Substituted catechols include both natural and synthetic compounds found in the environment and foods. Some of them are flavonoid metabolites formed by the gut microbiota which are absorbed afterwards. Our previous findings showed that one of these metabolites, 4-methylcatechol, exerts potent vasorelaxant effects in rats. In the current study, we aimed at testing of its 22 structural congeners in order to find the most potent structure and to investigate the mechanism of action. 3-methoxycatechol (3-MOC), 4-ethylcatechol, 3,5-dichlorocatechol, 4-tert-butylcatechol, 4,5-dichlorocatechol, 3-fluorocatechol, 3-isopropylcatechol, 3-methylcatechol and the parent 4-methylcatechol exhibited high vasodilatory activities on isolated rat aortic rings with EC50s ranging from ∼10 to 24 μM. Some significant sex-differences were found. The most potent compound, 3-MOC, relaxed also resistant mesenteric artery but not porcine coronary artery, and decreased arterial blood pressure in both male and female spontaneously hypertensive rats in vivo without affecting heart rate. It potentiated the vasodilation mediated by cAMP and cGMP, but did not impact L-type Ca2+-channels. By using two inhibitors, activation of voltage-gated potassium channels (KV) was found to be involved in the mechanism of action. This was corroborated by docking analysis of 3-MOC with the KV7.4 channel. None of the most active catechols decreased the viability of the A-10 rat embryonic thoracic aorta smooth muscle cell line. Our findings showed that various catechols can relax vascular smooth muscles and hence could provide templates for developing new antihypertensive vasodilator agents without affecting coronary circulation.
- Klíčová slova
- Blood vessel, Catechol, K(V) channel, Phenolic, Vasorelaxant,
- MeSH
- aorta thoracica účinky léků metabolismus MeSH
- arteriae mesentericae * účinky léků metabolismus MeSH
- arteriální tlak účinky léků MeSH
- draslíkové kanály řízené napětím metabolismus antagonisté a inhibitory účinky léků MeSH
- guanosinmonofosfát cyklický metabolismus MeSH
- hypertenze farmakoterapie patofyziologie metabolismus MeSH
- katecholy * farmakologie chemie MeSH
- koronární cévy účinky léků metabolismus MeSH
- krysa rodu Rattus MeSH
- modely nemocí na zvířatech MeSH
- myocyty hladké svaloviny účinky léků metabolismus MeSH
- potkani inbrední SHR * MeSH
- prasata MeSH
- sexuální faktory MeSH
- simulace molekulového dockingu * MeSH
- svaly hladké cévní účinky léků metabolismus MeSH
- vazodilatace * účinky léků MeSH
- vazodilatancia * farmakologie chemie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- draslíkové kanály řízené napětím MeSH
- guanosinmonofosfát cyklický MeSH
- katecholy * MeSH
- vazodilatancia * MeSH
- MeSH
- antihypertenziva * terapeutické užití škodlivé účinky MeSH
- arteriální tlak účinky léků MeSH
- hypertenze indukovaná těhotenstvím * diagnóza terapie patofyziologie farmakoterapie MeSH
- kardiovaskulární komplikace v těhotenství diagnóza terapie MeSH
- krevní tlak účinky léků MeSH
- lidé MeSH
- rizikové faktory MeSH
- směrnice pro lékařskou praxi jako téma * MeSH
- těhotenství MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- úvodníky MeSH
- Názvy látek
- antihypertenziva * MeSH
The development of methods for measuring blood pressure (BP) in newborns and small children has a rich history. Methods for BP measuring in adults had to be adapted to this age group. For measuring BP in direct invasive way, a suitable approach had to be found to access the arterial circulation through the umbilical and later radialis artery. Currently, results obtained from direct invasive BP measurement are considered the "gold standard". The development of non-invasive methods for BP measuring in newborns and children began with the use of von Basch's sphygmomanometer (1880). In 1899, Gustav Gärtner constructed the device, which was the basis for the flush method. After the discovery of the palpation and auscultation methods, these methods were also used for BP measurement in newborns and children, however, the BP values obtained in these ways were typically underestimated using excessively wide cuffs. From the auscultation method, methods utilizing ultrasound and infrasound to detect arterial wall movement and blood flow were later developed. The oscillometric method for BP measurement was introduced by E. J. Marey so early as in 1876. In 1912, P. Balard used the oscillometric technique to measure blood pressure in a large group of newborns. Through different types of oscillometers using various methods for detecting vascular oscillations (such as xylol method, impedance and volume plethysmography, etc.), the development has continued to assessment of vascular oscillations by modern sensor technology and software. For continuous non-invasive blood pressure measurement, the volume-clamp method, first described by Jan Peňáz in 1968, was developed. After modification for use in newborns, application of the cuff to the wrist instead of the finger, it is primarily used in clinical physiological studies to evaluate beat-to-beat BP and heart rate pressure variability, such as in the determination of the baroreflex sensitivity.
- MeSH
- arteriální tlak * MeSH
- arterie MeSH
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- krevní tlak MeSH
- lidé MeSH
- měření krevního tlaku * metody MeSH
- novorozenec MeSH
- prsty ruky MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Oral contraceptive pills (OCPs) have some strong advantages over more traditional types of contraception, including their consistently high contraceptive effect as well as multiple additional positive side effects. OCPs went through decades of intense pharmaceutical development and current formulas are well optimized - however, a handful of their negative side effects remain, including some that affect cardiovascular system, for example higher risk of hypertension, venous thromboembolism and increased arterial stiffness. The gold standard for arterial stiffness assessment is currently applanation tonometry, a method that relies on arterial pulse wave velocity measurement (PWV). Another possible method for arterial stiffness measurement is the use of the VaSera device, which measures cardio-ankle vascular index (CAVI). The aim of this study was to discover the effect of OCPs use on selected cardiovascular parameters related to arterial stiffness. We measured these cardiovascular parameters in the OCPs using group (OCP) and in the control group (CTRL) using applanation tonometer Sphygmocor and the VaSera device. Comparison of the data from both groups showed us significantly increased diastolic blood pressure (DBP) and carotid-radial pulse wave velocity (crPWV) as well as significantly lower subendocardial viability index (SVI) in the OCP. These results imply a negative effect of hormonal contraceptives on the cardiovascular system with most of the negative changes affecting the peripheral arteries. Despite this evidence supporting the hypothesis of OCPs having a negative effect on cardiovascular health, further research is necessary.
- MeSH
- analýza pulzové vlny * MeSH
- arteriae carotides MeSH
- arteriální tlak MeSH
- hormonální antikoncepce * škodlivé účinky MeSH
- krevní tlak fyziologie MeSH
- lidé MeSH
- mladiství MeSH
- pilotní projekty MeSH
- tuhost cévní stěny * fyziologie MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- Publikační typ
- časopisecké články MeSH
The pressure reactivity index (PRx) is a parameter for the assessment of cerebrovascular autoregulation, but its calculation is affected by artifacts in the source biosignals-intracranial pressure (ICP) and arterial blood pressure. We sought to describe the most common short-duration artifacts and their effect on the PRx. A retrospective analysis of 935 h of multimodal monitoring data was conducted, and five types of artifacts, characterized by their shape, duration, and amplitude, were identified: rectangular, fast impulse, isoline drift, saw tooth, and constant ICP value. Subsequently, all types of artifacts were mathematically modeled and inserted into undisturbed segments of biosignals. Fast impulse, the most common artifact, did not alter the PRx index significantly when inserted into one or both signals. Artifacts present in one signal exceeded the threshold PRx in less than 5% of samples, except for isoline drift. Compared to that, the shortest rectangular artifact inserted into both signals changed PRx to a value above the set threshold in 55.4% of cases. Our analysis shows that the effect of individual artifacts on the PRx index is variable, depending on their occurrence in one or both signals, duration, and shape. This different effect suggests that potentially not all artifacts need to be removed.
Arterial compliance (C) is a complex parameter influencing ventricular-arterial coupling depending on structural (arterial wall remodeling) and functional (blood pressure, smooth muscles tone) changes. Based on Windkessel model, C can be calculated as the ratio of a time constant Tau characterizing diastolic blood pressure decay and total peripheral resistance (TPR). The aim of this study was to assess changes of C in the context of systolic arterial pressure (SAP) perturbations during four physiological states (supine rest, head-up tilt, supine recovery, mental arithmetic). In order to compare pressure independent changes of C a new index of C120 was proposed predicting C value at 120 mm Hg of SAP. Eighty-one healthy young subjects (48 f, average age 18.6 years) were examined. Hemodynamic parameters were measured beat-to-beat using volume-clamp photoplethysmographic method and impedance cardiography. We observed that C was strongly related to SAP values on the beat-to-beat time scale. Interestingly, C120 decreased significantly during stress phases. In conclusion, potential changes of SAP should be considered when measuring C. Arterial compliance changes in the opposite direction to TPR pointing towards influence of vascular tone changes on its value.
- MeSH
- arteriální tlak * MeSH
- časové faktory MeSH
- cévní rezistence MeSH
- fyziologická adaptace MeSH
- lidé MeSH
- matematické pojmy MeSH
- mladiství MeSH
- mladý dospělý MeSH
- modely kardiovaskulární MeSH
- polohování pacienta MeSH
- supinační poloha MeSH
- systola MeSH
- test na nakloněné rovině MeSH
- tuhost cévní stěny * MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
BACKGROUND: The impact of the permissive hypotension approach in clinically well infants on regional cerebral oxygen saturation (rScO2) and autoregulatory capacity (CAR) remains unknown. METHODS: Prospective cohort study of blinded rScO2 measurements within a randomized controlled trial of management of hypotension (HIP trial) in extremely preterm infants. rScO2, mean arterial blood pressure, duration of cerebral hypoxia, and transfer function (TF) gain inversely proportional to CAR, were compared between hypotensive infants randomized to receive dopamine or placebo and between hypotensive and non-hypotensive infants, and related to early intraventricular hemorrhage or death. RESULTS: In 89 potentially eligible HIP trial patients with rScO2 measurements, the duration of cerebral hypoxia was significantly higher in 36 hypotensive compared to 53 non-hypotensive infants. In 29/36 hypotensive infants (mean GA 25 weeks, 69% males) receiving the study drug, no significant difference in rScO2 was observed after dopamine (n = 13) compared to placebo (n = 16). Duration of cerebral hypoxia was associated with early intraventricular hemorrhage or death. Calculated TF gain (n = 49/89) was significantly higher reflecting decreased CAR in 16 hypotensive compared to 33 non-hypotensive infants. CONCLUSIONS: Dopamine had no effect on rScO2 compared to placebo in hypotensive infants. Hypotension and cerebral hypoxia are associated with early intraventricular hemorrhage or death. IMPACT: Treatment of hypotension with dopamine in extremely preterm infants increases mean arterial blood pressure, but does not improve cerebral oxygenation. Hypotensive extremely preterm infants have increased duration of cerebral hypoxia and reduced cerebral autoregulatory capacity compared to non-hypotensive infants. Duration of cerebral hypoxia and hypotension are associated with early intraventricular hemorrhage or death in extremely preterm infants. Since systematic treatment of hypotension may not be associated with better outcomes, the diagnosis of cerebral hypoxia in hypotensive extremely preterm infants might guide treatment.
- MeSH
- arteriální tlak * účinky léků MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- dopamin terapeutické užití MeSH
- gestační stáří MeSH
- homeostáza MeSH
- hypotenze krev farmakoterapie mortalita patofyziologie MeSH
- intraventrikulární krvácení do mozku mortalita patofyziologie MeSH
- kojenec MeSH
- kojenecká mortalita MeSH
- kyslík krev MeSH
- lidé MeSH
- mortalita v nemocnicích MeSH
- mozková hypoxie krev mortalita patofyziologie MeSH
- mozkový krevní oběh * MeSH
- novorozenci extrémně nezralí * MeSH
- prospektivní studie MeSH
- saturace kyslíkem * MeSH
- sympatomimetika terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Evropa MeSH
- Názvy látek
- biologické markery MeSH
- dopamin MeSH
- kyslík MeSH
- sympatomimetika MeSH
High dependency of arterial blood pressure (ABP) on enhanced sympathetic activity, which maintains vascular tone, leads to hypotension after hemodynamic insults that blunt the sympathetic activity. Therefore, we hypothesized that sympathovagal balance before tourniquet deflation (TD) determines the extent of a reduction in ABP after TD during total knee arthroplasty (TKA). Fifty-four hypertensive female patients undergoing TKA under spinal anesthesia were analyzed. The sympathovagal balance [low-to-high frequency ratio of heart rate variability (LF/HF)] before TD was defined as (LF/HF during 5 min before TD-preanesthetic LF/HF)/preanesthetic LF/HF (%). An increase in its value represents a shift in sympathovagal balance toward sympathetic predominance. The percent change in the mean ABP (MAP) after TD was defined as (minimum MAP during 10 min after TD-averaged MAP during 5 min before TD)/averaged MAP during 5 min before TD (%). Simple linear regression was performed to assess the correlation between the sympathovagal balance before TD and change in MAP after TD. The correlation was also assessed by multiple linear regression controlling for age, duration of tourniquet inflation, and spinal anesthesia-induced hypotension. Thirty-two minutes (on average) after tourniquet inflation, the MAP was decreased by 12.1 (-3.0 to 47.9) % [mean (range)] upon TD (P<0.001). The sympathovagal balance before TD was negatively proportional to the change in MAP after TD in both simple and multiple linear regression models (R2=0.323 and 0.340, P<0.001). A shift in sympathovagal balance toward sympathetic predominance before TD is associated with a decrease in ABP after TD.
- MeSH
- arteriální tlak * MeSH
- hypertenze patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nervus vagus patofyziologie MeSH
- peroperační doba MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spinální anestezie MeSH
- srdeční frekvence MeSH
- stárnutí MeSH
- sympatický nervový systém patofyziologie MeSH
- totální endoprotéza kolene * MeSH
- turnikety * MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The study analyzes changes in lung function, pulmonary pressure and diffusing capacity of the lung in patients with mitral valve regurgitation (MR) treated by MitraClip implantation. METHODS: A total of 43 patients (19 women and 24 men with an average age of 78.0 ± 6.6 years) who were able to perform pulmonary function testing including diffusing capacity of the lung for carbon monoxide (DLCO), vital capacity (VC), total lung capacity (TLC), residual volume (RV) and forced expiratory volume in 1 s (FEV1) before and 6 weeks after MitraClip implantation participated in this study. Furthermore, clinical and echocardiographic parameters including systolic pulmonary artery pressure (sPAP), left ventricular ejection fraction (LVEF) and left atrial diameter (LAD) measurements were recorded in all patients. RESULTS: The procedure was performed successfully in all 43 patients leading to a reduction of MR in 97.7% of cases. One patient died on day 4 after the intervention most likely due to pulmonary artery embolism. Six weeks after the implantation 79.1% of patients showed a MR of at most mild to moderate. Furthermore, we could demonstrate a significant reduction of systolic pulmonary artery pressure during follow-up (from 48.8 ± 11.4 mmHg to 42.9 ± 9.0 mmHg (t(41) = - 2.6, p = 0.01). However, no changes in LVEF were detected. Comparing pre and post implant lung function tests, no significant alterations were seen for VC, TLC, DLCO and FEV1. Though, in a subgroup of patients with moderate to severe preexisting deterioration of DLCO at the baseline (max. 50%) the MitraClip procedure resulted in a significant improvement in DLCO (37.8% ± 9.0 to 41.6% ± 10.0, p < 0.001). CONCLUSIONS: Treatment of MR with the MitraClip system successfully reduces MR severity in the vast majority of patients. Consecutively, a reduction in pulmonary pressure could be observed, however no changes in LVEF were obvious. Lung function tests remained unaltered during follow-up. However, in a subgroup of patients with severe preexisting deterioration of DLCO the MitraClip procedure resulted in a significant improvement in DLCO. TRIAL REGISTRATION: Name of the registry: Die Auswirkung der interventionellen Mitralklappenreparatur mit MitraClip-System auf die Ergebnisse der Lungenfunktionsmessung. TRIAL REGISTRATION NUMBER: DRKS00022435; Date of registration: 09/07/2020 'Retrospectively registered'; URL of trial registry record: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022435 .
- Klíčová slova
- MitraClip, Patient registry, Pulmonary function, Structural intervention, Valvular disease,
- MeSH
- arteria pulmonalis diagnostické zobrazování patofyziologie MeSH
- arteriální tlak * MeSH
- časové faktory MeSH
- chirurgická náhrada chlopně škodlivé účinky přístrojové vybavení MeSH
- difuzní kapacita plic * MeSH
- lidé MeSH
- mitrální chlopeň diagnostické zobrazování patofyziologie chirurgie MeSH
- mitrální insuficience diagnostické zobrazování patofyziologie chirurgie MeSH
- obnova funkce MeSH
- plíce patofyziologie MeSH
- prospektivní studie MeSH
- protézy - design MeSH
- registrace MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- srdeční chlopně umělé * MeSH
- srdeční katetrizace škodlivé účinky přístrojové vybavení MeSH
- stupeň závažnosti nemoci 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
- pozorovací studie MeSH
During general anesthesia (GA), direct analysis of arterial pressure or aortic flow waveforms may be inconclusive in complex situations. Patient-specific biomechanical models, based on data obtained during GA and capable to perform fast simulations of cardiac cycles, have the potential to augment hemodynamic monitoring. Such models allow to simulate Pressure-Volume (PV) loops and estimate functional indicators of cardiovascular (CV) system, e.g. ventricular-arterial coupling (Vva), cardiac efficiency (CE) or myocardial contractility, evolving throughout GA. In this prospective observational study, we created patient-specific biomechanical models of heart and vasculature of a reduced geometric complexity for n = 45 patients undergoing GA, while using transthoracic echocardiography and aortic pressure and flow signals acquired in the beginning of GA (baseline condition). If intraoperative hypotension (IOH) appeared, diluted norepinephrine (NOR) was administered and the model readjusted according to the measured aortic pressure and flow signals. Such patients were a posteriori assigned into a so-called hypotensive group. The accuracy of simulated mean aortic pressure (MAP) and stroke volume (SV) at baseline were in accordance with the guidelines for the validation of new devices or reference measurement methods in all patients. After NOR administration in the hypotensive group, the percentage of concordance with 10% exclusion zone between measurement and simulation was >95% for both MAP and SV. The modeling results showed a decreased Vva (0.64±0.37 vs 0.88±0.43; p = 0.039) and an increased CE (0.8±0.1 vs 0.73±0.11; p = 0.042) in hypotensive vs normotensive patients. Furthermore, Vva increased by 92±101%, CE decreased by 13±11% (p < 0.001 for both) and contractility increased by 14±11% (p = 0.002) in the hypotensive group post-NOR administration. In this work we demonstrated the application of fast-running patient-specific biophysical models to estimate PV loops and functional indicators of CV system using clinical data available during GA. The work paves the way for model-augmented hemodynamic monitoring at operating theatres or intensive care units to enhance the information on patient-specific physiology.
- MeSH
- algoritmy MeSH
- arteriální tlak fyziologie MeSH
- biomechanika MeSH
- celková anestezie metody MeSH
- hemodynamické monitorování metody MeSH
- hypotenze farmakoterapie patofyziologie MeSH
- krevní tlak MeSH
- lidé středního věku MeSH
- lidé MeSH
- minutový srdeční výdej fyziologie MeSH
- modely kardiovaskulární * MeSH
- noradrenalin aplikace a dávkování MeSH
- ověření koncepční studie MeSH
- prospektivní studie MeSH
- tepový objem fyziologie MeSH
- vazokonstriktory aplikace a dávkování MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- noradrenalin MeSH
- vazokonstriktory MeSH