Chronic Cardiac Adaptation Flashcards
What happens to heart with chronic exercise and pregnancy
physiological hypertrophy
incr myocyte length, incr end diastolic volume, incr volume
no fibrosis
no cardiac dysfunction
What causes physiological hypertrophy
chronic exercise
pregnancy
What happens to heart with chronic hypertension and aortic valve stenosis
pathological hypertrophy
incr myocyte width
maybe cardiac dysfunction
decr end diastolic volume
what causes pathological hypertrophy
chronic HTN
aortic valve stenosis
what happens to heart with MI and DCM
cardiac dilation INCR MYOCYTE length extensive fibrosis myocyte death advanced cardiac dysfunction
thin walls
what was historical view of heart
relatively inert
cardiac enlargement doesn’t affect intrinsic contractile properties
2 myosin heavy chain isoforms
alpha and beta
each myosin has ___ heads and ___ chains
2 heads
2 chains
what are the different heterodimers
aa
ab
bb
what makes heterodimers of myosin distinct?
distinct ATPase activity
which has greater ATPase activity, alpha or beta
ALPHA HAS GREATER ATPase activity
alpha and beta myosin heavy chain are ___
encoded by different genes and transcriptionally regulated expression
Physiological hypertrophy has ____ ATPase and ___ MHC
increase in ATPase
aa MHC
Pathological hypertrophy has ___ ATPase and ___ MHC
Decrease in ATPase
bb MHC
Contemporary view of heart
Heart has both phenotypic and genotypic plasticity
Phenotypic adaptations may involve both ___ and ___
transcriptional and post-translational modifications
Long term effect of HTN
heart ejecting against high pressure so cardiac contraction slower
(less ATPase) –> slower contraction
Over time, the effect of HTN
1) HTN
2) develop LVH and increase EDV
3) heart eject against increased afterload (hypertrophy)
4) Frank starling curve shifts down
5) as heart fails, PV curve shifts right so volume incr but SV decr
Cellular effects of LVH
1) incr Ca2+ current via L-type Ca2+
2) decr SR pump function by incr PLB/SERCA2 ratio so more cyto Ca2+
3) decr myofilament relax
4) incr cytosolic Ca2+ and new steady state
What is Calcineurin?
Phosphatase activated in response to Calcium
long onset so need sustained Ca2+ to activate
Effect of calcineurin
1) calcineurin dephos NFAT
2) NFAT translocate to nucleus
3) heart looks like dilated cardiomyopathy
Effect of P4H on LVH function
NO EFFECT!!!!
Positive feedback in CHF
1) Primary muscle damage
2) Pump dysfunction
3) decr CO
4) neurohumoral activation
5) apoptosis
2nd positive feedback loop in CHF
1) Primary muscle damage
2) Pump dysfunction
3) decr CO
4) LVH
5) ventricular remodeling
Effects of CHF
edema
tachycardia
congestion
