Influences on Pulmonary and Muscular V’O2-Kinetics

Introduction Muscular and respiratory V’O2-kinetics are influenced by many factors. At cellular level muscular V’O2 (V’O2musc) is affected by O2-delivery and O2-consumption. Further, these factors can be divided into muscle perfusion, capillary density, enzyme activity, mitochondrial proliferation, muscle fiber composition and some more. Focusing on the difference between V’O2resp and V’O2musc the venous blood volume, the venous O2-stores and the dynamics of cardiac output can be identified as influences. These influences result in a time delay and a distortion of V’O2resp. Usually exercise step responses are used for estimating V’O2resp-kinetics. But it has to be recognized, that V’O2resp may be influenced by the cardio-respiratory system during the transition phases, so that the calculated time constants using an exponential data fitting method could lead to incorrect estimations. In succession, discrepancies to static or dynamic linearity as well as asymmetries in on- and off-kinetics may be observed. To avoid these possibly wrong estimations a backward calculation model considering the influences of the cardio-respiratory system can be applied for calculating V’O2musc-kinetics (Fig. 1). Furthermore, the combination of the backward calculation model and the time-series analysis describes an alternative approach for the kinetic analysis. In addition, only a single exercise test for this approach has to be performed for estimating the kinetic responses. Methods 11 volunteers (Age: 30 ± 8 years; Height: 175 ± 7 cm; Weight: 72 ± 10 kg; BMI: 23 ± 2 kg•m-2; V’O2peak: 4 ± 1 L•min-1; relV’O2peak: 54 ± 5 ml•min-1•kg-1) were subjected to dynamic workload (WL) changes between 30 and 80 Watt. Gas exchange was assessed breath-by-breath and heart rate (HR) was estimated by applying ECG. For modeling of V’O2musc a two compartment model representing the exercising and the non-exercising segments of the body was used. The model accounts for a muscular venous blood volume (Vvmusc) and a constant blood flow to the non-exercising segments (Q’rem). Pseudo random binary workload changes (PRBS) between 30 and 80 W were used as workload protocol and as a prerequisite for the time-series analysis. For adjustment of Vvmusc and Q’rem auto- and cross-correlation functions (ACF, CCF) of workload and calculated V’O2musc as well as V’O2resp were applied. Higher CCF peaks indicate faster system responses. The following criteria were utilized for estimating Vvmusc and Q’rem: 1) Arterio-venous O2-content difference for the muscle and the remaining compartment was preset to 200 ml•L-1. 2) Fluctuations in the CCF (Workload/V’O2musc) course were minimized in the range of initial increase. 3) On the decreasing part the course of the CCF (Workload/V’O2musc) had to be as smooth as possible, indicating no or small deflections. Results Vvmusc and Q’rem were calculated as 2.9 ± 0.5 L and 3.6 ± 1.6 L • min-1, respectively. By focusing the kinetic responses respiratory (0.33 ± 0.09; equal to a time constant of 41 s) are slower than muscular (0.39 ± 0.07; 32 s) V’O2-kinetics (Fig. 2). The fastest kinetics can be observed for this population in HR (0.44 ± 0.10; 26 s). Conclusion 1) Vvmusc, venous O2-stores and the dynamics of cardiac output may be responsible for the time delays and the distortion between V’O2resp- and V’O2musc-kinetics. 2) The approach of using a PRBS workload protocol in combination with time-series analysis can be applied for estimating V’O2musc-kinetics by a single exercise test at moderate exercise intensity. 3) It has to be noticed, that V’O2resp with this kind of analysis rely on the complete distorted and time delayed response measured at the mouth, so that differences with the estimation of the kinetic responses using exponential fitting procedures are evidently in the time-series analysis

Towards demand-side management of the chlor-alkali electrolysis: Dynamic, pressure-driven modeling and model validation of the 1,2-dichloroethane synthesis

A promising application of demand-side management is the chlor-alkali electrolysis. However, storing the produced chlorine for flexibility should be avoided whenever possible. If PVC is produced from chlorine, storing the intermediate 1,2-dichloroethane resulting from direct chlorination of ethene is a better alternative as it is less toxic than chlorine and can be easily stored. Currently, no dynamic process models to study the process behavior or to develop optimal trajectories for the 1,2-dichloroethane production under different demand response scenarios are available. Hence, we formulate and solve a dynamic, pressure-driven model of the synthesis of 1,2-dichloroethane and validate it with real process data in this contribution. As part of this dynamic model, differentiable formulations for weeping and the flow over a weir of a distillation tray are presented, which are also valid whenever certain trays run dry.BMWi, 0350013A, Verbundvorhaben: ChemEFlex - Umsetzbarkeitsanalyse zur Lastflexibilisierung elektrochemischer Verfahren in der Industrie; Teilvorhaben: Modellierung der Chlor-Alkali-Elektrolyse sowie anderer Prozesse und deren Bewertung hinsichtlich Wirtschaftlichkeit und möglicher Hemmniss

Breath‐by‐breath oxygen uptake during running: Effects of different calculation algorithms

New Findings What is the central question of this study? Breath‐by‐breath gas exchange analysis during treadmill exercise can be disturbed by different breathing patterns depending on cadence, and the flow sensor might be subjected to variable mechanical stress. It is still unclear whether the outcomes of the gas exchange algorithms can be affected by running at different speeds. What is the main finding and its importance? Practically, the three investigated breath‐by‐breath algorithms ('Wessel', 'expiration‐only' and 'independent breath') provided similar average gas exchange values for steady‐state conditions. The 'independent breath' algorithm showed the lowest breath‐by‐breath fluctuations in the gas exchange data compared with the other investigated algorithms, both at steady state and during incremental exercise. AbstractRecently, a new breath‐by‐breath gas exchange calculation algorithm (called 'independent breath') was proposed. In the present work, we aimed to compare the breath‐by‐breath O2 uptake () values assessed in healthy subjects undergoing a running protocol, as calculated applying the 'independent breath' algorithm or two other commonly used algorithms. The traces of respiratory flow, O2 and CO2 fractions, used by the calculation algorithms, were acquired at the mouth on 17 volunteers at rest, during running on a treadmill at 6.5 and 9.5 km h−1, and thereafter up to volitional fatigue. Within‐subject averages and standard deviations of breath‐by‐breath were calculated for steady‐state conditions; the data of the incremental phase were analysed by means of linear regression, and their root mean square was assumed to be an index of the breath‐by‐breath fluctuations. The average values obtained with the different algorithms were significantly different (P < 0.001); nevertheless, from a practical point of view the difference could be considered 'small' in all the investigated conditions (effect size <0.3). The standard deviations were significantly lower for the 'independent breath' algorithm (post hoc contrasts, P < 0.001), and the slopes of the relationships with the corresponding data yielded by the other algorithms were <0.70. The root mean squares of the linear regressions calculated for the incremental phase were also significantly lower for the 'independent breath' algorithm, and the slopes of the regression lines with the corresponding values obtained with the other algorithms were <0.84. In conclusion, the 'independent breath' algorithm yielded the least breath‐by‐breath O2 uptake fluctuation, both during steady‐state exercise and during incremental running

A pressure-driven, dynamic model for distillation columns with smooth reformulations for flexible operation

Dynamic models for plants including the startup or shutdown phase are still scarce as the (dis-)appearence of phases or streams is challenging to implement. We present an approach to model a distillation column, in which these operation modes are also considered without exchanging equations. For this purpose, the well-known modeling equations for distillation columns are reformulated robustly to allow for the disappearance of the vapor phase without discontinuities. The reformulation does not depend on solving an optimization problem and could easily be applied to other column types or different unit operations. The proposed model is solved in two case studies with 10 and 40 trays, respectively. In these case studies, the influence of single phenomena on the obtained dynamic profiles is investigated, e.g., weeping, which are often neglected. The proposed modeling approach yields a dynamic model that can be solved without reinitialization for a realistically large number of trays.BMBF, 0350013A, Verbundvorhaben: ChemEFlex - Umsetzbarkeitsanalyse zur Lastflexibilisierung elektrochemischer Verfahren in der Industrie; Teilvorhaben: Modellierung der Chlor-Alkali-Elektrolyse sowie anderer Prozesse und deren Bewertung hinsichtlich Wirtschaftlichkeit und möglicher Hemmniss

Methylprednisolone blocks interleukin 1 beta induced calcitonin gene related peptide release in trigeminal ganglia cells

Background Methylprednisolone (MPD) is a rapid acting highly effective cluster headache preventive and also suppresses the recurrence of migraine attacks. Previously, we could demonstrate that elevated CGRP plasma levels in a cluster headache bout are normalized after a course of high dose corticosteroids. Here we assess whether MPD suppresses interleukin-1β (IL-1β)- and prostaglandin E2 (PGE2)-induced CGRP release in a cell culture model of trigeminal ganglia cells, which could account for the preventive effect in migraine and cluster headache. Metoprolol(MTP), a migraine preventive with a slow onset of action, was used for comparison. Methods Primary cultures of rat trigeminal ganglia were stimulated for 24 h with 10 ng/ml IL-1β or for 4 h with 10 μM PGE2 following the exposure to 10 or 100 μM MPD or 100 nM or 10 µM MTP for 45 min or 24 h. CGRP was determined by using a commercial enzyme immunoassay. Results MPD but not MTP blocked IL-1β-induced CGRP release from cultured trigeminal cells. PGE2-stimulated CGRP release from trigeminal ganglia cell culture was not affected by pre-stimulation whether with MPD or MTP. Conclusion MPD but not MTP suppresses cytokine (IL-1β)-induced CGRP release from trigeminal ganglia cells. We propose that blockade of cytokine mediated trigeminal activation may represent a potential mechanism of action that mediates the preventive effect of MTP on cluster headache and recurrent migraine attacks

Retreatment with interferon-alpha and ribavirin in primary interferon-alpha non-responders with chronic hepatitis C

Background/Aims: Combination therapy with interferon-alpha (IFN-alpha) plus ribavirin is more efficacious than IFN-alpha monotherapy in previously untreated patients with chronic hepatitis C and patients with IFN-alpha relapse. Only limited data are available in IFN-alpha non-responders. In a multicenter trial we therefore evaluated the efficacy of combination therapy in IFN-alpha-resistant chronic hepatitis C. Methods: Eighty-two patients (mean age 46.8 years, 54 males, 28 females) with chronic hepatitis C were treated with IFN-alpha-2a (3 x 6 MIU/week) and ribavirin (14 mg/kg daily) for 12 weeks. Thereafter, treatment was continued only in virological responders (undetectable serum HCV RNA at week 12) with an IFN-alpha dose of 3 x 3 MIU/week and without ribavirin for a further 9 months. The primary study endpoint was an undetectable HCV RNA by RT-PCR at the end of the 24-week follow-up period. Results: After 12 weeks of combination therapy, an initial virological response was observed in 29 of 82 (35.4%) patients. Due to a high breakthrough rate after IFN-a dose reduction and ribavirin discontinuation, an end-of-treatment response was only achieved in 12 of 82 (14.6%) patients. After the follow-up period, a sustained virological response was observed in 8 of 82 (9.8%) patients. Infection with HCV genotype 3 was the only pretreatment parameter, which could predict a sustained response (HCV-1, 5%; HCV-3, 57.1%; p < 0.001). Conclusions: Despite a high initial response rate of 35.4%, sustained viral clearance was achieved only in 9.8% of the retreated primary IFN-alpha non-responders. Higher IFN-alpha induction and maintenance dose, as well as prolonged ribavirin treatment may possibly increase the virological response rates in non-responders, particularly in those infected by HCV-1