Lecture 2: Cardiac electrophysiology and arrhythmia Flashcards
Describe the direction of electrical spread:
Endo -> Epi
Apex -> Base
Describe the refractory period:
FRT: Full (total) refractory period
ARP: Absolute (effective) refractory period
RRP
SNP: Super-normal period
What are considerations of the RRP and SNP:
RRP & SNP: AP are relatively smaller and slower conducted
What are the two potential sources of arrhythmias?
Disorders of impulse formation
Disorders of impulse conduction
What are some disorders of impulse formation:
- Early discharge of a pacemaker (abnormal automacity)
- Activity triggered by an unstable resting membrane potential in working myocardial cells (DAD,EAD)
= Extra systoles
Where is the vulnerable period for re-entrant arrhythmia?
During the T wave because not all cells are doing the same thing at the same time.
How long do re-entrant arrhythmias last?
Dont last long before it rapidly decats into VT->VF
What are the types of re-entrant arrhythmias?
- Atrial flutter (fast regular rate (250-300bpm) heart block may develop)
- Atrial fibrillation
- Ventricular tachycardia (impaired mechanical function)
What is the re-entrant circuit model?
When fibrous tissue or scar tissue exists in the tissue, it creates refractory tissue.
This is unidirectional block.
What does re-entrant activation require and what does it result in?
Re-entrant activation requires:
- A trigger
- A circuit (anatomical or functional)
- Unidirectional block
Thus:
- Decreased conduction velocity
- Decreased refractory period (ERP)
- Long circuits (Dilated atria or ventricles)
Slow conduction and unidirectional block can occur when repolarisation is not spatially homogenous
What is the rate of propagation of electrical activation determined by?
Electrical properties of myocytes
- Increased electrical coupling between myocytes increases propagation rate (pH)
- Propagation rate is greatest in large diameter cells
Inward current during excitation
- Density and status of sodium channels is important here - greater current - faster propogation
Describe the rate of propagation of ectopic beat (potential for reentry):
If ectopic activation occurs during vulnerable period (T wave)
- Na channels not fully reset so reduced Na current (slower prop)
- Depolarisation non-uniform (greater probability of local conduction block).
What does myocardial ischeamia result in for the AP?
- Slow conduction
- Reduced AP duration
- Non-uniform repolarisation
- Ectopic activations
What does myocardial ischeamia result in?
- Slow conduction
- Reduced AP duration
- Non-uniform repolarisation
- Ectopic activations (DADs)
Describe the slow conduction from ischeamia:
- Theres a reduced sodium current = reduced rate of spread
-> Low ATP
-> Na/K ATPase reduced = reduced gradients
-> Partial membrane depolarisation
-> Inactivation of Na channels
-> Reduced gap junction coupling (low pH due to regional metabolic acidosis)
Describe the action potential change in ischeamic tissue:
- Na/K ATPase reduced = Na(i) and K(o) increased
= Transmembrane K gradient reduced - Na(I) reduced.
- Hyperkalaemia shortens AP duration (Increased K(o), increases I(Kr))
- Activation of Inwards K channels shortens AP duration
(In the ischeamic regions hence inhomogenous electrical properties)
What are DADs in myocardial ischeamia?
- Impaired Ca homeostasis in myocardial ischeamia leads to elevated Ca(i) in diastole
- May lead to Ca induced Ca release from SR
- Increased efflux of Ca via NCX
- NCX reversal may trigger activation (DADs)
How does VT lead to VF?
VT:
- Positive feedback
- Rapid rate, poor contraction
- Increased O2 demand, reduced O2 supply
- Ischeamia more severe
= VF
Describe cardiac rhythm with healed MI:
- Scar tissue can anchor arrhythmia
- Infarct border; Complex, structural heterogeneity etc
= Often monomorphic VT - Stabilised by structure
What can happen to cardiac rhythm in heart failure?
HF -> Structural and cellular changes in the A+V = Substrate for ectopic electrical activity and reentrant activation
Dilated atria -> Atrial fibrillation
Increased risk of VF and VT
How do dilated atria increase the risk fo atrial fibrillation?
Increased atrial pressure -> Stimulates stretch activated ion channels
HF -> atrial fibrosis (marked regional slowing of conduction)
-> Altered NCX expression (can lead to DADs which trigger re-entrant arrhythmia)
-> Altered ANS
-> Sustained AF leads to electrical changes that can result in AT
What are EADs caused by?
Prolonged action potentials which enable Ica(L) to re-activate (during S3 of myocyte AP)
(translates to the T wave)
What can cause increased AP duration? (that lead to EADs)
- Drugs i.e amiodarone
- Reduced ECF K conc. (hypokalekmia -> Decreased Ikr current)
- K ion channel mutation that reduce effectiveness of delayed rectifier
- Na ion channel mutations that affect inactivation of I(Na)
What can EADs result in?
- Varying polymorphic VT
- Torsade de pointes (twisting of the points)
- May resolve spontaneously or progress to VF
= No structural anchor therefore can change (torsade de points)
Insert some ECG strips
now
