Electrical conduction and arrhythmias Flashcards
parameters that affect the AP propagation velocity:
Resistance of the cytopasm (Ri) and the inward depolarising current (maximal upstroke velocity (dV/dt) - corresponds to phase 0)
Propagation velocity is proportional to the square root of max dV/dt and inversely proportional to the square root of Ri.
what factors determine the magnitude of Ri?
Ri becomes smaller as cell diameter decreases (cell size), and its value along the strand of cells depends on the number andtype of gap junctions that connect the cells.
WHy does AP propagate unidirectionally?
normally, the region just behind the wave of depolarisation will be refractory
what does the success of propagation depend on?
the safety factor (SF): it is a quantity describing the source-sink relationship. it is defined as the ratio of charge generated by the source cell to charge consumed by the sink cells.
A value greater than 1 indicates that more charge is produced during excitation than is needed to excite the sink cell, so successful propagation ensues.
what happens to the AP propagation if there are less sodium channels available eg due to pharmacological blockade?
in this area of reduced Na channel activity less source current may be produced.
this affects both conduction velocity (it depends on the square root of dV/dt) and the SF because less current is produced.
if the Na channel activity is too low, the SF becomes <1, and impulse propagation ceases.
Is there anisotropy in cardiac cells?
Yes, cardiomyocytes are coupled to one another in both transverse and longitudinal directions. The conduction velocity (CV) is much greater longitudinally, compared with transversely because the cells are much more electrically coupled (via gap junctions) at their longitudinal ends.
Anisotropy ration (AR)= CV(longitudinal)/CV(transverese)
the highest AR is found in the crista treminalis in the superior portion of right atrium where AR=10, the lowest is in the ventricles AR=2. this is consistent with their functions because crista terminalis provides highly directed propagation from the SAN to the right atrium.
What types of arrhyhmias are there
Can be related to disorders in impulse formation or impulse propagation.
Impulse formation refers to autommaticity which, when abnormal, can produce an ectopic focus of impulse generartion) and triggered activity (DADs, EADs)
Impulse conduction disorders are typically associated with reentry mechanisms, which are further subclassified into anatomic and functional.
Abnormal automaticity
Ectopic foci, not in the SAN, can initiate umpulsse generation and either cause additional beats in the background of the impulses generated by SAN or take over the normal pacemkaer impulses.
the foci result from hypoxic or ischaemic insults to the tissue, sympathetic overstimulation, as a result of cardiomyocyte ultrastructural changes eg in HF, electrolyte disturbances and drug actions.
these altered conditions may also cuase triggered arrhythmias.
triggered arrhythmias
triggered arrhythmias are due to extra action potentials that are produced as a result of spontaneous depolarisations during which inappropriate channel reactivation, relating to altered calcium hanndling, occurs . this can happen at several different stages of the AP.:
It is termed EAD (early afterdepolarisation) if ocurring during the repolarisation phases (phase 3 or late phase 2)
or DAD if occuring during the diastolic (phase 4) periods..
both EADs and DADs can innitiate ventricular arrhythmias.
prerequisites for ree-entry arrhythmias
re-entry describes depolarisation occurin in a closed circuit. it requires:
A substrate: the presence of joined myocardial tissue with different electrophysiological properties, conduction, and refractoriness.
An area of block (anatomical, functional, or both): an area of inexcitable tissue around which the wavefront can circulate.
A unidirectional conduction block.
A path of slowed conduction that allows sufficient delay in the conduction of the circulating wavefront to enable the recovery of the refractory tissue proximal to the site of unidirectional block.
A critical tissue mass to sustain the circulating reentrant wavefronts.
An initiating trigger.
When the wavefront encounters the obstacle, it will travel down one pathway (unidirectional block), propagating until the point of block, thus initiating a reentrant circuit.
Initiation and maintenance of reentry will depend on the conduction velocity and refractory period of each pathway, which determines the wavelength (wavelength=conduction velocity (?) refractory period).
For reentry to occur, the wavelength must be shorter than the length of the pathway.
Conditions that decrease conduction velocity or shorten the refractory period will allow the creation of smaller circuits, facilitating the initiation and maintenance of reentry.
The excitable gap is a key concept essential to understanding the mechanism of reentry (Fig. 8). The excitable gap refers to the excitable myocardium that exists between the head of the reentrant wavefront and the tail of the preceding wavefront.
This gap allows the reentrant wavefront to continue propagation around the circuit.
The presence of an excitable gap also makes it possible to enter in the reentrant circuit using external pacing and explains the phenomena of resetting, entrainment, and termination of the tachycardia with electrical stimulation.
The excitable gap
The excitable gap is a key concept essential to understanding the mechanism of reentry (Fig. 8). The excitable gap refers to the excitable myocardium that exists between the head of the reentrant wavefront and the tail of the preceding wavefront.
This gap allows the reentrant wavefront to continue propagation around the circuit.
The presence of an excitable gap also makes it possible to enter in the reentrant circuit using external pacing and explains the phenomena of resetting, entrainment, and termination of the tachycardia with electrical stimulation.
wavelength and pathway length: relation to reentry
For reentry to occur, the wavelength must be shorter than the length of the pathway.
functional re-entry
In functional reentry, the circuit is not determined by anatomic obstacles; it is defined by dynamic heterogeneities in the electrophysiologic properties of the involving tissue. The location and size of functional reentrant circuits can vary, but they are usually small and unstable.
functionally determined reentrant circuits can occur due to different mechanism:
1) leading circle reentry where the impulse circulates around a central core that is maintained in a refractory state. it is the smallest possible pathway in ehich the impulse can continue to circulate.
2) Anisotropic reentry. Anisotropic conduction relates to directionally dependent conduction velocity in cardiac muscle27 and depends on the structure and organization of myocytes within cardiac tissue.
3) figure of eight
4) reflection - unique in that it occurs in a linear segment of tissue
5) spiral wave (rotor) activity: spital wave activation is organised aroun a core which remainsunstimulated because of the pronounced curvature of the spiral.. in contrast to the leading circle model, there is a fully excitable gap.
antiarrhythmic strategies
1) altering conduction velocity
2) altering cell excitability and changing the duration of effective refractory period
3) suppressing abnormal automaticity
Na channel blockers
generally bind to inactivated Na channels, thus repetitive shifts to more depolarised potentials by trains of stimuli promote binding of more drug molecules to the channels (use dependent). the drugs bind to the S6 regions of domains III and IV.
All slow the upstroke of AP and thus slow conduction and increaqse the threshold for excitation
1A procainamide: increase APD prolonging the effective refractory period.
1C flecainide - no change in APD.
1B lodocaine - small decrease in APD
