L7.1 Cardiomyocyte growth remodelling

Question 1

Concentric cardiac hypertrophy

Answer 1

• Thick walls, Decrease lumen size
• Fatter myocytes → failure is ‘pathological’
• From resistance exercise/hypertension

Question 2

Eccentric cardiac hypertrophy

Answer 2

• Wall thickness maintained, Increase lumen size
• Longer myocytes → maintained function ‘physiological’

Question 3

Why is there a cardiac hypertrophic response?

Answer 3

• Hypertrophy is the response to altered mechanical conditions
• Compensatory mechanism to decrease wall stress (Load per cell)
• Optimise thermodynamic state

Question 4

Physiological hypertrophy

Answer 4

• Athletes adaptation to CV training
  
  • Remodeling in ~50% of athletes
  • Endurance → Increase in LVEDV = increase in LVWT
  • Resistance → Increase in LVEDV < Increase in LVWT
• Remodeling is reversible/benign when training stops

Question 5

Determinants of LVEDV

Answer 5

• Body size (50%)
• Type (14%) - Endurance > Resistance
• Sex & age (11%)
• ‘Others’ (25%) - genetic factors (e.g. endogenous trophic influences)

Question 6

Pathological hypertrophy (relatively irreversible): Chronic

Answer 6

• Hypertension (load & stretch)
• Renal disease (Increase BV)
• Hormonal disturbance (RAS, SNS)

Question 7

Pathological hypertrophy: Acute

Answer 7

• Valve disease (rigidity, obstruction, backflow)
• Infarction

Question 8

When are different chambers affected by hypertrophy?

Answer 8

• LV = from systemic load effect
• LV + RV = trophic influences (i.e. hormone mediator)

Question 9

What leads to dysfunction and failure?

Answer 9

• Dispropotionate increase in myocardiocyte width size → dysfunction and failure

Question 10

Subcellular ‘remodeling’ pathology

Answer 10

• Transition of a (fast) → b (slow) MyHC
• Changes in Ca transport
• Decrease in Vmax to economise on energy
• Reactivation of fetal & embryonic expression patterns
  
  • Adaptive process to make energy utilisation better → but ultimately are short term adaptations and will decompensate

Question 11

Changes in Ca transport during contraction

Answer 11

• Decrease L-type (generally position next to RyR → triggers SR Ca release maximally)
• Increase T-type (When moving twds failing state)
  
  • Not optimally positioned
  • Ca directly acts on myofilaments → less Ca release from SR → Decrease EC coupling
  • May have a lower threshold for activation (more energy efficient)
• Decrease SR Ca release channels
• But Ca current is still maintained

Question 12

Changes in Ca transport during relaxation

Answer 12

• Decrease SERCA
  
  • Delay Ca reuptake (don’t need fast MyHC → more energy efficient)
• Increase Na/Ca exchanger
  
  • Increase reliance on Na/Ca exchange → relaxation associated with depol → arrhythmia
• Increase Na/H exchanger
  
  • To deal with acid loading

Question 13

Ca/H handling changes

Answer 13

• Shifts to increase dependence on extracellular Ca cycling (enhanced Na/Ca exchange Ca influx)
• Increase capacity to export acid
• Prolonged Ca signals
• Delayed relaxation (diastole beat compromised)

Question 14

Outcome of compensation

Answer 14

• Chronic exposure to growth promoting agents
  
  • Increase heart muscle mass & WT
  • Arrhythmia vulnerability
  • Functional decompensation & failure

Question 15

What attributes to decompensation?

Answer 15

• Hypertrophy → myocyte loss → failure
  
  • Loss through necrosis, apoptosis autophagy