Publications by authors named "Jan Azarov"

25 Publications

  • Page 1 of 1

Prolongation of experimental diabetes mellitus increased susceptibility to reperfusion ventricular tachyarrhythmias.

Can J Physiol Pharmacol 2021 May 5:1-5. Epub 2021 May 5.

Department of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, 50 Pervomayskaya Street, 167982 Syktyvkar, Russia.

Diabetes mellitus (DM) is associated with increased risk of sudden cardiac death, but its role in arrhythmogenesis is not clear. We evaluated contributions of DM duration and hyperglycemia level to development of proarrhythmic electrophysiological changes in the experimental ischemia/reperfusion model. Ventricular epicardial 64-lead mapping and arrhythmia susceptibility burst-pacing testing were performed in 43 healthy and 55 diabetic (alloxan model) anesthetized rabbits undergoing 15 min left anterior descending coronary artery occlusion, followed by 15 min reperfusion. During ischemia, arrhythmia inducibility did not differ between the groups, but the number of reperfusion ventricular tachycardias and (or) fibrillations (VT/VFs) were higher in the DM group (14 out of 55) as compared with control (3 out of 43, = 0.017). In the diabetic animals, both DM duration and glucose concentration were associated with reperfusion VT/VF development in univariate logistic regression analysis (odds ratio (OR) 1.058, 95% confidence interval (CI) 1.025-1.092, < 0.001; and OR 1.119, 95% CI 1.045-1.198, = 0.001, respectively). Only the DM duration, however, remained an independent predictor of reperfusion VT/VF in multivariate logistic regression analysis (OR 1.060, 95% CI 1.006-1.117, = 0.029). Among mapping parameters, DM duration was associated with the prolongation of total ventricular activation duration (regression coefficient 0.152, 95% CI 0.049-0.255, = 0.005) and activation-repolarization intervals (ARIs) (regression coefficient 0.900, 95% CI 0.315-1.484, = 0.003). The prolonged ARI was the only mapping characteristic predicting reperfusion VT/VF development (OR 1.028, 95% CI 1.009-1.048, = 0.004). The DM duration-dependent prolongation of ventricular repolarization presents a link between DM development and reperfusion VT/VF inducibility.
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http://dx.doi.org/10.1139/cjpp-2020-0743DOI Listing
May 2021

J wave is an underestimated ECG marker of risk in acute ischemia.

J Electrocardiol 2021 May-Jun;66. Epub 2021 Feb 14.

(a)Department of Cardiology, Clinical Sciences, Lund University, 22185 Lund, Sweden. Electronic address:

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http://dx.doi.org/10.1016/j.jelectrocard.2021.01.023DOI Listing
July 2021

Melatonin Prevents Early but Not Delayed Ventricular Fibrillation in the Experimental Porcine Model of Acute Ischemia.

Int J Mol Sci 2020 Dec 30;22(1). Epub 2020 Dec 30.

Department of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, 167000 Syktyvkar, Russia.

Antiarrhythmic effects of melatonin have been demonstrated ex vivo and in rodent models, but its action in a clinically relevant large mammalian model remains largely unknown. Objectives of the present study were to evaluate electrophysiological and antiarrhythmic effects of melatonin in a porcine model of acute myocardial infarction. Myocardial ischemia was induced by 40-min coronary occlusion in 25 anesthetized pigs. After ischemia onset, 12 animals received melatonin (4 mg/kg). 48 intramyocardial electrograms were recorded from left ventricular wall and interventricular septum (IVS). In each lead, activation time (AT) and repolarization time (RT) were determined. During ischemia, ATs and dispersion of repolarization (DOR = RTmax - RTmin) increased reaching maximal values by 3-5 and 20-25 min, respectively. Ventricular fibrillation (VF) incidence demonstrated no relations to redox state markers and was associated with increased DOR and delayed ATs (specifically, in an IVS base, an area adjacent to the ischemic zone) ( = 0.031). Melatonin prevented AT increase in the IVS base, ( < 0.001) precluding development of early VF (1-5 min, = 0.016). VF occurrence in the delayed phase (17-40 min) where DOR was maximal was not modified by melatonin. Thus, melatonin-related enhancement of activation prevented development of early VF in the myocardial infarction model.
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http://dx.doi.org/10.3390/ijms22010328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795598PMC
December 2020

Stretch-excitation correlation in the toad heart.

J Exp Biol 2020 12 7;223(Pt 23). Epub 2020 Dec 7.

Department of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, Syktyvkar, 167982, Komi Republic, Russia

The activation sequence of the ventricular myocardium in ectotherms is a matter of debate. We studied the correlation between the ventricular activation sequence and the pattern of local stretches in 13 toads (). Epicardial potential mapping was done with a 56-lead sock array. Activation times were determined as d/d (min) in each lead. Initial epicardial foci of activation were found on the left side of the ventricular base, whereas regions on the apex and the right side of the base demonstrated late activation. Video recordings (50 frames s) showed that the median presystolic stretch in left-side ventricular regions was greater than that in right-side regions [4.70% (interquartile range 3.25-8.85%) versus 1.45% (interquartile range 0.38-3.05%), =0.028, respectively]. Intracardiac bolus injection elicited ventricular activation with a similar sequence and duration. Thus, ventricular areas of earliest activation were associated with greater presystolic stretch, implying the existence of a stretch-excitation relationship in ectotherm hearts.
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http://dx.doi.org/10.1242/jeb.228882DOI Listing
December 2020

Contribution of Depolarization and Repolarization Changes to J-Wave Generation and Ventricular Fibrillation in Ischemia.

Front Physiol 2020 30;11:568021. Epub 2020 Sep 30.

Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.

: Activation delay in ischemic myocardium has been found to contribute to J-wave appearance and to predict ventricular fibrillation (VF) in experimental myocardial infarction. However, the role of ischemia-related repolarization abnormalities in J-wave generation remains unclear. : The objective of our study was to assess a contribution of myocardial repolarization changes to J-wave generation in the body surface ECG and VF in a porcine acute myocardial infarction model. : In 22 anesthetized pigs, myocardial ischemia was induced by occlusion of the left anterior descending coronary artery (LAD, = 14) and right coronary artery (RCA, = 8). Body surface ECGs were recorded simultaneously with intramyocardial unipolar electrograms led from flexible electrodes positioned across the left ventricular (LV) wall, interventricular septum (IVS), and right ventricular (RV) wall at apical, middle and basal levels of the ventricles (a total of 48 leads). Local activation times (ATs) and activation-repolarization intervals (ARIs, differences between dV/dt maximum during T-wave and dV/dt minimum during QRS) were measured. : J-waves appeared in left precordial leads (in 11 out of 14 animals with LAD occlusion) and right precordial leads (in six out of eight animals with RCA occlusion). During ischemic exposure, ATs prolonged, and the activation delay was associated with J-wave development (OR = 1.108 95% CI 1.072-1.144; < 0.001) and VF incidence (OR = 1.039 95% CI 1.008-1.072; = 0.015). ARIs shortened in the ischemic regions (in the IVS under LAD-occlusion and the lateral RV base under RCA-occlusion). The difference between maximal ARI in normal zones and ARI in the ischemic zones (ΔARI) was associated with J-wave appearance (OR = 1.025 95% CI 1.016-1.033, < 0.001) independently of AT delay in multivariate logistic regression analysis. : Both AT delay and increase of ΔARIs contributed to the development of J-wave in body surface ECG. However, only AT delay was associated with VF occurrence.
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http://dx.doi.org/10.3389/fphys.2020.568021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556294PMC
September 2020

ECG markers of local but not global increase in dispersion of ventricular repolarization (simulation study).

J Electrocardiol 2020 May - Jun;60:54-59. Epub 2020 Mar 20.

Department of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, 50, Pervomayskaya st., Syktyvkar 167982, Russia; Department of Physiology, Medical Institute of Pitirim Sorokin, Syktyvkar State University, 11, Babushkin st., Syktyvkar 167000, Russia.

Background: An increase in local dispersion of repolarization (DOR) may contribute more to arrhythmogenesis as compared to changes of global DOR. The aim of this simulation study was to find ECG markers of local increase in DOR in conditions where global DOR remains normal.

Methods: In the framework of van Oosterom and Oostendorp ECGSIM model, the local DOR was increased in 10 different ventricular locations by (1) action potential duration (APD) shortening/lengthening both on epi- and endocardium, (2) epicardial APD shortening, and (3) endocardial APD shortening. The simulation cases where the increase in local DOR was accompanied by increase in global DOR were excluded from consideration. T-wave parameters were analyzed in the simulated precordial and anatomically ordered limb leads.

Results: The increase in local DOR resulted in increased lead-to‑lead differences in Tpeak and Tend instants in 28 out of 32 simulated scenarios, and in an increased dispersion of Tpeak-Tend interval throughout 12 standard leads in 8 out of 32 simulated scenarios. In all simulations, the global DOR measured as a difference between earliest and latest repolarization times and standard APD deviation was the same.

Conclusions: The local increase in DOR was expressed in increased lead-to‑lead differences in Tpeak and Tend instants between adjacent anatomically ordered standard leads (aVL, I, aVR(-), II, aVF, III, and V1-V6), even if global DOR, Tpeak-Tend interval and Tpeak-Tend dispersion were within a normal range.
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http://dx.doi.org/10.1016/j.jelectrocard.2020.03.009DOI Listing
June 2021

Association Between Antiarrhythmic, Electrophysiological, and Antioxidative Effects of Melatonin in Ischemia/Reperfusion.

Int J Mol Sci 2019 Dec 15;20(24). Epub 2019 Dec 15.

Institute of Physiology, Federal Research Centre, Komi Science Centre, Ural Branch of Russian Academy of Sciences, Pervomayskaya st. 50, 167982 Syktyvkar, Russia.

Melatonin is assumed to confer cardioprotective action via antioxidative properties. We evaluated the association between ventricular tachycardia and/or ventricular fibrillation (VT/VF) incidence, oxidative stress, and myocardial electrophysiological parameters in experimental ischemia/reperfusion under melatonin treatment. Melatonin was given to 28 rats (10 mg/kg/day, orally, for 7 days) and 13 animals received placebo. In the anesthetized animals, coronary occlusion was induced for 5 min followed by reperfusion with recording of unipolar electrograms from ventricular epicardium with a 64-lead array. Effects of melatonin on transmembrane potentials were studied in ventricular preparations of 7 rats in normal and "ischemic" conditions. Melatonin treatment was associated with lower VT/VF incidence at reperfusion, shorter baseline activation times (ATs), and activation-repolarization intervals and more complete recovery of repolarization times (RTs) at reperfusion (less baseline-reperfusion difference, ΔRT) ( < 0.05). Superoxide dismutase (SOD) activity was higher in the treated animals and associated with ΔRT ( = 0.001), whereas VT/VF incidence was associated with baseline ATs ( = 0.020). In vitro, melatonin led to a more complete restoration of action potential durations and resting membrane potentials at reoxygenation ( < 0.05). Thus, the antioxidative properties of melatonin were associated with its influence on repolarization duration, whereas the melatonin-related antiarrhythmic effect was associated with its oxidative stress-independent action on ventricular activation.
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http://dx.doi.org/10.3390/ijms20246331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941092PMC
December 2019

Prolongation of The Activation Time in Ischemic Myocardium is Associated with J-wave Generation in ECG and Ventricular Fibrillation.

Sci Rep 2019 08 21;9(1):12202. Epub 2019 Aug 21.

Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.

J-wave pattern has been recognized as an arrhythmic risk marker, particularly in myocardial infarction patients. Mechanisms underlying J-wave development in ischemia remain unknown. In myocardial infarction model, we evaluated activation time delay as a prerequisite of J-wave appearance and predictor of ventricular fibrillation. Body surface ECGs and myocardial unipolar electrograms were recorded in 14 anesthetized pigs. 48 intramural leads were positioned across ventricular free walls and interventricular septum. Myocardial ischemia was induced by ligation of the left anterior descending coronary artery and the recordings were done during 40-minute coronary occlusion. The local activation times were determined as instants of dV/dt minimum during QRS complex in unipolar electrograms. During occlusion, ventricular local activation time prolonged in the middle portion of the left ventricular free wall, and basal and middle portions of septum, while J-waves appeared in precordial leads in 11 animals. In logistic regression and ROC curve analyses, activation time delay at a given time-point was associated with J-wave development, and a longer activation time was associated with ventricular fibrillation appearance. In experimental coronary occlusion, activation delay in ischemic myocardium was associated with generation of the J waves in the body surface ECG and predicted ventricular fibrillation.
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http://dx.doi.org/10.1038/s41598-019-48710-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704253PMC
August 2019

Multi-lead vs single-lead T -T interval measurements for prediction of reperfusion ventricular tachyarrhythmias.

J Cardiovasc Electrophysiol 2019 10 21;30(10):2090-2097. Epub 2019 Aug 21.

Department of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, Syktyvkar, Russia.

Introduction: Electrocardiographic T -T interval (Tp-Te) is a promising marker for the prediction of ventricular tachycardia and/or ventricular fibrillation (VT/VF). The study was aimed to compare single-lead vs multilead Tp-Te variables as VT/VF predictors in experimental ischemia/reperfusion model.

Methods And Results: Computer simulations were done using the ECGSIM model with an ischemic region set in anterior left ventricular apex. In 18 anesthetized cats, myocardial ischemia was induced by 30-minute ligation of left anterior descending coronary artery followed by reperfusion. Body surface ECGs in limb leads and modified precordial leads were recorded. Tp-Te was detected automatically in individual leads with a custom-designed parametric algorithm. Tp-Te dispersion and total Tp-Te were calculated as a difference between the maximal and minimal value of individual Tp-Te(s) and an interval between the earliest Tpeak and the latest Tend throughout all leads, respectively. Simulations showed that the increase of local, but not total, dispersion of repolarization characteristic for ischemic damage led to nonuniform shortening of T-peak times across 12 standard leads, which in turn resulted in the increase of single-lead Tp-Te(s), total Tp-Te and Tp-Te dispersion. Animals experienced VT/VF showed increased Tp-Te dispersion and total Tp-Te during reperfusion. In univariate logistic regression analysis, only the Tp-Te dispersion at the beginning of reperfusion was associated with the VT/VF incidence. According to ROC curve analysis, the optimal cut-off value of the Tp-Te dispersion was 17 ms (sensitivity 0.71, specificity 0.80).

Conclusions: The reperfusion VT/VFs were independently predicted by increased Tp-Te dispersion, which suggests the importance of multi-lead evaluation of Tp-Te intervals.
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http://dx.doi.org/10.1111/jce.14105DOI Listing
October 2019

Excitation of murine cardiac myocytes by nanosecond pulsed electric field.

J Cardiovasc Electrophysiol 2019 03 17;30(3):392-401. Epub 2019 Jan 17.

Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, Virginia.

Introduction: Opening of voltage-gated sodium channels takes tens to hundreds of microseconds, and mechanisms of their opening by nanosecond pulsed electric field (nsPEF) stimuli remain elusive. This study was aimed at uncovering the mechanisms of how nsPEF elicits action potentials (APs) in cardiomyocytes.

Methods And Results: Fluorescent imaging of optical APs (FluoVolt) and Ca -transients (Fluo-4) was performed in enzymatically isolated murine ventricular cardiomyocytes stimulated by 200-nanosecond trapezoidal pulses. nsPEF stimulation evoked tetrodotoxin-sensitive APs accompanied or preceded by slow sustained depolarization (SSD) and, in most cells, by transient afterdepolarization waves. SSD threshold was lower than the AP threshold (1.26 ± 0.03 vs 1.34 ± 0.03 kV/cm, respectively, P < 0.001). Inhibition of l-type calcium and sodium-calcium exchanger currents reduced the SSD amplitude and increased the AP threshold ( P < 0.05). The threshold for Ca -transients (1.40 ± 0.04 kV/cm) was not significantly affected by a tetrodotoxin-verapamil cocktail, suggesting the activation of a Ca entry pathway independent from the opening of Na or Ca voltage-gated channels. Removal of external Ca decreased the SSD amplitude ( P = 0.004) and blocked Ca -transients but not APs. The incidence of transient afterdepolarization waves was decreased by verapamil and by removal of external Ca ( P = 0.002).

Conclusions: The study established that nsPEF stimulation caused calcium entry into cardiac myocytes (including routes other than voltage-gated calcium channels) and SSD. Tetrodotoxin-sensitive APs were mediated by SSD, whose amplitude depended on the calcium entry. Plasma membrane electroporation was the most likely primary mechanism of SSD with additional contribution from l-type calcium and sodium-calcium exchanger currents.
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http://dx.doi.org/10.1111/jce.13834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422740PMC
March 2019

Repolarization in perfused myocardium predicts reperfusion ventricular tachyarrhythmias.

J Electrocardiol 2018 May - Jun;51(3):542-548. Epub 2017 Dec 6.

Laboratory of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, Pervomayskaya st., 50, Syktyvkar, Russia; Department of Physiology, Medical Institute of Pitirim Sorokin Syktyvkar State University, Oktyabrskiy pr., 55, Syktyvkar, Russia.

Background: Aim of the study was to find out which myocardial repolarization parameters predict reperfusion ventricular tachycardia and fibrillation (VT/VF) and determine how these parameters express in ECG.

Methods: Coronary occlusion and reperfusion (30/30min) was induced in 24 cats. Local activation and end of repolarization times (RT) were measured in 88 intramyocardial leads. Computer simulations of precordial electrograms were performed.

Results: Reperfusion VT/VF developed in 10 animals. Arrhythmia-susceptible animals had longer RTs in perfused areas [183(177;202) vs 154(140;170) ms in susceptible and resistant animals, respectively, P<0.05]. In logistic regression analysis, VT/VFs were associated with prolonged RTs in the perfused area (OR 1.068; 95% CI 1.012-1.128; P=0.017). Simulations demonstrated that prolonged repolarization in the perfused/border zone caused precordial terminal T-wave inversion.

Conclusions: The reperfusion VT/VFs were independently predicted by the longer RT in the perfused zone, which was reflected in the terminal negative phase of the electrocardiographic T-wave.
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http://dx.doi.org/10.1016/j.jelectrocard.2017.12.003DOI Listing
March 2019

Effect of action potential duration on T-T interval, T-wave area and T-wave amplitude as indices of dispersion of repolarization: Theoretical and simulation study in the rabbit heart.

J Electrocardiol 2017 Nov - Dec;50(6):919-924. Epub 2017 Jul 11.

Laboratory of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, 50, Pervomayskaya st., Syktyvkar 167982, Russia; Department of Physiology, Medical Institute of Pitirim Sorokin Syktyvkar State University, 11, Babushkin st., Syktyvkar 167000, Russia.

Background: The aim of the study was to differentiate the effect of dispersion of repolarization (DOR) and action potential duration (APD) on T-wave parameters being considered as indices of DOR, namely, Tpeak-Tend interval, T-wave amplitude and T-wave area.

Methods: T-wave was simulated in a wide physiological range of DOR and APD using a realistic rabbit model based on experimental data. A simplified mathematical formulation of T-wave formation was conducted.

Results: Both the simulations and the mathematical formulation showed that Tpeak-Tend interval and T-wave area are linearly proportional to DOR irrespectively of APD range, while T-wave amplitude is non-linearly proportional to DOR and inversely proportional to the minimal repolarization time, or minimal APD value.

Conclusion: Tpeak-Tend interval and T-wave area are the most accurate DOR indices independent of APD. T-wave amplitude can be considered as an index of DOR when the level of APD is taken into account.
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http://dx.doi.org/10.1016/j.jelectrocard.2017.07.001DOI Listing
August 2018

Progressive increase of the Tpeak-Tend interval is associated with ischaemia-induced ventricular fibrillation in a porcine myocardial infarction model.

Europace 2018 05;20(5):880-886

Department of Cardiology, Clinical Sciences, Lund University, SE-221 85, Lund, Sweden.

Aims: Repolarization indices of ECG have been widely assessed as predictors of ventricular arrhythmias. However, little is known of the dynamic changes of these parameters during continuous monitoring in acute ischaemic episodes. The objective of the study was to evaluate repolarization-related predictors of ventricular fibrillation (VF) during progression of experimental myocardial infarction.

Methods And Results: Myocardial infarction was induced in 27 pigs by 40-min balloon inflation in the left anterior descending coronary artery, and 12-lead ECG was continuously recorded. Rate-corrected durations of the total Tpeak-Tend intervals measured from the earliest T-wave peak to the latest T-wave end in any lead were determined at baseline and at minute 1, 2, 5, and then every 5th minute of occlusion. There were 7 early (1-3 min) and 10 delayed (15-30 min) VFs in 16 pigs. Baseline Tpeak-Tend did not differ between animals with and without VF. Tpeak-Tend interval rapidly increased immediately after balloon inflation and was greater in VF-susceptible animals at 2-15 min compared with the animals that never developed VF (P < 0.05). Tpeak-Tend was tested as a predictor of delayed VFs. Median Tpeak-Tend at 10th min of occlusion was higher in delayed VF group (n = 10) than in animals without VF (n = 11): 138 [IQR 121-148] ms vs. 111 [IQR 106-127] ms, P = 0.02. Tpeak-Tend  ≥123 ms (10th min) predicted delayed VF episodes with HR = 4.5 95% CI 1.1-17.8, P = 0.031.

Conclusion: Tpeak-Tend prolongation during ischaemia progression predicts VF in the experimental porcine myocardial infarction model and warrants further testing in clinical settings of acute coronary syndromes.
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http://dx.doi.org/10.1093/europace/eux104DOI Listing
May 2018

The Role of Transmural Repolarization Gradient in the Inversion of Cardiac Electric Field: Model Study of ECG in Hypothermia.

Ann Noninvasive Electrocardiol 2017 Jan 28;22(1). Epub 2016 Mar 28.

Laboratory of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, Syktyvkar, Russia.

Background: The changes in ventricular repolarization gradients lead to significant alterations of the electrocardiographic body surface T waves up to the T wave inversion. However, the contribution of a specific gradient remains to be elucidated. The objective of the present investigation was to study the role of the transmural repolarization gradient in the inversion of the body surface T wave with a mathematical model of the hypothermia-induced changes of ventricular repolarization.

Methods: By means of mathematical simulation, we set the hypothermic action potential duration (APD) distribution on the rabbit ventricular epicardium as it was previously experimentally documented. Then the parameters of the body surface potential distribution were tested with the introduction of different scenarios of the endocardial and epicardial APD behavior in hypothermia resulting in the unchanged, reversed or enlarged transmural repolarization gradient.

Results: The reversal of epicardial repolarization gradients (apicobasal, anterior-posterior and interventricular) caused the inversion of the T waves regardless of the direction of the transmural repolarization gradient. However, the most realistic body surface potentials were obtained when the endocardial APDs were not changed under hypothermia while the epicardial APDs prolonged. This produced the reversed and increased transmural repolarization gradient in absolute magnitude. The body surface potentials simulated under the unchanged transmural gradient were reduced in comparison to those simulated under the reversed transmural gradient.

Conclusions: The simulations demonstrated that the transmural repolarization gradient did not play a crucial role in the cardiac electric field inversion under hypothermia, but its magnitude and direction contribute to the T wave amplitude.
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http://dx.doi.org/10.1111/anec.12360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931437PMC
January 2017

Action potential duration gradients in the heart ventricles and the cardiac electric field during ventricular repolarization (a model study).

J Electrocardiol 2015 Jul-Aug;48(4):678-85. Epub 2015 Mar 12.

Laboratory of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, 50, Pervomayskaya St., Syktyvkar, Russia.

Background: We simulated contributions of transmural, apicobasal, anteroposterior and interventricular action potential duration (APD) gradients to the body surface potential distribution (BSPD) with constant or varied magnitudes of the transmural and apicobasal gradients.

Methods: Simulations were done in the framework of the discrete computer model of the rabbit heart ventricles on the basis of realistic activation sequence and APDs. The APD gradients were set constant at 20 ms or varied in the range of ±80 ms.

Results: The apicobasal, transmural and interventricular APD gradients of 20 ms produced similar BSPDs, whereas the BSPD inversion was caused by the inverted apicobasal or transmural 80 ms gradients. The transmural APD gradient produced transversal and mainly apicobasal T-wave vectors due to wall curvature and cancellation effects. The "normal" transversal and apicobasal repolarization gradients were decreased and increased by activation sequence, respectively.

Conclusion: The different APD gradients contributed consistently to the development of BSPD.
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http://dx.doi.org/10.1016/j.jelectrocard.2015.03.010DOI Listing
March 2016

Functional role of myocardial electrical remodeling in diabetic rabbits.

Can J Physiol Pharmacol 2015 Apr 22;93(4):245-52. Epub 2014 Dec 22.

Laboratory of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, 50 Pervomayskaya Street, 167982 Syktyvkar, Russia., First Department of Internal Diseases of Komi Branch of Kirov State Medical Academy, 11 Babushkin Street, Syktyvkar 167000, Russia., Department of Physiology, Medical Institute of Syktyvkar State University, 11 Babushkin Street, Syktyvkar 167000, Russia.

The objective of the study was to investigate the role of electrical remodeling of the ventricular myocardium in hemodynamic impairment and the development of arrhythmogenic substrate. Experiments were conducted with 11 healthy and 12 diabetic (alloxan model, 4 weeks) rabbits. Left ventricular pressure was monitored and unipolar electrograms were recorded from 64 epicardial leads. Aortic banding was used to provoke arrhythmia. The diabetic rabbits had prolonged QTc, with activation-recovery intervals (surrogates for repolarization durations) being relatively short on the left ventricular base and long on the anterior apical portions of both ventricles (P < 0.05). In the diabetic rabbits, a negative correlation (-0.726 to -0.817) was observed between dP/dt(max), dP/dt(min), and repolarization dispersions. Under conditions of systolic overload (5 min), tachyarrhythmias were equally rare and the QTc and activation-recovery intervals were shortened in both groups (P < 0.05), whereas QRS was prolonged in the diabetic rabbits only. The repolarization shortening was more pronounced on the apex, which led to the development of apicobasal and interventricular end of repolarization gradients in the healthy animals, and to the flattening of the repolarization profile in the diabetic group. Thus, the diabetes-related pattern of ventricular repolarization was associated with inotropic and lusitropic impairment of the cardiac pump function.
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http://dx.doi.org/10.1139/cjpp-2014-0293DOI Listing
April 2015

Effects of echinochrome on ventricular repolarization in acute ischemia.

J Electrocardiol 2015 Mar-Apr;48(2):181-6. Epub 2015 Jan 8.

Laboratory of Cardiac Physiology, Institute of Physiology, Komi Science Centre, Ural Branch, Russian Academy of Sciences, 50, Pervomayskaya St, Syktyvkar, Russian Federation; Department of Physiology, Medical Institute of Syktyvkar State University, 11, Babushkin St, Syktyvkar, Russian Federation.

Background: Myocardial ischemic electrophysiological alterations are associated with the generation of reactive oxygen species. However, electrophysiological effects of antioxidants are unclear. Our objective was to determine the effects of the antioxidant echinochrome on ventricular repolarization in a feline model of 30-min ischemia.

Methods And Results: Activation-recovery intervals were measured from 64 ventricular electrograms recorded before and during the LAD ligation in untreated animals (controls, n=5) and animals given echinochrome (1mg/kg, n=5 and 2mg/kg, n=7). In controls, ischemia resulted in the increase of repolarization dispersion, QTc and Tpeak-Tend intervals and precordial T wave amplitude dispersion. Echinochrome attenuated the ischemic increase of repolarization dispersion. The increased dose of echinochrome abolished the ischemic ECG repolarization changes but did not modify the incidence of ventricular arrhythmias.

Conclusion: Echinochrome modified ischemic alterations of repolarization dispersion that were associated with the changes of the body surface T wave amplitude dispersion and Tpeak-Tend interval.
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http://dx.doi.org/10.1016/j.jelectrocard.2015.01.003DOI Listing
November 2015

What does the T(peak)-T(end) interval reflect? An experimental and model study.

J Electrocardiol 2013 Jul-Aug;46(4):296.e1-8. Epub 2013 Mar 6.

Laboratory of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, 50, Pervomayskaya st, Syktyvkar, Russia.

Background: It is unclear whether the Tpeak-Tend interval is an index of the transmural or the total dispersion of repolarization.

Methods: We examined the Tpeak-Tend interval using a computer model of the rabbit heart ventricles based on experimentally measured transmural, apicobasal, and interventricular gradients of action potential duration.

Results: Experimentally measured activation-recovery intervals increased from apex to base, from the left ventricle to the right ventricle, and in the apical portion of the left ventricle from epicardium to endocardium and from the right side of septum to the left side. The simulated Tpeak corresponded to the earliest end of repolarization, whereas the Tend corresponded to the latest end of repolarization. The different components of the global repolarization dispersion were discerned by simulation.

Conclusions: The Tpeak-Tend interval corresponds to the global dispersion of repolarization with distinct contributions of the apicobasal and transmural action potential duration gradients and apicobasal difference in activation times.
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http://dx.doi.org/10.1016/j.jelectrocard.2013.02.001DOI Listing
January 2014

Load-induced changes in ventricular repolarization: evidence of autonomic modulation.

Can J Physiol Pharmacol 2011 Dec 24;89(12):935-44. Epub 2011 Nov 24.

a Laboratory of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, 50 Pervomayskaya Street, Syktyvkar, 167982 Russia.

Augmented hemodynamic load increases the risk of arrhythmogenesis by modulating cardiac repolarization duration. We hypothesized that the intervention on the autonomic tone may affect the load-dependent changes in ventricular repolarization. Activation-recovery intervals were measured in unipolar electrograms simultaneously recorded from 64 ventricular epicardial leads, in a total of 26 chinchilla rabbits in resting conditions, and after 1 and 10 min of aortic stenosis. Eleven animals were given atropine and propranolol before the loading. The short-term stenosis decreased the activation-recovery intervals in the right ventricle, whereas the prolonged overload increased the repolarization duration in both ventricles. The treatment with the β-adrenergic and M-cholinergic blockers prolonged the activation-recovery intervals, especially at the left ventricle, attenuating the apicobasal and interventricular gradients of repolarization duration seen in the baseline state. Further ventricular loading shortened the repolarization duration in both ventricles in animals with autonomic blockade. Thus, the autonomic tone was shown to be essential for the development of repolarization heterogeneity across the ventricles. The autonomic blockade transformed the biphasic changes of activation-recovery intervals into their monophasic shortening at aortic stenosis.
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http://dx.doi.org/10.1139/y11-098DOI Listing
December 2011

Acute effects of pacing site on repolarization and haemodynamics of the canine ventricles.

Europace 2011 Jun 18;13(6):889-96. Epub 2011 Mar 18.

Laboratory of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Division, Russian Academy of Sciences, 50 Pervomayskaya St., Syktyvkar, 167982 Russia.

Aims: To determine the repolarization duration gradients in different ventricular regions at atrial and ventricular pacing and to test the hypothesis that acute haemodynamic response to ventricular pacing is related to the lead position with respect to repolarization gradients.

Methods And Results: Repolarization durations estimated as activation-recovery intervals (ARIs) were measured from unipolar electrograms recorded in the subepicardial (Epi), mid-myocardial (Mid), and subendocardial (Endo) layers of the apical and basal parts of the right ventricle (RV) and left ventricle (LV) of 15 healthy dogs under atrial and ventricular pacing. Cardiac haemodynamic variables were measured as well. At atrial pacing, ARIs were shorter in Epi than in the innermost layers (P< 0.05) in the RV apex and LV base, but not in the LV apex and RV base. Activation-recovery intervals increased from apex to base and from base to apex in RV and LV, respectively (P ≤ 0.05). At apical or basal pacing of RV and LV, repolarization gradients decayed. The dispersion of repolarization increased at LV apical pacing and preserved at RV apical pacing. The pump function of a ventricle was altered dramatically at pacing of the area with the shorter ARIs and to a lesser degree at pacing of the area with the longer ARIs (P ≤ 0.051).

Conclusion: The transmural and apicobasal differences in repolarization durations were heterogeneously distributed at atrial pacing. The acute haemodynamic response of the individual ventricle was better with pacing of the region with the longest repolarization suggesting a promising criterion for the lead position selection on the basis of ARIs measurements.
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http://dx.doi.org/10.1093/europace/eur053DOI Listing
June 2011

The contribution of ventricular apicobasal and transmural repolarization patterns to the development of the T wave body surface potentials in frogs (Rana temporaria) and pike (Esox lucius).

Comp Biochem Physiol A Mol Integr Physiol 2011 May 31;159(1):39-45. Epub 2011 Jan 31.

Laboratory of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, 50, Pervomayskaya st., Syktyvkar, 167982, Russia.

The study aimed at the simultaneous determination of the transmural and apicobasal differences in the repolarization timing and the comparison of the contributions of these two repolarization gradients to the development of the body surface T wave potentials in animals with the single heart ventricle (fishes and amphibians). Unipolar potentials were measured on the body surface, epicardium and in the intramural (subepicardial, Epi; midmyocardial; and subendocardial, Endo) ventricular layers of 9 pike and 8 frogs. Activation times, repolarization times and activation-recovery intervals were determined. A transmural gradient in repolarization durations in frogs (Endo>Epi, P<0.024) corresponds to the gradient in repolarization times. No significant transmural difference in repolarization duration is observed in pike that produces a repolarization sequence from Endo to Epi (Endo
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http://dx.doi.org/10.1016/j.cbpa.2011.01.016DOI Listing
May 2011

Epicardial activation-to-repolarization coupling differs in the local areas and on the entire ventricular surface.

J Electrocardiol 2011 Mar-Apr;44(2):131-7. Epub 2011 Jan 8.

Laboratory of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, Syktyvkar, Russia.

Hypothesis: Local and global activation-to-repolarization coupling differ from each other. Experiments were done in 12 dogs and 7 frogs. Activation times (ATs), end of repolarization times (RTs), and activation-recovery intervals (ARIs) were measured in 24 or 64 leads on the entire ventricular surface and on the epicardial patch 5 × 5 mm. The ARI and RT dispersions were greater than AT dispersion on the entire ventricular epicardium but not in the local patch. Both ATs and ARIs were inversely related to each other in the patch but not necessarily on the entire epicardium. The RT sequence depended on the AT sequence within the local patch but not on the entire surface. The contributions of the AT sequence and ARI distribution to the RT sequence was determined by the AT/ARI dispersion ratio. Thus, the AT sequence strongly influenced the RT sequence of the local epicardial fragment but not of the entire ventricular surface.
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http://dx.doi.org/10.1016/j.jelectrocard.2010.11.007DOI Listing
July 2011

The effects of renovascular hypertension on repolarization of ventricular epicardium.

Exp Clin Cardiol 2009 ;14(2):e51-6

Laboratory of Cardiac Physiology, Institute of Physiology, Komi Science Centre, Ural Branch of the Russian Academy of Sciences;

Background And Objective: Alterations in the recovery sequence of hypertrophied myocardium favour the development of cardiac arrhythmias. The aim of the present study was to investigate apex-to-base and interventricular heterogeneities in the duration of epicardial ventricular repolarization in rats with renovascular hypertension.

Method: Renovascular hypertension was induced in six Wistar rats by constricting the left renal artery for one month. Six sham-operated Wistar rats served as normotensive controls. Epicardial mapping was performed using 32 unipolar leads distributed over the apex and base of the heart ventricles under sinus rhythm. Activation-recovery intervals (ARIs) were calculated from electrograms.

Results: The ratio of left ventricular weight to body weight was increased in hypertensive rats compared with controls. In control rats, ARIs at the base of both ventricles were shorter than those at the apex. In hypertrophied hearts, ARIs were prolonged on both the left and right ventricular epicardium. Heterogeneous prolongation was observed via reduced apex-to-base differences in ARIs and increased interventricular differences, with a trend toward increasing dispersion of ARIs. In rats with renovascular hypertension, nonuniform prolongation of epicardial ARIs on both ventricles and the changes in the ARI distribution resulted in a reduction of the repolarization time gradient between the ventricles.

Conclusion: Nonuniformly prolonged ARIs across the ventricular epicardium and the interventricular electrical inhomogeneity in rats with renovascular hypertension should be considered when interpreting the T wave alterations together with the reduction of the transmural and apex-to-base repolarization gradients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722461PMC
July 2011

Effect of the left ventricular overload on epicardial repolarization in the rabbit.

Anadolu Kardiyol Derg 2007 Jul;7 Suppl 1:93-4

Institute of Physiology, Komi Science Center, Ural Division, Russian Academy of Sciences, Syktyvkar, Komi, Russia.

Objective: We have investigated the local durations and sequence of repolarization in the ventricular epicardium in the rabbit under the increase of the left ventricular (LV) afterload.

Methods: The LV overload was produced by the 1-minute aortic stenosis up to systolic blood pressure of 140 mm Hg. The experiments were carried out on eight anaesthetized rabbits (urethane, 1.5 g/kg, ip). Unipolar electrograms were simultaneously recorded from 64 ventricular epicardial leads at 33 degrees C.

Results: At baseline state, the shortest activation-recovery intervals (ARIs) were observed in the right ventricular (RV) base, the longest ARIs in the LV apex and lateral wall, and ARIs of intermediate durations in the RV apex and LV base. According to ARI distribution, a significant gradient in repolarization times was observed between the apex and base (p<0.01). Under acute LV overload, the repolarization duration increased significantly (p<0.01) locally at the LV apex and adjacent area of the free wall. Dispersion of repolarization is increased in the apex. A decrease of ARIs (p<0.05) was observed at the RV base, as well.

Conclusion: Under acute increase in the LV afterload, ventricular epicardial activation sequence remained largely unaltered which, along with changes in local repolarization durations, resulted in the repolarization sequence being quite similar to the baseline one. The earliest repolarization occurred in posterobasal region of RV whereas the areas over the LV apex and adjacent area of the free wall were the last to repolarize.
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July 2007

Activation and repolarization patterns in the ventricular epicardium under sinus rhythm in frog and rabbit hearts.

Comp Biochem Physiol A Mol Integr Physiol 2007 Mar 10;146(3):310-6. Epub 2006 Nov 10.

Laboratory of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Division, Russian Academy of Sciences, 50, Pervomayskaya st., Syktyvkar, 167982, Russia.

Our study compared the contributions of activation sequence and local repolarization durations distribution in the organization of epicardial repolarization in animals with fast (rabbit) and slow (frog) myocardial activation under sinus rhythm. Activation times, repolarization times and activation-recovery intervals (ARI) were obtained from ventricular epicardial unipolar electrograms recorded in 13 Chinchilla rabbits (Oryctolagus cuniculus) and 10 frogs (Rana temporaria). In frogs, depolarization travels from the atrioventricular ring radially. ARIs increased progressively from the apex to the middle portion and finally to the base (502+/-75, 557+/-73, 606+/-79 ms, respectively; P<0.01). In rabbits, depolarization spread from two epicardial breakthroughs with the duration of epicardial activation being lower than that in frogs (17+/-3 vs. 44+/-18 ms; P<0.001). ARI durations were 120+/-37, 143+/-45, and 163+/-40 ms in the left ventricular apex, left, and right ventricular bases, respectively (P<0.05). In both species, repolarization sequence was directed from apex to base according to the ARI distribution with dispersion of repolarization being higher than that of activation (P<0.001). Thus, excitation spread sequence and velocity per se do not play a crucial role in the formation of ventricular epicardial repolarization pattern, but the chief factor governing repolarization sequences is the distribution of local repolarization durations.
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http://dx.doi.org/10.1016/j.cbpa.2006.10.036DOI Listing
March 2007
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