L6.3 Cardiomyocyte growth physiology

Question 1

Cardiac workload response

Answer 1

Question 2

How a1 R increase Ca sensitivity

Answer 2

• mediated by Na/H exchanger
• Activated by PKC
• Increases pH → Increases sensitivity of cardiomyocytes

Question 3

Function of intracardiac RAS

Answer 3

Question 4

AT1 & ETa receptors

Answer 4

• AT1R (by ANG II) & ETa (by ET-1) acts on Na/H exhanger (by PKC)
  
  • Exchange H out → Increases pH → Increase sensitivity

Question 5

What happens when there is no workload/inotropic demands

Answer 5

• Varied levels of normal ANG II, can be pro-growth
• Significant correlation with heart mass
• Chronic increase [ANGII] → increase heart size

Question 6

What happens during short-term sustained demands

Answer 6

• Increase [Ca], alkalinity maintained → cardiomyocyte growth signals → oncogene induction (i.e. c-fos; c-myc) → Structural & functional adaptation

Question 7

Developmental growth and neo-natal window

Answer 7

• ANG II important regulator of rapid developmental heart growth (inotrophy → trophic)
  
  • AT1 & 2
• AT2 more abundant pre & neo-natally → remodelling (R loading → L loading)
• AT1 signals myocyte growth post-natally (hypertrophy)

Question 8

What are mechanical heart devices for?

Answer 8

• used as ‘bridge to transplants’ or ‘destination therapy’ (palliative)
• Whole heart replacement
• Ventricular assist device
• Cost-effectiveness measured in ‘Quality adjusted life years’

Question 9

The 1st mechanical heart

Answer 9

• Abiocor
  
  • 5-9k rev/min (more pumps but 1/1000 SV pumped)
  • No sense of own heartbeat
  • Fatal clots → not very functional

Question 10

What are ventricular assist devices?

Answer 10

• Only to patients with severe bed rest and has no response to treatment for 60 days are eligible
• Used to bypass ventricles into aorta

Question 11

Adv of 2nd gen ventricular assist devices

Answer 11

• Good design
• increased reliability
• 7-10L blood/min

Question 12

DisAdv of 2nd gen ventricular assist device

Answer 12

• Increases Infection
• Risk of coagulation
• Device malfunction
• No pulse

Question 13

Problems with heart designs

Answer 13

• Risk of clot, need anticoagulant therapy
  
  • Heparine coating (anticoagulant coating)
• May have long term bleeding & hypertension problems
• Encourages endothelial tissue growth