Cardiac Electrophysiology III: Clinical Applications

Question 1

Describe the difference between regulated variables and control variables

Answer 1

• Regulated variables:
  
  • homeostatic variables
  • “tightly” regulated (narrow range)
• Control variables
  
  • what we are changing to maintain regulated variables
  • wide variation

Question 2

How do we treat regulated variables?

Provide examples for blood pressure.

Answer 2

• Treatment: treat control variables to establish “normalcy” or fegulated variables
• Blood Pressure (regulated variable)
  
  • Control varaibles:
    
    • heart rate - rate and/or rhythm
    • blood volume - diuretics
    • vascular resistance - vasodilators
• When you change control variables, you change their abilty to respond to stress
  
  • treatment = altered variation
  • change either rate or rhythm

Question 3

Why is variation in biological systems important?

What are characteristics of a disease state?

Answer 3

1. Optimizing function
2. flexibility - response to change
3. reducing system fatigue

Variation precludes response, allows adaptation (plastic- as a response to stressors) to a changing environment

Disease state - fatigue

• invariable, fragile
• limited/no responsiveness to changing environment
• reduced physiological reserve
• reduced survivability

Question 4

How does fitness impact variability?

What is the overall impact of this on a person’s health?

Answer 4

• Increasing Variability
  
  • increasing fitness increases variability
  • However, what we start to see in highly trained athletes is they start to express arrhythmias b/c the large variablility
    
    • reaching a level of variability that can be problematic
• Decrease in variability
  
  • seen with ovetraining & heart failure

Question 5

How is the leading pacemaker cell chosen?

Is it always the same?

Answer 5

• SA very robust - couple thousand could serve as leading pace-maker
  
  • The leading pacemaker is not static, it moves a little bit
  • changes accordign to conditions
  • shifts based on which cell is least suppressed
• heterogeneous ionic currents
  
  • provide multiple mechanisms within SAN
  • ‘back-up’ plan in (leading pacemaker site) LPS in suppressed/dysfunctional
  • system is robust (antifragile)
    
    • variability is a good thing & allows responsiveness to a number of issues

Question 6

What factors affect cardiovascular rhythm?

What is an R-R interval?

Answer 6

• Blood pressure
  
  • heart rate
    
    • beat-to-beat variation (R-R interval)
• Factors affecting Rhythm
  
  • autonomic nervous system
  • conduction pathway
  • conduction velocity
  • conduction block
  • reentry

Question 7

What factors can cause dysfunction of rate, rhythme or force generation?

Answer 7

• Attenuates or accentuates
  
  • membrane channels/currents
  • cell-to-cell conduction (gap junctions fibrotic tissues, etc.)
• alters
  
  • AP morphology-duration - & can change their abilty to be conducted
  • refractory period
    
    • anytime you change, you increase the risk for arrhythmias
  • Ca²⁺ handling

Question 8

Describe the following bolded terms & name situations that can cause these problems to occur

Action potential morphology

altered refractoriness

decremental conduction

conduction block

reentry

circus rhythm

Answer 8

• decremental conduction
  
  • things that would change the ability of an AP to travel where it needs to travel
• reentry
  
  • when AP depolarization turns around & comes back from where it came from
• circus rhythm
  
  • a specific reentry situation

Causes

• Disease processes
  
  • tissue remodeling
• Mutations
  
  • structural
  • channelpathies
• Pharmacological intervention
  
  • so, if someone has a fast heart rate, you give them a drug to change refractory period, but this opens them up to arrhythmias

Question 9

What are factors that affect conduction velocity?

Answer 9

• Decreased conduction
  
  • as the AP is propogating, something happens to cause it to be extinguished
  • amplitude decreases until it doesn’t meet the threshold
  • Causes
    
    • ishemia or injury to cells
    • excess [Ca²⁺]_i in injured cells
    • block of AV node ocnduction
    • AP’s during the relative refractory period (RRR) = early after depolarization (EAD)
      
      • when change refractory period, Na⁺ can sometimes fire off &
    • unidirectional block
      
      • asymmetricla lesion & loss of excitability, change in intracellular coupling (gap junctions), intracellular variations due to regional ischemia
• shortened refractory period
  
  • sympathetic stimulation
  • drugs
  • electrical stimulation
• conduction path
  
  • eccentric hypertrophy
    
    • or chamber gets bigger from a volume standpoint
  • concentric hypertrophy
  • cell architecture
    
    • gap junction structure/expression
    • fibrosis, necrosis, etc

Question 10

Why is reentry a problem?

What conditons can lead to reentry?

Answer 10

• Reentry: a common mechanism for arrhythmias
• Conditions for re-entry
  
  • a closed loop
  • unidirectional block
  • transit time > refractory period
    
    • when the action potential returns, the tissue it returns to is no longer refractory & so it can be conducted
• Abnormal
  
  • rhythm, ignores pace setting
  • pattern of cardiac contraction
• Image
  
  • red arrow = AP conducting
  • when in all purple, in absolute refractory, so no movement
  • when AP gets around & reaches cells that are in refractory, it is extinguished
  • when you change the conduction path (ie. it gets bigger) if the conduction path is longer it will take the AP longer to transverse it, so as it comes around it can re-enter & you get a re-entry loop

Question 11

Describe what is happening in each of these 4 situations

Which is an example of reentry?

Answer 11

• In the normal situation, the APs will bump into each other in the middle of the bottom side of the triangle & extinguish
  
  • all of the tissue will be appropriately depolarized
• A
  
  • bidirectional block, still get appropriate depolarization
• B
  
  • blocks on both sides, so the AP would just extinguish
• C: Reentry
  
  • unidirectional block
  • when the AP was traveling down the right side, it was extinguished becasue it was blocked
  • however, when the left AP makes it way around, it is able to conduct through the unidirectional block, reentering the other circut –
    
    • if this was the av node, it would head back into the atria and depolarize the atria at the relatively same time that the ventricles are depolarized
    • a problem to both rate & rhytm
    • potentially life threatening
  • This can also happen if one side is slow & the other side is blocked (additional image)

Question 12

What is the difference between flutter & fibrilation?

Why do they happen?

Answer 12

• Circus movements: flutter vs. fibrillation
  
  • potential consequence of premature impulses
• Flutter
  
  • single, long wave (usually regular)
  • unidirectional
    
    • 250-350 b/min
  • hemispheric contractions
    
    • half will contract with half is repolarized
• Fibrillation
  
  • if certain conditions are present, flutter can turn to fibrilation, which is chaos
  • blocked impulses in some direction; transmission of impulses in other direction
  • rapid stimulation leads to (will happen fast)
    
    • slowed conduction
    • shortened refractory
  • division of impulses - division leads to “chain reaction”
    
    • all of a sudden a very chaotic pattern to reactivation

Question 13

What are the consequences of atrial & ventricular flutter & fibrillation?

Answer 13

• Loss of coordinated contration & reduction in blood flow
• In atria not necessarily life threatening
• Ventricular Flutter quickly leads to Fibrillation
  
  • Ventricular fibrillation is immediately life threatening