Hypoxic pulmonary vasoconstriction (HPV) rapidly and reversibly matches lung ventilation (V) and perfusion (Q), optimizing oxygen uptake and systemic oxygen delivery. HPV occurs in small pulmonary arteries (PA), which uniquely constrict to hypoxia. Although HPV is modulated by the endothelium the core mechanism of HPV resides in PA smooth muscle cells (PASMC). The PASMC's mitochondrial oxygen sensor lies within the electron transport chain (ETC) and includes NDUFS2 in ETC Complex-I. PASMC mitochondria respond to hypoxia by varying production of reactive oxygen species (ROS) and hydrogen peroxide in proportion to alveolar oxygen tension. Hypoxic ROS inhibition results in a state of reduction which triggers a redox-mediated inhibition of oxygen-sensitive, voltage-gated, potassium channels, including Kv1.5 and Kv2.1. Kv channel inhibition depolarizes the PASMC, opening of large-conductance calcium channels (CaL), elevating cytosolic calcium and activating the contractile apparatus. HPV is strongest in small PAs where sensors (hypoxia-responsive mitochondria) and effectors (oxygen-sensitive K+ channels) are enriched. Oxygenation at birth reverses fetal HPV, contributing to the rapid neonatal drop in pulmonary vascular resistance (PVR). A similar mitochon-drial-K+ channel sensor-effector mechanism exists in the ductus arteriosus (DA), however in DASMC it is oxygen-induced increases in mitochondrial ROS that inhibit DASMC K+ channels, causing DA constriction. Atelectasis and pneumonia elicit HPV, which optimises V/Q matching, increasing systemic oxygenation. Whilst HPV in response to localized hypoxia in a single lung lobe does not increase PA pressure; global airway hypoxia, as occurs with altitude or sleep apnea, causes pulmonary hypertension. HPV can be inhibited by drugs, including calcium channel blockers, or used to maintain a dry operative field during single lung anesthesia for lung surgery. HPV does not normally cause lung edema but excessive, heterogenous HPV contributes to high altitude pulmonary edema. HPV is suppressed in COVID-19 pneumonia by a SARS-CoV-2 mitochondriopathy. HPV is a component of the body's homeostatic oxygen sensing system. Keywords: Ductus arteriosus, Redox, NDUFS2, Oxygen sensitive potassium, Channels, High altitude pulmonary edema (HAPE), Mitochondrial electron transport chain, COVID-19 pneumonia, Atelectasis.

• MeSH
• arteria pulmonalis metabolismus   MeSH
• COVID-19 metabolismus   komplikace   MeSH
• homeostáza * fyziologie   MeSH
• hypoxie * metabolismus   patofyziologie   MeSH
• kyslík * metabolismus   MeSH
• lidé MeSH
• vazokonstrikce * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

IMPORTANCE: Impaired exercise capacity is a cardinal manifestation of obstructive hypertrophic cardiomyopathy (HCM). The Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic Obstructive HCM (SEQUOIA-HCM) is a pivotal study characterizing the treatment effect of aficamten, a next-in-class cardiac myosin inhibitor, on a comprehensive set of exercise performance and clinical measures. OBJECTIVE: To evaluate the effect of aficamten on exercise performance using cardiopulmonary exercise testing with a novel integrated measure of maximal and submaximal exercise performance and evaluate other exercise measures and clinical correlates. DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified analysis from SEQUOIA-HCM, a double-blind, placebo-controlled, randomized clinical trial. Patients were recruited from 101 sites in 14 countries (North America, Europe, Israel, and China). Individuals with symptomatic obstructive HCM with objective exertional intolerance (peak oxygen uptake [pVO2] ≤90% predicted) were included in the analysis. Data were analyzed from January to March 2024. INTERVENTIONS: Randomized 1:1 to aficamten (5-20 mg daily) or matching placebo for 24 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was change from baseline to week 24 in integrated exercise performance, defined as the 2-component z score of pVO2 and ventilatory efficiency throughout exercise (minute ventilation [VE]/carbon dioxide output [VCO2] slope). Response rates for achieving clinically meaningful thresholds for change in pVO2 and correlations with clinical measures of treatment effect (health status, echocardiographic/cardiac biomarkers) were also assessed. RESULTS: Among 282 randomized patients (mean [SD] age, 59.1 [12.9] years; 115 female [40.8%], 167 male [59.2%]), 263 (93.3%) had core laboratory-validated exercise testing at baseline and week 24. Integrated composite exercise performance improved in the aficamten group (mean [SD] z score, 0.17 [0.51]) from baseline to week 24, whereas the placebo group deteriorated (mean [SD] z score, -0.19 [0.45]), yielding a placebo-corrected improvement of 0.35 (95% CI, 0.25-0.46; P <.001). Further, aficamten treatment demonstrated significant improvements in total workload, circulatory power, exercise duration, heart rate reserve, peak heart rate, ventilatory efficiency, ventilatory power, and anaerobic threshold (all P <.001). In the aficamten group, large improvements (≥3.0 mL/kg per minute) in pVO2 were more common than large reductions (32% and 2%, respectively) compared with placebo (16% and 11%, respectively). Improvements in both components of the primary outcome, pVO2 and VE/VCO2 slope throughout exercise, were significantly correlated with improvements in symptom burden and hemodynamics (all P <.05). CONCLUSIONS AND RELEVANCE: This prespecified analysis of the SEQUOIA-HCM randomized clinical trial found that aficamten treatment improved a broad range of exercise performance measures. These findings offer valuable insight into the therapeutic effects of aficamten. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05186818.

• MeSH
• dvojitá slepá metoda MeSH
• hypertrofická kardiomyopatie * patofyziologie   farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• spotřeba kyslíku fyziologie   MeSH
• srdeční myosiny MeSH
• tolerance zátěže * fyziologie   MeSH
• zátěžový test * metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

• MeSH
• hodnocení rizik MeSH
• lidé MeSH
• oxid uhličitý * MeSH
• předoperační péče * metody   MeSH
• spotřeba kyslíku MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• dopisy MeSH
• komentáře MeSH
• úvodníky MeSH

BACKGROUND: Participation in cardio-oncological rehabilitation is low, and the effects incline to decrease after the initial rehabilitation term. Home-based exercise has the potential to enhance involvement in cardio-oncology rehabilitation and was demonstrated to be feasible, safe, and helpful in increasing short-term cardiorespiratory fitness. The lasting effects on cardiorespiratory fitness and physical activity are uncertain. Hence, a novel approach via telehealth management based on objectively measured exercise at home was proposed. OBJECTIVES: To improve self-monitoring, such as self-confidence, behavioral change, and goal setting for individual exercise, and afterward, increase long-term effects concerning cardiorespiratory fitness. DESIGN: This randomized controlled trial compares a 12-week guided home exercise telehealth intervention with a center-based exercise intervention of the same duration and intensity of exercise in lymphoma cancer survivors entering cardio-oncology rehabilitation after treatment. Participants will be instructed to exercise gradually at 60-85% of their maximum heart rate for 30-50 min 3 times a week. Participants will receive individual remote guidance (feedback about frequency, duration, and exercise intensity) by preferred contact (phone call, text message) once a week based on shared exercise data through the web platform. The primary outcome is a change in cardiorespiratory fitness expressed as maximal oxygen uptake assessed through cardiopulmonary exercise test at baseline, 12 weeks, and 1 year. Secondary objectives are quality of life, muscle strength, body composition, incidence of adverse events, and exercise adherence. This study will determine whether a telehealth model is effective and safe compared to a center-based model in cancer survivors and whether exercise prescriptions are followed by participants. Additionally, an overview of the long-term effectiveness of telehealth cardio-oncology rehabilitation will be provided. This approach aligns with the trend of moving non-complex healthcare services into the patients' home environment. TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT05779605.

• Publikační typ
• časopisecké články MeSH

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.

• MeSH
• aminofenoly * terapeutické užití   MeSH
• benzodioxoly * terapeutické užití   MeSH
• chinolony * terapeutické užití   MeSH
• cystická fibróza * farmakoterapie   patofyziologie   MeSH
• dítě MeSH
• fixní kombinace léků * MeSH
• indoly * terapeutické užití   MeSH
• kardiorespirační zdatnost MeSH
• lidé MeSH
• mladiství MeSH
• pilotní projekty MeSH
• prospektivní studie MeSH
• pyrazoly * terapeutické užití   MeSH
• pyridiny * terapeutické užití   MeSH
• pyrrolidiny MeSH
• pyrroly terapeutické užití   MeSH
• spotřeba kyslíku MeSH
• tolerance zátěže účinky léků   MeSH
• zátěžový test MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

BACKGROUND: One of the major determinants of exercise intolerance and limiting symptoms among patients with obstructive hypertrophic cardiomyopathy (HCM) is an elevated intracardiac pressure resulting from left ventricular outflow tract obstruction. Aficamten is an oral selective cardiac myosin inhibitor that reduces left ventricular outflow tract gradients by mitigating cardiac hypercontractility. METHODS: In this phase 3, double-blind trial, we randomly assigned adults with symptomatic obstructive HCM to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for 24 weeks, with dose adjustment based on echocardiography results. The primary end point was the change from baseline to week 24 in the peak oxygen uptake as assessed by cardiopulmonary exercise testing. The 10 prespecified secondary end points (tested hierarchically) were change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), improvement in the New York Heart Association (NYHA) functional class, change in the pressure gradient after the Valsalva maneuver, occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver, and duration of eligibility for septal reduction therapy (all assessed at week 24); change in the KCCQ-CSS, improvement in the NYHA functional class, change in the pressure gradient after the Valsalva maneuver, and occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver (all assessed at week 12); and change in the total workload as assessed by cardiopulmonary exercise testing at week 24. RESULTS: A total of 282 patients underwent randomization: 142 to the aficamten group and 140 to the placebo group. The mean age was 59.1 years, 59.2% were men, the baseline mean resting left ventricular outflow tract gradient was 55.1 mm Hg, and the baseline mean left ventricular ejection fraction was 74.8%. At 24 weeks, the mean change in the peak oxygen uptake was 1.8 ml per kilogram per minute (95% confidence interval [CI], 1.2 to 2.3) in the aficamten group and 0.0 ml per kilogram per minute (95% CI, -0.5 to 0.5) in the placebo group (least-squares mean between-group difference, 1.7 ml per kilogram per minute; 95% CI, 1.0 to 2.4; P<0.001). The results for all 10 secondary end points were significantly improved with aficamten as compared with placebo. The incidence of adverse events appeared to be similar in the two groups. CONCLUSIONS: Among patients with symptomatic obstructive HCM, treatment with aficamten resulted in a significantly greater improvement in peak oxygen uptake than placebo. (Funded by Cytokinetics; SEQUOIA-HCM ClinicalTrials.gov number, NCT05186818.).

• MeSH
• aplikace orální MeSH
• benzylaminy MeSH
• dvojitá slepá metoda MeSH
• hypertrofická kardiomyopatie * farmakoterapie   patofyziologie   MeSH
• kardiovaskulární látky * farmakologie   terapeutické užití   MeSH
• kontrakce myokardu účinky léků   fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• obstrukce výtoku ze srdeční komory farmakoterapie   patofyziologie   etiologie   MeSH
• senioři MeSH
• spotřeba kyslíku účinky léků   MeSH
• srdeční myosiny antagonisté a inhibitory   MeSH
• tolerance zátěže účinky léků   MeSH
• uracil analogy a deriváty   MeSH
• Valsalvův manévr MeSH
• zátěžový test * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

S odvoláním na práci Yanga et al. (36) se v odborném tisku objevila doporučení jak odhalit riziko náhlé srdeční příhody pomocí jednoduchého motorického testu – schopnosti provést určitý počet kliků. Uvedená studie ukázala, že vyšší počet nepřetržitě provedených kliků (40 kliků a více) je v kohortě hasičů spojen s nižším výskytem kardiovaskulárních onemocnění (KVO) ve srovnání s těmi, kteří dosáhli méně než 10 kliků. Vyšší incidence KVO u skupiny nejméně výkonných hasičů však pravděpodobně souvisela také s dalšími zdravotními problémy a naopak, vyšší silově-vytrvalostní výkonnost v prevenci KVO není tím rozhodujícím faktorem. Navržený „klikový“ test tak může sloužit jako orientační snadno proveditelný screening k odhalení ohrožených osob.

Referring to the work of Yang et al. (36) several professional sources recommended how to detect the risk of a sudden heart attack using a simple motor test – the ability to perform a certain number of push-ups. The study showed that higher baseline push-up capacity (40 push-ups and more) in the cohort of firefighters is associated with lower incidence of cardiovascular diseases (CVD) compared with those completing less then 10 push-ups. However, the higher incidence of CVD events in the group of least powerful firefighters is probably also related to other health problems, and conversely, higher strength endurance performance in the prevention of CVD diseases is not the decisive factor. The proposed push-up test can thus serve as an orientation easy-to-perform screening to detect endangered persons.

• Klíčová slova
• "test 40 kliků",
• MeSH
• hasiči MeSH
• kardiovaskulární nemoci * prevence a kontrola   MeSH
• lidé MeSH
• spotřeba kyslíku MeSH
• věkové faktory MeSH
• zátěžový test * metody   MeSH
• Check Tag
• lidé MeSH

PURPOSE: The critical force (CF) concept, differentiating steady and non-steady state conditions, extends the critical power paradigm for sport climbing. This study aimed to validate CF for finger flexors derived from the 4 min all-out test as a boundary for the highest sustainable work intensity in sport climbers. METHODS: Twelve participants underwent multiple laboratory visits. Initially, they performed the 4 min intermittent contraction all-out test for CF determination. Subsequent verification visits involved finger-flexor contractions at various intensities, including CF, CF -2 kg, CF -4 kg, and CF -6 kg, lasting for 720 s or until failure, while monitoring muscle-oxygen dynamics of forearm muscles. RESULTS: CF, determined from the mean force of last three contractions, was measured at 20.1 ± 5.7 kg, while the end-force at 16.8 ± 5.2 kg. In the verification trials, the mean time to failure at CF was 440 ± 140 s, with only one participant completing the 720 s task. When the load was continuously lowered (-2 kg, -4 kg, and -6 kg), a greater number of participants (38%, 69%, and 92%, respectively) successfully completed the 720 s task. Changes of muscle-oxygen dynamics showed a high variability and could not clearly distinguish between exhaustive and non-exhaustive trials. CONCLUSIONS: CF, based on the mean force of the last three contractions, failed to reliably predict the highest sustainable work rate. In contrast, determining CF as the end-force of the last three contractions exhibited a stronger link to sustainable work. Caution is advised in interpreting forearm muscle-oxygen dynamics, lacking sensitivity for nuanced metabolic responses during climbing-related tasks.

• MeSH
• dospělí MeSH
• horolezectví * fyziologie   MeSH
• kosterní svaly * fyziologie   MeSH
• lidé MeSH
• mladý dospělý MeSH
• prsty ruky * fyziologie   MeSH
• spotřeba kyslíku fyziologie   MeSH
• svalová kontrakce fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• validační studie MeSH

Aims This study aims to retrospectively quantify skeletal muscle mass from cardiovascular imaging studies in total cavopulmonary connection (TCPC) patients and to correlate calculated muscle mass with clinical outcomes. Materials and methods Ninety-one TCPC patients at a mean age of 24.0 ±5.5 years (37 women; 40.7%) who underwent chest computed tomography (CT) or cardiac magnetic resonance imaging (MRI) as part of their follow-up were identified in a single-center database. The cross-sectional skeletal muscle index (SMI) at the Th4 and Th12 levels was calculated from CT images, and the dorsal skeletal muscle area (SMA) at the Th12 level was measured from an MRI. Results Calculated SMI at Th12 level was 38.0 (34.5; 42.0) cm2.m-2 or 89.6 (81.9; 101.6) % of predicted values. The median follow-up from CT was 5.9 (3.1; 8.5) years, and the composite endpoint (death N=5, heart transplant N=6) was reached in a total of 11 (26.8%) patients. Patients with SMI (Th12) less than 90% of predicted values had a hazard ratio of 5.8 (95% CI: 1.2; 28.3) (p=0.03) for endpoint achievement. In the MRI group, dorsal SMA at the Th12 level was 27.6 ±5.1 cm2 in men and 20.0 ±5.8 cm2 in women. Correlations were found between SMA/kg and peak oxygen uptake (VO2 peak) (r=0.48, p=0.0005) and fat-free mass (r=0.63, p<0.0001), respectively. Conclusions A low SMI at the Th12 level was associated with a higher risk of death or cardiac transplantation. Evaluation of skeletal muscle mass using cardiovascular imaging methods allows rapid identification of individuals at risk of sarcopenia.

• Publikační typ
• časopisecké články MeSH

INTRODUCTION: The subject of this study was the creation of a new type of laboratory walking stress test for the Special Forces of the Army of the Czech Republic. This study developed a test model that has been validated in practice and that reflects the fact that the performance of endurance without and with a load varies considerably. Especially, if we focus on operators, as their activities are always performed with loads/full gear (equipment, weapons, equipment, etc.). MATERIALS AND METHODS: 24 men/operators from the Special Forces of the Army of the Czech Republic volunteered for this study. The maximal exercise test/spiroergometry was designed to include performance at a load of 55 kg/121 lb, a constant speed of 5.3 km/h, and an increase in incline angle of 1 degree after each elapsed minute. The test was performed on a treadmill under standard time, location, and temperature conditions. During the test, the following values were recorded: VO2 = oxygen consumption indicating the intensity of the exercise was monitored, VO2/kg = oxygen consumption converted to body weight, VO2/HR = pulse oxygen (the amount of oxygen converted in one heartbeat), HR = heart rate, VE = ventilation, volume of air exhaled in 1 min, breathe frequency (BF) = respiratory rate in 1 min. RESULTS: Out of the total number of 24 respondents, the study found these mean values of variables. The variable mapping the oxygen consumption, which indicates the intensity of VO2 loading, was 3.8, with the lowest value being 3.2 and the highest being 4.5. After converting oxygen consumption to bodyweight, VO2/kg was 46, the lowest value of 38.8, and the highest 53.0 were measured for this variable. Pulse oxygen, i.e., the amount of oxygen calculated per heart contraction VO2/HR, was 20.5, the lowest value 16.0, and the highest 26.0. The average HR heart rate was 183.5, with the lowest value being recorded at 164 and the highest value is 205. Ventilation, i.e., the amount of exhaled air per minute in VE, was measured at 144.9, the lowest value was 114.7, and the highest was 176.6. The BF in 1 min was 58.5, the lowest value 35, and the highest 70. The mean time load was 10:20 min, the shortest test length was 7:25 min, and the longest was 13:23 min. These values correspond to the degree of inclination of the ascent, i.e., the mean value was 10 degrees, the smallest achieved slope was 7 degrees, and the largest 13 degrees. CONCLUSION: The designed weighted walking test proved to be fully functional and effective in measurement. The further established protocol corresponds to the requirements of the current needs of the Special Forces of the Army of the Czech Republic. Last but not least, the walking stress test is applied for the external and internal selection and screening of operators. Data obtained from testing were used to develop deployment requirements for patrol/nuclear combat missions.

• MeSH
• chůze MeSH
• cvičení * fyziologie   MeSH
• kyslík MeSH
• lidé MeSH
• spotřeba kyslíku * fyziologie   MeSH
• srdeční frekvence MeSH
• zátěžový test MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH