BACKGROUND: Patients with severe aortic stenosis present frequently (∼50%) with concomitant obstructive coronary artery disease. Current guidelines recommend combined surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) as the preferred treatment. Transcatheter aortic valve implantation (TAVI) and fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) represent a valid treatment alternative. We aimed to test the non-inferiority of FFR-guided PCI plus TAVI versus SAVR plus CABG in patients with severe aortic stenosis and complex coronary artery disease. METHODS: This international, multicentre, prospective, open-label, non-inferiority, randomised controlled trial was conducted at 18 tertiary medical centres across Europe. Patients (aged ≥70 years) with severe aortic stenosis and complex coronary artery disease, deemed feasible for percutaneous or surgical treatment according to the on-site Heart Team, were randomly assigned (1:1) to FFR-guided PCI plus TAVI or SAVR plus CABG according to a computer-generated sequence with random permuted blocks sizes stratified by site. The primary endpoint was a composite of all-cause mortality, myocardial infarction, disabling stroke, clinically driven target-vessel revascularisation, valve reintervention, and life-threatening or disabling bleeding at 1 year post-treatment. The trial was powered for non-inferiority (with a margin of 15%) and if met, for superiority. The primary and safety analyses were done per an intention-to-treat principle. This trial is registered with ClinicalTrials.gov (NCT03424941) and is closed. FINDINGS: Between May 31, 2018, and June 30, 2023, 172 patients were enrolled, of whom 91 were assigned to the FFR-guided PCI plus TAVI group and 81 to the SAVR plus CABG group. The mean age of patients was 76·5 years (SD 3·9). 118 (69%) of 172 patients were male and 54 (31%) patients were female. FFR-guided PCI plus TAVI resulted in favourable outcomes for the primary endpoint (four [4%] of 91 patients) versus SAVR plus CABG (17 [23%] of 77 patients; risk difference -18·5 [90% CI -27·8 to -9·7]), which was below the 15% prespecified non-inferiority margin (pnon-inferiority<0·001). FFR-guided PCI plus TAVI was superior to SAVR plus CABG (hazard ratio 0·17 [95% CI 0·06-0·51]; psuperiority<0·001), which was driven mainly by all-cause mortality (none [0%] of 91 patients vs seven (10%) of 77 patients; p=0·0025) and life-threatening bleeding (two [2%] vs nine [12%]; p=0·010). INTERPRETATION: The TCW trial is the first trial to compare percutaneous treatment versus surgical treatment in patients with severe aortic stenosis and complex coronary artery disease, showing favourable primary endpoint and mortality outcomes with percutaneous treatment. FUNDING: Isala Heart Centre and Medtronic.
- MeSH
- aortální stenóza * chirurgie komplikace MeSH
- chirurgická náhrada chlopně metody MeSH
- frakční průtoková rezerva myokardu * MeSH
- koronární angioplastika * metody MeSH
- koronární bypass * metody MeSH
- lidé MeSH
- nemoci koronárních tepen * chirurgie komplikace terapie MeSH
- prospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- transkatetrální implantace aortální chlopně * metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- hodnocení ekvivalence MeSH
- multicentrická studie MeSH
- srovnávací studie MeSH
University students frequently encounter stress and anxiety, impacting their autonomic nervous system and mental health. Rhythmic photic stimulation (RPS) at various frequencies is considered a potential intervention for anxiety and depression, but its effectiveness is not fully understood. This research aimed to assess the impact of RPS at theta (6 Hz), alpha (10 Hz), and beta (25 Hz) frequencies on autonomic nervous system regulation in university students, comparing the effects between those with and without depression symptoms. Conducted at a southern Taiwan university, this quasi-experimental study involved RPS interventions at specified frequencies, with pre and post assessments of heartbeat, blood pressure, and heart rate variability. Among 62 participants (average age 20.29±0.61), those without depression showed a notable blood pressure reduction following theta-frequency RPS compared to other frequencies (p<0.05). A similar pattern was observed when comparing non-depressed and depressed participants after theta-RPS, with depressed individuals experiencing an increase in sympathetic activity (p<0.05). RPS, particularly at theta frequency, can significantly influence the autonomic nervous system, suggesting a potential for reducing anxiety-related physiological markers in university students. Further verification with a larger and longitudinal study is warranted. Key words Binaural beat, Rhythmical photic stimulation, Autonomic nervous system, University student.
- MeSH
- autonomní nervový systém * fyziologie MeSH
- deprese patofyziologie psychologie MeSH
- krevní tlak fyziologie MeSH
- lidé MeSH
- mladý dospělý MeSH
- srdeční frekvence * fyziologie MeSH
- studenti * psychologie MeSH
- světelná stimulace * metody MeSH
- univerzity MeSH
- úzkost patofyziologie MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Hydrogen sulfide (H2S) is a gas neurotransmitter that is synthesized in various mammalian tissues including vascular tissues and regulates vascular tone. The aim of this study is to investigate whether the endogenous L-cysteine/H2S pathway is impaired due to aging and endothelial denudation in mouse isolated thoracic aorta. For this purpose, young (3-4 months) and old (23-25 months) mice were used in the experiments. The effects of aging and endothelium on endogenous and exogenous H2S-induced vasorelaxation were investigated by cumulative L-cysteine-(1 microM-10 mM) and NaHS-(1 microM-3 mM) induced vasorelaxations, respectively. The L-cysteine-induced relaxations were reduced in old mice aorta compared to the young mice. Also, vasorelaxant responses to L-cysteine (1 microM-10 mM) were reduced on aorta rings with denuded-endothelium of young and old mice. However, the relaxation responses to NaHS were not altered by age or endothelium denudation. The loss of staining of CSE in the endothelial layer was observed in old thoracic aorta. Ach-induced (1-30 microM) relaxation almost abolished in endothelium-denuded rings from both mice group. Also, relaxation Ach reduced in intact endothelium tissue of old mice aorta. In conclusion, the vasorelaxant responses to L-cysteine but not NaHS decreased and the protein expression of CSE reduced in old thoracic aorta rings consistent with a decrease in H2S concentration with aging and endothelium damage, suggesting that aging may be lead to decrease in enzyme expression and H2S signaling system due to endothelium damage in mouse thoracic aorta. Key words Aging, Hydrogen sulfide, L-cysteine, Endothelium, Thoracic aorta.
- MeSH
- aorta thoracica * účinky léků metabolismus fyziologie MeSH
- cévní endotel * metabolismus účinky léků MeSH
- cystein metabolismus farmakologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- signální transdukce MeSH
- stárnutí * metabolismus MeSH
- sulfan * metabolismus MeSH
- vazodilatace * účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The effects of a large arteriovenous fistula (AVF) on pulmonary perfusion remains to be elucidated. We aimed to study, for the first time, the real-time acute effects of a large AVF on regional distribution of pulmonary perfusion in a novel porcine model. Ten healthy swine under general anesthesia were studied. AVF was created by the connection of femoral artery and femoral vein using high-diameter perfusion cannulas. The AVF was closed and after 30 min of stabilization the first values were recorded. The fistula was then opened, and new data were collected after reaching stable state. Continuous hemodynamic monitoring was performed throughout the protocol. The following functional images were analyzed by electrical impedance tomography (EIT): perfusion and ventilation distributions. We found an increased cardiac output and right ventricular work, which was strongly correlated to an increased pulmonary artery mean pressure (r=0.878, P=0.001). The ventral/dorsal ratio of pulmonary perfusion decreased from 1.9+/-1.0 to 1.5+/-0.7 (P=0.025). The percentage of total pulmonary blood flow through the dorsal lung region increased from 38.6+/-11.7 to 42.2+/-10.4 (P=0.016). In conclusion, we have used EIT for the first time for studying the acute effects of a large AVF on regional distribution of pulmonary perfusion in a novel porcine model. In this new experimental model of hyperkinetic circulation caused by AVF, we documented an increased percentage of total pulmonary blood flow through the dorsal lung region and a more homogeneous perfusion distribution. Key words Arteriovenous fistula, Hyperkinetic circulation, Tissue perfusion, Animal model, Pulmonary blood flow.
- MeSH
- arteria pulmonalis diagnostické zobrazování patofyziologie MeSH
- arteriovenózní píštěl patofyziologie diagnostické zobrazování MeSH
- arteriovenózní zkrat MeSH
- plíce krevní zásobení diagnostické zobrazování MeSH
- plicní oběh * fyziologie MeSH
- prasata MeSH
- vena femoralis diagnostické zobrazování MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Východiská: Na význam stresu pri nádorových chorobách poukazovali lekári už od čias Galéna. Avšak až v posledných dvoch desaťročiach umožnil kombinovaný onkologický a neurovedný výskum exaktne preskúmať tento vzťah a popísať dráhy a mechanizmy, ktoré sprostredkúvajú stimulačný vplyv stresu na nádorový proces. Tento nepriaznivý účinok stresu je sprostredkovaný hlavne mediátormi sympatikoadrenálneho systému, noradrenalínom a adrenalínom. Tieto katecholamíny aktiváciou adrenergických receptorov v nádorovom mikro- a makroprostredí stimulujú proliferáciu nádorových buniek a neoangiogenézu a inhibujú protinádorovú imunitu a znižujú účinnosť štandardnej protinádorovej liečby. Zistilo sa tiež, že intervencie obmedzujúce pôsobenie stresu na organizmus nie len že zlepšujú kvalitu života onkologických pacientov, ale môžu zlepšovať aj ich prežívanie. Vzhľadom na komplexnosť vplyvu stresu na organizmus sa experimentálne a klinické štúdie v prevažnej väčšine zameriavajú na skúmanie účinku jednej intervencie obmedzujúcej stimulačný vplyv sympatikoadrenálneho systému na nádorový proces. Cieľ: Zámerom tohto názorového článku je poukázať na možnosť synergického účinku kombinácie viacerých intervencií obmedzujúcich aktiváciu sympatikoadrenálneho systému a na základe dostupných údajov navrhnúť takú kombináciu týchto intervencií, ktorá je aplikovateľná v podpornej liečbe onkologických pacientov už aj v súčasnosti. Záver: Protokol Synergy, ktorý zahŕňa nefarmakologické intervencie zamerané na obmedzenie pôsobenia stresu, má potenciál zlepšiť kvalitu života a u určitých pacientov aj prognózu ich choroby. Zavedenie tohto protokolu do bežnej klinickej praxe síce bude vyžadovať vyriešenie personálnych a finančných aspektov, ktoré s jeho implikáciou súvisia, výsledkom ale môže byť významné zvýšenie úrovne starostlivosti o onkologických pacientov.
Background: The importance of stress in cancer has been noted by physicians since the time of Galen. However, it is only in the last two decades that combined oncological and neuroscientific research has allowed to explore this relationship in an exact way and to describe the pathways and mechanisms that mediate the stimulatory effect of stress on cancer. This adverse effect of stress is mediated mainly by the mediators of the sympathoadrenal system, norepinephrine and epinephrine, which, by activating adrenergic receptors in the tumor micro- and macro-environment, stimulate tumor cell proliferation and neoangiogenesis and inhibit antitumor immunity, reducing the efficacy of standard anticancer therapies. It has also been found that interventions reducing the effects of stress on the body not only improve the quality of life of cancer patients but may also improve their survival. Given the complexity of the impact of stress on the organism, experimental and clinical studies have overwhelmingly focused on investigating the effect of a single intervention reducing the stimulatory influence of the sympathoadrenal system on the cancer process. Purpose: The aim of this opinion article is to highlight the possibility of a synergistic effect of a combination of several interventions limiting the activation of the sympathoadrenal system and, based on the available data, to propose a combination of these interventions that is applicable in the supportive treatment of cancer patients even nowadays. Conclusion: The Protocol Synergy, which includes non-pharmacological interventions aimed at reducing the effects of stress on the cancer patient, has the potential to improve the quality and, in certain patients, the prognosis of their disease. Although the introduction of this protocol into routine clinical practice will require addressing the personnel and financial aspects associated with its implementation, it has the potential to significantly improve the level of care for cancer patients.
- MeSH
- beta blokátory terapeutické užití MeSH
- cvičení MeSH
- klinické protokoly * MeSH
- kvalita života psychologie MeSH
- lidé MeSH
- nádory * etiologie psychologie MeSH
- nízká teplota škodlivé účinky MeSH
- psychický stres * MeSH
- psychoterapie metody MeSH
- relaxační terapie MeSH
- srdeční frekvence MeSH
- svépomocné skupiny MeSH
- sympatoadrenální systém MeSH
- Check Tag
- lidé MeSH
- MeSH
- ateroskleróza * farmakoterapie metabolismus patofyziologie prevence a kontrola MeSH
- hypolipidemika farmakologie terapeutické užití MeSH
- lidé MeSH
- lipoproteiny * klasifikace krev metabolismus škodlivé účinky MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- tuhost cévní stěny MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- diastolické srdeční selhání diagnóza farmakoterapie patofyziologie MeSH
- glifloziny farmakologie terapeutické užití MeSH
- kardiovaskulární nemoci diagnóza farmakoterapie klasifikace MeSH
- lékaři klasifikace MeSH
- lidé MeSH
- srdeční selhání * diagnóza farmakoterapie klasifikace MeSH
- tepový objem MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Animal models are an important tool for studying ischemic mechanisms of stroke. Among them, the middle cerebral artery occlusion (MCAO) model via the intraluminal suture method in rodents is closest to human ischemic stroke. It is a model of transient occlusion followed by reperfusion, thus representing cerebral ischemia-reperfusion model that simulates patients with vascular occlusion and timely recanalization. Although reperfusion is very beneficial for the possibility of preserving brain functions after ischemia, it also brings a great risk in the form of brain edema, which can cause the development of intracranial hypertension, and increasing morbidity and mortality. In this paper, we present the results of our own transient reperfusion model of MCAO in which we tested the permeability of the blood-brain barrier (BBB) using Evans blue (EB), an intravital dye with a high molecular weight (68,500 Da) that prevents its penetration through the intact BBB. A total of 15 animals were used in the experiment and underwent the following procedures: insertion of the MCA occluder; assessment of ischemia by 2,3,5 -Triphenyltetrazolium chloride (TTC) staining; assessment of the BBB permeability using brain EB distribution. The results are presented and discussed. The test of BBB permeability using EB showed that 120 minutes after induction of ischemia, the BBB is open for the entry of large molecules into the brain. We intend to use this finding to time the application of neuroprotective agents via ICA injection in our next stroke model. Keywords: Cerebral ischemia-reperfusion model, Middle cerebral artery occlusion, Blood-brain barrier, 2,3,5 -Triphenyltetrazolium chloride, Evans blue.
- MeSH
- Evansova modř MeSH
- hematoencefalická bariéra * metabolismus MeSH
- infarkt arteria cerebri media * metabolismus MeSH
- ischemie mozku metabolismus MeSH
- kapilární permeabilita MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech * MeSH
- permeabilita MeSH
- pilotní projekty MeSH
- potkani Sprague-Dawley MeSH
- reperfuzní poškození * metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Pulse Wave Velocity (PWV) is widely used to assess arterial elasticity and is an independent risk factor for cardiovascular disease, but it is influenced by multiple factors. Objective is to assess the impact of blood pressure and heart rate on PWV. Twenty healthy young individuals were enlisted as subjects. Real-time blood pressure monitoring was performed by non-invasive continuous blood pressure measuring instrument during the detection of subjects' carotid PWV. During real-time blood pressure monitoring, exercise load caused fluctuations in blood pressure and heart rate, and PWV changes of each subject under different blood pressure and heart rate conditions were recorded simultaneously. Among the 20 subjects, PWV was associated with blood pressure in four subjects and heart rate in one subject. PWV increased with rising blood pressure when the systolic pressure fluctuation range was >=30mmHg, diastolic pressure fluctuation range was >=18mmHg, and mean arterial pressure fluctuation range was >=20mmHg. PWV increased with rising heart rate, when the heart rate fluctuation range was >30 beats/min. Blood pressure and heart rate have some influence on PWV. However, the fluctuation range of blood pressure and heart rate should reach a certain value, the impact is significant. Keywords: Pulse wave velocity, Blood pressure, Heart rate.
- MeSH
- analýza pulzové vlny * metody MeSH
- dospělí MeSH
- krevní tlak * fyziologie MeSH
- lidé MeSH
- měření krevního tlaku metody MeSH
- mladý dospělý MeSH
- srdeční frekvence * fyziologie MeSH
- tuhost cévní stěny fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
