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 wave

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 μm 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) μm (1-2 cells in width, n = 7) and there was no conduction block in strands with a width of 31(8) μm (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) μm (1-2 cells

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 μm in Ebihara-Johnson and Beeler-Reuter models and 200 μm 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 μm 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 transitio

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 μm in Ebihara-Johnson and Beeler-Reuter models and 200 μm 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 μm 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

Real time, confocal imaging of Ca2+ waves in arterially perfused rat hearts

Objective: The aim of this study was to characterize the spatio-temporal dynamics of slow Ca2+ waves (SCW's) with cellular resolution in the arterially-perfused rat heart. Methods: Wister rat hearts were Langendorff-perfused with Tyrode solution containing bovine-albumine and Dextran. The heart was loaded with the Ca2+ sensitive dye Fluo-3 AM. Intracellular fluorescence changes reflecting changes in [Ca2+]i were recorded from subepicardial tissue layers using a slit hole confocal microscope with an image intensified video camera system at image rates of up to 50/s. Results: SCW's appeared spontaneously during cardiac rest or after trains of electrical stimuli. They were initiated preferentially in the center third of the cell and propagated to the cell borders, suggesting a relation between the cell nucleus and wave initiation. They were suppressed by Ca2+ transients and their probability of occurrence increased with the Ca2+ resting level. Propagation velocity within myocytes (40 to 180 μm/s) decreased with the resting Ca2+ level. Intercellular propagation was mostly confined to two or three cells and occurred bi-directionally. Intercellular unidirectional conduction block and facilitation of SCW's was occasionally observed. On average 10 to 20% of cells showed non-synchronized simultaneous SCW's within a given area in the myocardium. Conclusions: SCW's occurring at increased levels of [Ca2+]i in normoxic or ischemic conditions are mostly confined to two or three cells in the ventricular myocardium. Spatio-temporal summation of changes in membrane potential caused by individual SCW's may underlie the generation of triggered electrical ectopic impulse

ST-segment elevation in the electrocardiogram: a sign of myocardial ischemia

In 1972 Kjekshus et al. published the seminal article ‘Distribution of myocardial injury and its relations to epicardial ST-segment changes after coronary occlusion in the dog’ in Cardiovascular Research. In this article it was shown that the ST-segment elevation occurring early after occlusion of the left descending coronary artery was closely related to the depletion of the necrotic cells from creatine kinase and to flow reduction at a later stage (24 h). This correlation was especially prominent if the infarction was transmural. Starting from these phenomenological relationships, this article briefly describes and summarizes the experimental research which was carried out in other laboratories after the publication of Kjekshus et al. Special emphasis is laid on the discussion of the main basic mechanisms which underly the clinically observed ST-segment elevation and its evolution after the acute stage of ischemia, i.e. the changes in the transmembrane action potential and the alteration in electrical cell-to-cell coupling