OBJECTIVES: The aim of the study was to determine whether left ventricular electrical potential measured by electromechanical mapping with the NOGA XP system has predictive value for response to CRT. BACKGROUND: Approximately 30% of patients who undergo cardiac resynchronization therapy do not see the expected effects. METHODS: The group of 38 patients qualified for CRT implantation were included in the study, of which 33 patients were analyzed. A 15% reduction in ESV after 6 months of pacing was used as a criterion for a positive response to CRT. The mean value and sum of unipolar and bipolar potentials obtained by mapping with the NOGA XP system and their predictive value in relation to the effect of CRT were analyzed using a bulls-eye projection at three levels: 1) the global value of the left ventricular (LV) potentials, 2) the potentials of the individual LV walls and 3) the mean value of the potentials of the individual segments (basal and middle) of the individual LV walls. RESULTS: 24 patients met the criterion of a positive response to CRT vs. 9 non-responders. At the global analysis stage, the independent predictors of favorable response to CRT were the sum of the unipolar potential and bipolar mean potential. In the analysis of individual left ventricular walls, the mean bipolar potential of the anterior and posterior wall and in the unipolar system, mean septal potential was found to be an independent predictor of favorable response to CRT. In the detailed segmental analysis, the independent predictors were the bipolar potential of the mid-posterior wall segment and the basal anterior wall segment. CONCLUSIONS: Measurement of bipolar and unipolar electrical potentials with the NOGA XP system is a valuable method for predicting a favorable response to CRT.

• Klíčová slova
• cardiac electrical potential, cardiac mapping, cardiac pacing, heart failure, resynchronization therapy,
• Publikační typ
• časopisecké články MeSH

Mitochondria are involved in cellular functions that transcend the traditional role of these organelles as the energy factory of the cell. Their relative inaccessibility and the difficulties involved in attempts to study them in their natural environment -- the cytosol -- has delayed much of this understanding and they still have many secrets to yield. One of the relatively new fields in this respect is undoubtedly the analysis of mitochondrial membrane potential. The realization that its alteration may have important pathophysiological consequences has led to an increased interest in measuring this variable in a variety of biological settings, including cardiovascular diseases. Measurements of mitochondrial membrane potential tell us much about the role of mitochondria in normal cell function and in processes leading to cell death. However, we must be aware of the limitations of using isolated mitochondria, single cells and different fluorescent indicators.

• MeSH
• kardiomyocyty fyziologie   MeSH
• membránové potenciály fyziologie   MeSH
• mitochondrie fyziologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Electrical restitution (ER) of cardiac cells is an aggregate of events that rhythmically restore the initial conditions of electric signal (action potential) generation. Its analysis represents an important insight into cardiac arrhythmogenesis. The aim of this work is to theoretically substantiate and verify a novel approach allowing for the quantification of the individual ionic current components of ER. A method of analysis of the primary, initial conditions-setting restitution processes (apart from the secondary, test pulse-affected ones) is proposed. Both processes are described as sums of their measurable constituents. It is demonstrated that the optimum parameter of ER is the electric charge that is transferred through ionic channels and carriers during the test impulse. The theory was tested by using voltage-clamped canine ventricular preparations and by computer simulations. The experimental ER curve of canine ventricular muscle was constructed using action potential (AP) plateau voltage and half-repolarization time as parameters. At 30 degrees C and 0.5 Hz stimulation, the ER curve peaked, on average, after 400 ms with a 10% overshoot. Of this plateau elevation, 50% was due to 4-aminopyridine-sensitive transient outward current and 44% was due to verapamil-sensitive current. The delayed outward current antagonized the overshoot by about 6%. It was found that the initial conditions (i.e. the primary restitution processes) tend to strongly alter the plateau voltage of the premature AP. However, the final deviation is by about one order less. It is concluded that the voltage-dependent secondary processes counteract the effect of the primary processes, thereby suggesting strong negative feedback control of natural APs.

• MeSH
• akční potenciály MeSH
• biofyzika MeSH
• biofyzikální jevy MeSH
• buněčná membrána metabolismus   fyziologie   MeSH
• elektrofyziologie * MeSH
• endoplazmatické retikulum metabolismus   fyziologie   MeSH
• ionty MeSH
• psi MeSH
• software MeSH
• srdeční komory patologie   MeSH
• statistické modely MeSH
• zvířata MeSH
• Check Tag
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ionty MeSH

T-tubules (TT) form a complex network of sarcolemmal membrane invaginations, essential for well-co-ordinated excitation-contraction coupling (ECC) and thus homogeneous mechanical activation of cardiomyocytes. ECC is initiated by rapid depolarization of the sarcolemmal membrane. Whether TT membrane depolarization is active (local generation of action potentials; AP) or passive (following depolarization of the outer cell surface sarcolemma; SS) has not been experimentally validated in cardiomyocytes. Based on the assessment of ion flux pathways needed for AP generation, we hypothesize that TT are excitable. We therefore explored TT excitability experimentally, using an all-optical approach to stimulate and record trans-membrane potential changes in TT that were structurally disconnected, and hence electrically insulated, from the SS membrane by transient osmotic shock. Our results establish that cardiomyocyte TT can generate AP. These AP show electrical features that differ substantially from those observed in SS, consistent with differences in the density of ion channels and transporters in the two different membrane domains. We propose that TT-generated AP represent a safety mechanism for TT AP propagation and ECC, which may be particularly relevant in pathophysiological settings where morpho-functional changes reduce the electrical connectivity between SS and TT membranes. KEY POINTS: Cardiomyocytes are characterized by a complex network of membrane invaginations (the T-tubular system) that propagate action potentials to the core of the cell, causing uniform excitation-contraction coupling across the cell. In the present study, we investigated whether the T-tubular system is able to generate action potentials autonomously, rather than following depolarization of the outer cell surface sarcolemma. For this purpose, we developed a fully optical platform to probe and manipulate the electrical dynamics of subcellular membrane domains. Our findings demonstrate that T-tubules are intrinsically excitable, revealing distinct characteristics of self-generated T-tubular action potentials. This active electrical capability would protect cells from voltage drops potentially occurring within the T-tubular network.

• Klíčová slova
• cardiac electrophysiology, excitation-contraction coupling, imaging,
• MeSH
• akční potenciály fyziologie   MeSH
• buněčná membrána MeSH
• kardiomyocyty * metabolismus   MeSH
• membránové potenciály MeSH
• optogenetika * MeSH
• sarkolema metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH

Spontaneous depolarization similar to that from the sinus node was documented from the myocardial sleeves of pulmonary veins (PV) after isolation procedures. It was then hypothesized that sinus node-like tissue is present in the PVs of humans. Based on a number of features, the myocardium of myocardial sleeves (MS) is highly arrhythmogenic. Membrane potentials originating from MS are invariably recordable at the PVs ostia in patients with atrial fibrillation (AF) and delayed conduction around the PVs ostia may play a role in re-entry process responsible for the initiation and maintenance of AF. Diagnostic and therapeutic evidence of premature atrial beats induced in MS of PVs and resulting in launch of AF was detected by 3D electroanatomic method of monophasic action potential (MAP). MAP recording plays an important role in a direct view of human myocardial electrophysiology under both physiological and pathological conditions. Its crucial importance lies in the fact that it enables the study of the action potential of myocardial cell in vivo and, therefore, the study of the dynamic relation of this potential with all the organism variables. The knowledge of pathological MAPs from PV myocardial sleeves can help us to confirm a diagnosis when finding the similar action potential morphology. MAP can be also used to evaluate the therapeutic efficiency of vagal nerves suppression, radiofrequency ablation or other treatment procedures in PVs myocardial sleeves as well as for post-treatment following up.

• MeSH
• akční potenciály fyziologie   MeSH
• elektrická stimulace metody   MeSH
• lidé MeSH
• mapování potenciálů tělesného povrchu metody   MeSH
• převodní systém srdeční fyziologie   MeSH
• srdeční frekvence fyziologie   MeSH
• venae pulmonales fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

AIMS: The standard deviation of activation time (SDAT) derived from body surface maps (BSMs) has been proposed as an optimal measure of electrical dyssynchrony in patients with cardiac resynchronization therapy (CRT). The goal of this study was two-fold: (i) to compare the values of SDAT in individual CRT patients with reconstructed myocardial metrics of depolarization heterogeneity using an inverse solution algorithm and (ii) to compare SDAT calculated from 96-lead BSM with a clinically easily applicable 12-lead electrocardiogram (ECG). METHODS AND RESULTS: Cardiac resynchronization therapy patients with sinus rhythm and left bundle branch block at baseline (n = 19, 58% males, age 60 ± 11 years, New York Heart Association Classes II and III, QRS 167 ± 16) were studied using a 96-lead BSM. The activation time (AT) was automatically detected for each ECG lead, and SDAT was calculated using either 96 leads or standard 12 leads. Standard deviation of activation time was assessed in sinus rhythm and during six different pacing modes, including atrial pacing, sequential left or right ventricular, and biventricular pacing. Changes in SDAT calculated both from BSM and from 12-lead ECG corresponded to changes in reconstructed myocardial ATs. A high degree of reliability was found between SDAT values obtained from 12-lead ECG and BSM for different pacing modes, and the intraclass correlation coefficient varied between 0.78 and 0.96 (P < 0.001). CONCLUSION: Standard deviation of activation time measurement from BSM correlated with reconstructed myocardial ATs, supporting its utility in the assessment of electrical dyssynchrony in CRT. Importantly, 12-lead ECG provided similar information as BSM. Further prospective studies are necessary to verify the clinical utility of SDAT from 12-lead ECG in larger patient cohorts, including those with ischaemic cardiomyopathy.

• Klíčová slova
• AV delay optimization, Body surface potential mapping, Cardiac resynchronization therapy, ECG imaging, Heart failure, LV lead positioning,
• MeSH
• elektrokardiografie MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• prostředky srdeční resynchronizační terapie MeSH
• reprodukovatelnost výsledků MeSH
• senioři MeSH
• srdeční arytmie terapie   MeSH
• srdeční resynchronizační terapie * metody   MeSH
• srdeční selhání * diagnóza   terapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: During electrophysiological mapping of tachycardias, putative target sites are often only truly confirmed to be vital after observing the effect of ablation. This lack of mapping specificity potentiates inadvertent ablation of innocent cardiac tissue not relevant to the arrhythmia. But if myocardial excitability could be transiently suppressed at critical regions, their suitability as targets could be conclusively determined before delivering tissue-destructive ablation lesions. We studied whether reversible pulsed electric fields (PFREV) could transiently suppress electrical conduction, thereby providing a means to dissect tachycardia circuits in vivo. METHODS: PFREV energy was delivered from a 9-mm lattice-tip catheter to the atria of 12 swine and 9 patients, followed by serial electrogram assessments. The effects on electrical conduction were explored in 5 additional animals by applying PFREV to the atrioventricular node: 17 low-dose (PFREV-LOW) and 10 high-dose (PFREV-HIGH) applications. Finally, in 3 patients manifesting spontaneous tachycardias, PFREV was applied at putative critical sites. RESULTS: In animals, the immediate post-PFREV electrogram amplitudes diminished by 74%, followed by 78% recovery by 5 minutes. Similarly, in patients, a 69.9% amplitude reduction was followed by 84% recovery by 3 minutes. Histology revealed only minimal to no focal, superficial fibrosis. PFREV-LOW at the atrioventricular node resulted in transient PR prolongation and transient AV block in 59% and 6%, while PFREV-HIGH caused transient PR prolongation and transient AV block in 30% and 50%, respectively. The 3 tachycardia patients had atypical atrial flutters (n=2) and atrioventricular nodal reentrant tachycardia. PFREV at putative critical sites reproducibly terminated the tachycardias; ablation rendered the tachycardias noninducible and without recurrence during 1-year follow-up. CONCLUSIONS: Reversible electroporation pulses can be applied to myocardial tissue to transiently block electrical conduction. This technique of pulsed field mapping may represent a novel electrophysiological tool to help identify the critical isthmus of tachycardia circuits.

• Klíčová slova
• catheters, electroporation, follow-up studies, swine, transients and migrants,
• MeSH
• atrioventrikulární blokáda * MeSH
• atrioventrikulární nodální reentry tachykardie * MeSH
• elektrofyziologické techniky kardiologické MeSH
• elektrokardiografie MeSH
• katetrizační ablace * škodlivé účinky   metody   MeSH
• lidé MeSH
• nodus atrioventricularis MeSH
• prasata MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Although cardiac resynchronization therapy (CRT) is beneficial in heart failure patients with left bundle branch block, 30% of these patients do not respond to the therapy. Identifying these patients before implantation of the device is one of the current challenges in clinical cardiology. METHODS: We verified the diagnostic contribution and an optimized computerized approach to measuring ventricular electrical activation delay (VED) from body surface 12-lead ECGs. We applied the method to ECGs acquired before implantation (baseline) in the MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation-Cardiac Resynchronization Therapy). VED values were dichotomized using its quartiles, and we tested the association of VED values with the MADIT-CRT primary end point of heart failure or death. Multivariate Cox proportional models were used to estimate the risk of study end points. In addition, the association between VED values and hemodynamic changes after CRT-D implantation was examined using 1-year follow-up echocardiograms. RESULTS: Our results showed that left bundle branch block patients with baseline VED <31.2 ms had a 35% risk of MADIT-CRT end points, whereas patients with VED ≥31.2 ms had a 14% risk (P<0.001). The hazard ratio for predicting primary end points in patients with low VED was 2.34 (95% confidence interval, 1.53-3.57; P<0.001). Higher VED values were also associated with beneficial hemodynamic changes. These strong VED associations were not found in the right bundle branch block and intraventricular conduction delay cohorts of the MADIT-CRT trial. CONCLUSIONS: Left bundle branch block patients with a high baseline VED value benefited most from CRT, whereas left bundle branch block patients with low VED did not show CRT benefits.

• Klíčová slova
• bundle-branch block, cardiac resynchronization therapy, electrocardiography, heart failure, prognosis,
• MeSH
• akční potenciály * MeSH
• blokáda Tawarova raménka diagnóza   mortalita   patofyziologie   terapie   MeSH
• časové faktory MeSH
• defibrilátory implantabilní * MeSH
• elektrická defibrilace škodlivé účinky   přístrojové vybavení   mortalita   MeSH
• elektrokardiografie * MeSH
• klinické rozhodování MeSH
• lidé středního věku MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• obnova funkce MeSH
• prediktivní hodnota testů MeSH
• randomizované kontrolované studie jako téma MeSH
• retrospektivní studie MeSH
• senioři MeSH
• srdeční frekvence MeSH
• srdeční resynchronizační terapie * škodlivé účinky   mortalita   MeSH
• srdeční selhání diagnóza   mortalita   patofyziologie   terapie   MeSH
• výběr pacientů MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The course of the total transmembrane ionic current (Ii) during a natural action potential (AP) was reconstructed from a family of current traces recorded for single voltage clamp depolarization steps to various levels. The experiments were performed on 9 papillary cat muscles driven at 0.5 per second in oxygenated 31 degrees C Tyrode. Under varying experimental conditions very good agreement was found between the resulting Ii curve and another indicator of Ii, the first time derivative of the AP (dV/dt). Furthermore, the coefficient needed to adjust dV/dt to reconstructed Ii may serve as an indicator of the membrane capacity. The results suggest the validity of the employed approximation and, in general, the adequacy of the sucrose gap technique applied to cardiac muscle.

• MeSH
• akční potenciály MeSH
• hypoxie patofyziologie   MeSH
• kočky MeSH
• kontrakce myokardu MeSH
• membránové potenciály MeSH
• papilární svaly patofyziologie   MeSH
• srdce fyziologie   MeSH
• zvířata MeSH
• Check Tag
• kočky MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The heart is the first organ required to function during embryonic development and is absolutely necessary for embryo survival. Cardiac activity is dependent on both the sinoatrial node (SAN), which is the pacemaker of heart's electrical activity, and the cardiac conduction system which transduces the electrical signal though the heart tissue, leading to heart muscle contractions. Defects in the development of cardiac electrical function may lead to severe heart disorders. The Erbb2 (Epidermal Growth Factor Receptor 2) gene encodes a member of the EGF receptor family of receptor tyrosine kinases. The Erbb2 receptor lacks ligand-binding activity but forms heterodimers with other EGF receptors, stabilising their ligand binding and enhancing kinase-mediated activation of downstream signalling pathways. Erbb2 is absolutely necessary in normal embryonic development and homozygous mouse knock-out Erbb2 embryos die at embryonic day (E)10.5 due to severe cardiac defects. We have isolated a mouse line, l11Jus8, from a random chemical mutagenesis screen, which carries a hypomorphic missense mutation in the Erbb2 gene. Homozygous mutant embryos exhibit embryonic lethality by E12.5-13. The l11Jus8 mutants display cardiac haemorrhage and a failure of atrial function due to defects in atrial electrical signal propagation, leading to an atrial-specific conduction block, which does not affect ventricular conduction. The l11Jus8 mutant phenotype is distinct from those reported for Erbb2 knockout mouse mutants. Thus, the l11Jus8 mouse reveals a novel function of Erbb2 during atrial conduction system development, which when disrupted causes death at mid-gestation.

• MeSH
• akční potenciály MeSH
• missense mutace MeSH
• myši inbrední C57BL MeSH
• myši kmene 129 MeSH
• myši transgenní MeSH
• převodní systém srdeční embryologie   patofyziologie   MeSH
• receptor erbB-2 genetika   metabolismus   MeSH
• srdce - funkce síní MeSH
• srdeční síně embryologie   metabolismus   patofyziologie   MeSH
• vrozené srdeční vady genetika   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Erbb2 protein, mouse MeSH Prohlížeč
• receptor erbB-2 MeSH