Cardiac Arrhythmias

Types of cardiac arrhythmias:

•Bradyarrhythmias

•Tachyarrhythmias

•Bradyarrhythmias: treat with atropine, pacing

•Tachyarrhythmias can occur due to:

Enhanced automaticity

Afterdepolarization and triggered activity

Re-entry

Tachyarrhythmias:

•Enhanced automaticity:

In tissues undergoing spontaneous depolarization

-stimulation, hypokalemia, mechanical stretch of cardiac muscle

Automatic behaviour in tissues that normally lack spontaneous pacemaker activity e.g. ventricular ischaemia depolarizes ventricular cells and can cause abnormal rhythm

•Afterdepolarization:

EAD: when APD is markedly prolonged

Occur in phase 3

May be due to inwards Na+ or Ca2+ current

Excessive prolongation of APD- torsades de pointes syndrome

EAD

DAD

Torsades de pointes: polymorphic ventricular tachycardia along with prolonged QT interval

DAD: precipitating conditions are intracellular or sarcoplasmic Ca2+ overload, adrenergic stress, digitalis intoxication, heart failure

If afterdepolarizations reach a threshold, an AP is genererated which is called ‘triggered beat’

DAD occur when the HR is fast, EAD occur when the HR is slow

•Re-entry: when a cardiac impulse travels in a path such as to return to and reactivate its original site and self perpetuate rapid reactivation independent of normal sinus node conduction

Requirements for re-entry rhythm:

slowing or conduction failure due to either an anatomic or functional barrier

Anatomic barrier- Wolff-Parkinson-White syndrome

Functional barrier- ischaemia, differences in refractoriness

Presence of an anatomically defined circuit

Heterogenecity in refractoriness among regions in the circuit

Slow conduction in one part of the circuit

•What are channels? – they are macromolecular complexes consisting of a pore forming subunit, subunits and accessory proteins

•They are:

Transmembrane proteins

Consist of a voltage sensitive domain

A selectivity filter

A conducting pore and,

An inactivating particle

•In response to changes in membrane voltage, the channel changes conformation so as to allow or prevent the flow of ions through it along their concentration gradient

Na+

K+ (Transient)

Ca2+

K+ (delayed rectifier)

Ca2+

Na+K+ATPase

K+

Na+

Na+ channel blocker

K+ channel blocker

-blocker, CCB

Ca2+ channel blocker & -blocker

How can drugs slow the cardiac rhythm?

Decreasing phase 4 slope

Increase in threshold potential for excitation

Increase in maximum diastolic potential

Increase in APD

•Fast response tissues

•Slow response tissues

Na+ channel blocker:

•Na+ channel block depends on:

HR

Membrane potential

Drug specific physiochemical characteristic- recovery

•Blockade of Na+ channels results in:

Threshold for excitability is increased (more current)

Increase in pacing and defibrillation threshold

Decrease conduction velocity in fast response tissues

Increase QRS interval

Some drugs tend to prolong PR interval- flecainide (possibly Ca2+ channel blockade)

•Some sodium channel blockers shorten the PR interval (quinidine; vagolytic effect)

•APD unaffected or shortened

•Increase in threshold for excitation also decreases automaticity

•Can also inhibit DAD/EAD

•Delays conduction so can block re-entry

•In some cases, it can exacerbate re-entry by delaying conduction

•Shift voltage dependence of recovery of sodium channels from inactivated state to more negative potentials and so increases refractoriness

•Net effect- whether it will suppress or exacerbate re-entry arrhythmia depends on its effect on both factors- conduction velocity and refractoriness

•Most Na+ channel blockers bind to either open or inactivated state and have very little affinity for channels in closed state, drug binds to channels during systole & dissociates during diastole

•ADRs:

Decrease in conduction rate in atrial flutter- slows rate of flutter and increases HR due to decrease in AV blockade

Especially common with quinidine due to its vagolytic property; also seen with flecainide and propafenone

Cases of ventricular tachycardia due to re-entrant rhythm following MI may worsen due to slowing of conduction rate

Slowing of conduction allows the re-entrant rhythm to persist within the circuit so that complicated arrhythmias can occur

Several Na+ channel blockers have been reported to exacerbate neuromuscular paralysis by d-tubocurarine

•K+ Channel blockers:

Prolong APD (QT interval) and reduces automaticity

Increase in APD also increases refractoriness

Effective in treating re-entrant arrhythmias

Reduce energy requirement for defibrillation

Inhibit ventricular arrhythmias in cases of myocardial ischemia

Many K+ channel blockers also have blocking activity also like sotalol

Disproportionate prolongation of APD can result in torsaides de pointes, specially when basal HR is slow

•CCBs:

Major effect on nodal tissues

Verapamil, diltiazem and bepridil cause slowing of HR, nifedipine and other dihydropyridines reflexly increase HR

Decrease AV nodal conduction so PR interval increases

AV nodal block occurs due to decremental conduction and increase in AV nodal refractoriness

DAD leading to ventricular tachycardia respond to verapamil

Verapamil and diltiazem are recommended for treatment of PSVT

Bepridil increases APD in many tissues and can exert antiarrhythmic action in atria and ventricles but it use is associated with increased incidence of torsades de pointes- rarely used