Arrhythmias Flashcards
what are EADs?
depolarisations that take off during the AP plateau or Phase 3, in the voltage ranges between +10 and +20mV
when are EADs more likely to occur?
examples
when there is:
1) AP prolongation and reduction of outward repolarising current
2) bradycardia
3) LQTS
eg in hypokalaemia and a resultant decrease in Ik1
or congenital channel defects producing long QT
what mediates the EADs?
the reactivation of ICa,L that has recovered from Ca-dependent inactivation during long APs near plateau Em once [Ca]i has significantly declined.
there is a significant region of overlap between the activation and inactivation versus voltage relationship, giving rise to a “window”»_space; this means that as the AP repolarises into this range of voltages, a proportion of ICa,L can activate or reactivate..
If the current is large enough, this can trigger more SR Ca release and an aftercontraction. In addition, Ca released from Ca causes more inward current mediated by INCX and this adds to the formation of EAD.
what are DADs?
they are depolarisations that take off from the RESTING Em after AP repolarisation (diastolic interval)
what causes DADs?
DADs are caused by spontaneous SR Ca release events that occur at relatively high SR Ca levels, and also increased cytoplasmic [Ca]. This SR Ca release causes an aftercontraction and a transient inward current (Iti) that depolarises Em toward threshold for an AP. The Iti is provided by the NCX, whose activity is increased as a result of increased cytosolic Ca.
when are DADs more likely to occur?
when there is increased Ca in the cytoplasm and SR, eg in high heart rates, B-AR stimulation or in the presence of cardiotonic steroids.
can a DAD in a single cell cause an arrhythmia?
No, because neighbouring cells would provide a current sink, dissipating the Iti. However if DADs occur in a cluster of adjacent cells, the impulse can escape and propagate through the heart.
what is the role of INsP3 receptors?
How is it different in heart failure?
G protein-coupled receptors (eg endothelin-1) can induce InsP2-dependent local SR Calcium release, which activates neighbouring RyRs and precipitates DAD-like arrhythmias.
InsP3 receptors are low in number in ventricular myocytes but in the atria they are much more numerous and coexist with RYR on the SR.
In heart failure, InsP3 receptors are upregulated in the ventricle, so this arrhythmogenic mechanism may be relevant under these circumstances.
generally, what is the cause of triggered arrhythmias?
DADs, EADs, or increased automaticity, all can be attributes in part to Ca signalling or transport.
what is electrical alternans?
when APD alternated between long and short, thought to be a diagnostivc precursos for severe arrhythmias such as VT or VF.
what is electrical alternans thought to be due to?
APD alternans is thought to be secondary to Ca transient amplitude alternans.
Ca handling may be impaired due to incomplete ICa or RyR recovery and alternating SR content.
Many Ca-dependent currents may contribute, but Ica and INCX are probably key.
At the larger beat, there is more inward INCX, which would prolong the APD, but also less integrated ICa (and more inactivation) which would shorten the APD. The greater INCX predominates over the smaller ICa, thus resulting in prolonged APD.
alternans occurring during increased pacing frequency is mainly due to what?
mainly due to the slow resolution of Ryr availability. that is, slow RyR recovery after a large SR release results in a smaller SR Ca release at the next beat such that the RyRs that did not fire are ready for activation on the next beat, which again has larger SR Ca release.
When the larger SR Ca releases and Ca transients occur, there is more Ca extrusion via NCX and less Ca entry via ICa (and NCX) because of greater Ca-dependent inactivation of ICa.»_space;> This leads to an alternation of SR Ca content.
