Effects of electrode-myocardial separation on cardiac stimulation in conductive solution.

INTRODUCTION: Effects of a conductive bath and electrode-myocardial separation on cardiac stimulation have not been elucidated. These factors may play a role in endocardial catheter stimulation or defibrillation. METHODS AND RESULTS: We studied effects of a bath and separation on transmembrane voltage changes during stimulation (deltaVm) and excitation thresholds in rabbit hearts, cultured rat cardiac cell monolayers, and cardiac bidomain computer models. Similar to previous epicardial measurements with no bath, a dogbone pattern of deltaVm during stimulation was found in bathed epicardium and right ventricular septal endocardium and in models of bathed anisotropic myocardium. Electrode-myocardial separation altered spatial distributions of deltaVm, moved reversals of the sign of deltaVm farther from the stimulation epicenter, and decreased aspect ratio of deltaVm (i.e., length/width of dogbone contours of deltaVm). The separation increased thresholds and reduced maximal deltaVm, while deltaVm at sites away from maxima increased or decreased. Anodal thresholds in models initially were larger than those in experiments and decreased when models were altered to include nonuniform cellular coupling. Existence of nonuniformity in monolayers was indicated by irregular excitation patterns. CONCLUSION: Electrode-myocardial separation alters spatial distributions of deltaVm, which may impact on arrhythmia induction by altering distributions of states of deltaVm-sensitive ion channels. The results also indicate that excitation thresholds may depend on tissue nonuniformities.

Nonlinear changes of transmembrane potential during defibrillation shocks: role of Ca(2+) current.

Defibrillation shocks induce complex nonlinear changes of transmembrane potential (DeltaV(m)). To elucidate the ionic mechanisms of nonlinear DeltaV(m), we studied the effects of ionic channel blockers on DeltaV(m) in geometrically defined myocyte cultures. Experiments were carried out in cell strands with widths of 0.2 mm (narrow strands) and 0.8 mm (wide strands) produced using a technique of directed cell growth. Uniform-field shocks were applied across strands during the action potential (AP) plateau, and the distribution of shock-induced DeltaV(m) was measured using an optical mapping technique. Nifedipine and 4-aminopyridine were applied to inhibit the L-type calcium current (I:(Ca)) and the transient outward current (I:(to)), respectively. In control conditions, the distribution of DeltaV(m) across cell strands was highly asymmetrical with a large ratio of negative to positive DeltaV(m) (DeltaV(-)(m)/DeltaV(+)(m)) measured at the opposite strand borders. Application of nifedipine caused a large increase of DeltaV(+)(m) and a decrease of DeltaV(-)(m)/DeltaV(+)(m), indicating involvement of I:(Ca) in the asymmetrical DeltaV(m), likely as a result of the outward flow of I:(Ca) when V(m) exceeded the I:(Ca) reversal potential. DeltaV(-)(m) decreased in the narrow strands but remained unchanged in the wide strands, indicating that the changes of DeltaV(-)(m) were caused by electrotonic interaction with an area of depolarization. 4-Aminopyridine did not change DeltaV(-)(m)/DeltaV(+)(m). These results provide evidence that (1) the asymmetry of shock-induced DeltaV(m) during the AP plateau is due to outward flow of I:(Ca) in the depolarized portions of the strands, (2) I:(to) is not involved in the mechanism of DeltaV(m) asymmetry, and (3) the effects of drugs on DeltaV(m) are modulated by the tissue geometry.

Simultaneous optical mapping of transmembrane potential and intracellular calcium in myocyte cultures.

INTRODUCTION: Fast spatially resolved measurements of transmembrane potential (Vm) and intracellular calcium (Ca(i)2+) are important for studying mechanisms of arrhythmias and defibrillation. The goals of this work were (1) to develop an optical technique for simultaneous multisite optical recordings of Vm and Ca(i)2+, and (2) to determine the relationship between Vm and Ca(i)2+ during normal impulse propagation in myocyte cultures. METHODS AND RESULTS: Monolayers of neonatal rat myocytes were stained with fluorescent dye RH-237 (Vm) and Fluo-3AM (Ca(i)2+). Both dyes were excited at the same wavelength range. The emitted fluorescence was optically separated into components corresponding to changes in Vm and Ca(i)2+ and measured using two 16 x 16 photodiode arrays at a spatial resolution of up to 27.5 microm per diode and sampling rate of 2.5 kHz. The optical setup was adjusted so that there was no optical cross-talk between the two types of measurements, which was validated in experiments involving staining with either RH-237 or Fluo-3. The amplitude of Fluo-3 signals rapidly decreased during experiments due to dye leakage. Dye leakage was substantially reduced by application of 1 mM probenecid, a blocker of organic anion transport, which had no effect on action potential duration and only minor effect on conduction velocity. In double-stained preparations, during regular pacing Ca(i)2+ transients had a rise time of 14.2 +/- 2 msec, and they followed Vm upstrokes with a delay of 5.3 +/- 1 msec (n = 9). Durations of Vm and Ca(i)2+ transients determined at 50% level of signal recovery were 54.6 +/- 10 msec and 136 +/- 8 msec, respectively. Application of 2 microM nifedipine reduced the amplitude and duration of Ca(i)2+ transients without significantly affecting conduction velocity. CONCLUSION: The results demonstrate feasibility of simultaneous optical recordings of Vm and Ca(i)2+ transients with high spatial and temporal resolution.

Mechanism of ventricular defibrillation. The role of tissue geometry in the changes in transmembrane potential in patterned myocyte cultures.

BACKGROUND: The geometry of the myocardium may influence changes in transmembrane potential (DeltaVm) during defibrillation. To test this hypothesis, specific nonlinear structures (bifurcations, expansions, and curved strands or "bends") were created in patterned cultures of neonatal rat myocytes. METHODS AND RESULTS: Extracellular field stimuli (EFS; 7 to 11 V/cm field strength) were applied parallel to the strands. Changes in Vm were measured with microscopic resolution using optical mapping techniques. In bifurcations, EFS produced 2 DeltaVm maxima (so-called secondary sources) at the shoulder of each limb that were separated by a decrease of either hyperpolarization or depolarization at the insertion of the stem strand. In expansions, EFS produced a significant decrease in DeltaVm at the insertion site of the expansion compared with the DeltaVm maxima measured at the lateral borders. In 50% of experiments, tertiary sources of opposite polarity appeared in the strand due to local electrotonic currents. New action potentials were propagated from the sites of DeltaVm maxima located at the lateral borders of the expansions. In bends, the strand oriented in parallel to the field dominated electrotonically and partially cancelled the sources produced by the perpendicular segment. CONCLUSIONS: In electrically well-coupled nonlinear structures, EFS produced changes in Vm at resistive boundaries that were determined by the electrotonic interaction between sources of different, direction-dependent strength. In addition, the interaction between localized secondary sources at nonlinear boundaries generated local current circuits, which gave rise to further changes in Vm (tertiary sources).

Nonlinear changes of transmembrane potential caused by defibrillation shocks in strands of cultured myocytes.

Organization of cardiac tissue into cell strands and layers has been implicated in changes of transmembrane potential (DeltaV(m)) during defibrillation. To determine the shock-induced DeltaV(m) in such structures, cell strands of variable width [strand width (SW) = 0.15-2 mm] were grown in culture. Uniform-field shocks with variable strength [shock strength (SS) = 2-50 V/cm] were applied across strands during the action potential (AP) plateau, and DeltaV(m) were measured optically. Three different types of DeltaV(m) were observed. Small DeltaV(m) [<40%AP amplitude (APA)] were linearly dependent on SS and SW and were symmetrically distributed about a strand centerline with maximal positive and negative DeltaV(m) on opposite strand sides being equal. Intermediate DeltaV(m) (<200%APA) were strongly asymmetric with negative DeltaV(m) > positive DeltaV(m) because of a negative time-dependent shift of V(m) at the depolarized side of the strands. For large DeltaV(m) (>200%APA), a second time-dependent shift of V(m) to more positive levels was observed in the hyperpolarized portions of strands, causing reduction of the DeltaV(m) asymmetry. We conclude that during application of shocks to cell strands during the AP plateau, passive changes of V(m) were followed by two voltage- and time-dependent shifts of V(m), possibly reflecting changes of ionic currents or membrane electroporation.

Activation of cardiac tissue by extracellular electrical shocks: formation of 'secondary sources' at intercellular clefts in monolayers of cultured myocytes.

This study investigated the activation of cardiac tissue by "secondary sources," which are localized changes of the transmembrane potential (Vm) during the application of strong extracellular electrical shocks far from the shock electrodes, in cultures of neonatal rat myocytes. Cell monolayers with small intercellular clefts (length, 45 to 270 microm; width, 20 to 70 microm [mean+/-SD, 54+/-13 microm]; n = 46) were produced using a technique of directed cell growth. Changes in Vm relative to the action potential amplitude (deltaVm/APA) were measured using a fluorescent voltage-sensitive dye and a 10 x 10 photodiode array. Shocks with voltage gradients of 4 to 18 V/cm were applied across the clefts during either the action potential (AP) plateau or diastole. During the AP plateau, shocks induced secondary sources in the form of localized hyperpolarizations and depolarizations in the regions immediately adjacent to opposite sides of the clefts. The strength of the secondary sources, defined as the difference of deltaVm/APA across a cleft, increased with increasing cleft length or increasing electrical field gradient. For shocks with a gradient of 8.5 V/cm, the estimated critical cleft length necessary to reach a Vm level corresponding to the diastolic threshold of excitation was 171+/-7 microm. Accordingly, shocks with average strength of 8.2 V/cm applied during diastole produced secondary sources that directly excited cells adjacent to the clefts when the cleft length was 196+/-53 microm (n = 14) and that failed when the cleft length was 84+/-23 microm (n = 9, P<.001). The area of earliest excitation in such cases coincided with the area of maximal depolarization induced during the plateau phase. These data suggest that small inexcitable obstacles may contribute to the Vm changes during the application of strong extracellular electrical shocks in vivo.

Paradoxical improvement of impulse conduction in cardiac tissue by partial cellular uncoupling.

Generally, impulse propagation in cardiac tissue is assumed to be impaired by a reduction of intercellular electrical coupling or by the presence of structural discontinuities. Contrary to this notion, the spatially uniform reduction of electrical coupling induced successful conduction in discontinuous cardiac tissue structures exhibiting unidirectional conduction block. This seemingly paradoxical finding can be explained by a nonsymmetric effect of uncoupling on the current source and the current sink in the preparations used. It suggests that partial cellular uncoupling might prevent the initiation of cardiac arrhythmias that are dependent on the presence of unidirectional conduction block.

Role of wavefront curvature in propagation of cardiac impulse.

It is traditionally assumed that impulse propagation in cardiac muscle is determined by the combination of two factors: (1) the active properties of cardiac cell membranes and (2) the passive electrical characteristics of the network formed by cardiac cells. However, advances made recently in the theory of generic excitable media suggest that an additional factor-the geometry of excitation wavefronts -may play an important role. In particular, impulse propagation strongly depends on the wavefront curvature on a small spatial scale. In the heart, excitation wavefronts have pronounced curvatures in several situations including waves initiated by small electrodes, waves emerging from narrow tissue structures, and waves propagating around the sharp edges of anatomical obstacles or around a zone of functional conduction block during spiral wave rotation. In this short review we consider the theoretical background relating impulse propagation to wavefront curvature and we estimate the role of wavefront curvature in electrical stimulation, formation of conduction block, and the dynamic behavior of spiral waves.

Molecular and cellular aspects of re-entrant arrhythmias.

In recent years it has become evident that myocardial tissue undergoes remodeling in diseased states such as myocardial infarction and hypertrophy which affects membrane channels, cell-to-cell coupling as well as the connective tissue matrix. Although the detailed mechanisms of ventricular arrhythmias in ventricular hypertrophy are not known, studies carried out by computer simulations or high resolution mapping of electrical activity have suggested a complex interaction between changing ionic currents at the level of the cell membranes, altered cell-to-cell coupling and altered macroscopie-structure. The present report summarises these recent developments and their potential relevance for arrhythmogenesis.

Spatial changes in transmembrane potential during extracellular electrical shocks in cultured monolayers of neonatal rat ventricular myocytes.

This study investigated the role of different types of discontinuities in tissue architecture on the spatial distribution of the transmembrane potential. Specifically, we tested the occurrence of so-called "secondary sources," ie, localized hyperpolarizations and depolarizations during the application of extracellular electrical shocks (EESs). Changes in transmembrane potential relative to action potential amplitude (delta Vm/APA) were measured in patterned cultures of neonatal rat myocytes, stained with voltage-sensitive dye (RH-237), by optical mapping (96-channel photodiode array, 6- to 30-micron resolution) during the application of EES (field strength, 8 to 22 V/cm; duration, 6 ms). Across narrow cell strands (width, 218 +/- 59 [mean +/- SD] microns), EES applied during the relative refractory period produced a linear and symmetrical profile of delta Vm/APA (-65 +/- 23% maximal hyperpolarization versus +64 +/- 15% maximal depolarization). In contrast, the profile of delta Vm/APA was asymmetrical when EESs were applied during the action potential plateau (-95 +/- 32% versus +37 +/- 14%). At high magnification, no secondary sources were observed at the borders between cells. In dense isotropic cell monolayers or in monolayers and strands showing intercellular clefts, secondary sources were frequently observed. Intercellular clefts of the size of one to several myocytes were sufficient to produce secondary sources of the same magnitude as those that elicited action potentials in dense cell strands. There was a close correlation between the location of secondary sources during EES and localized conduction slowing during propagation. Thus, densely packed cultured cell strands behave as an electrical continuum with no secondary sources occurring at cell borders. Small intercellular clefts can create secondary sources of sufficient magnitude to exert a stimulatory effect.

Functional and structural assessment of intercellular communication. Increased conduction velocity and enhanced connexin expression in dibutyryl cAMP-treated cultured cardiac myocytes.

Remodeling of conduction pathways in the hypertrophic response to myocardial injury is a potential mechanism leading to the development of anatomic substrates of lethal arrhythmias. To delineate the responsible mechanisms and to directly relate changes in intercellular coupling at gap junctions with electrophysiological alterations, we studied the effects of cAMP, a mediator of cardiac hypertrophy, on action potential conduction velocity and connexin expression in neonatal rat ventricular myocyte cultures. Conduction velocity was measured with an optical activation mapping technique in cells loaded with the voltage-sensitive dye RH-237. Action potentials were conducted 24% to 29% more rapidly (P < .005) after incubating cultures for 24 hours with the cAMP analogue dibutyryl cAMP (db-cAMP, 1 mmol/L). However, db-cAMP caused no change in the maximum rate of rise of the action potential upstroke, Vmax. Electron and immunofluorescence microscopy revealed a significant increase in the number and size of gap junctions in db-cAMP-treated cells. Immunoblotting showed that the total amounts of the ventricular gap junction proteins connexin43 and connexin45 (Cx43 and Cx45, respectively) increased 2- to 4-fold. Immuno-precipitation of metabolically labeled connexin proteins revealed a dose-dependent increase in the rate of Cx45 protein synthesis in myocytes exposed to db-cAMP ( > 2-fold after a 4-hour exposure) but no change in the Cx43 synthesis rate. Northern blot analysis demonstrated a time-dependent increase in the amount of Cx43 mRNA, with a maximum 3.3-fold increase after 4 hours of exposure to 1 mmol/L db-cAMP; cycloheximide did not block this effect. In contrast, Cx45 mRNA levels were not altered significantly after db-cAMP treatment. Thus, cAMP causes a significant increase in conduction velocity that appears to be attributable largely to enhanced expression of proteins responsible for intercellular communication. Cx43 and Cx45 levels appear to be upregulated by cAMP by disparate molecular mechanisms.

Anisotropic activation spread in heart cell monolayers assessed by high-resolution optical mapping. Role of tissue discontinuities.

The role of tissue discontinuities in anisotropic impulse propagation was assessed in two-dimensional anisotropic monolayers of neonatal rat myocytes cultured on a growth-directing substrate of collagen. Activation spread and distribution of maximal upstroke rate of rise (Vmax) of the action potential were measured with an optical system using a voltage-sensitive fluorescent dye (RH-327) and a 10x10 photodiode array with a spatial resolution ranging from 7 to 15 microns. Activation maps were compared with the cellular architecture and the distribution of gap junctions obtained from immunostaining the gap junction protein connexin43 (Cx43). Four types of structures were studied: (1) dense cell cultures, (2) cultures with anisotropic intercellular clefts of variable size, (3) discontinuities created by inclusion of nonmyocyte cells, and (4) discontinuities resulting from nonuniform expression of gap junctions. In dense monolayers, activation spread was continuous with microinhomogeneities in both longitudinal and transverse directions. The average cell dimensions in such monolayers were smaller than in adult canine myocardium. However, the degree of cellular anisotropy (length-to-width ratio of 5.3 +/- 1.4) and connectivity were similar. The presence of small intercellular clefts (less than one cell in length) did not disturb the general pattern of transverse or longitudinal activation spread, but it was associated with wave front microcollisions during transverse propagation and a concomitant increase of Vmax beyond the cleft. Long intercellular clefts caused discontinuous transverse propagation. Conduction velocity and Vmax decreased significantly at narrow isthmuses formed by closely apposed clefts, rendering such sites susceptible for conduction block. In contrast Vmax increased when the wave front faced the borders of the clefts. Nonmyocyte cells were electrically connected to myocytes and served as sinks for electrotonic currents, thereby producing localized conduction slowing and a decrease in Vmax. Localized inhomogeneity in Cx43 distribution correlated accurately with circumscribed conduction block and changes in Vmax. Our results provide direct experimental evidence that the cellular structure and gap junction distribution correlate with action potential propagation and distribution of Vmax. We suggest that in tissue with a nonuniform anisotropy, connective tissue separating fiber bundles or sites of inhomogeneous connexin distribution may represent predilective sites for block in transverse direction.

[Physiology and pathophysiology of cardiac impulse conduction]. / Physiologie und Pathophysiologie der kardialen Erregungsleitung.

Representation of cardiac tissue by a continuous electrical cable provides a simple tool to explain impulse propagation and to make a comparison between heart, skeletal muscle and nerve. Recent experimental and theoretical studies have shown, however, that the process of electrical impulse propagation in heart is complex, due to the presence of cell borders and septa of connective tissue. At sites where propagation deviates from a linear profile, action potential generation gets delayed, and in cases of decreased excitability, unidirectional block may occur. At such sites, propagation is carried by the slow Ca++ inward current, in addition to the rapid Na+ inward current. As a consequence, local propagation may become sensitive to inhibition of Ca++ channels. Moreover, computer simulations have shown that electrical cell-to-cell uncoupling an gap junctions can reverse unidirectional block at such sites to bidirectional conduction. This complex interaction between function and structure which is likely to play a major role in remodeled tissue (hypertrophy, chronic infarction) has to be taken into account in the evaluation of the mechanisms of action of antiarrhythmic drugs.

Block of impulse propagation at an abrupt tissue expansion: evaluation of the critical strand diameter in 2- and 3-dimensional computer models.

OBJECTIVE: Unidirectional conduction block in the heart can occur at a site where the impulse is transmitted from a small to a large tissue volume. The aim of this study was to evaluate the occurrence of conduction block in a 2-dimensional and 3-dimensional computer model of cardiac tissue consisting of a narrow strand abruptly emerging into a large area. In this structure, the strand diameter critical for the occurrence of block, hc, was evaluated as a function of changes in the active and passive electrical properties of both the strand and the large medium. METHODS: The effects of changes in the following parameters on hc were analysed: (1) maximum sodium conductance (gNamax), (2) longitudinal (Rx) and transverse (Ry) intracellular resistivities, and (3) inhomogeneities in gNamax and Rx and Ry between the strand and the large area. Three ionic models for cardiac excitation described by Beeler-Reuter, Ebihara-Johnson, and Luo-Rudy ionic current kinetics were compared. RESULTS: In the 2-dimensional simulations, hc was 175 microns in Ebihara-Johnson and Beeler-Reuter models and 200 microns in the Luo-Rudy model. At the critical strand diameter, the site of conduction block was located beyond the transition, i.e. a small circular area was activated in the large medium, whereas with narrower strands conduction block occurred within the strands. The decrease of gNamax resulted in a large increase of hc. This increase was mainly due to the change of gNamax in the large area, while hc was almost independent of gNamax in the strand. Changing Rx had no effect on hc, whereas the increase of Ry decreased hc and reversed conduction block. Inhomogeneous changes of Rx and Ry in the strand versus the large medium had opposite effects on hc. When the resistivities of the strand alone were increased, hc also increased. In contrast, the increase of the resistivities in the large area reduced hc. In the 3-dimensional model, hc was 2.7 times larger than the corresponding 2-dimensional values at the various levels of gNamax and resistivity. CONCLUSIONS: (1) At physiological values for active and passive electrical properties, hc in the 2D simulations is close to 200 microns in all three ionic models. In the 3-dimensional simulations, hc is 2.7 larger than in the 2-dimensional models. (2) The excitable properties of the large area but not of the strand modify hc. The decrease of intercellular coupling in the large medium facilitates impulse conduction and reduces hc, while the same change in the strand increases hc. (3) Occurrence of conduction block at an abrupt geometrical transition can be explained by both the impedance mismatch at the transition site and the critical curvature beyond the transition.

Cardiac tissue geometry as a determinant of unidirectional conduction block: assessment of microscopic excitation spread by optical mapping in patterned cell cultures and in a computer model.

OBJECTIVE: Unidirectional conduction block (UCB) and reentry may occur as a consequence of an abrupt tissue expansion and a related change in the electrical load. The aim of this study was to evaluate critical dimensions of the tissue necessary for establishing UCB in heart cell culture. METHODS: Neonatal rat heart cell cultures with cell strands of variable width emerging into a large cell area were grown using a technique of patterned cell growth. Action potential upstrokes were measured using a voltage sensitive dye (RH-237) and a linear array of 10 photodiodes with a 15 microns resolution. A mathematical model was used to relate action potential wave shapes to underlying ionic currents. RESULTS: UCB (block of a single impulse in anterograde direction - from a strand to a large area - and conduction in the retrograde direction) occurred in narrow cell strands with a width of 15(SD 4) microns (1-2 cells in width, n = 7) and there was no conduction block in strands with a width of 31(8) microns (n = 9, P < 0.001) or larger. The analysis of action potential waveshapes indicated that conduction block was either due to geometrical expansion alone (n = 5) or to additional local depression of conduction (n = 2). In wide strands, action potential upstrokes during anterograde conduction were characterised by multiple rising phases. Mathematical modelling showed that two rising phases were caused by electronic current flow, whereas local ionic current did not coincide with the rising portions of the upstrokes. CONCLUSIONS: (1) High resolution optical mapping shows multiphasic action potential upstrokes at the region of abrupt expansion. At the site of the maximum decrement in conduction, these peaks were largely determined by the electrotonus and not by the local ionic current. (2) Unidirectional conduction block occurred in strands with a width of 15(4) microns (1-2 cells).

Anisotropic conduction in monolayers of neonatal rat heart cells cultured on collagen substrate.

Anisotropic impulse conduction was studied in neonatal rat heart cell monolayers produced by culturing cells on a growth-directing substrate of collagen. Monolayers consisting of parallel-oriented cells without visible intercellular clefts were selected for experiments; cell lengths and widths were 65.8 +/- 12.5 and 12.2 +/- 3.2 microns (n = 49), respectively. Action potential upstrokes were measured by using 12 photodiodes selected within a 10x10 diode array and a voltage-sensitive dye (RH-237). The size of the area sensed by a single diode was 14 x 14 microns. High-density multiple recordings (resolution, up to 15 microns) demonstrated the variability of local activation delays and of the maximal rate of rise of the action potential upstroke (Vmax), which are presumably related to the microscopic cellular architecture. Mean macroscopic conduction velocities measured over distances of 135 microns were 34.6 +/- 4.5 and 19.0 +/- 4.3 cm/s (mean +/- SD, n = 13, P < .0001) in longitudinal and transverse directions, respectively. The anisotropic velocity ratio was 1.89 +/- 0.38 (n = 13). Mean Vmax was not significantly different in two directions (122.0 +/- 17.4 V/s longitudinally versus 125.2 +/- 15.6 V/s transversely, n = 13, P = NS). In conclusion, we developed an anisotropic cell culture model suitable for studying impulse conduction with cellular resolution. The anisotropic velocity ratio was close to values measured in vivo. By contrast, Vmax was not dependent on the direction of propagation.

Microscopic conduction in cultured strands of neonatal rat heart cells measured with voltage-sensitive dyes.

Microscopic discontinuities in electrical activation were assessed in synthetic strands of neonatal rat myocytes cultured on a growth-directing matrix. An optical method using voltage-sensitive dye (RH-237) and a photodiode technique was used for recordings of membrane potential changes with subcellular resolution. Spatial resolution of the method (diameter of measurement area, 5.5 microns; interdiode distance, 30 microns) allowed for simultaneous measurements of cytoplasmic conduction time within a single cell and junctional conduction time across the cell border. In one-dimensional cell chains, where cells were juxtaposed by end-to-end connections but devoid of lateral connections, propagation of the excitation wave was strongly nonuniform: cytoplasmic conduction time was 38 +/- 30 (mean +/- SD) microseconds (n = 37), whereas junctional conduction time was 118 +/- 40 microseconds (n = 27, P < .0001). A mean delay introduced by a single junction was 80 microseconds, or 51% of conduction time. In two-dimensional strands consisting of several cells in width, which exhibited lateral as well as end-to-end connections, inhomogeneity of conduction was smaller: the cytoplasmic and junctional conduction times were 57 +/- 30 (n = 46) and 89 +/- 40 (n = 48) microseconds, respectively (P < .0001); mean junctional conduction delay was 32 microseconds (22% of conduction time). Mathematical modeling suggested that the averaging effect of lateral connections is caused by lateral convergence of local excitatory current beyond and lateral divergence before end-to-end connections. Our results demonstrate that the current flow through lateral cell-to-cell connections smooth the excitation wave front during longitudinal conduction in myocardial tissue.

[Isolated right ventricle after coronary perfusion as a model for the study of ischemic and reperfusion-induced arrhythmia in rats]. / Izolirovannyi koronarno-perfuziruemyi pravyi zheludochek krysy kak model' dlia issledovaniia ishemicheskikh i reperfuzionnykh aritmii.

A catheter through which perfusion was performed with oxygenated saline (2.1 ml/min) was introduced into the right coronary artery ostium of the rat right ventricle that had been isolated during cardioplegia. Super perfusion (12 ml/min) was simultaneously made. Termination of the perfusion caused arrhythmias at minutes 6 to 28 of ischemia. The highest likelihood of occurrence of such arrhythmias was observed on minutes 16-20 (premature beats being seen in 86% of the experiments, extrastimulus-induced tachycardias in 75%, spontaneous tachycardias in 25%). Reperfusion was made at 3, 5, 7, 10, 13, 15, 20, 30 and 60 min following ischemia (n = 7 in each case). The occurrence of reperfusion arrhythmias is likely to be related to the duration of ischemia with the highest likelihood of 20 minutes after ischemia (tachycardia and fibrillation were observed in 100 and 71%, respectively).