on the 10mWT, but only two did so for the 2 minWT. No effects of the use of FES for 12 weeks were found for MSWS, MSIS29, FSS or step count.

Conclusion

Although FES to treat foot-drop appears to offer the potential for a medium term training effect on ankle kinematics and walking speed, this was not reflected in the patient reported outcomes. This observed lack of relationship between objective walking performance and patient reported outcomes warrants further investigation.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01977287","term_id":"NCT01977287"}}NCT01977287     

Model testing, prediction and experimental protocols in neuroscience: A case study

In their theoretical and experimental reflections on the capacities and behaviours of living systems, neuroscientists often formulate generalizations about the behaviour of neural circuits. These generalizations are highly idealized, as they omit reference to the myriads of conditions that could perturb the behaviour of the modelled system in real-world settings. This article analyses an experimental investigation of the behaviour of place cells in the rat hippocampus, in which highly idealized generalizations were tested by comparing predictions flowing from them with real-world experimental results. The aim of the article is to identify (1) under what conditions even single prediction failures regarding the behaviour of single cells sufficed to reject highly idealized generalizations, and (2) under what conditions prima facie counter-examples were deemed to be irrelevant to the testing of highly idealized generalizations. The results of this analysis may contribute to understanding how idealized models are tested experimentally in neuroscience and used to make reliable predictions concerning living systems in real-world settings.     

The ventilation, lactate and electromyographic thresholds during incremental exercise tests in normoxia, hypoxia and hyperoxia

These experiments examined the effect of hypoxia and hyperoxia on ventilation, lactate concentration and electromyographic activity during an incremental exercise test in order to determine if coincident chances in ventilation and electromyographic activity occur during an incremental exercise test, despite an enhancement or reduction of peripheral chemoreceptor activity. In addition, these experiments were completed to determine if electromyographic activity and ventilation are enhanced or reduced in response to the inspiration of oxygen-depleted and oxygen-enriched air, respectively. Seven subjects performed three incremental exercise tests, until volitional exhaustion was achieved, while inspiring air with a fractional concentration of oxygen of either 66%, 21% or 17%. In addition, another single subject completed two tests while inspiring air with a fractional concentration of either 17% or 21%. During the tests, ventilation, mixed expired oxygen and carbon dioxide, arterialized venous blood and the electromyographic activity from the vastus lateralis were sampled. From these values ventilation, electromyographic and lactate thresholds were detected during normoxia, hypoxia and hyperoxia. The results showed that although ventilation and lactate concentration were significantly less during hyperoxia as compared to normoxia or hypoxia, the carbon dioxide production values were not significantly different between the normoxic, hypoxic and hyperoxic conditions. For a particular condition, the time, carbon dioxide production and oxygen consumption values that corresponded to the ventilation and electromyographic thresholds were not significantly different, but the values corresponding to the lactate threshold were significantly less than those for the electromyographic and ventilation thresholds. Comparisons between the three conditions showed that the time, carbon dioxide production and oxyen consumption values corresponding to each of these thresholds were not significantly different. These findings have led us to conclude that the changes in lactate concentration observed during exercise may not be directly related to the fractional concentration of inspired oxygen, and that the peripheral chemoreceptors may not be the sole mediators of the first ventilatory threshold. It is suggested that this threshold may be mediated by an increase in neural activity originating from higher motor centers or the exercising limbs, induced in response to the need to progressively recruit fast twitch muscle fibers as exercise power output is increased and as individual muscle fibers begin to fatigue.     

A distributed three-channel wireless Functional Electrical Stimulation system for automated triggering of stimulation to enable coordinated task execution by patients with neurological disease

Functional Electrical Stimulation (FES) is a technique used to improve mobility and function for patients suffering some neurological related diseases such us Multiple Sclerosis (MS) and stroke. Some patients might require FES applied in more than one location depending on the extent of the neurological condition. Currently, this can be achieved using multi-channel FES systems. However, these systems can be bulky and impractical in daily usage. This research investigates using a wireless distributed FES system to overcome some of the limitations of the current multi-channel systems. A prototype of a three-channel FES system was built and tested. The prototype is used for drop foot stimulation and reciprocal arm swing stimulation while the user is walking, and for elbow extension and wrist/fingers opening stimulation if triggered while standing or sitting. A pilot study was designed to evaluate the reliability and repeatability of the system with 11 healthy volunteers without applying stimulation. This was followed by a case study with a hemiplegic person. The results indicate that the system can successfully detect and generate output responses appropriate to the input signals from the body sensors.     

Alterations in plasma volume, electrolytes and protein during incremental exercise at different pedal speeds

We investigated the effects of pedal speed on changes in plasma volume, electrolytes and protein during incremental exercise. Ten adult males participated in two, 30 minute incremental cycle ergometer exercise tests at room temperature (22° C, rh=56%). Exercise load was increased from 20 to 70% of peak . Five minutes were spent at each of six stages which were equally spaced in exercise intensity. Subjects pedaled at 50 (50 RPM) and 90 (90 RPM) rev · min^–1. Venous blood samples were drawn prior to exercise and during the last minute of each stage. Relative plasma volume changes showed a progressive hemoconcentration during the exercise. There were no significant differences due to pedal speed as plasma volume loss averaged –7.3% during exercise. [Na+], [Cl–], and [K+] increased significantly during exercise but were not influenced by pedal speed. Changes in plasma protein and albumin concentrations indicated that there was a loss of globulin from the vascular volume in both conditions and an addition of albumin to the plasma in 50 RPM. The difference in plasma albumin dynamics was possibly related to an effect of pedal speed on movement of fluid in the lymphatic vessels of the legs.This work was supported in part by Grants from the Theresa Monaco Endowment of the University of Houston College of Education and Nautilus Sports/Medical Industries     

Integration of Functional,Psychophysiological, and Biochemical Processes in Athletes after Audiovisual Stimulation

We studied intra- and inter-system structural interactions between functional, psychophysiological, and biochemical processes in athletes after audiovisual stimulation (AVS). We used multiple linear regression and correlation analysis after AVS to investigate the formation of new relations between the nervous, hormonal, cardiorespiratory, and metabolic systems. AVS training leads to an increase in physical working capacity (PWC₁₇₀) and in the number of its correlations, e.g., with the amplitude of alpha-rhythm, resting heart rate (HR), concentrations of thyroxine, phosphorus, glucose, bilirubin, and triglycerides, antioxidant status, and the level of life satisfaction, which indicates the elevation in inter-system integration processes at different functional levels. An increase in the number and effects of factors contributing to PWC₁₇₀ (chronoinotropic reserve, lung capacity, reaction of individual α-rate power depth, reaction to the moving object, and the concentrations of glucose, creatinine, bilirubin, and thyroxine) eventually resulted in higher PWC₁₇₀. This indicates that the rate of synchronization between the studied parameters increases under the influence of sensory impact, which results in the improvement of adaptive capacity and provides a lower cost of adaptation to physical loads at the competitive stage of sports training.     

Plasma potassium and ventilation during incremental exercise in humans: modulation by sodium bicarbonate and substrate availability.

It has recently been demonstrated that, compared to normal conditions, ventilation (VE) was increased during exercise after glycogen depletion, in spite of a marked increase in plasma pH (pHP). It was further demonstrated that VE in patients with McArdle's syndrome was reduced when substrate availability was improved. In the present experiments, six endurance trained men performed two successive cyclo-ergometric incremental exercise tests (tests A, B) after normal nutrition (N) and after a fatty meal in conjunction with a sodium bicarbonate (NaHCO3) solution (FSB) or without NaHCO3 (F), and the relationship between VE, plasma potassium concentration ([K+]P), and pHP was checked. Plasma free fatty acid concentration ([FFA]P) was markedly increased in the F and FSB trials (P < 0.001). In FSB pHP was significantly increased, compared to N and F (P < 0.001). In all the B tests, pHP increased during moderate and intense exercise and in FSB, remained alkalotic even during maximal exercise intensity. In contrast, VE and [K+]P changes were almost equal in all the trials and in tests A and B. It was found that exercise-induced changes of VE and [K+]P in the present experiments were not markedly affected by [FFA]P or pHP values and that these changes also occurred independently of changes in pHP or plasma bicarbonate concentration. The often used glycogen depletion strategy may have slightly increased VE but apparently did not overcompensate for a possible decrease in VE due to increased pHP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased Acetylcholine Content Induced by Adenosine in a Sympathetic Ganglion and Its Subsequent Mobilization by Electrical Stimulation

Abstract: The present study was initiated to examine the effects of ATP on acetylcholine (ACh) synthesis. The exposure of superior cervical ganglia to ATP increased ACh stores by 25%, but this effect was also evident with ADP, AMP, and adenosine, but not with βγ-methylene ATP, a nonhydrolyzable analogue of ATP, or with inosine, the deaminated product of adenosine. Thus, we attribute the enhanced ACh content caused by ATP to the presence of adenosine derived from its hydrolysis by 5′-nucleotidase. The adenosine-induced increase of tissue ACh was not the consequence of an adenosine-induced decrease of ACh release. The extra ACh remained in the tissue for more than 15 min after the removal of adenosine, but it was not apparent when ganglia were exposed to adenosine in a Ca²⁺-free medium. Incorporation of radiolabelled choline into [³H]ACh was also enhanced in the presence of adenosine, suggesting an extracellular source of precursor. Moreover, the synthesis of radiolabelled forms of phosphorylcholine and phospholipid was not reduced in adenosine's presence, suggesting that the extra ACh was not likely derived from choline destined for phospholipid synthesis. Aminophylline did not prevent the adenosine effect to increase ACh content; this effect was blocked by dipyridamole, but not by nitrobenzylthioinosine (NBTI). In addition, two benzodiazepine stereoisomers known to inhibit stereoselectively the NBTI-resistant nucleoside transporter displayed a similar stereoselective ability to block the effect of adenosine. Together, these results argue that adenosine is transported through an NBTI-resistant nucleoside transporter to exert an effect on ACh synthesis. The extra ACh accumulated as a result of adenosine's action was releasable during subsequent preganglionic nerve stimulation, but not in the presence of vesamicol, a vesicular ACh transporter inhibitor. We conclude that the mobilization of ACh is enhanced as a result of adenosine pretreatment.     

Effectiveness of Bisphosphonate Analogues and Functional Electrical Stimulation on Attenuating Post-Injury Osteoporosis in Spinal Cord Injury Patients- a Systematic Review and Meta-Analysis

Background

Various pharmacologic and non-pharmacologic approaches have been applied to reduce sublesional bone loss after spinal cord injury (SCI), and the results are inconsistent across the studies. The objective of this meta-analysis was to investigate whether the two most-studied interventions, bisphosphonate analogues and functional electrical stimulation (FES), could effectively decrease bone mineral density (BMD) attenuation and/or restore lost BMD in the SCI population.

Methods

Randomized controlled trials, quasi-experimental studies, and prospective follow-up studies employing bisphosphonates or FES to treat post-SCI osteoporosis were identified in PubMed and Scopus. The primary outcome was the percentage of BMD change from baseline measured by dual-energy X-ray absorptiometry (DEXA) or computed tomography (CT). Data were extracted from four points: the 3rd, 6th, 12th, and 18th month after intervention.

Results

A total of 19 studies were included in the analysis and involved 364 patients and 14 healthy individuals. Acute SCI participants treated with bisphosphonate therapy demonstrated a trend toward less bone loss than participants who received placebos or usual care. A significant difference in BMD decline was noted between both groups at the 3rd and 12th month post-medication. The subgroup analysis failed to show the superiority of intravenous bisphosphonate over oral administration. Regarding FES training, chronic SCI patients had 5.96% (95% CI, 2.08% to 9.84%), 7.21% (95%CI, 1.79% to 12.62%), and 9.56% (95% CI, 2.86% to 16.26%) increases in BMD at the 3rd, 6th, and 12th months post-treatment, respectively. The studies employing FES ≥5 days per week were likely to have better effectiveness than studies using FES ≤3 days per week.

Conclusions

Our meta-analysis indicated bisphosphonate administration early following SCI effectively attenuated sublesional bone loss. FES intervention for chronic SCI patients could significantly increase sublesional BMD near the site of maximal mechanical loading.     

胃多导电刺激及胃液体排空犬动物模型的建立

目的建立胃浆膜多导联电刺激和胃排空动物模型。方法在12条英国比格犬的胃大弯浆膜层包埋四对心内起搏电极,距幽门40cm空肠近端行一造瘘口。结果①造瘘管收集食糜的方法简单易行,通过其排空量,能了解不同的电刺激和不同的电刺激参数对胃动力的作用。②胃浆膜多导联电极记录的胃体、胃窦慢波电信号清晰、稳定,能准确地记录不同时间和不同实验的胃慢波变化。③单导联和多导长脉冲电刺激均能控制胃慢波。结论胃浆膜多导联电极是研究胃电生理、胃电起搏及胃电起搏对胃排空的影响较理想的方法。英国比格犬是此模型的理想材料。     

低频神经和肌肉电刺激对产程、分娩方式、母婴结局的影响分析

目的:观察低频神经和肌肉刺激仪用于分娩镇痛对产程、分娩方式、产后出血、会阴完整度、母婴结局的影响.方法:随机选择2019年8月～2020年3月在我院分娩的足月妊娠产妇220名,根据第一产程是否应用低频神经和肌肉刺激仪分为观察组112例及对照组108例,两组均接受常规分娩护理,观察组为自愿接受低频神经和肌肉电刺激镇痛的产...     

功能性电刺激联合循环运动系统对老年脑卒中后肌肉衰减综合征患者肢体功能、平衡能力以及认知功能的影响

摘要 目的：研究功能性电刺激联合循环运动系统对老年脑卒中后肌肉衰减综合征患者肢体功能、平衡能力以及认知功能的影响。方法：选择2020年6月到2021年6月在我院进行康复治疗的老年脑卒中后肌肉衰减综合征患者64例,据其治疗方式的不同分为对照组和研究组,两组患者均给予常规康复治疗,对照组患者在常规治疗的基础上加用功能性电刺激治疗,而研究组在对照组基础上加用脑循环系统治疗仪进行治疗,比较两组患者临床治疗疗效。使用运动功能评分法（FMA）和上肢功能评定（STEF）评价肢体患者功能,使用平衡量表（BBS）和Fuglg-Meyer平衡量表（FM-B）评价患者平衡能力,使用自拟认知量表评价患者认知功能。结果：（1）研究组患者临床治疗总有效率较对照组高（93.75 % vs 75.00 %,P<0.05）;（2）两组患者治疗后FMA和STEF评分均显著增高（P<0.05）,并且研究组患者治疗后BBS和FM-B评分显著高于对照组患者（P<0.05）;（3）两组患者治疗后BBS和FM-B评分均显著增高,并且研究组患者治疗后BBS和FM-B评分显著高于对照组患者（P<0.05）;（4）两组患者治疗后认知功能评分均升高,并且研究组患者较对照组患者高（P<0.05）。结论：功能性电刺激联合循环运动系统对老年脑卒中后肌肉衰减综合征患者具有显著的临床治疗效果,可显著改善患者肢体功能、平衡能力和认知功能。     

Pharmacological and Functional Heterogeneity of Astrocytes: Regional Differences in Phospholipase C Stimulation by Neuromediators

Carbamylcholine stimulated phospholipase C activity in astrocytes in primary culture from the mesencephalon but not from the striatum or cerebral cortex of the mouse embryo. An alpha 1-adrenergic-mediated response was observed in all astrocyte populations. 2-Chloroadenosine potentiated the alpha 1-adrenergic response in mesencephalic and striatal astrocytes but not in cortical astrocytes. It also stimulated the carbamylcholine-evoked response in mesencephalic astrocytes. Through cell-cell cooperation, 2-chloroadenosine potentiated the neuronal carbamylcholine-evoked activation of phospholipase C in homotopic cocultures (neuro-glial) from the striatum but not in homotopic cocultures (neuro-glial) from the cerebral cortex or in heterotopic cocultures (cortical astrocytes-striatal neurons; striatal astrocytes-cortical neurons.