The long-term effect of elexacaftor/tezacaftor/ivacaftor on cardiorespiratory fitness in adolescent patients with cystic fibrosis: a pilot observational study.

BACKGROUND: Physical activity is a crucial demand on cystic fibrosis treatment management. The highest value of oxygen uptake (VO2peak) is an appropriate tool to evaluate the physical activity in these patients. However, there are several other valuable CPET parameters describing exercise tolerance (Wpeak, VO2VT1, VO2VT2, VO2/HRpeak, etc.), and helping to better understand the effect of specific treatment (VE, VT, VD/VT etc.). Limited data showed ambiguous results of this improvement after CFTR modulator treatment. Elexacaftor/tezacaftor/ivacaftor medication improves pulmonary function and quality of life, whereas its effect on CPET has yet to be sufficiently demonstrated. METHODS: We performed a single group prospective observational study of 10 adolescent patients with cystic fibrosis who completed two CPET measurements between January 2019 and February 2023. During this period, elexacaftor/tezacaftor/ivacaftor treatment was initiated in all of them. The first CPET at the baseline was followed by controlled CPET at least one year after medication commencement. We focused on interpreting the data on their influence by the novel therapy. We hypothesized improvements in cardiorespiratory fitness following treatment. We applied the Wilcoxon signed-rank test. The data were adjusted for age at the time of CPET to eliminate bias of aging in adolescent patients. RESULTS: We observed significant improvement in peak workload, VO2 peak, VO2VT1, VO2VT2, VE/VCO2 slope, VE, VT, RQ, VO2/HR peak and RR peak. The mean change in VO2 peak was 5.7 mL/kg/min, or 15.9% of the reference value (SD ± 16.6; p= 0.014). VO2VT1 improved by 15% of the reference value (SD ± 0.1; p= 0.014), VO2VT2 improved by 0.5 (SD ± 0.4; p= 0.01). There were no differences in other parameters. CONCLUSION: Exercise tolerance improved after elexacaftor/tezacaftor/ivacaftor treatment initiation. We suggest that the CFTR modulator alone is not enough for recovering physical decondition, but should be supplemented with physical activity and respiratory physiotherapy. Further studies are needed to examine the effect of CFTR modulators and physical therapy on cardiopulmonary exercise tolerance.

Association of anthropometric and body composition parameters with the presence of hypertension in the Central European population: results from KardioVize 2030 study.

BACKGROUND: Hypertension is one of the most prevalent chronic non-communicable diseases and affects more than 60% of individuals over 60 years of age. Additionally, hypertension is a prominent risk factor for the development of cardiovascular diseases (CVDs). Human body composition is both the result and predictor of an individual's health status, and hypertension has consistently been shown to be more prevalent among obese individuals. In the current study, we focussed on the association between body composition parameters and hypertension occurrence. METHODS: Data from KardioVize 2030, a population-based study (n = 1988), was used to determine the association between the body composition parameters related to both fat and water content with hypertension. Body composition was assessed using the direct segmental multi-frequency bioelectrical impedance analysis method (DSM-BIA). RESULTS: Using logistic regression modelling we found that the majority of hypertension incidence could be determined by body fat and water content, as hypertension occurrence was positively correlated with increased fat-related body composition parameters and water content. Specifically, results from this study demonstrate that increased intracellular fluid was positively associated with higher hypertension incidence in men (14%) and women (16%). CONCLUSION: Body composition reflects the occurrence of hypertension and may serve as a novel therapeutic goal that can be easily implemented in the clinical setting using DSM-BIA.

The risk of post-operative pulmonary complications in lung resection candidates with normal forced expiratory volume in 1 s and diffusing capacity of the lung for carbon monoxide: a prospective multicentre study.

Introduction: According to the guidelines for preoperative assessment of lung resection candidates, patients with normal forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lung for carbon monoxide (D LCO) are at low risk for post-operative pulmonary complications (PPC). However, PPC affect hospital length of stay and related healthcare costs. We aimed to assess risk of PPC for lung resection candidates with normal FEV1 and D LCO (>80% predicted) and identify factors associated with PPC. Methods: 398 patients were prospectively studied at two centres between 2017 and 2021. PPC were recorded from the first 30 post-operative days. Subgroups of patients with and without PPC were compared and factors with significant difference were analysed by uni- and multivariate logistic regression. Results: 188 subjects had normal FEV1 and D LCO. Of these, 17 patients (9%) developed PPC. Patients with PPC had significantly lower pressure of end-tidal carbon dioxide (P ETCO2 ) at rest (27.7 versus 29.9; p=0.033) and higher ventilatory efficiency (V'E/V'CO2 ) slope (31.1 versus 28; p=0.016) compared to those without PPC. Multivariate models showed association between resting P ETCO2 (OR 0.872; p=0.035) and V'E/V'CO2 slope (OR 1.116; p=0.03) and PPC. In both models, thoracotomy was strongly associated with PPC (OR 6.419; p=0.005 and OR 5.884; p=0.007, respectively). Peak oxygen consumption failed to predict PPC (p=0.917). Conclusions: Resting P ETCO2 adds incremental information for risk prediction of PPC in patients with normal FEV1 and D LCO. We propose resting P ETCO2 be an additional parameter to FEV1 and D LCO for preoperative risk stratification.

Prediction of Postoperative Complications: Ventilatory Efficiency and Rest End-tidal Carbon Dioxide.

BACKGROUND: Cardiopulmonary exercise testing parameters including ventilatory efficiency (VE/VCO2 slope) are used for risk assessment of lung resection candidates. However, many patients are unable or unwilling to undergo exercise. VE/VCO2 slope is closely related to the partial pressure of end-tidal carbon dioxide (PETCO2). We hypothesized PETCO2 at rest predicts postoperative pulmonary complications. METHODS: Consecutive lung resection candidates were included in this prospective multicenter study. Postoperative respiratory complications were assessed from the first 30 postoperative days or from the hospital stay. Student t test or Mann-Whitney U test was used for comparison. Multivariate stepwise logistic regression analysis was used to analyze association with the development of postoperative pulmonary complications. The De Long test was used to compare area under the curve (AUC). Data are summarized as median (interquartile range). RESULTS: Three hundred fifty-three patients were analyzed, of which 59 (17%) developed postoperative pulmonary complications. PETCO2 at rest was significantly lower (27 [24-30] vs 29 [26-32] mm Hg; P < .01) and VE/VCO2 slope during exercise significantly higher (35 [30-40] vs 29 [25-33]; P < .01) in patients who developed postoperative pulmonary complications. Both rest PETCO2 with odds ratio 0.90 (95% confidence interval [CI] 0.83-0.97); P = .01 and VE/VCO2 slope with odds ratio 1.10 (95% CI 1.05-1.16); P < .01 were independently associated with postoperative pulmonary complications by multivariate stepwise logistic regression analysis. There was no significant difference between AUC of both models (rest PETCO2: AUC = 0.79 (95% CI 0.74-0.85); VE/VCO2 slope: AUC = 0.81 (95% CI 0.75-0.86); P = .48). CONCLUSIONS: PETCO2 at rest has similar prognostic utility as VE/VCO2 slope, suggesting rest PETCO2 may be used for postoperative pulmonary complications prediction in lung resection candidates.

Ventilatory efficiency is superior to peak oxygen uptake for prediction of lung resection cardiovascular complications.

INTRODUCTION: Ventilatory efficiency (VE/VCO2 slope) has been shown superior to peak oxygen consumption (VO2) for prediction of post-operative pulmonary complications in patients undergoing thoracotomy. VE/VCO2 slope is determined by ventilatory drive and ventilation/perfusion mismatch whereas VO2 is related to cardiac output and arteriovenous oxygen difference. We hypothesized pre-operative VO2 predicts post-operative cardiovascular complications in patients undergoing lung resection. METHODS: Lung resection candidates from a published study were evaluated by post-hoc analysis. All of the patients underwent preoperative cardiopulmonary exercise testing. Post-operative cardiovascular complications were assessed during the first 30 post-operative days or hospital stay. One-way analysis of variance or the Kruskal-Wallis test, and multivariate logistic regression were used for statistical analysis and data summarized as median (IQR). RESULTS: Of 353 subjects, 30 (9%) developed pulmonary complications only (excluded from further analysis), while 78 subjects (22%) developed cardiovascular complications and were divided into two groups for analysis: cardiovascular only (n = 49) and cardiovascular with pulmonary complications (n = 29). Compared to patients without complications (n = 245), peak VO2 was significantly lower in the cardiovascular with pulmonary complications group [19.9 ml/kg/min (16.5-25) vs. 16.3 ml/kg/min (15-20.3); P<0.01] but not in the cardiovascular only complications group [19.9 ml/kg/min (16.5-25) vs 19.0 ml/kg/min (16-23.1); P = 0.18]. In contrast, VE/VCO2 slope was significantly higher in both cardiovascular only [29 (25-33) vs. 31 (27-37); P = 0.05] and cardiovascular with pulmonary complication groups [29 (25-33) vs. 37 (34-42); P<0.01)]. Logistic regression analysis showed VE/VCO2 slope [OR = 1.06; 95%CI (1.01-1.11); P = 0.01; AUC = 0.74], but not peak VO2 to be independently associated with post-operative cardiovascular complications. CONCLUSION: VE/VCO2 slope is superior to peak VO2 for prediction of post-operative cardiovascular complications in lung resection candidates.

Poor ventilatory efficiency during exercise may predict prolonged air leak after pulmonary lobectomy.

Poor ventilatory efficiency, defined as the increase in minute ventilation relative to carbon dioxide production during exercise (VE/VCO2 slope), may be associated with dynamic hyperinflation and thereby promote the development of prolonged air leak (PAL) after lung resection. Consecutive lung lobectomy candidates (n = 96) were recruited for this prospective two-centre study. All subjects underwent pulmonary function tests and cardiopulmonary exercise testing prior to surgery. PAL was defined as the presence of air leaks from the chest tube on the 5th postoperative day and developed in 28 (29%) subjects. Subjects with PAL were not different in terms of age, sex, American Society of Anesthesiologists class, type of surgery (thoracotomy/video-assisted thoracoscopic surgery) and site of surgery (right/left lung; upper/lower lobes). Subjects with PAL had more frequent pleural adhesions (50% vs 21%; P = 0.006) and steeper VE/VCO2 slope (35 ± 7 vs 30 ± 5; P = 0.001). Stepwise logistic regression showed that only the presence of pleural adhesions [odds ratio (OR) 3.9, 95% confidence interval (CI) 1.4-10.9; P = 0.008] and VE/VCO2 slope (OR 1.1, 95% CI 1.0-1.2; P = 0.003) were independently associated with PAL (AUC 0.74, 95% CI 0.62-0.86). We conclude that a high VE/VCO2 slope during exercise may be helpful in identifying patients at greater risk for the development of PAL after lung lobectomy. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT03498352.

Ventilatory Efficiency Identifies Patients Prone to Hypoxemia During One-Lung Ventilation.

OBJECTIVES: One-lung ventilation (OLV) may be complicated by hypoxemia. Ventilatory efficiency, defined as the ratio of minute ventilation to carbon dioxide output (VE/VCO2), is increased with ventilation/perfusion mismatch and pulmonary artery hypertension, both of which may be associated with hypoxemia. Hence, the authors hypothesized increased VE/VCO2 will predict hypoxemia during OLV. DESIGN: Prospective observational study. SETTING: Single-center, university, tertiary care hospital. PARTICIPANTS: The study comprised 50 consecutive lung resection candidates. INTERVENTIONS: All patients underwent cardiopulmonary exercise testing before surgery. Patients who required inspired oxygen fraction (FiO2) ≥0.7 to maintain arterial oxygen (O2) saturation >90% after 30 minutes of OLV were considered to be hypoxemic. The Student t or Mann-Whitney U test were used for comparison of patients who became hypoxemic and those who did not. Multiple regression analysis adjusted for age, sex, and body mass index was used to evaluate which parameters were associated with the VE/VCO2 slope. Data are summarized as mean ± standard deviation. MEASUREMENTS AND MAIN RESULTS: Twenty-four patients (48%) developed hypoxemia. There was no significant difference in age, sex, and body mass index between hypoxemic and nonhypoxemic patients. However, patients with hypoxemia had a significantly higher VE/VCO2 slope (30 ± 5 v 27 ± 4; p = 0.04) with exercise and lower partial pressure of oxygen/FiO2 (129 ± 92 v 168 ± 88; p = 0.01), higher mean positive end-expiratory pressure (6.6 ± 1.5 v 5.6 ± 0.9 cmH2O; p = 0.02), and lower mean pulse oximetry O2 saturation/FiO2 index (127 ± 20 v 174 ± 17; p < 0.01) during OLV. Multiple regression showed VE/VCO2 to be independently associated with the mean pulse oximetry O2 saturation/FiO2 index (b = -0.28; F = 3.1; p = 0.05). CONCLUSIONS: An increased VE/VCO2 slope may predict hypoxemia development in patients who undergo OLV.

[Irregular breathing during the cardiopulmonary exercise test - from mildly irregular breathing pattern to periodic breathing of oscillatory ventilation type]. / Nepravidelnosti dýchání pri spiroergometrickém vysetrení - od mírné nepravidelnosti dechového vzoru az po periodické dýchání typu oscilující ventilace.

The fluctuating course of tidal volume (VT), breathing frequency (DF) and minute ventilation (VE) during the cardio-pulmonary exercise test using a ramp incremental protocol occurs not only in patients, but relatively frequently also in healthy individuals. It can account for a number of irregularities in the course of the curves VO2, VCO2 and in particular of those of ventilatory equivalents for O2 and CO2 (EQO2, EQCO2) as well as curves of partial pressure of end-tidal oxygen and partial pressure of end-tidal carbon dioxide (PETO2, PETCO2), which are also used, inter alia, to establish ventilatory thresholds. The presence of exercise oscillatory ventilation (EOV) reflects the severity of heart failure and it is an independent predictor of the increased morbidity, cardiac and total mortality and sudden death caused by heart failure. However there is not a generally accepted universal definition of EOV available at present, as different criteria are used. We have not found a comparison which would indicate whether and how the "strength" of the prognostic criteria for EOV - established according to different methods - differs. Therefore it is very important to specify what method, or what criteria were used in the establishment of EOV.Key words: breathing pattern - EOV - exercise oscillatory ventilation - periodic breathing.

[An assessment of VO2 kinetics in the recovery phase of cardiopulmonary exercise test in patients with heart disease - importance and classification]. / Vyhodnocení kinetiky VO2 v zotavovací fázi spiroergometrického vysetrení u kardiologicky nemocných - význam a klasifikace.

The article reviews the course of VO2 in the phase of recovery kinetics of oxygen uptake (VO2rec) cardiopulmonary exercise test. VO2rec kinetics cannot be completely defined using a single parameter. The article describes the three most frequently used methods: %VO2-REC2, T1/2 VO2rec and TC VO2, and provides detailed procedures of their analysis. The three aforementioned parameters are also at the heart of our classification of VO2rec. The method %VO2-REC2 is an essential one, in our view, since its prognostic significance is proven and it can be also easily applied only based on a data record of the cardiopulmonary exercise test. %VO2-REC2 should be seen, together with VO2peak, VE/VCO2 slope and exercise oscillatory ventilation (EOV) - as one of the four elementary prognostic markers establishing an advanced chronic heart failure.Key words: cardiopulmonary exercise test - chronic heart failure - prognosis - recovery kinetics of oxygen uptake.

Resting End-Tidal Carbon Dioxide Predicts Respiratory Complications in Patients Undergoing Thoracic Surgical Procedures.

BACKGROUND: Ventilatory efficiency (V˙e/V˙co2 slope [minute ventilation to carbon dioxide output slope]) has been shown to predict morbidity and mortality in lung resection candidates. Patients with increased V˙e/V˙co2 during exercise also exhibit an increased V˙e/V˙co2 ratio and a decreased end-tidal CO2 at rest. This study hypothesized that ventilatory values at rest predict respiratory complications and death in patients undergoing thoracic surgical procedures. METHODS: Inclusion criteria for this retrospective, multicenter study were thoracotomy and cardiopulmonary exercise testing as part of routine preoperative assessment. Respiratory complications were assessed from the medical records (from the hospital stay or from the first 30 postoperative days). For comparisons, Student's t test or the Mann-Whitney U test was used. Logistic regression and receiver operating characteristic analyses were performed for evaluation of measurements associated with respiratory complications. Data are summarized as mean ± SD; p <0.05 is considered significant. RESULTS: Seventy-six subjects were studied. Postoperatively, respiratory complications developed in 56 (74%) patients. Patients with postoperative respiratory complications had significantly lower resting tidal volume (0.8 ± 0.3 vs 0.9 ± 0.3L; p = 0.03), lower rest end-tidal CO2 (28.1 ± 4.3vs 31.5 ± 4.2 mm Hg; p < 0.01), higher resting V˙e/V˙co2 ratio (45.1 ± 7.1 vs 41.0 ± 6.4; p = 0.02), and higher V˙e/V˙co2 slope (34.9 ± 6.4 vs 31.2 ± 4.3; p = 0.01). Logistic regression (age and sex adjusted) showed resting end-tidal CO2 to be the best predictor of respiratory complications (odds ratio: 1.21; 95% confidence interval: 1.06 to 1.39; area under the curve: 0.77; p = 0.01). CONCLUSIONS: Resting end-tidal CO2 may identify patients at increased risk for postoperative respiratory complications of thoracic surgical procedures.

Histopathology Image Analysis in Two Long-Term Animal Experiments with Helical Flow Total Artificial Heart.

Histopathological analysis can provide important information in long-term experiments with total artificial heart (TAH). Recently, a new type of blood pump, the helical flow total artificial heart (HF-TAH) was developed. This study aimed to investigate the changes in selected vital organs in animal experiments with implanted HF-TAH. Samples from lung, liver, and kidneys from two female goats (No. 1301 and No. 1304) with implanted HF-TAH were analyzed. Tissue samples were fixed in 10% formaldehyde and 4 µm thick transverse sections were stained with hematoxylin-eosin (HE). Additional staining was done for detection of connective tissue (Masson-Goldner stain) and for detection of iron (hemosiderin) deposits (Perls stain). Sections were scanned at 100× and 500× magnification with a light microscope. Experiment no. 1301 survived 100 days (cause of termination was heavy damage of the right pump); experimental goat no.1304 survived 68 days and was sacrificed due to severe right hydrodynamic bearing malfunction. Histopathological analysis of liver samples proved signs of chronic venostasis with limited focal necrotic zones. Dilated tubules, proteinaceous material in tubular lumen, and hemosiderin deposits were detected in kidney samples. Contamination of the organs by embolized micro-particles was suspected at the autopsy after discovery of visible damage (scratches) of the pump impeller surface (made from titanium alloy) in both experiments. Sporadic deposits of foreign micro-particles (presumably titanium) were observed in most of the analyzed parenchymal organs. However, the described deposits were not in direct connection with inflammatory reactions in the analyzed tissues. Histopathological analysis showed the presence of minimal contamination of the lung, kidney, and liver tissue samples by foreign material (titanium very likely). The analysis showed only limited pathological changes, especially in liver and kidneys, which might be attributed to the influence of artificial perfusion often observed in chronic TAH experiments.

Chronobiological changes in arterial blood pressure in participants of the 5th and 6th Czech Antarctic Scientific Expeditions.

OBJECTIVE: To evaluate potential changes in arterial blood pressure (ABP) and heart rate (HR) during a 2-month stay in Antarctica, using chronobiological analysis. METHODS: An observational study performed at Mendel research base, Antarctica, during 2011 and 2012. The studied group consisted of 24 participants of the 5th and 6th Czech Antarctic Scientific Expeditions. Three series of 24-hour ABP monitoring were performed, of these two in Antarctica and one in the Czech Republic. Chronobiological analyses of the data were performed (Halberg Chronobiology Center, Minnesota) using population-mean cosinor. The values of MESOR (Midline Estimating Statistic Of Rhythm), double amplitude and the acrophase were obtained for SBP (Systolic Blood Pressure), DBP (Diastolic Blood Pressure) and HR. These rhythm characteristics were compared between the two locations by parameter tests and by the paired t-test. RESULTS: On the average, the MESORs of SBP, DBP and HR were significantly higher in Antarctica than in the Czech Republic, as were the double amplitudes of the 12-hour component of SBP and DBP. High prevalence of CHAT (Circadian Hyper-Amplitude-Tension) was detected in Antarctica (8/24 = 33%); only 2 persons had CHAT in the Czech Republic (χ²=3.945, p=0.047). CONCLUSIONS: A prolonged stay in Antarctica clearly affected certain chronobiological parameters of ABP and HR.

Exercise training combined with electromyostimulation in the rehabilitation of patients with chronic heart failure: A randomized trial.

AIM: Both aerobic training (AT) and electromyostimulation (EMS) of leg muscles improve exercise tolerance in patients suffering from chronic heart failure (CHF). It was speculated that combination of both methods might have an additive effect. This study was performed to evaluate the effects of a combination of AT and EMS in rehabilitation (RHB) of CHF patients. PATIENTS AND METHODS: Patients (n=71; age 59 ± 10.2 yrs, NYHA II/III, EF 32 ± 7.1%) were randomized into 3 groups: a) group AT, b) group EMS, and c) group AT+EMS. AT protocol included standard activity on bicycle 3x a week at the level of individual anaerobic threshold. EMS (10 Hz, mode 20s "on"/20s "off") was applied to leg extensors for 2 h/day. Total time of given type of RHB was 12 weeks. RESULTS: Data analysis revealed statistically significant improvements of patients in all experimental groups (averaged difference after 12 weeks of exercise as related to initial value: ∆VO2peak: +12.9%, ∆VO2AT: +9.3%, ∆Wpeak: +22.7%). No statistically significant difference among experimental groups was found. Quality of life (Minnesota Living with Heart Failure - MLHF) global score was significantly improved in all 3 groups: AT (∆MLHF: -27.9%; P=0.001), AT+EMS (∆MLHF: -29.1%; P=0.002), and EMS (∆MLHF: -16.6%; P=0.008). MLHF score in EMS group showed the smallest time-related improvement compared to AT and AT+EMS groups, and this difference in improvement between the groups was statistically significant (P=0.021). CONCLUSION: No significant difference was found between the two types of exercise training.and nor did, their combination have any significant additional improvement.

Effects of neuromuscular electrical stimulation and aerobic exercise training on arterial stiffness and autonomic functions in patients with chronic heart failure.

Neuromuscular electrical stimulation (NMES) of leg muscles has been introduced in clinical practice as a rehabilitation (RHB) method in patients with chronic heart failure (CHF); however, the role of NMES on the reduction of arterial stiffness and autonomic disbalance in these patients has not yet been studied. Sixty-one patients with stable CHF (mean age 58.9 [2.1] years; mean ejection fraction 31 [4.2]%, New York Heart Association II-III) were randomly assigned into two groups. Patients in (i) exercise training group (ET; n = 30) underwent 12 weeks of bicycle ET (3 × 40 min/week); (ii) group NMES (n = 31) performed 12 weeks of NMES of quadriceps and calf muscles (frequency 10 Hz, mode "20 s on-20 s off," intensity 60 mA), 2 × 60 min/day. Noninvasive assessment of arterial stiffness was done using the cardio-ankle vascular index (CAVI). CAVI and heart rate variability (HRV) and ·VO(2peak) were evaluated before and after RHB program. Both types of RHB reduced significantly CAVI (ET from 9.6 [0.2] to 8.9 [0.2], P < 0.012; NMES from 9.3 [0.2] to 8.7 [0.2], P < 0.013), increased high frequency (HF) component of HRV (+65.6%; P = 0.001) and decreased ratio of low frequency (LF) component with HF component (LF/HF ratio) in group ET (-39.8%; P < 0.001). Changes of HRV parameters in group NMES were not significant; however, a marked tendency to autonomic stabilization was present. Both types of RHB led also to significant increase of ·VO(2peak) (ET from 18.7 [0.7] to 20.8 [0.7] mL/kg/min, P < 0.004; NMES from 17.3 [0.7] to 19.0 [0.7] mL/kg/min, P < 0.001). ET or NMES has been shown to improve significantly arterial stiffness and to stabilize autonomic balance.

Intra-dialytic electrostimulation of leg extensors may improve exercise tolerance and quality of life in hemodialyzed patients.

Hemodialyzed (HD) patients with end-stage renal disease (ESRD) exhibit lower fitness as a consequence of chronic uremic changes that trigger various structural, metabolic, and functional abnormalities in skeletal muscles. The aim of this randomized study was to compare the effect of rehabilitation (RHB) training on a bicycle ergometer and electromyostimulation (EMS) of leg extensors in HD patients with ESRD. Thirty-two HD patients (18 men/14 women; mean age 61.1 ± 8.8 years) were randomized into three groups: (i) exercise training (ET; n = 11) on bicycle ergometer 2 × 20 min; (ii) EMS (n = 11) where stimulation (10 Hz) of leg extensors was applied for 60 min; and (iii) controls (CON; n = 10) without exercise. Exercising was performed between the 2nd and the 3rd hour of HD, three times a week, 20 weeks in total. Ergometric test was performed in order to evaluate peak workload (W(peak)), 6-min corridor walking test (CWT) to evaluate the distance walked, and dynamometry of leg extensors to assess muscle power (F(max)). Urea clearance was monitored and expressed as standard parameters: spKt/V, spKt/V equilibrated (spKt/V-e), and the urea removal ratio (URR). Quality of life (QoL) was assessed by the questionnaire SF-36. A significant increase of F(max) (P = 0.040 in group ET; P = 0.032 in group EMS), of 6-min CWT (P < 0.001 in ET group; P = 0.042 in EMS group), and of W(peak) (P = 0.041 in ET group) was observed. In both exercising groups, significant increase of spKt/V, spKt/V-e, and URR was found as compared with initial values (P < 0.05). In both exercising groups, highly significant changes in summarized mental functions were found (P = 0.001); in summarized physical components, significant improvement was observed in the ET group (P = 0.006). Intradialytic RHB showed comparable positive effects on functional parameters, urea clearance, and QoL. Intradialytic EMS might represent wide therapeutic possibility in the near future.

Home C-ABPM for Preventive and Curative Health Care and Transdisciplinary Science.

The clinical everyday management of blood pressure (BP) and heart rate (HR) can be greatly improved by the mapping of time structures in home ambulatory BP and HR assessment. Thereby, we change focus from the BP and the HR to the dynamics of these variables. This change is achieved by computer-implemented chronomics, the mapping of chronomes, consisting of cyclicities (our concern herein) along with chaos and trends, in the service of cardiologists, general health care providers, the educated public, and transdisciplinary science. We here further illustrate the yield of chronomics in research on long BP and HR series covering years, some several decades long, and on archives of human sudden cardiac death revealing magnetoperiodisms, e.g., "years" longer than a calendar year, i.e., transyears. In this case of cardiac arrest, what we do not see, the 16- to 20-month transyear is prominent, in the absence of any signature of the calendar year, and so can be a cis-half-year of about 5 months.

Chronoastrobiology: proposal, nine conferences, heliogeomagnetics, transyears, near-weeks, near-decades, phylogenetic and ontogenetic memories.

"Chronoastrobiology: are we at the threshold of a new science? Is there a critical mass for scientific research?" A simple photograph of the planet earth from outer space was one of the greatest contributions of space exploration. It drove home in a glance that human survival depends upon the wobbly dynamics in a thin and fragile skin of water and gas that covers a small globe in a mostly cold and vast universe. This image raised the stakes in understanding our place in that universe, in finding out where we came from and in choosing a path for survival. Since that landmark photograph was taken, new astronomical and biomedical information and growing computer power have been revealing that organic life, including human life, is and has been connected to invisible (non-photic) forces, in that vast universe in some surprising ways. Every cell in our body is bathed in an external and internal environment of fluctuating magnetism. It is becoming clear that the fluctuations are primarily caused by an intimate and systematic interplay between forces within the bowels of the earth--which the great physician and father of magnetism William Gilbert called a 'small magnet'--and the thermonuclear turbulence within the sun, an enormously larger magnet than the earth, acting upon organisms, which are minuscule magnets. It follows and is also increasingly apparent that these external fluctuations in magnetic fields can affect virtually every circuit in the biological machinery to a lesser or greater degree, depending both on the particular biological system and on the particular properties of the magnetic fluctuations. The development of high technology instruments and computer power, already used to visualize the human heart and brain, is furthermore making it obvious that there is a statistically predictable time structure to the fluctuations in the sun's thermonuclear turbulence and thus to its magnetic interactions with the earth's own magnetic field and hence a time structure to the magnetic fields in organisms. Likewise in humans, and in at least those other species that have been studied, computer power has enabled us to discover statistically defined endogenous physiological rhythms and further direct effects that are associated with these invisible geo- and heliomagnetic cycles. Thus, what once might have been dismissed as noise in both magnetic and physiological data does in fact have structure. And we may be at the threshold of understanding the biological and medical meaning and consequences of these patterns and biological-astronomical linkages as well. Structures in time are called chronomes; their mapping in us and around us is called chronomics. The scientific study of chronomes is chronobiology. And the scientific study of all aspects of biology related to the cosmos has been called astrobiology. Hence we may dub the new study of time structures in biology with regard to influences from cosmo- helio- and geomagnetic rhythms chronoastrobiology. It has, of course, been understood for centuries that the movements of the earth in relation to the sun produce seasonal and daily cycles in light energy and that these have had profound effects on the evolution of life. It is now emerging that rhythmic events generated from within the sun itself, as a large turbulent magnet in its own right, can have direct effects upon life on earth. Moreover, comparative studies of diverse species indicate that there have also been ancient evolutionary effects shaping the endogenous chronomic physiological characteristics of life. Thus the rhythms of the sun can affect us not only directly, but also indirectly through the chronomic patterns that solar magnetic rhythms have created within our physiology in the remote past. For example, we can document the direct exogenous effects of given specific solar wind events upon human blood pressure and heart rate. We also have evidence of endogenous internal rhythms in blood pressure and heart rate that are close to but not identical to the period length of rhythms in the solar wind. These were installed genetically by natural selection at some time in the distant geological past. This interpretive model of the data makes the prediction that the internal and external influences on heart rate and blood pressure can reinforce or cancel each other out at different times. A study of extensive clinical and physiological data shows that the interpretive model is robust and that internal and external effects are indeed augmentative at a statistically significant level. Chronoastrobiological studies are contributing to basic science--that is, our understanding is being expanded as we recognize heretofore unelaborated linkages of life to the complex dynamics of the sun, and even to heretofore unelaborated evolutionary phenomena. Once, one might have thought of solar storms as mere transient 'perturbations' to biology, with no lasting importance. Now we are on the brink of understanding that solar turbulences have played a role in shaping endogenous physiological chronomes. There is even documentation for correlations between solar magnetic cycles and psychological swings, eras of belligerence and of certain expressions of sacred or religious feelings. Chronoastrobiology can surely contribute to practical applications as well as to basic science. It can help develop refinements in our ability to live safely in outer space, where for example at the distance of the moon the magnetic influences of the sun will have an effect upon humans unshielded by the earth's native magnetic field. We should be better able to understand these influences as physiological and mechanical challenges, and to improve our estimations of the effects of exposure. Chronoastrobiology moreover holds great promise in broadening our perspectives and powers in medicine and public health right here upon the surface of the earth. Even the potential relevance of chronoastrobiology for practical environmental and agricultural challenges cannot be ruled out at this early stage in our understanding of the apparently ubiquitous effects of magnetism and hence perhaps of solar magnetism on life. The evidence already mentioned that fluctuations in solar magnetism can influence gross clinical phenomena such as rates of strokes and heart attacks, and related cardiovascular variables such as blood pressure and heart rate, should illustrate the point that the door is open to broad studies of clinical implications. The medical value of better understanding magnetic fluctuations as sources of variability in human physiology falls into several categories: 1) The design of improved analytical and experimental controls in medical research. Epidemiological analyses require that the multiple sources causing variability in physiological functions and clinical phenomena be identified and understood as thoroughly as possible, in order to estimate systematic alterations of any one variable. 2) Preventive medicine and the individual patients'care. There are no flat 'baselines', only reference chronomes. Magnetic fluctuations can be shown statistically to exacerbate health problems in some cases. The next step should be to determine whether vulnerable individuals can be identified by individual monitoring. Such vulnerable patients may then discover that they have the option to avoid circumstances associated with anxiety during solar storms, and/or pay special attention to their medication or other treatments. Prehabilitation by self-help can hopefully complement and eventually replace much costly rehabilitation. 3) Basic understanding of human physiological mechanisms. The chronomic organization of physiology implies a much more subtle dynamic integration of functions than is generally appreciated. All three categories of medical value in turn pertain to the challenges for space science of exploring and colonizing the solar system. The earth's native magnetic field acts like an enormous umbrella that offers considerable protection on the surface from harsh solar winds of charged particles and magnetic fluxes. The umbrella becomes weaker with distance from the earth and will offer little protection for humans, other animals, and plants in colonies on the surface of the moon or beyond. Thus it is important before more distant colonization is planned or implemented to better understand those magnetism-related biological- solar interactions that now can be studied conveniently on earth. (ABSTRACT TRUNCATED)

Engineering and governmental challenge: 7-day/24-hour chronobiologic blood pressure and heart rate screening: Part I.

This review provides evidence that the bioengineering community needs to develop cost-effective, fully unobtrusive, truly ambulatory instrumentation for the surveillance of blood pressure and heart rate. With available instrumentation, we document a disease risk syndrome, circadian blood pressure overswinging (CHAT, short for circadian hyper-amplitude-tension). Circadian hyper-amplitude-tension is defined as a week-long overall increase in the circadian amplitude or otherwise-measured circadian variability of blood pressure above a mapped threshold, corresponding to the upper 95% prediction limit of clinically healthy peers of the corresponding gender and age. A consistently reduced heart rate variability, gauged by a circadian standard deviation below the lower 5% prediction limit of peers of the corresponding gender and age, is an index of a separate yet additive major risk, a deficient heart rate variability (DHRV). The circadian amplitude, a measure of the extent of reproducible variability within a day, is obtained by linear curve-fitting, which yields added parameters: a midline-estimating statistic of rhythm, the MESOR (a time structure or chronome-adjusted mean), the circadian acrophase, a measure of timing of overall high values recurring in each cycle, and the amplitudes and acrophases of the 12-hour (and higher order) harmonic(s) of the circadian variation that, with the characteristics of the fundamental 24-hour component, describe the circadian waveform. The MESOR is a more precise and more accurate estimate of location than the arithmetic mean. The major risks associated with CHAT and/or DHRV have been documented by measurements of blood pressure and heart rate at 1-hour or shorter intervals for 48 hours on populations of several hundred people, but these risks are to be assessed in a 7-day/24-hour record in individuals before a physical examination, for the following reasons. (1) The average derived from an around-the-clock series of blood pressure measurements, computed as its MESOR, the proven etiopathogenetic factor of catastrophic vascular disease, can be above chronobiologic as well as World Health Organization limits for 5 days or longer and can be satisfactory for months thereafter, as validated by continued automatic monitoring. The MESOR can be interpreted in light of clock-hour-, gender-, and age-specified reference limits and thus can be more reliably estimated with a systematic account of major sources of variability than by casual time-unspecified spot checks (that conventionally are interpreted by a fixed and, thus, rhythm, gender-, and age-ignoring limit). With spot checks, in a diagnostically critical range of "borderline" blood pressures, an inference can depend on the clock-hour of the measurement, usually providing a diagnosis of normotension in the morning and of hypertension in the afternoon (for the same diurnally active, nocturnally resting patient!). Long-term treatment must not be based upon the possibility of an afternoon vs a morning appointment. Moreover, the conventional approach will necessarily miss cases of CHAT that are not accompanied by MESOR hypertension. (2) Circadian hyper-amplitude-tension indicates a greater risk for stroke than does an increase in the around-the-clock average blood pressure (above 130/80 mm Hg) or old age, whereas (3) CHAT can be asymptomatic, as can MESOR hyptertension. (4) Deficient heart rate variability, the fall below a threshold of the circadian standard deviation of heart rate, an entity in its own right, is also a chronome alteration of heart rate variability (CAHRV). Deficient heart rate variability can be present together with CHAT, doubling the relative risk of morbid events. In each case--either combined with CHAT or as an isolated CAHRV--a DHRV constitutes an independent diagnostic assessment provided as a dividend by current blood pressure monitors that should be kept in future instrumentation designs. CHAT and DHRV can be screened by systematic focus on variability, preferably by the use of automatic instrumentation and analyses, which are both available (affordably) for research in actual practice, in conjunction with the Halberg Chronobiology Center at the University of Minnesota.