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The spatial–temporal organization of the activation, repolarization and hemodynamics of the heart ventricle in rainbow trout, Oncorhynchus mykiss, adapted to a temperature of 5–7 °C, were studied from the normal sinus rhythm (21.6 ± 4.9 bpm) to the highest possible heart rhythm (HR) (60 bpm), during which deterioration of the contractile activity of the myocardium occurred. Regardless of the HR, the main pattern of excitation of the heart ventricle was the movement of the depolarization wave from the dorsal areas of the base in the base-apical and ventral directions with the capture of the entire thickness of the walls, with a slight difference in the time of activation of the subendocardium compared to the subepicardium. The increase in HR above the sinus rhythm caused significant shortening of local repolarization durations in all areas and layers (endocardial, intramural and subepicardial) of the heart ventricle. Changes in local durations of repolarization led to an increase in the heterogeneity of repolarization of the ventricular myocardium; as a result, a deterioration of its contractility was observed. In relation to the sinus rhythm, the maximal systolic pressure in the heart ventricle decreased, the diastolic and end-diastolic pressure increased, and the maximum rates of pressure rise and fall decreased. In rainbow trout adapted to a temperature of 5–7 °C at sinus rhythm, the pumping function of the heart was probably within the upper limit of the physiological norm, and a further increase in the heart rate led to a decline in myocardial contractility.

In this work, we investigated the effect of high heart rate (HR) in vivo on the electrical properties and pumping functions of the heart ventricle of the rainbow trout (Oncorhynchus mykiss) at low ambient temperatures. HR was altered by atrial pacing. The electrocardiogram (ECG) parameters and hemodynamic parameters of the heart ventricle of rainbow trout adapted to a temperature of 5–7 °C were studied from the normal sinus rhythm (21.6 ± 4.9 bpm) to the maximum possible HR. Results show that a HR of about 60 bpm is the upper limit of the normal functional activity of the ventricle of the heart. An increase in heart rate up to 60 bpm leads to an increase in the PQ interval and QRS complex, a decrease in the QT interval on the ECG, and a violation of the rhythmic activity of the heart (i.e., the occurrence of extrasystole), as well as to a considerable change in the hemodynamic parameters of the ventricle of the heart and a decrease in its contractile properties. After a period of ventricular extrasystole for several minutes (10–15 min), the activity of the sinus node resumes but with a lower HR compared with the initial HR. The duration of the QRS complex recovers to the initial one, and the PQ and QT intervals increase. Maximum systolic pressure and end-diastolic pressure also return to their original values after extrasystolic contraction. After the experimental extrasystole, the phenomenon of the absence of an increase in HR is observed. The arising extrasystole probably has a functional nature and is one of the mechanisms of electromechanical homeostatic control in the heart.

This study investigated the effect of heart rate (HR) on the pumping function of the heart ventricle (HV) in rainbow trout Oncorhynchus mykiss acclimated to a temperature of 5–7ºC, and in adult frogs Rana temporaria at an ambient temperature of 10–12ºC. The dynamics of intracavitary ventricular pressure was recorded by transmural catheterization. HR was changed by atrial electrocardiostimulation. The increase in HR in rainbow trout resulted in a decrease in the maximal systolic ventricular pressure (MSVP), an increase of end-diastolic ventricular pressure (EDVP), and a reduction in the maximum rates of the rising and falling pressures. In the frog, MSVP and isovolumic parameters (dP/dtmax and dP/dtmin) also decreased as HR increased from 24bpm to 42bpm. The preload of the frog's HV did not change significantly, compared to the sinoatrial rhythm (SR). The maximum increase in the frequency of atrial stimulation up to 60bpm in fish and up to 42bpm in frogs resulted in a significant decrease in the myocardial contractility and deterioration of the pumping function of HV under low ambient temperature conditions.

Depolarization of the heart ventricles at an increasing heart rate was investigated in a rainbow trout Oncorhynchus mykiss (n = 14). It was shown that at an imposed supraventricular rhythm ranging from 30 to 60 bpm the depolarization wave initially propagates from the loci of earliest atrial excitation located near the atrioventricular orifice to the subendocardial trabecular layer of the noncompact myocardium and then travels towards the epicardium as well as along the wall. This indicates some preferential pathways of cardiac excitation conduction from the pacemaker zone to subendocardial myocytes. Regardless of the heart rate, the basic pattern of ventricular excitation in the rainbow trout heart consists in the propagation of the depolarization wave, which captures the entire thickness of the myocardial wall and activates the subendocardium faster than the subepicardium, from the dorsal regions of the cardiac base in basoapical and ventral directions. At a rhythm of 50–60 bpm, propagation of the depolarization wave in the basal ventricular areas is inverted from the dorsoventral to ventrodorsal direction.

We studied the effect of hypokinesia alone and in combination with cold exposure on HR and total cholesterol content in the blood serum of Wistar, WKY, and SHR rats. Irrespectively of the season, hypokinesia was associated with a decrease in HR, which is probably a result of reduced body needs due to deceleration of metabolic processes. A significant increase in total cholesterol was found under conditions of cold exposure combined with hypokinesia, which indicates qualitative structural rearrangement of energy metabolism under the influence of environmental factors. In winter, the increase in total cholesterol concentration was more pronounced (by 51.5%) in the group of hypertensive animals. Presumably, the increase in the serum concentration of total cholesterol under conditions of hypokinesia and cold exposure is a predictor of structural changes in the heart.

The contractile function of the heart was studied in adult frogs Rana temporaria under the influence of a toxic dose of isoprenaline under conditions of natural sinoatrial rhythm and during heart pacing. The dynamics of ventricular pressure was recorded with a Prucka MacLab 2000 instrument via a catheter introduced into the ventricle through the ventricular wall. Reduced (p

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.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.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, P0.05]. 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.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.

The aim of the study was to investigate the electrical activity and contractility of the heart ventricle in frogs Rana temporaria (n=14) under different heart rates. The activation time (AT, as dV/dtmin during QRS complex), the repolarization time (RT, as dV/dtmax during ST-T wave), and the activation-recovery intervals (ARIs, as difference between RT and AT) were measured. The hemodynamic variables were determined with the Prucka MacLab 2000 system. Heart rate (HR) was changed by the use of right atrium pacing from 0.6 to 1.1Hz with step 0.1Hz. The increasing HR from 0.6 Hz to 1.1Hz led to the increased duration of ARIs on the ventral and dorsal fragments of ventricular epicardium as compared with initial sinus rhythm. During the high HR, more prolonged ARIs were observed on the ventral side of the epicardium than on the dorsal surface (exclusion is supraventricular rhythm with rate of 1.1Hz). The repolarization dispersion of epicardium on the whole, as well as repolarization of both epicardial sides separately, decreased under the higher rate. Repolarization sequence depended on the activation sequence and the distribution of local repolarization durations only at supraventricular rhythm with a frequency of 1.1Hz. The indexes of pump function decreased under high HR. Thus, the increased HR resulted in a decrease in the dispersion of repolarization and ARIs; the repolarization duration of ventricular epicardium at supraventricular rhythms was shortened as compared with sinus rhythm. During an increase in HR, repolarization sequence is formed in association with the level of ARI dispersion and changes of the repolarization duration.

We studied the effect of hypokinesia combined with cold exposure on morphological parameters of the heart in Wistar-Kyoto rats and rats with spontaneous genetically determined hypertension (SHR). The pathological processes developing in the heart of white laboratory rats significantly affected cardiac function and manifested in the deterioration of the morphological structure of the heart: reduction of heart weight, thinning of the free wall of the left ventricle. These changes indicate transition to a lower energy level of functioning. At the same time, hypertrophy of the right free wall develops in both rat lines. Combined effect of hypokinesia and cold is probably a factor indirectly promoting the development of pulmonary heart.

Background — The aim of the work was to study the influence of myocardial repolarization on the indices of the pump function in animals with different types of the myocardial activation (dog, amphibians) under ectopic excitation of the ventricles. Material and Methods — Intraventricular blood pressure in animals was measured using a hemodynamic Prucka MacLab 2000 system under basal and apical locations of the stimulating electrode on the ventricles of the heart. The activation-recovery intervals (ARIs) were determined from unipolar myocardial electrograms recorded in the intramural layers of apical and basal parts of the ventricles in dog (n=16) and amphibians (toads Bufo bufo, n=11; frogs Rana temporaria, n=23). Data are presented as median with lower and upper quartiles. Results — The pacing of the left ventricle apical area in dogs with more prolonged ARIs, as compared with the base, does not change the isovolumic indices of the left ventricle pump function. However, ARIs were longer at the ventricular base – 248 (206, 260) ms for dog’s right ventricle and 742 (680, 929) ms for froggy ventricle, as compared with the apex in the canine right ventricle – 238 (219, 249) ms, and the ventricle in the amphibians – 692 (637, 860) ms. Therefore, pacing of the right ventricle in the apical area in dog and ventricular apex in amphibians leads to a significant decrease of their pump function. Conclusion — In the animals with successive (amphibians) and flash-successive (dog) types of activation of the myocardium, parameters of the pump function of ventricles were better at pacing of the area with the longest repolarization at the baseline and worse at pacing of the shortest repolarization area.

We studied electrophysiological mechanisms of ventricular arrhythmias in dogs (n=7) under conditions of antiorthostatic hypokinesia (head-down tilt 45°). Abnormal transmural heterogeneity of repolarization in the base and apex of the left ventricle and increased dispersion of myocardial repolarization were revealed. By minute 30 of antiorthostatic hypokinesia, an increase in the duration of repolarization was revealed after a period of ventricular arrhythmia in all segments and regions of heart ventricles, which was accompanied by impairment of the pumping function of the heart. A hypothesis on the physiological role of ventricular tachycardia as a mechanism of electromechanical homeostatic stabilization in the heart was proposed. The obtained results suggest that under conditions of antiorthostatic hypokinesia, canine heart after a paroxysm of irregular ventricular tachycardia becomes more resistant to arrhythmia.

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 (1 mg/kg, n = 5 and 2 mg/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.

Doxorubicin, one of the most effective anticancer drugs, is characterized by severe cardiotoxic effects, which induce cardiac remodeling and congestive heart failure. The aim of the study was to evaluate remodeling of ventricular repolarization heterogeneity in chronic doxorubicin cardiotoxicity in rats. Doxorubicin cardiotoxicity was produced by six equal intraperitoneal injections of the drug in a cumulative dose of 15 mg/kg in a 2-week period. Electrophysiological mapping of the ventricular epicardium in situ was performed 6 weeks after the last injection of doxorubicin. Activation-recovery intervals (ARIs) were used for the evaluation of the heterogeneity in repolarization durations. The major findings were as follows: (1) ARIs on the ventricular epicardium of both ventricles were significantly prolonged in the doxorubicin group and (2) this inhomogeneous prolongation of ARIs on the ventricular epicardium resulted in (i) the increase in the dispersion of repolarization across the ventricular epicardium and (ii) the inhomogeneous alterations of the regional ARI gradients on the ventricular epicardium. These changes in repolarization could explain the electrocardiographic alterations, that is, the prolongation of the QT interval and flattening of the T wave.

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.

Objective—To characterize systolic intervals of the left ventricle and their relationship with heart rate in conscious sheep. Animals—11 healthy Romanov sheep (age range, 3 months to 10 years). Procedures—Systolic intervals and indices of myocardial contractility of the left ventricle were measured in conscious sheep by use of polycardiography. Results—The mean ± SD pre-ejection period was 59 ± 12 milliseconds, and the mean left ventricular ejection time was 194 ± 34 milliseconds. The mean myocardial tension index was 0.22 ± 0.05, and the mean ratio of the pre-ejection period to ejection time was 0.30 ± 0.09. Total electromechanical systole, mechanical systole, and ejection time varied inversely with heart rate. The electromechanical delay and pre-ejection period were not correlated with heart rate, nor were the myocardial tension index and the ratio of the pre-ejection period to ejection time. The isovolumetric contraction index and isovolumetric contraction time were not significantly correlated with heart rate, although the values for the correlation coefficient were moderate (r = −0.561 and r = −0.482, respectively). Conclusions and Clinical Relevance—Although a larger study would be needed to provide reference intervals for healthy sheep, the results of the study reported here provided useful information for the cardiac evaluation of sheep.

The sequence of ventricular epicardium repolarization in rabbits with hypokalemia is directed from the apex of the heart to its base in accordance with distribution of local repolarization intervals. Under conditions of hyperkalemia, the propagation of excitation wave is inhibited without changes in its sequence; while the duration of repolarization decrease mainly in zones where it was initially long (the base of the right ventricle), as a result of which the distribution of local repolarization intervals becomes more uniform and a relationship between the repolarization and activation sequences is formed.

The duration of ventricular myocardium excitation increases during atrioventricular stimulation of dog heart and the sequence of depolarization of the right and left ventricles is desynchronized. Significant shortening of the activation-recovery interval in the intramural and subendocardial layers of the left ventricular base leads to modification of the repolarization sequence in this area and to an increase of total dispersion of activation-recovery intervals in the cardiac ventricles, as a result of which repolarization sequence starts partially repeating the depolarization sequence.

Aim: Prolongation of ventricular repolarization is characteristic of myocardial cooling. In the present study, we investigated whether this prolongation is uniform or not throughout ventricular epicardium and how these hypothermia-induced changes express in the body surface potential distribution. Methods: Epicardial and body surface potential mapping from 64 unipolar leads was carried out in 18 anaesthetized adult rabbits. Mild hypothermia documented by lowering the mediastinal and rectal temperature from 38 to 32 °C was elicited by perfusion of the mediastinum with cooled saline. Activation times, repolarization times and activation–recovery intervals were determined in each epicardial lead. Results: Baseline activation–recovery intervals distributed non-uniformly on the ventricular epicardium, increasing progressively from the apex to the base and from the left ventricular (LV) sites to the right ventricular (RV) sites (P

Multichannel mapping of electrical field on heart ventricle epicardium and the body surface in frogs Rana esculenta and Rana temporaria was performed at periods of the ventricular myocardium depolarization and repolarization. The zone of the epicardium early depolarization is located on epicardium of the ventricle base posterior wall, while the late depolarization zone—on its apex and on the base anterior wall. The total vector of sequence of the ventricle epicardium depolarization is directed from the base to the apex. The zone of the early repolarization is located in the apical area, while that of the late one—in the area of the base. On the frog body surface the cardioelectric field with the cranial zone of negative and the caudal zone of positive potentials is formed before the appearance of the QRS complex on ECG. At the period of the heart ventricle repolarization the zone of the cardioelectric field negative potentials is located in the cranial, while that of the positive ones—in the body surface caudal parts. The cardioelectric field on the frog body surface at the periods of depolarization and repolarization of the ventricle myocardium reflects adequately the projection of sequence of involvement with excitation and of distribution of potentials on epicardium.

Based on a multichannel synchronous mapping of heart electric potentials, the sequence in time of the ventricle myocardium depolarization was compared with dynamics of distribution of cardioelectric potentials on the dog body surface. The cardioelectric field on the dog body surface at the period of the initial ventricular activity has been shown to be characterized by the presence of two inversions of the mutual disposition of areas of positive and negative potentials. Contribution to formation of distribution of the cardioelectric potentials on the body surface at each moment of the period of initial ventricular activity was made by all myocardial layers involved in excitation.

The ventricular distributions of activation-repolarization intervals (ARIs) were determined in control and diabetic (DM) rabbits (alloxan model, 1 and 2 months). In DM (1 month), the epicardial ARI...

The aim of the study was to advance our knowledge regarding the activation process of the ventricular myocardium in birds in which Purkinje fibres penetrate into the ventricular wall to reach the epicardium. A depolarization pattern of the left ventricular free wall was studied in chickens (Gallus gallus) during ventricular paced beats. Duration of the activation process of the left ventricular free wall is significantly increased during ventricular ectopic excitation as compared with sinus rhythm. Its lowest increase occurs during subendocardial pacing of the middle part of the left ventricle, but its greatest increase is observed during subepicardial pacing of the left ventricular base. Multifocality and mosaicity of depolarization of the left ventricular free wall myocardium in chicken are expressed in a considerably less degree during ventricular paced beats in comparison with sinus rhythm. During ventricular paced beats, excitation of the left ventricular free wall is mostly due to the successive spreading of the depolarization wave from pacing sites.

The avian cardiovascular system is of special interest because avian hearts are relatively larger than mammalian hearts, and activation of ventricular myocardium in birds has a "flash" pattern. Systolic time intervals and indices of myocardial contractility were examined in anaesthetized open-chest chickens by polycardiography, including synchronous recordings of electrocardiogram, phonocardiogram, and apex cardiogram. The asynchronous contraction time, isometric contraction time, pre-ejection period and ejection time were 26 +/- 3 (Mean +/- SD), 21 +/- 9, 47 +/- 12, and 83 +/- 23 ms, respectively, for heart rates of 260 +/- 57 bpm. The myocardial tension index, isometric contraction index and the pre-ejection period/ejection time ratio were 0.39 +/- 0.11, 0.42 +/- 0.10, and 0.54 +/- 0.14, respectively. A "flash" pattern of ventricular myocardial depolarization causes more rapid excitation and as a consequence shorter asynchronous contraction time of relatively larger chicken hearts compared with rabbit hearts. Inverse relation (P0.05) of the asynchronous contraction time to the heart rate in chickens is probably associated with the specific activation pattern of avian ventricles. Establishment of the values of systolic time intervals will facilitate a better understanding of cardiac function in birds. The obtained results are discussed in comparison with the rabbit. The indices calculated from the systolic time intervals show disadvantageous contractile function of chicken heart compared to rabbit heart.

Cardioelectric field (CEF) on the body surface of birds (hen and pigeon) at the period of atrial excitation was studied by the method of the 64-channel synchronous electrocardiotopography. At the period of the atrial depolarization in the birds the zone of CEF negative potentials on the body surface is located cranially with respect to the zone of positive potentials. At the initial moments of P wave the minimum is located in the cranial (hen) or middle (pigeon) third of the dorsal body surface, while the maximum—in the area of the heart projection onto the ventral (hen) or left-lateral (pigeon) body surface. The maximum and minimum of the potential reach the greatest value at the period of the middle part of the P wave (near the peak), their amplitude being higher in pigeons. The distribution dynamics of the CEF potentials on the body surface is similar in different bird species and is characterized by stability in mutual disposition of positive and negative zones. The interspecies and intraspecies CEF variability on the body surface at the period of the atrial activation seems to be due to differences in the heart disposition in the chest. At the period of the atrial myocardium activation, CEF on the bird body surface reflects adequately projection of the potential distribution on epicardium and the sequence of spreading of excitation in the atrial myocardium, including that in the presence of several fronts of depolarization waves.

The present study is the first attempt to examine the effect of left ventricular hypertrophy (LVH) on the excitation pattern of the ventricular epicardium in experimental hypertensive rats. The left renal artery was clipped in Wistar rats (n = 8; 6-8 months old; weight, 174-295 g) to produce two-kidney one-clip (2K1C) hypertension. After 4 weeks, blood pressure was measured, and epicardial potential mapping was performed under sinus rhythm from 64 unipolar electrodes regularly distributed over the ventricular epicardium. Systolic blood pressure was approximately 40% higher in the rats with a clipped renal artery (162 +/- 14 mmHg, mean +/- s.d.) than in the normotensive rats (115 +/- 3 mmHg). LVH (approximately 23% increase in the ratio of the left ventricular weight to the body weight, P < 0.05) was observed in the 2K1C hypertensive rats. The depolarization pattern of the ventricular epicardium in the normotensive rats was similar to that in the rats with 2K1C hypertensive LVH. The duration of ventricular epicardial activation was shown to increase (approximately 35%, P < 0.05) in the hypertensive rats as compared to the normotensive animals. This study provides an explanation for alterations of the body surface potential distribution in hypertensive patients with LVH.

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.

Spatial and temporal non-uniform and polyfocal depolarization of the subendocardial, intramural, and subepicardial layers of the ventricle myocardium in the chicken have been established experimentally. Different depth and time of formation of activation centers in the ventricular myocardium provide the appearance of groups of multiple depolarization foci on the epicardial surface of the ventricles. During the initial ventricular activity the cardioelectric field (CEF) on the chicken body surface is characterized by three periods of the dynamics of distribution of potentials: (1) the period of their gradual changes reflecting the electrical activity of excitation foci in the subendocardial, intramural, and subepicardial ventricular layers of myocardium on CEF; (2) the period of inversion consisting of an alteration of the mutual arrangement of the positive and negative CEF areas, this alteration corresponding in time to polyfocal depolarization of the epicardial surface of the ventricles; (3) the period of stability, during which the arrangement of the positive and negative CEF regions does not change, which is due to depolarization of multiple myocardium zones at the final phase of the heart ventricle activation.

The statistical analysis is performed of changes of the bimolecular rate constant value (Δlog kII) of inhibition of human AChE, mouse AChE, AChE of flies Musca domestica and Calliphora vicina, and horse BuChE by dialkylphosphates with the general formula (AlkO) 2P(O)X at elongation of alkyl radicals and change of their branching in comparison with three physical-chemical characteristics (hydrophobicity, polarity, and volume of the side chain) of 6 amino acid residues in acyl and alkoxyl pockets variable in the studied ChE (Nos. 282, 287, 288, 290, 330, 335 in Torpedo ray AChE sequence). It has been shown that depending on structure of alkyl radicals, the rate of ChE interaction with OPI is determined by sterical hindrances to sorption (residues 282, 287, 290, 335), hydrophobic interactions (288) or polarity of microenvironment (287). This dependence in most cases is statistically significant; however, rather low values of the correlation coefficient indicate influence of structure of the OPI leaving part. The decrease of the statistical significance with elongation of alkyl radicals seems to be due to an increase of the number of possible conformational states of the OPI molecule.

Summary Isoproterenol in high doses induces infarction-like myocardial damage and structural and functional remodelling of the ventricular myocardium. The purpose of the present study was to investigate ventricular repolarization in a rat model of isoproterenol-induced heart failure. Isoproterenol was administered twice to female Wistar rats (170 mg/kg, s.c., 24 h apart). Four weeks after the injections, cardiac output was measured and unipolar epicardial ventricular electrograms were recorded in situ. Activation–recovery intervals were calculated to assess repolarization. Histological examination of the heart ventricles was also performed. Heart failure in rats treated with isoproterenol was indicated by myocardial histopathological damage and reduced cardiac output. In rats with heart failure, the regional differences in activation–recovery interval prolongation over the ventricular epicardium resulted in increasing heterogeneity in the activation–recovery interval distribution and increasing repolarization heterogeneity of the ventricular subepicardium. Myocardial damage and haemodynamic changes in heart failure induced by isoproterenol were accompanied by significant changes in ventricular repolarization, which were not associated with myocardial hypertrophy.

Anthracycline chemotherapy produces cardiac repolarization abnormalities and arrhythmias because of cardiac toxicity of drugs. Ventricular arrhythmogenesis is attributable to increase in repolarization heterogeneity that is characterized by spatial dispersion of repolarization. The purpose of this work was to study the delayed effects of doxorubicin, the most frequently used anthracycline, on repolarization heterogeneity of the ventricular epicardium. Doxorubicin was administered to rats in a cumulative dose of 15 mg/kg (six equal intraperitoneal injections over a period of 2 weeks). Six weeks after the last injection, electrophysiological mapping of the ventricular epicardium was performed by sequential superimposition of a 64-electrode array on the left ventricular base, left ventricular apex, right ventricular base, and right ventricular apex. Activation–recovery intervals (ARIs) were measured. In doxorubicin-treated rats, ARIs were inhomogeneously prolonged, the overall ARI dispersion and local ARI dispersions were increased, and the interregional differences in ARI dispersion were decreased. These data demonstrate that doxorubicin-induced inhomogeneous prolongation of repolarization of the ventricular epicardium results in increasing heterogeneity of ventricular repolarization because of increasing intraregional heterogeneity while interregional differences are lost. Repolarization of the right ventricle is more sensitive to doxorubicin than that of the left one.

Doxorubicin, one of the most effective anticancer drugs, is characterized by severe cardiotoxic effects, which induce cardiac remodeling and congestive heart failure. The aim of the study was to evaluate remodeling of ventricular repolarization heterogeneity in chronic doxorubicin cardiotoxicity in rats. Doxorubicin cardiotoxicity was produced by six equal intraperitoneal injections of the drug in a cumulative dose of 15 mg/kg in a 2-week period. Electrophysiological mapping of the ventricular epicardium in situ was performed 6 weeks after the last injection of doxorubicin. Activation-recovery intervals (ARIs) were used for the evaluation of the heterogeneity in repolarization durations. The major findings were as follows: (1) ARIs on the ventricular epicardium of both ventricles were significantly prolonged in the doxorubicin group and (2) this inhomogeneous prolongation of ARIs on the ventricular epicardium resulted in (i) the increase in the dispersion of repolarization across the ventricular epicardium and (ii) the inhomogeneous alterations of the regional ARI gradients on the ventricular epicardium. These changes in repolarization could explain the electrocardiographic alterations, that is, the prolongation of the QT interval and flattening of the T wave.

Parameters of cardioelectric field on body surface and propagation of excitation in ventricular myocardium during initial activation were studied using multichannel synchronous electrocardiotopography. It was shown that inversion of areas of negative and positive potentials of cardioelectric field on body surface at the moment of excitation propagation to the epicardium reflected changes in the main direction of excitation wavefront in ventricles.

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 (EndoEpi, P0.024) 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 (EndoEpi, P0.02) according to the activation sequence. On the apicobasal axis in both species, the repolarization sequence proceeds from apex to base (P0.024) which is expressed in similar body surface potential distributions during the T wave in spite of the opposite transmural repolarization patterns. The present study suggests that the apicobasal repolarization gradient provides the major contribution to the development of the T wave potentials on the body surface in pike and frogs.

The duration of repolarization of subendocardial, intramural, and epicardial layers of dog ventricles was studied under conditions of volume overload of the heart in situ. Increased preload was modeled by rapid intravenous infusion of saline and rheopolygluquine. The activation-recovery interval was measured by flexible intramural electrodes inserted into the right and left ventricles. The level of preload was evaluated by the increase in left-ventricular end-diastolic pressure. The increase in preload from 11+/-6 to 26+/-10 mm Hg led to a significant (p0.05) prolongation of the activation-recovery interval in the subepicardial layers of apex, all layers of the lateral wall, and subepicardial and intramural layers of the base of the left ventricle and in subendocardial layers of the apex and base of the right ventricle. Further elevation of the end-diastolic pressure to 34+/-11 mm Hg led to shortening of the activation-recovery interval (p0.05) in the subepicardial layers of the apex and lateral wall of the left ventricle and in the subepicardial layers of right-ventricular base and left-ventricular lateral wall. Hence, different areas of the myocardium differently react to volume overload of the heart. Changes in repolarization length in response to preload increase are biphasic.

Overload of the cardiac left ventricle causes opposite local changes in repolarization duration (activation-recovery intervals) on the right- and left-ventricular epicardium, which depend on the duration of overload. The activation-recovery intervals on the right-ventricular lateral surface decrease after 1-min overload, but increase after 10-min overload. The length of activation-recovery intervals on the lateral surface of the left-ventricular apex increases after 10-min aortic stenosis more markedly in comparison with that after 1-min overload. Decrease/increase of local lengths of activation-recovery intervals results in modification of the general sequence of cardiac ventricular surface repolarization.

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.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.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 (p0.01). Under acute LV overload, the repolarization duration increased significantly (p0.01) locally at the LV apex and adjacent area of the free wall. Dispersion of repolarization is increased in the apex. A decrease of ARIs (p0.05) was observed at the RV base, as well.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.

This study was planned to investigate ventricular myocardial excitation in birds in which Purkinje fibres penetrate into the ventricular wall and reach the epicardium to advance our knowledge about the evolution of the ventricular activation process in vertebrates.A depolarization pattern of the left ventricular free wall in seven open-chest laying hens was mapped by 14 seven-electrode plunge needles under ventricular pacing from different sites.Duration of activation of the left ventricular free wall is significantly increased during ventricular ectopic excitation as compared with sinus rhythm. Its lowest increase occurs during subendocardial pacing of the middle part of the left ventricle, but its greatest increase is observed during subepicardial pacing of the left ventricular base. Multifocality and mosaicity of depolarization of the left ventricular myocardium are expressed in a considerably less degree during ventricular pacing in comparison with sinus rhythm.Ectopic excitation of avian heart ventricles occurs mostly due to successive spreading of the activation wave from a pacing site during both ipsi- and contraventricular pacing. During ipsiventricular pacing at least, ectopic excitation of the heart ventricles with the "rich" Purkinje network behaves like one of the mammalian ventricles with the subendocardial Purkinje network.

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

Experimental and theoretical methods were employed to study the effects of torso shape and heart orientation in the thoracic cavity on peculiarities of the formation cardiac electric field on the body surface in dogs. It was found that heart orientation to a greater extent than torso shape affected projections of cardiac electric potentials from the epicardium onto the body surface.

The aim of this study was to investigate body surface potential distribution during the P wave in Wistar rats. We performed body surface potential mapping by means of a 64-channel synchronous electrocardiotopography. The positive area covered the caudal part of the thorax, and the negative one covered the cranial part of the thorax. During the P wave, we observed 1 maximum and 1 minimum on the body surface. The dynamics of the P-wave body surface potential distribution in rats was characterized by minor movement of the positive and negative areas, and a counterclockwise shift of the extrema on the ventral body surface. The obtained results are discussed in comparison with those in dogs and humans.

Left ventricular hypertrophy of the hearts in Wistar rats caused by renovascular hypertension prolongs depolarization of epicardial surface of the ventricles and increases the duration of excitation phase in the left ventricular epicardium. Sex-related differences in changes of myocardial contractility were revealed during hypertrophy of the left ventricle caused by renovascular hypertension.