L6.3 Cardiomyocyte growth physiology Flashcards Preview

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Flashcards in L6.3 Cardiomyocyte growth physiology Deck (13)
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Cardiac workload response


How a1 R increase Ca sensitivity

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


Function of intracardiac RAS 


AT1 & ETa receptors

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


What happens when there is no workload/inotropic demands

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


What happens during short-term sustained demands

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


Developmental growth and neo-natal window

  • 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)


What are mechanical heart devices for?

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


The 1st mechanical heart

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


What are ventricular assist devices?

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


Adv of 2nd gen ventricular assist devices

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


DisAdv of 2nd gen ventricular assist device

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


Problems with heart designs

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