Lecture 2: Cardiac electrophysiology and arrhythmia

Question 1

Describe the direction of electrical spread:

Answer 1

Endo -> Epi
Apex -> Base

Question 2

Describe the refractory period:

Answer 2

FRT: Full (total) refractory period
ARP: Absolute (effective) refractory period
RRP
SNP: Super-normal period

Question 3

What are considerations of the RRP and SNP:

Answer 3

RRP & SNP: AP are relatively smaller and slower conducted

Question 4

What are the two potential sources of arrhythmias?

Answer 4

Disorders of impulse formation

Disorders of impulse conduction

Question 5

What are some disorders of impulse formation:

Answer 5

• Early discharge of a pacemaker (abnormal automacity)
• Activity triggered by an unstable resting membrane potential in working myocardial cells (DAD,EAD)

= Extra systoles

Question 6

Where is the vulnerable period for re-entrant arrhythmia?

Answer 6

During the T wave because not all cells are doing the same thing at the same time.

Question 7

How long do re-entrant arrhythmias last?

Answer 7

Dont last long before it rapidly decats into VT->VF

Question 8

What are the types of re-entrant arrhythmias?

Answer 8

• Atrial flutter (fast regular rate (250-300bpm) heart block may develop)
• Atrial fibrillation
• Ventricular tachycardia (impaired mechanical function)

Question 9

What is the re-entrant circuit model?

Answer 9

When fibrous tissue or scar tissue exists in the tissue, it creates refractory tissue.

This is unidirectional block.

Question 10

What does re-entrant activation require and what does it result in?

Answer 10

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

Question 11

What is the rate of propagation of electrical activation determined by?

Answer 11

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

Question 12

Describe the rate of propagation of ectopic beat (potential for reentry):

Answer 12

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).

Question 13

What does myocardial ischeamia result in for the AP?

Answer 13

• Slow conduction
• Reduced AP duration
• Non-uniform repolarisation
• Ectopic activations

Question 13

What does myocardial ischeamia result in?

Answer 13

• Slow conduction
• Reduced AP duration
• Non-uniform repolarisation
• Ectopic activations (DADs)

Question 14

Describe the slow conduction from ischeamia:

Answer 14

• 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)

Question 15

Describe the action potential change in ischeamic tissue:

Answer 15

• 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)

Question 16

What are DADs in myocardial ischeamia?

Answer 16

• 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)

Question 17

How does VT lead to VF?

Answer 17

VT:
- Positive feedback
- Rapid rate, poor contraction
- Increased O2 demand, reduced O2 supply
- Ischeamia more severe

= VF

Question 18

Describe cardiac rhythm with healed MI:

Answer 18

• Scar tissue can anchor arrhythmia
• Infarct border; Complex, structural heterogeneity etc

= Often monomorphic VT - Stabilised by structure

Question 19

What can happen to cardiac rhythm in heart failure?

Answer 19

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

Question 20

How do dilated atria increase the risk fo atrial fibrillation?

Answer 20

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

Question 21

What are EADs caused by?

Answer 21

Prolonged action potentials which enable Ica(L) to re-activate (during S3 of myocyte AP)

(translates to the T wave)

Question 22

What can cause increased AP duration? (that lead to EADs)

Answer 22

• 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)

Question 23

What can EADs result in?

Answer 23

• 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)

Question 24

Insert some ECG strips

Answer 24

now