Extracellular potassium concentration might modify electrophysiological properties in the border zone of ischemic myocardium. We evaluated the depolarization and repolarization characteristics across the ischemic-normal border under [K+] variation. Sixty-four-lead epicardial mapping was performed in 26 rats ([K+] 2.3-6.4 mM) in a model of acute ischemia/reperfusion. The animals with [K+] < 4.7 mM (low-normal potassium) had an ischemic zone with ST-segment elevation and activation delay, a border zone with ST-segment elevation and no activation delay, and a normal zone without electrophysiological abnormalities. The animals with [K+] >4.7 mM (normal-high potassium) had only the ischemic and normal zones and no transitional area. Activation-repolarization intervals and local conduction velocities were inversely associated with [K+] in linear regression analysis with adjustment for the zone of myocardium. The reperfusion extrasystolic burden (ESB) was greater in the low-normal as compared to normal-high potassium animals. Ventricular tachycardia/fibrillation incidence did not differ between the groups. In patch-clamp experiments, hypoxia shortened action potential duration at 5.4 mM but not at 1.3 mM of [K+]. IK(ATP) current was lower at 1.3 mM than at 5.4 mM of [K+]. We conclude that the border zone formation in low-normal [K+] was associated with attenuation of IK(ATP) response to hypoxia and increased reperfusion ESB.

• MeSH
• akční potenciály * fyziologie   MeSH
• draslík * krev   metabolismus   MeSH
• ischemická choroba srdeční * patofyziologie   krev   metabolismus   MeSH
• krysa rodu rattus MeSH
• potkani Wistar MeSH
• reperfuzní poškození myokardu krev   patofyziologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Aminophylline, a bronchodilator mainly used to treat severe asthma attacks, may induce arrhythmias. Unfortunately, the underlying mechanism is not well understood. We have recently described a significant, on average inhibitory effect of aminophylline on inward rectifier potassium current IK1, known to substantially contribute to arrhythmogenesis, in rat ventricular myocytes at room temperature. This study was aimed to examine whether a similar effect may be observed under clinically relevant conditions. Experiments were performed using the whole cell patch clamp technique at 37°C on enzymatically isolated healthy porcine and failing human ventricular myocytes. The effect of clinically relevant concentrations of aminophylline (10-100 μM) on IK1 did not significantly differ in healthy porcine and failing human ventricular myocytes. IK1 was reversibly inhibited by ∼20 and 30 % in the presence of 30 and 100 μM aminophylline, respectively, at -110 mV; an analogical effect was observed at -50 mV. To separate the impact of IK1 changes on AP configuration, potentially interfering ionic currents were blocked (L-type calcium and delayed rectifier potassium currents). A significant prolongation of AP duration was observed in the presence of 100 μM aminophylline in porcine cardiomyocytes which well agreed with the effect of a specific IK1 inhibitor Ba2+ (10 μM) and with the result of simulations using a porcine ventricular cell model. We conclude that the observed effect of aminophylline on healthy porcine and failing human IK1 might be involved in its proarrhythmic action. To fully understand the underlying mechanism, potential aminophylline impact on other ionic currents should be explored.

• MeSH
• akční potenciály účinky léků   MeSH
• aminofylin * farmakologie   MeSH
• draslíkové kanály dovnitř usměrňující * metabolismus   MeSH
• kardiomyocyty * účinky léků   metabolismus   MeSH
• lidé MeSH
• metoda terčíkového zámku MeSH
• prasata MeSH
• srdeční komory účinky léků   metabolismus   MeSH
• srdeční selhání metabolismus   farmakoterapie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD. This results in reduced inhibitory control of compulsive behavior and, eventually, relapse. We reasoned here that prefrontal dysfunction, which underlies vulnerability to relapse, is evidenced by altered neuroelectric signatures and should be restored by pharmacological interventions that specifically target prefrontal dysfunction. To test this, we applied our recently developed biocompatible neuroprosthesis to measure prefrontal neural function in a well-established rat model of alcohol addiction and relapse. We monitored neural oscillations and event-related potentials in awake alcohol-dependent rats during abstinence and following treatment with psilocybin or LY379268, agonists of the serotonin 2A receptor (5-HT2AR), and the metabotropic glutamate receptor 2 (mGluR2), that are known to reduce prefrontal dysfunction and relapse. Electrophysiological impairments in alcohol-dependent rats are reduced amplitudes of P1N1 and N1P2 components and attenuated event-related oscillatory activity. Psilocybin and LY379268 were able to restore these impairments. Furthermore, alcohol-dependent animals displayed a dominance in higher beta frequencies indicative of a state of hyperarousal that is prone to relapse, which particularly psilocybin was able to counteract. In summary, we provide prefrontal markers indicative of relapse and treatment response, especially for psychedelic drugs.

• MeSH
• alkoholismus * farmakoterapie   patofyziologie   MeSH
• aminokyseliny MeSH
• bicyklické sloučeniny heterocyklické * farmakologie   MeSH
• biologické markery MeSH
• evokované potenciály účinky léků   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech * MeSH
• prefrontální mozková kůra * účinky léků   patofyziologie   metabolismus   MeSH
• psilocybin * farmakologie   MeSH
• receptory metabotropního glutamátu MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Among inherited cardiomyopathies involving the left ventricle, whether dilated or not, certain genotypes carry a well-established arrhythmic risk, notably manifested as sustained monomorphic ventricular tachycardia (SMVT). Nonetheless, the precise localization and electrophysiological profile of this substrate remain undisclosed across different genotypes. METHODS: Patients diagnosed with cardiomyopathy and left ventricle involvement due to high-risk genetic variants and SMVT treated by electrophysiological study were recruited from 18 European/US centers. Electrophysiological study, imaging, and outcomes data after ablation were assessed in relation to genotype. RESULTS: Seventy-one patients were included (49.6 Q1-Q3 [40-60] years, 76% men). They were divided into 4 groups according to the affected protein: desmosomal (DSP, PKP2, DSG2, and DSC2), nuclear membrane (LMNA and TMEM43), cytoskeleton (FLNC and DES), and sarcoplasmic reticulum (PLN). Desmosomal genes, TMEM43, and PLN were associated with biventricular disease, while variants in LMNA and cytoskeleton genes had predominant left ventricle involvement (P=0.001). The location of the clinical-SMVT substrate was significantly different based on genotype (P=0.005). DSP and cytoskeleton genes presented SMVTs with right bundle branch block morphology, which origin was identified in the inferolateral segments of the left ventricle. The other desmosomal genes (PKP2 and DSG2), along with TMEM43, showed SMVTs with left bundle branch block morphology and predominantly right ventricular substrate. In contrast, LMNA substrate was mainly observed in the interventricular septum. During a median of 26 Q1-Q3 (10.6-65) months, 27% of patients experienced recurrences of clinical SMVT with differences between genotypes (log-rank 0.016). Nuclear membrane genes demonstrated the highest recurrence rate compared with desmosomal genes (hazard ratio, 4.56 [95% CI, 1.5-13.8]). CONCLUSIONS: The anatomic substrate of SMVTs shows a strong correlation with the underlying genotype, electrocardiographic morphology, and recurrence rate. Particularly, patients with nuclear membrane gene variants have a significantly higher recurrence rate compared with those with desmosomal gene variants.

• MeSH
• akční potenciály MeSH
• dospělí MeSH
• elektrofyziologické techniky kardiologické MeSH
• fenotyp * MeSH
• genetická predispozice k nemoci * MeSH
• genetické asociační studie MeSH
• genotyp MeSH
• hodnocení rizik MeSH
• kardiomyopatie genetika   patofyziologie   diagnóza   MeSH
• katetrizační ablace MeSH
• komorová tachykardie * genetika   patofyziologie   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• rizikové faktory MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• Geografické názvy
• Evropa MeSH

The somatostatin (SST) receptor family controls pituitary hormone secretion, but the distribution and specific roles of these receptors on the excitability and voltage-gated calcium signaling of hormone producing pituitary cells have not been fully characterized. Here we show that the rat pituitary gland expressed Sstr1, Sstr2, Sstr3, and Sstr5 receptor genes in a cell type-specific manner: Sstr1 and Sstr2 in thyrotrophs, Sstr3 in gonadotrophs and lactotrophs, Sstr2, Sstr3, and Sstr5 in somatotrophs, and none in corticotrophs and melanotrophs. Most gonadotrophs and thyrotrophs spontaneously fired high-amplitude single action potentials, which were silenced by SST without affecting intracellular calcium concentrations. In contrast, lactotrophs and somatotrophs spontaneously fired low-amplitude plateau-bursting action potentials in conjunction with calcium transients, both of which were silenced by SST. Moreover, SST inhibited GPCR-induced voltage-gated calcium signaling and hormone secretion in all cell types expressing SST receptors, but the inhibition was more pronounced in somatotrophs. The pattern of inhibition of electrical activity and calcium signaling was consistent with both direct and indirect inhibition of voltage-gated calcium channels, the latter being driven by cell type-specific hyperpolarization. These results indicate that the action of SST in somatotrophs is enhanced by the expression of several types of SST receptors and their slow desensitization, that SST may play a role in the electrical resynchronization of gonadotrophs, thyrotrophs, and lactotrophs, and that the lack of SST receptors in corticotrophs and melanotrophs keeps them excitable and ready to responses to stress.

• MeSH
• akční potenciály účinky léků   MeSH
• gonadotropní buňky metabolismus   účinky léků   MeSH
• hypofýza * metabolismus   MeSH
• krysa rodu rattus MeSH
• potkani Wistar MeSH
• receptory somatostatinu * metabolismus   genetika   MeSH
• somatostatin metabolismus   MeSH
• vápník metabolismus   MeSH
• vápníková signalizace * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: Catheter ablation is an effective treatment method for recurrent ventricular tachycardias (VTs). However, at least in part, procedural and clinical outcomes are limited by challenges in generating an adequate lesion size in the ventricular myocardium. We investigated procedural and clinical outcomes of VT ablation using a novel 'large-footprint' catheter that allows the creation of larger lesions either by radiofrequency (RF) or by pulsed field (PF) energy. METHODS AND RESULTS: In prospectively collected case series, we describe our initial experience with VT ablation using a lattice-tip, dual-energy catheter (Sphere-9, Medtronic), and a compatible proprietary electroanatomical mapping system (Affera, Medtronic). The study population consisted of 18 patients (aged 55 ± 15 years, one woman, structural heart disease: 94%, ischaemic heart disease: 56%, left ventricular ejection fraction: 34 ± 10%, electrical storm: 22%) with recurrent sustained VTs and ≥1 previously failed endocardial RF ablation with conventional irrigated-tip catheter in 66% of patients. On average, 12 ± 7 RF and 8 ± 9 PF applications were delivered per patient. In three-fourths of patients undergoing percutaneous epicardial ablation, spasms in coronary angiography were observed after PF applications. All resolved after intracoronary administration of nitrates. No acute phrenic nerve palsy was noted. One patient suffered from a stroke that resolved without sequelae. Post-ablation non-inducibility of VT was achieved in 89% of patients. Ventricular-arrhythmia-free survival at three months was 78%. CONCLUSION: VT ablation using a dual-energy lattice-tip catheter and a novel electroanatomical mapping system is feasible. It allows rapid mapping and effective substrate modification with good outcomes during short-term follow-up.

• MeSH
• akční potenciály MeSH
• časové faktory MeSH
• design vybavení MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• elektrofyziologické techniky kardiologické * MeSH
• katetrizační ablace * metody   přístrojové vybavení   škodlivé účinky   MeSH
• komorová tachykardie * chirurgie   patofyziologie   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• recidiva MeSH
• senioři MeSH
• srdeční katétry * MeSH
• studie proveditelnosti * MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Úvod: Recentně narůstá klinický význam hodnocení čichových evokovaných potenciálů – olfactory event-related potentials (OERPs) a trigeminálních evokovaných potenciálů – trigeminal event-related potentials (TERPs) v diagnostice poruch čichu. Výhodou objektivní metody je, že OERPs jsou méně zkreslené než rutinně užívané psychofyzikální čichové testy. Klinický olfaktometr dává přesně definované čichové podněty potřebné k vyvolání OERPs a TERPs. Princip metody je založen na prezentaci odorantu pomocí speciálního zařízení v nosní dutině pacienta a registraci odpovědi mozku pomocí elektroencefalografie (EEG) na čichové a trigeminální podněty. U OERPs a TERPs hodnotíme latence a amplitudy jednotlivých peaků a intervalu N1–P2. Absence OERPs je silným prediktorem přítomnosti čichové dysfunkce. Cíl této studie: Podat první informaci o této v České republice unikátní metodě, demonstrovat OERPs a TERPs křivky u jednotlivých onemocnění spojených s poruchou čichu. Tyto výsledky budou dobrým základem pro další výzkumné projekty v oblasti poruch čichu. Metoda a materiál: V období 3/2021–6/2024 bylo do prospektivní studie zařazeno 187 subjektů (99 žen a 88 mužů). Pro měření jsme použili klinický olfaktometr OL 024 Burghart a 8kanálový EEG systém OL 026 Burghart. Výsledky: Předkládáme příkladové křivky OERPs a TERPs z jednolivých skupin zařazených subjektů: 1. skupina zařazených normosmických subjektů jsou zdraví participanti, subjekty s deviací nosního septa; 2. skupinu tvoří subjekty s chronickou rinosinusitidou s nosní polypózou; 3. skupina zahrnuje subjekty po prodělání covidu-19; 4. skupina zařazených jsou subjekty s neurodegenerativním onemocněním, s Parkinsonovou chorobou, s roztroušenou sklerózou; 5. skupina zahrnuje subjekty s tumory vedlejších nosních dutin, olfaktorní oblasti, hypofýzy; 6. skupina je tvořena subjekty s poruchou čichu, které byly indikovány k vyšetření z mediko-legálních důvodů; 7. skupinou jsou zařazené subjekty s poúrazovou ztráta čichu. Závěr: Jsou demonstrovány příkladové křivky OERPs a TERPs. Získaná data mohou být velmi dobře aplikována v budoucnu jako vnitřní vodítko pro naše další probíhající výzkumné studie čichu. Absence čichových evokovaných potenciálů je silným prediktorem přítomnosti čichové dysfunkce. Objektivní olfaktometrie se jeví jako metoda s narůstajícím potenciálem, a to hlavně u osob, které obtížně zvládají běžně dostupné psychofyzické testování čichu, u pacientů s neurodegenerativním onemocněním, a v oblasti lékařsko-pracovně-právní.

Introduction: The clinical importance of olfactory evoked potentials (OERPs) and trigeminal evoked potentials (TERPs) in the diagnosis of olfactory disorders has recently increased. The advantage of the objective method is that OERPs are less biased than routinely used psychophysical olfactory tests. The clinical olfactometer gives precisely defined olfactory stimuli needed to elicit OERPs and TERPs. The principle of the method is based on the presentation of an odorant by a special device in the patient‘s nasal cavity and the registration of the brain response by electroencephalography (EEG) to the olfactory and trigeminal stimuli. For OERPs and TERPs, we evaluate the latencies and amplitudes of individual peaks and the N1–P2 interval. The absence of OERPs is a strong predictor of the presence of olfactory dysfunction. Aim of this study: These data will be a good basis for further research projects in the field of olfactory disorders. Materials and methods: Between 3/2021 and 6/2024, 187 subjects (99 females and 88 males) were enrolled in a prospective study. A clinical olfactometer OL 024 Burghart and an 8-channel EEG system OL 026 Burghart were used for measurements. Results: We present sample OERPs and TERPs curves from single groups of enrolled subjects. The 1st group of normosmic subjects – healthy participants, subjects with a deviation of the nasal septum. The 2nd group consists of subjects with chronic rhinosinusitis with nasal polyposis. The 3rd group includes subjects after undergoing COVID-19. The 4th group of enrolees are subjects with neurodegenerative disease, Parkinson‘s disease, and multiple sclerosis. The 5th group includes subjects with tumors of the paranasal sinuses, olfactory region, and pituitary gland. The 6th group consists of subjects with olfactory disorders who were indicated for examination for medico-legal reasons. The 7th group consists of subjects with post-traumatic loss of smell. Conclusion: Sample OERPs and TERPs curves are demonstrated. The data obtained may very well be applied in the future as an internal guide for our other ongoing olfaction research studies. The absence of olfactory evoked potentials is a robust predictor of the presence of olfactory dysfunction. Objective olfactometry appears to be a method with increasing potential, especially in persons who have difficulty with commonly available psychophysical testing of the sense of smell, in patients with neurodegenerative disease, and in the medicolegal field.

• Klíčová slova
• čichové evokované potenciály, trigeminální evokované potenciály,
• MeSH
• evokované potenciály * MeSH
• lidé MeSH
• odoranty MeSH
• olfaktometrie * metody   MeSH
• poruchy čichu diagnostické zobrazování   MeSH
• prospektivní studie MeSH
• somatosenzorické evokované potenciály MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

The relationship between working memory (WM) and neuronal oscillations can be studied in detail using brain stimulation techniques, which provide a method for modulating these oscillations and thus influencing WM. The endogenous coupling between the amplitude of gamma oscillations and the phase of theta oscillations is crucial for cognitive control. Theta/gamma peak-coupled transcranial alternating current stimulation (TGCp-tACS) can modulate this coupling and thus influence WM performance. This study investigated the effects of TGCp-tACS on WM in older adults and compared their responses with those of younger participants from our previous work who underwent the same experimental design. Twenty-eight older subjects underwent both TGCp-tACS and sham stimulation sessions at least 72 h apart. Resting-state electroencephalography (EEG) was recorded before and after the interventions, and a WM task battery with five different WM tasks was performed during the interventions to assess various WM components. Outcomes measured included WM task performance (e.g., accuracy, reaction time (RT)) and changes in power spectral density (PSD) in different frequency bands. TGCp-tACS significantly decreased accuracy and RT on the 10- and 14-point Sternberg tasks and increased RT on the Digit Symbol Substitution Test in older adults. In contrast, younger participants showed a significant increase in accuracy only on the 14-item Sternberg task. Electrophysiological analysis revealed a decrease in delta and theta PSD and an increase in high gamma PSD in both younger and older participants after verum stimulation. In conclusion, theta-gamma coupling is essential for WM and modulation of this coupling affects WM performance. The effects of TGCp-tACS on WM vary with age due to natural brain changes. To better support older adults, the study suggests several strategies to improve cognitive function, including: Adjusting stimulation parameters, applying stimulation to two sites, conducting multiple sessions, and using brain imaging techniques for precise targeting.

• MeSH
• dospělí MeSH
• elektroencefalografie MeSH
• gama rytmus EEG * fyziologie   MeSH
• krátkodobá paměť * fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• přímá transkraniální stimulace mozku * MeSH
• reakční čas fyziologie   MeSH
• senioři MeSH
• stárnutí fyziologie   MeSH
• theta rytmus EEG * fyziologie   MeSH
• zdraví MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The current study examines the effects of trait aggressiveness, inhibitory control and emotional states on aggressive behavior in a laboratory paradigm. One hundred and fifty-one adult participants took part (73 men, 71 women, and 7 nondisclosed). Event Related Potentials (ERPs) during a Go/No-Go task were utilized to capture the extent of inhibitory processing, with a laboratory provocation paradigm used to assess aggression. Contrary to the expectations, negative affective responses to provocation were negatively associated only with short-lived aggression and only among those with high past aggressiveness. Furthermore, past aggressiveness was related to a continuous increase in laboratory aggressive behavior regardless of the level of inhibitory control (P3 difference amplitude). However, feeling hostile was associated with short-lived aggressive behavior, only in those with lower levels of inhibitory control. These findings demonstrate the effect of distinct mechanisms on different patterns of aggressive behavior.

• MeSH
• agrese * psychologie   fyziologie   MeSH
• dospělí MeSH
• elektroencefalografie MeSH
• emoce * fyziologie   MeSH
• evokované potenciály fyziologie   MeSH
• inhibice (psychologie) * MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nepřátelství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

This work presents results on the efficiency of newly designed zinc phthalocyanine-mediated photodynamic therapy of both tumoral and nontumoral cell models using the MTT assay. Further detailed examinations of mechanistic and cell biological effects were focused on the HELA cervical cancer cell model. Here, ROS production, changes in the mitochondrial membrane potential, the determination of genotoxicity, and protein changes determined by capillary chromatography and tandem mass spectrometry with ESI were analyzed. The results showed that, in vitro, 5 Jcm-2 ZnPc PDT caused a significant increase in reactive oxygen species. Still, except for superoxide dismutase, the levels of proteins involved in cell response to oxidative stress did not increase significantly. Furthermore, this therapy damaged mitochondrial membranes, which was proven by a more than 70% voltage-dependent channel protein 1 level decrease and by a 65% mitochondrial membrane potential change 24 h post-therapy. DNA impairment was assessed by an increased level of DNA fragmentation, which might be related to the decreased level of DDB1 (decrease in levels of more than 20% 24 h post-therapy), a protein responsible for maintaining genomic integrity and triggering the DNA repair pathways. Considering these results and the low effective concentration (LC50 = 30 nM), the therapy used is a potentially very promising antitumoral treatment.

• MeSH
• fotochemoterapie * metody   MeSH
• fotosenzibilizující látky * farmakologie   chemie   MeSH
• HeLa buňky MeSH
• indoly * farmakologie   chemie   MeSH
• isoindoly * MeSH
• lidé MeSH
• membránový potenciál mitochondrií * účinky léků   MeSH
• organokovové sloučeniny * farmakologie   chemie   MeSH
• oxidační stres účinky léků   MeSH
• poškození DNA účinky léků   MeSH
• reaktivní formy kyslíku * metabolismus   MeSH
• sloučeniny zinku * farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH