The ultrastructure of alligator conductive tissue: an electron microscopic study of the sino-atrial node

A combined electrophysiological and morphological study was made to distinguish between the conductive and contractile elements of the alligator mississippiensis heart. Microelectrophysiological recordings revealed a frequent occurrence of cells in the sino-atrial node that showed spontaneous diastolic depolarization, while light and electronmicroscopic studies indicated that the corresponding area is characterized by cells with a high glycogen content, poorly developed sarcoplasmic reticulum and a relative absence of contractile material. The findings provide evidence that the alligator heart is a non-avian and non-mammalian heart that possesses a specialized stimulus-generating and conductive system.     

Heterogeneous Expression of NO-Activated Soluble Guanylyl Cyclase in Mammalian Heart: Implications for NO- and Redox-Mediated Indirect Versus Direct Regulation of Cardiac Ion Channel Function

Nitrogen oxides exert significant but diverse regulatory effects on cardiac myocytes. Many of these effects are due to modulation of voltage-sensitive ion channel function. The redox-status of NO-related compounds is a critical factor in determining whether indirect (cGMP-dependent) versus direct (cGMP-independent) effects are dominant. However, molecular mechanisms by which different cardiac myocyte types, and associated different ion channel types expressed within them, could achieve selectivity between NO-related indirect versus direct effects are unclear We have previously demonstrated heterogeneous expression gradients of Type III NO synthase (eNOS) and sarcolemmal superoxide dismutase (ECSOD) in ferret and human ventricle, with both enzymes being highly expressed in right ventricle and left ventricular subepicardium but markedly reduced in left ventricular subendocardium. In this study we extend this previous analysis by analyzing NO-activated soluble guanylyl cyclase (sGC) expression in the heart (ferret and human). We demonstrate that, at both tissue and single myocyte levels, sGC protein expression is heterogeneous, being high in sinoatrial node, right atrium, right ventricle and left ventricular subepicardium, but markedly reduced to absent in left atrium and left ventricular subendocardium. Thus, there is a significant overlap in expression gradients of sGC, eNOS, and ECSOD among distinct cardiac tissue and myocyte types. These gradients positively correlate with both: i) experimentally measured basal NO production levels; and ii) expression gradients of specific voltage-gated ion channels (particularly Kv1 and Kv4 channels). Our results provide the first demonstration in the heart of an expressed coupled multienzymatic system for selective regulation of indirect (sGC-dependent) versus direct (sGC-independent) NO- and redox-related modulation of voltage-gated ion channel function in different myocyte types. Our results also have functional implications for NO. / redox - related modulation of ion channels expressed in other cell types, including neurons, skeletal muscle and smooth muscle.     

Heterogeneous expression of NO-activated soluble guanylyl cyclase in mammalian heart: implications for NO- and redox-mediated indirect versus direct regulation of cardiac ion channel function

Nitrogen oxides exert significant but diverse regulatory effects on cardiac myocytes. Many of these effects are due to modulation of voltage-sensitive ion channel function. The redox-status of NO-related compounds is a critical factor in determining whether indirect (cGMP-dependent) versus direct (cGMP-independent) effects are dominant. However, molecular mechanisms by which different cardiac myocyte types, and associated different ion channel types expressed within them, could achieve selectivity between NO-related indirect versus direct effects are unclear We have previously demonstrated heterogeneous expression gradients of Type III NO synthase (eNOS) and sarcolemmal superoxide dismutase (ECSOD) in ferret and human ventricle, with both enzymes being highly expressed in right ventricle and left ventricular subepicardium but markedly reduced in left ventricular subendocardium. In this study we extend this previous analysis by analyzing NO-activated soluble guanylyl cyclase (sGC) expression in the heart (ferret and human). We demonstrate that, at both tissue and single myocyte levels, sGC protein expression is heterogeneous, being high in sinoatrial node, right atrium, right ventricle and left ventricular subepicardium, but markedly reduced to absent in left atrium and left ventricular subendocardium. Thus, there is a significant overlap in expression gradients of sGC, eNOS, and ECSOD among distinct cardiac tissue and myocyte types. These gradients positively correlate with both: (i) experimentally measured basal NO production levels; and (ii) expression gradients of specific voltage-gated ion channels (particularly Kv1 and Kv4 channels). Our results provide the first demonstration in the heart of an expressed coupled multienzymatic system for selective regulation of indirect (sGC-dependent) versus direct (sGC-independent) NO- and redox-related modulation of voltage-gated ion channel function in different myocyte types. Our results also have functional implications for NO(*)/redox-related modulation of ion channels expressed in other cell types, including neurons, skeletal muscle and smooth muscle.     

Volume changes in cardiac ventricles from Aplysia brasiliana upon exposure to hyposmotic shock

We investigated the possible role of ion channels and transporters in cell volume control using Aplysia brasiliana ventricular tissues exposed to a 26% hyposmotic shock, by assessing changes in wet weight, intracellular water and ionic contents. Thirty minutes after the shock, the wet weight of isolated ventricles increase about 20% above control levels and then attain near original weight within 60 min after the shock. At the time when the wet weight returned to control values, intracellular water and KCl contents are decreased by 22 and 20%, respectively. The K(+) channel blockers, 4-AP and TEA, but not the cotransport blockers, hydrochlorothiazide and furosemide, greatly affect the magnitude of wet weight gain and the time course of weight recovery, indicating that KCl loss occur through conductive pathways. Intracellular recordings performed on ventricular myocytes during exposure to the osmotic shock showed an immediate membrane hyperpolarization and blockade of spontaneous electrical activity; diastolic membrane potential recover over time and spontaneous action potentials are completely restored 60 min after the hyposmotic shock. Because significant weight loss is observed during the exposure of ventricular tissues to 26% hypo-ionic, but isosmotic saline, it is suggested that ventricular volume restoration is accomplished by two distinct but simultaneously occurring processes: a volume-dependent and a volume-independent mechanism. Because wet weight restoration is completely prevented by exposing ventricular tissue to a Ca(2+)-free hyposmotic solution, we postulate that both processes involved in A. brasiliana ventricular weight restoration are Ca(2+)-dependent mechanisms.     

The Effect of Aging on the Specialized Conducting System: A Telemetry ECG Study in Rats over a 6 Month Period

Advanced age alone appears to be a risk factor for increased susceptibility to cardiac arrhythmias. We previously observed in the aged rat heart that sinus rhythm ventricular activation is delayed and characterized by abnormal epicardial patterns although conduction velocity is normal. While these findings relate to an advanced stage of aging, it is not yet known when and how ventricular electrical impairment originates and which is the underlying substrate. To address these points, we performed continuous telemetry ECG recordings in freely moving rats over a six-month period to monitor ECG waveform changes, heart rate variability and the incidence of cardiac arrhythmias. At the end of the study, we performed in-vivo multiple lead epicardial recordings and histopathology of cardiac tissue. We found that the duration of ECG waves and intervals gradually increased and heart rate variability gradually decreased with age. Moreover, the incidence of cardiac arrhythmias gradually increased, with atrial arrhythmias exceeding ventricular arrhythmias. Epicardial multiple lead recordings confirmed abnormalities in ventricular activation patterns, likely attributable to distal conducting system dysfunctions. Microscopic analysis of aged heart specimens revealed multifocal connective tissue deposition and perinuclear myocytolysis in the atria. Our results demonstrate that aging gradually modifies the terminal part of the specialized cardiac conducting system, creating a substrate for increased arrhythmogenesis. These findings may open new therapeutic options in the management of cardiac arrhythmias in the elderly population.     

Electrical and mechanical effects induced by cold temperatures in the ventricle of isolated Rana ridibunda hearts

A temperature decrease changes the contractility of the amphibian heart, but the underlying mechanisms are not totally understood. The objectives of the present work were to better understand the intrinsic mechanisms supporting contractility changes induced by a rapid temperature decrease in the ventricle of Rana ridibunda, and to investigate how fast they develop. Ventricular mechanical cycles (VMCs) and monophasic action potentials (MAPs) recorded from 15 isolated hearts were measured at 15, 30, 45, 60, 90, 120 and 150 s after the application of Ringer solutions of 20, 10 and 5 degrees C. Treatment with 10 and 5 degrees C Ringer solutions decreased the heart rate, and increased the magnitude of the ventricular contraction and the duration of the contraction and relaxation periods. The electrical changes included prolongation of the MAP depolarization plateau, which also decreased in amplitude as an effect of perfusion with 5 degrees C Ringer solution. In addition, treatment with 5 degrees C Ringer solution increased the latency of contraction. The block of L-type channels totally abolished the depolarization plateau at all perfusion temperatures, but failed to inhibit ventricular contraction. In conclusion, treatment with cold temperatures changes the electrical activity of the ventricular myocardium in R. ridibunda hearts, which results in modified ventricular contractility. Data suggest that in addition to L-type Ca2+ channels, other components that support calcium elevation are present R. ridibunda ventricular cells.     

Stem cell‐mediated natural tissue engineering

Recently, we demonstrated that a fully differentiated tissue developed on a ventricular septal occluder that had been implanted due to infarct‐related septum rupture. We suggested that this tissue originated from circulating stem cells. The aim of the present study was to evaluate this hypothesis and to investigate the physiological differentiation and transdifferentiation potential of circulating stem cells. We developed an animal model in which a freely floating membrane was inserted into each the left ventricle and the descending aorta. Membranes were removed after pre‐specified intervals of 3 days, and 2, 6 and 12 weeks; the newly developed tissue was evaluated using quantitative RT‐PCR, immunohistochemistry and in situ hybridization. The contribution of stem cells was directly evaluated in another group of animals that were by treated with granulocyte macrophage colony‐stimulating factor (GM‐CSF) early after implantation. We demonstrated the time‐dependent generation of a fully differentiated tissue composed of fibroblasts, myofibroblasts, smooth muscle cells, endothelial cells and new blood vessels. Cells differentiated into early cardiomyocytes on membranes implanted in the left ventricles but not on those implanted in the aortas. Stem cell mobilization with GM‐CSF led to more rapid tissue growth and differentiation. The GM‐CSF effect on cell proliferation outlasted the treat ment period by several weeks. Circulating stem cells contributed to the development of a fully differentiated tissue on membranes placed within the left ventricle or descending aorta under physiological conditions. Early cardiomyocyte generation was identified only on membranes positioned within the left ventricle.     

Quantitative analysis of Na+-Ca2+ exchanger expression in guinea-pig heart.

In previous studies, regional variations in the expression of the Na+-Ca2+ exchanger (NCX) have been examined qualitatively in human heart using the C2C12 monoclonal antibody [Wang, J., Schwinger, R.H., Frank, K., Muller-Ehmsen, J., Martin-Vasallo, P., Pressley, T.A., Xiang, A., Erdmann, E. & McDonough, A.A. (1996) J. Clin. Invest. 98, 1650-1658]. Although NCX expression was found to be significantly lower in the atria compared to the septum, no significant differences were found between atrial and ventricular tissue. NCX has been located in the general sarcolemma and t-tubules of ventricular muscle and as t-tubules are sparse in atrial tissue compared to ventricular tissue, it is surprising that NCX expression was found to be similar in both atria and ventricles [Wang et al. (1996)]. To reinvestigate this, we have used SDS/PAGE and a quantitative Western blotting technique to determine the pattern of expression of NCX in guinea-pig heart in tissue samples from left atrium, right atrium, septum, left ventricle and right ventricle. NCX protein expression was 17.5 +/- 3.9 pmol.mg-1 of protein in the left atrium and 29.2 +/- 6.1 pmol.mg-1 of protein in the right atrium, which were both significantly lower (P < 0.05) than NCX expression in the septum, left ventricle and right ventricle (64.7 +/- 15.2, 76.8 +/- 19.5 and 69.4 +/- 14.1 pmol.mg-1 of protein, respectively, n = 7). These differences in NCX expression may reflect variations in the cellular location of NCX protein in these regions. To study this, we used confocal immunofluorescence of single isolated myocytes to examine differences in the proportion of fluorescent staining on the general surface membrane compared with the interior of the cell (which presumably reflects a t-tubular location). We found that the general membrane staining was 79.0 +/- 1.2% in cells from the atria which was significantly higher (P < 0. 001) than that seen in cells from the septum, left ventricle and right ventricle, with 48.1 +/- 1.1%, 48.2 +/- 1.8% and 45.6 +/- 1.3%, respectively (n = 20). These results illustrate a similar pattern of NCX expression in guinea-pig and human, with expression in atrial tissue significantly lower than in ventricular tissue. However, the cellular location of NCX differs regionally; in atrial tissue, the majority of the NCX protein is located in the general sarcolemma whereas in ventricular and septal tissue, approximately 50% of NCX protein is located within the cell (presumably at the level of the t-tubules).     

Cardiac electric field at the period of depolarization and repolarization of the frog heart ventricle

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.     

Functional and morphological evidence for a ventricular conduction system in zebrafish and Xenopus hearts

Zebrafish and Xenopus have become popular model organisms for studying vertebrate development of many organ systems, including the heart. However, it is not clear whether the single ventricular hearts of these species possess any equivalent of the specialized ventricular conduction system found in higher vertebrates. Isolated hearts of adult zebrafish (Danio rerio) and African toads (Xenopus laevis) were stained with voltage-sensitive dye and optically mapped in spontaneous and paced rhythms followed by histological examination focusing on myocardial continuity between the atrium and the ventricle. Spread of the excitation wave through the atria was uniform with average activation times of 20 +/- 2 and 50 +/- 2 ms for zebrafish and Xenopus toads, respectively. After a delay of 47 +/- 8 and 414 +/- 16 ms, the ventricle became activated first in the apical region. Ectopic ventricular activation was propagated significantly more slowly (total ventricular activation times: 24 +/- 3 vs. 14 +/- 2 ms in zebrafish and 74 +/- 14 vs. 35 +/- 9 ms in Xenopus). Although we did not observe any histologically defined tracts of specialized conduction cells within the ventricle, there were trabecular bands with prominent polysialic acid-neural cell adhesion molecule staining forming direct myocardial continuity between the atrioventricular canal and the apex of the ventricle; i.e., the site of the epicardial breakthrough. We thus conclude that these hearts are able to achieve the apex-to-base ventricular activation pattern observed in higher vertebrates in the apparent absence of differentiated conduction fascicles, suggesting that the ventricular trabeculae serve as a functional equivalent of the His-Purkinje system.     

Electrical Transmission between Mammalian Neurons is Supported by a Small Fraction of Gap Junction Channels

Electrical synapses formed by gap junctions between neurons create networks of electrically coupled neurons in the mammalian brain, where these networks have been found to play important functional roles. In most cases, interneuronal gap junctions occur at remote dendro-dendritic contacts, making difficult accurate characterization of their physiological properties and correlation of these properties with their anatomical and morphological features of the gap junctions. In the mesencephalic trigeminal (MesV) nucleus where neurons are readily accessible for paired electrophysiological recordings in brain stem slices, our recent data indicate that electrical transmission between MesV neurons is mediated by connexin36 (Cx36)-containing gap junctions located at somato-somatic contacts. We here review evidence indicating that electrical transmission between these neurons is supported by a very small fraction of the gap junction channels present at cell-cell contacts. Acquisition of this evidence was enabled by the unprecedented experimental access of electrical synapses between MesV neurons, which allowed estimation of the average number of open channels mediating electrical coupling in relation to the average number of gap junction channels present at these contacts. Our results indicate that only a small proportion of channels (~0.1?%) appear to be conductive. On the basis of similarities with other preparations, we postulate that this phenomenon might constitute a general property of vertebrate electrical synapses, reflecting essential aspects of gap junction function and maintenance.     

A conducting state with properties of a slow inactivated state in a shaker K(+) channel mutant

In Shaker K(+) channel, the amino terminus deletion Delta6-46 removes fast inactivation (N-type) unmasking a slow inactivation process. In Shaker Delta6-46 (Sh-IR) background, two additional mutations (T449V-I470C) remove slow inactivation, producing a noninactivating channel. However, despite the fact that Sh-IR-T449V-I470C mutant channels remain conductive, prolonged depolarizations (1 min, 0 mV) produce a shift of the QV curve by about -30 mV, suggesting that the channels still undergo the conformational changes typical of slow inactivation. For depolarizations longer than 50 ms, the tail currents measured during repolarization to -90 mV display a slow component that increases in amplitude as the duration of the depolarizing pulse increases. We found that the slow development of the QV shift had a counterpart in the amplitude of the slow component of the ionic tail current that is not present in Sh-IR. During long depolarizations, the time course of both the increase in the slow component of the tail current and the change in voltage dependence of the charge movement could be well fitted by exponential functions with identical time constant of 459 ms. Single channel recordings revealed that after prolonged depolarizations, the channels remain conductive for long periods after membrane repolarization. Nonstationary autocovariance analysis performed on macroscopic current in the T449V-I470C mutant confirmed that a novel open state appears with increasing prepulse depolarization time. These observations suggest that in the mutant studied, a new open state becomes progressively populated during long depolarizations (>50 ms). An appealing interpretation of these results is that the new open state of the mutant channel corresponds to a slow inactivated state of Sh-IR that became conductive.     

Effects of acute reduction of temperature on ventricular fibrillation activation patterns

Because of its electrophysiological effects, hypothermia can influence the mechanisms that intervene in the sustaining of ventricular fibrillation. We hypothesized that a rapid and profound reduction of myocardial temperature impedes the maintenance of ventricular fibrillation, leading to termination of the arrhythmia. High-resolution epicardial mapping (series 1; n = 11) and transmural recordings of ventricular activation (series 2; n = 10) were used to analyze ventricular fibrillation modification during rapid myocardial cooling in Langendorff-perfused rabbit hearts. Myocardial cooling was produced by the injection of cold Tyrode into the left ventricle after induction of ventricular fibrillation. Temperature and ventricular fibrillation dominant frequency decay fit an exponential model to arrhythmia termination in all experiments, and both parameters were significantly correlated (r = 0.70, P < 0.0001). Termination of the arrhythmia occurred preferentially in the left ventricle and was associated with a reduction in conduction velocity (-60% in left ventricle and -54% in right ventricle; P < 0.0001) and with activation maps predominantly exhibiting a single wave front, with evidence of wave front extinction. We conclude that a rapid reduction of temperature to <20 degrees C terminates ventricular fibrillation after producing an important depression in myocardial conduction.     

Multichannel recordings from membranes which contain gap junctions.

We have studied multichannel patch-clamp recordings in earthworm axon septal membranes that contain gap junctions. Though all channels have the same conductance and selectivity, the probabilities of the conductance levels in the majority of the recordings could not be fit by assuming independent and identical channels; in these cases, we found that at least two different open probabilities were required to explain the data. The data thus suggest that, within one junctional membrane complex, there exists a heterogenous channel population of similar but not identical channel types. The analysis also revealed cases where cooperativity between individual channels was the only explanation for the amplitude histograms of the observed multichannel activity. The conclusions drawn are based on a theoretical analysis of multichannel current-amplitude histograms. We derive two tests for independent and identical channels. We analyze the effects of mode shifting. These results are based on the ratio of peaks in the histograms; they are independent of the number of channels in the patch and the model of channel gating. In some cases failure to fulfill the criteria of these tests implied an interdependence or cooperativity between channels. Lastly, we have devised statistical tests for stability of the recording in the presence of variance due to finite sample size.     

Cardiac electric field at the period of depolarization and repolarization of the frog heart ventricle

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.     

Effects of hirsutine and dihydrocorynantheine on the action potentials of sino-atrial node, atrium and ventricle

The effects of hirsutine, an indole alkaloid from Uncaria rhynchophylla MIQ. JACKSON with antihypertensive, negative chronotropic and antiarrhythmic activity, and its C3 structural epimer, dihydrocorynantheine, on membrane potentials of rabbit sino-atrial node and guinea-pig right ventricle and left atrium were studied with microelectrode techniques. In sino-atrial node preparations, hirsutine and dihydrocorynantheine (0.1 microM to 10 microM) concentration-dependently increased cycle length, decreased slope of the pacemaker depolarization (phase 4 depolarization), decreased maximum rate of rise and prolonged action potential duration. In atrial and ventricular preparations, both compounds (0.1 microM to 30 microM) concentration-dependently decreased maximum rate of rise and prolonged action potential duration. These results indicate that hirsutine and dihydrocorynantheine have direct effects on the action potential of cardiac muscle through inhibition of multiple ion channels, which may explain their negative chronotropic and antiarrhythmic activity.     

Anomalous L-type calcium channels of rat spinal motoneurons

Single channel patch-clamp recordings show that embryonic rat spinal motoneurons express anomalous L-type calcium channels, which reopen upon repolarization to resting potentials, displaying both short and long reopenings. The probability of reopening increases with increasing voltage of the preceding depolarization without any apparent correlation with inactivation during the depolarization. The probability of long with respect to short reopenings increases with increasing length of the depolarization, with little change in the total number of reopenings and in their delay. With less negative repolarization voltages, the delay increases, while the mean duration of both short and long reopenings decreases, remaining longer than that of the openings during the preceding depolarization. Open times decrease with increasing voltage in the range -60 to +40 mV. Closed times tend to increase at V > 20 mV. The open probability is low at all voltages and has an anomalous bell-shaped voltage dependence. We provide evidence that short and long reopenings of anomalous L-type channels correspond to two gating modes, whose relative probability depends on voltage. Positive voltages favor both the transition from a short-opening to a long-opening mode and the occupancy of a closed state outside the activation pathway within each mode from which the channel reopens upon repolarization. The voltage dependence of the probability of reopenings reflects the voltage dependence of the occupancy of these closed states, while the relative probability of long with respect to short reopenings reflects the voltage dependence of the equilibrium between modes. The anomalous gating persists after patch excision, and therefore our data rule out voltage-dependent block by diffusible ions as the basis for the anomalous gating and imply that a diffusible cytosolic factor is not necessary for voltage-dependent potentiation of anomalous L-type channels.     

The dorso-lateral recess of the hypothalamic ventricle in neonatal rats

Light and electron microscopy of the hypothalamic ventricle in neonatal rats demonstrate morphological specializations of the ventricular wall at the level of the premammillary region of the third ventricle. The morphological features are: (1) A ventricular recess that we have called the "hypothalamic dorso-lateral recess" (HDR). (2) The presence of intraventricular capillaries near the dorso-lateral recess. (3) The HDR possessing a specialized ependymal lining; this consists of non-ciliated cells with short microvilli and bleb-like processes. (4) The existence of cerebrospinal fluid-contacting neurons within the HDR. (5) The presence of numerous phagocytic supraependymal cells. The HDR is not found in adult rats. This indicates that the dorso-lateral recess may play a physiological role during development.     

Formation of Cardioelectric Field on the Body Surface at a Period of Activation of Ventricular Myocardium in the Chicken Gallus domesticus

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.     

Regional dysfunction correlates with myofiber disarray in transgenic mice with ventricular expression of ras

A hallmark of certain cardiac diseases such as familial hypertrophic cardiomyopathy is focal myofiber disarray. Regional ventricular dysfunction occurs in human subjects with hypertrophic cardiomyopathy; however, no direct evidence exists to correlate regional dysfunction with myofiber disarray. We used a transgenic mouse, which exhibits regional myofiber disarray via ventricular expression of the human oncogene ras, to investigate the relationship between myofiber disarray and septal surface strain. An isolated ejecting mouse heart preparation was used to record deformation of markers on the septal surface and to determine nonhomogeneous septal surface strain maps. Myofiber disarray made in histological tissue sections was correlated with gradients in surface systolic shortening. Significantly smaller maximum principal shortening was associated with disarray located near the right ventricle (RV) septal surface. There was also significantly smaller surface shear strain associated with disarray located either near the RV surface or at the midwall. Because surface shear is a local indicator of torsion, we conclude that myofiber disarray is associated with reduced septal torsion and reduced surface shortening.