Electrophysiology Lecture 2 -- Mechanisms of arrhythmia Flashcards
Define bradycardia
HR <60 bpm
Define tachycardia
HR >100 bpm
2 examples of physiologic arrhythmias
Sinus bradycardia in a trained athlete Sinus tachycardia during exercise
Two types of pathologic arrhythmias
Ectopic complexes (ectopic beats) Ectopic tachycardias
Definition of ectopic complex
A beat that arises from a site other than the sinus node (may be atrial, AV nodal/junctional, or ventricular)
2 types of premature ectopic complexes
Premature atrial ectopic complexes/beats (PACs, APCs, APBs) Premature ventricular ectopic complexes/beats (PVCs, VPCs, VPBs)
Location of ectopic tachycardias
Arise from a site other than the sinus node (in atrium or ventricles)
4 types of ectopic tachycardias
Paroxysmal Nonparoxysmal Sustained Nonsustained
Define a paroxysmal ectopic tachycardia
Start and stop abruptly, usually by initiating or terminating factor
Define a nonparoxysmal ectopic tachycardia
Present constantly, tend to appear or disappear by gradual changes in rate
Define a sustained ectopic tachycardia
Continuing for prolonged period or until stopped by an intervention
Define a nonsustained ectopic tachycardia
Terminating spontaneously
Most common types of ectopic tachycardia
Ventricular tachycardia (VT) Paroxysmal atrial tachycardia (PAT)
2 types of automaticity in pathologic arrhythmias + subgroups
Enhances Abnormal forms – Early Afterdepolarizations – Delayed afterdepolarizations
3 ways automaticity can be enhanced
Less negative diastolic potential (closer to threshold) Steeper slope of phase 4 More negative threshold (closer to max diastolic potential)
2 ways of suppressing enhanced automaticity
Make threshold potential more positive Antagonize components that enhance automaticity
Example of how to make the threshold potential more positive
Suppress: - current needed to fire cell during phase 0 - Ca++ current in SA/VA nodes - Na+ current in HP system
Example of how to antagonize compound that enhance automaticity
Beta blockers in situations where beta-adrenergic stimulation contributes to enhanced automaticity
AP curve of early afterdepolarizations
AP curve of delayed afterdepolarizations
How does an early afterdepolarizatoin occur?
When the action potential has been parkedly prolonged, causing Ca++ current to depolarize cell.
Around what phase does an early afterdepolarization occur?
On the plateau phase (2) of the action potential (before full repolarization)
Potential consequence of early afterdepolarization
Ventricular tachycardia, often with characteristic ECG appearance (“Torsades de Pointes”)
Define Torsades de Pointes
ECG appearance characteristic of EAD-induced VT, which is a rapid VT with alternation of the points of the QRS
3 common factors that cause EAD-induced arrhythmias
Factors that increase APD:
- Certain antiarrhythmic drugs that block K+ channels involved in repolarization
- Slow heart rate
- Hypokalemia (low EC K+)
What largely determines the QT interval on a ECG
Ventricular APD
Common ECG association to EAD-Induced afterdepolarizations
Marked QT prolongation (“long QT syndrome”)
3 ways to treat EAD-induced arrhythmias
- Eliminate reversible factors (i.e. drug therapy) that may be causative or contributory
- Treat hypokalemia if present
- Increase HR (i.e. electrical pacemaker or isoproterenol)
Cause of delayed afterdepolarizations (DAD)
Cellular calcium overload in fast channel tissues –> diastolic spillover of Ca++ from SR release channels (ryanodine receptors)
What causes ryanodine (RyR2) receptors to open?
High intra-SR Ca++ concentrations
What are two pathological situations where RyR2 is hypersensitive to intra-SR Ca++?
CHF
Come RyR2 mutations
Define a premature beat
Premature activation of an action potential if an afterdepolarization reaches threshold
When can DAD’s cause a tachycardia?
A series of afterdepolarizations which reach a threshold
4 factors enhancing DAD’s and how they contribute to the problem
- Increase HR, premature complexes (increase intracellular Ca++)
- Hypercalcemia (increase intracellular Ca++)
- Catecholamines (increase intracellular Ca++, increase RyR2 sensitivity to Ca++)
- Mutations of RyR2 –> hypersentivity to Ca++
2 ways to treat DAD-induced arrhythmias
- Eliminate reversible contributory or causative factors
- Various drugs can reduce DAD’s
Purpose of Ca++ antagonists for DAD-induced arrhythmia
Reduce calcium entry during each action potential (may be problematic with negative inotropy)
What is the importance of re-entrant cardiac arrhythmias
Cause of many important cardiac arrhythmias, including many that are implicated in sudden cardiac death
2 examples of drugs that can reduce DAD’s
Ca++ antagonists (i.e. verapamil)
Na+ channel blockers (i.e. lidocaine, quinidine)
Purpose of Na+ channel blockers for DAD-induced arrhythmias
Make threshold potential more positive, so harder for DAD to reach threshold
Diagram of normal activation of cardiac rhythm
Diagram of re-entrant cardiac arrhythmia
Where can re-entrant arrhythmias occur?
Anywhere in the heart provided there are two pathways connected proximally (X) and distally (Y)
Also, anywhere with fibers interconnected at more than one point
Where is a common anatomic arrangement for reentrant arrhythmias?
AV node (there can be 2 distinct alternative conduction pathways)
Necessary impulse condition for a reentrant arrhythmia to occur
Impulse must first arrive from X at a time when one pathway (B) is still refractory, but the other (A) has recovered excitability
Why is a premature beat much more likely than a sinus beat to encounter refractoriness in a pathway conducive to reetrant arrhythmia?
Refractory period is usually over wel before the next expected sinus beat
Why is timing crucial for a reentrant arrhythmia to occur?
If the premature beat arrives too early, both A and B will be refractory
Impulse pathway if the distal end of pathway B has recovered excitability
Can travel retrogradely over pathway B –> arrive at proximal end of pathway A
Impulse pathway is the proximal end of pathway A has recovered excitability after retrogradely flowing through B
Propagation antegradely down pathway A
How can one premature impulse initiate a self-sustaining tachycardia?
If reetrance can be sustained; distal end of B and proximal end of A always regain excitability when the reentrant impulse reaches them
3 conditions necessary for reentrance
- Premature beats
- Differences in refractoriness between alternate pathways
- Conduction which is slow enough so that the reentrant impulse never encounters refractory tissue (would be blocked)
Equation for the time to complete one circuit of the reetrant pathway
T = L/V
where:
- T = time
- L = total length of reetrant pathway
- V = conduction velocity
Time condition for successful sustained reentry
T > RP
(L/V > RP)
Circuit time has to be longer than the longest refractory period
Consequence of the circuit time not being longer than the longest refractory period
The impulse would leave the area of greatest refractoriness and return to it before excitability is restored
How can reentrant arrhythmias be terminated or prevented?
Increasing the refractory period so that it exceeds conduction time (short refractoriness increases re-entrant likelihood)
Effect of conduction on reentrant arrhythmia likelihood
Fast conduction (V large) makes reentry less likely
Slow conduction facilitates reentry (EXCEPT when sufficient to completely block conduction in reentry circuit)
