Propagation In Cardiac Tissue Research Articles

Structure-activity relations of the cardiac gap junction channel

Cardiac gap junction channels play the important roles of synchronizing pacemaker cells and allowing impulse propagation along the conduction system and throughout the ventricular myocardium. These channels, which support current flow in both longitudinal and tranverse directions, are permeable to anions and cations with radii less than approximately 0.5 nm and in rat heart have unitary conductances on the order of 50 pS. This unitary conductance is consistent with channel geometry described by a right cylindrical pore with diameter large enough for the brilliantly fluorescent dye molecule lucifer yellow to pass between cells. These channels, like others in biological systems, are opened and closed by various treatments, a process termed gating. Cytoplasmic acidification reduces junctional conductance (gj), an effect that is apparently potentiated by elevated myoplasmic Ca ions. Reduced gj also occurs in response to a variety of lipophilic molecules, including halothane, heptanol, and unsaturated fatty acids; the mechanism of action may involve disruption of the protein-lipid microenvironment of the gap junction channel. Arachidonic acid uncouples, and this effect is partially, but incompletely, blocked by an inhibitor of the lipoxygenase metabolic pathways. Cyclooxygenase inhibitors have no protective effects. Certain cyclic nucleotides can rapidly increase gj [adenosine 3',5'-cyclic monophosphate (cAMP)] or slightly decrease it [guanosine 3',5'-cyclic monophosphate (cGMP)], and agents that use these cyclic nucleotides as second messengers (isoproterenol and perhaps carbachol, respectively) produce consistent effects. Agents expected to cause protein kinase C activation (tumor-promoting phorbol esters and diacylglycerol) increase gj rapidly. The gap junction protein from rat heart has been cloned and sequenced. From the primary sequence for the protein, plausible sites of action within the putative cytoplasmic domains are proposed for each of these treatments. In response to gating stimuli that close the channel (halothane, CO2, heptanol), unitary channel conductance is unchanged, suggesting that these agents act by reducing open time probability. Together, these properties constitute the beginnings of our endeavor to define pharmacological agents that are potentially useful in therapeutic manipulation of synchronous discharge, conduction velocity, and isochronous wavefront propagation in cardiac tissue.

A model study of the effects of the discrete cellular structure on electrical propagation in cardiac tissue.

The effects of the discrete cellular structure on propagation of electrical excitation in cardiac muscle were studied in a one-dimensional fiber model containing a periodic intercalated disk structure. Globally, the macroscopic velocity of propagation follows the behavior associated with propagation in a continuous tissue (except for high values of disk resistance). In addition, the computed spatial extracellular potential along the fiber is a smooth biphasic waveform and does not reflect the underlying discrete cellular structure of the tissue. Other results of the simulations demonstrate the discontinuous nature of propagation and the importance of the structure in arrhythmogenesis. Vmax displays a biphasic behavior as a function of increasing intercalated disk resistance. An initial "paradoxical" increase in Vmax (with a simultaneous decrease in conduction velocity) is followed by a decrease that leads to decremental propagation and conduction block. The time constant of the foot of the action potential (tau foot) increases monotonically with increasing intercalated disk resistance. An increase in the leakage current to extracellular space brings about a significant decrease in the action potential duration and a loss of the plateau. This major effect is accompanied by a relatively smaller decrease in conduction velocity. Collision of two activation wavefronts results in a significant (100%) increase in Vmax and a very small (0.6%) decrease in tau foot.

Arrhythmias in Patients with Drug Toxicity, Electrolyte, and Endocrine Disturbances

The common rhythm disturbances related to electrolyte imbalance are due predominantly to abnormalities of potassium. An understanding of the mechanism underlying these abnormalities is facilitated by a brief review of normal electrical activity during impulse propagation in cardiac tissue. Also discussed are the actions of all cardioactive and antiarrhythmic drugs on membrane permeability to ions. Lastly, the nonspecific arrhythmias associated with endocrine disturbances are outlined.

Structural basis for cardiac function.

Structural basis for cardiac function.

The Third-order Action Potential Model For Computer Simulation Of Electrical Wave Propagation In Cardiac Tissue

Computer simulation of heart arrhythmia and fibrillation in 2D and 3D cardiac tissue requires adequate mathematical models. The models based on the latest physiological data are very complicated even for modern supercomputers. The widely used second - order simplified models give only qualitative results and do not reproduce properly the cell recovery processes, which affect the appearance of spiral waves, the character of their propagation and possible breakup of the wavefront. In order to overcome the limitations of second - order simplified models third - order models are introduced. The synthesis of these models is based on up - to - date physiological data and includes the effect of the gate variable j on a fast inward current and the total effect of a time - independent outward current and time - dependent slow inward current on the shape of action potential (AP). The reduction of the eighth - order Luo and Rudy (LR) model to the third - order simplified model is used to illustrate the proposed approach. The third - order simplified model retains all the major characteristics and parameters of AP of the original model including the shape of AP, AP duration (APD) and (dEfdt)max restitution.

Large Scale Modelling Of Two-dimensional Cardiac Tissue Using Parallel Methods

Finite difference and iterative methods are used to simulate two-dimensional impulse propagation in cardiac tissue. The model used takes explicitly into account the effects of cytoplasmic and junctional resistances. An initial parallel approach for the implementation of the iterative methods (Gauss-Seidel in our case) based on the systolic array method is presented. The number of iterations needed for convergence of the iterative methods at each time step is examined in conjunction with changes in the spatial distribution of the electrophysiologic parameters such as coupling resistance. Electrograms and propagating action potentials (PAP) are calculated for cases simulating infarcted hearts by placing dead cell bariers in the model cardiac tissue sheet. The shapes of the electrograms and PAPs are critically depending on the position of the recording site relative to the dead cell barriers.