Physiology and Pharmacology 21: (Davies) Arrhythmias

Question 1

What is Arrhythmias?

Answer 1

Group of heart conditions where beat is irregular, too slow (bradycardia) or too fast (tachycardia)

Question 2

Mechanisms that lead to arrhythmia?

Answer 2

1) Re-Entry
- Action potential returns to region that has just fired an action potential

2) After depolarisations
- Premature depolarisation of cardiac tissue during the repolarisation or just after an AP

3) Abnormal pacemaker activity
- Regions of heart normally quiescent may begin pacemaker

4) Heart block
- The passage of electrical activity through the AV node is compromised

Question 3

What ensures that an action potential does not reverse its direction of travel?

Answer 3

Refractory period (sodium channels inactivated at this time)

Question 4

What can result in unidirectional block? Why?

Answer 4

Damaged cardiac tissue

• changes in tissue resistance in one part of the tissue due to damaged cells
• AP cannot propagate in that direction

May be able to propagate in other direction elsewhere

Leads to re-entrant arrhythmia

Question 5

Types of afterdepolarisation?

Answer 5

Early afterdepolarisation
-> depolarisation occurs before AP repolarisation is complete

Delayed afterdepolarisation
-> occurs after complete repolarisation

Question 6

Mechanisms / defects leading to early afterdepolarisation?

Answer 6

More likely to happen in long action potentials, because L-Type Ca2+ channels partially recover from inactivation during long APs

Reactivation of these channels in late plateau period can lead to depolarisation

Question 7

Mechanisms / defects leading to late afterdepolarisation?

Answer 7

Cells with higher calcium that usual (perhaps due to tissue damage) increasingly stimulate the Na/Ca exchanger (NCX)

Higher intracellular Ca2+ conc. also leads to increased spontaneous Ca release by SR further adding to increased conc.

Increased iConc -> Gradient less severe -> increased calcium extrusion + sodium intake

Leads to depolarisation(3Na+ in (3+), 1 Ca2+ out (2+))
- Net positive intake

Question 8

What happens in abnormal pacemaker activity? What causes it?

Answer 8

Cells usually quiescent begin pacemaking

More likely to happen when B-adrenoceptors are activated (increased automaticity)
- can also result from partial depolarisation in damaged tissue

Can be triggered by long AP causing early afterdepolarisation

Question 9

Difference between partial and complete heart block? How are they caused?

Answer 9

Caused by damage to nodal tissue -> failure to conduct AP properly through heart e.g. AVN block

Complete: atria and ventricles beat independently - ventricular rate is slower

Partial: only some sinus beats trigger ventricles, can be 2:1 ratio etc.

Question 10

How could you tell looking at an electrocardiograph that heart block had occurred?

Answer 10

May see P wave, but no following QRS complex

Question 11

Usual treatment of arrhythmias? Describe action of the drugs/treatments, when they work + examples

Answer 11

Anti-arrhythmic drugs

Emergency treatment is electrical e.g. defibrillation on pacing
- inhibit pacemaker potential, plateau

Na+ channel blockers e.g. disopyramide

• inhibit rapid depolarisation
• different classes 1b (bind + unbind quick) 1c (slow) 1a (intermediate)

B-adrenoceptor blockers e.g. propranolol

Drugs that prolong AP and refractory period e.g. sotalol
- work at repolarisation

Ca2+ channel blockers e.g. diltiazem
- work at plateau