Myocardial Adaptations/Failure & Metabolism Flashcards
Is the heart a post-mitotic organ?
No, it has small regeneration properties
What percent of the volume do each of the organelles in the myocyte take up?
Myofibrils 60
Mitochondria 23
Sarcoplasmic reticulum 2
TT-system 1
What three subcellular biochemical systems are central to muscle function?
Metabolism
Calcium-regulating
Contractile unit
What is a physiological response?
If the heart is completely able to compensate to an overload condition
What is a pathological response?
If the heart is not adequately able to completely adapt to an overload response
When does compensatory cardiac hypertrophy take place?
In response to an increase in cardiac afterload
What is afterload?
The pressure which the left ventricle must pump against to eject the blood
Why does hypertrophy occur?
In an attempt to normalize wall stress
LaPlace’s Law:
T (wall stress) = (pressure x radius)/(2 x wall thickness)
What signals for concentric hypertrophy?
Tension
What signals for eccentric (longitudinal) hypertrophy?
Stretch
What does a pressure overload cause?
Myocytes to become greater in diameter not in length
What does a volume overload cause?
Myocytes to become elongated with and increase in mitochondria
How do myofibrils change with concentric hypertrophy?
Myofibrils increase in number added in parallel but not in diameter
How do myofibrils change with eccentric hypertrophy?
Increase in diameter and are added in series and some parallel
Does hypertrophy cause a lack of oxygen supply due to decreased capillary density?
No
In endurance sports what type of stress is placed on the left ventricle?
An increase in volume so sarcomeres are added in series
In strength training what type of stress is placed on the heart?
Increased afterload = increased wall stress; concentric hypertrophy thus sarcomeres are added in parallel
How can exercise stop maladaptive heart growth?
By promoting miRNA-222 which stops cardiac maladaptions and promotes healthy remodeling
What inhibits SERCA2 and how?
PLB (phospholamban) when it is not phosphorylated
Which channels are affect in a failing heart?
SERCA2 pumps are reduced
NCX activity is enhanced
What is the Bowditch effect?
Increases in HR increases in the force of contractions in normal heart due to increased concentrations of Ca2+ intracellularly
Why do failing hearts not respond with a Bowditch effect?
Either sarcoplasmic Ca2+ levels are not increased or filament activation is defective
What are earlier signs of cardiac failure when looking at autonomics?
Increased sympathetic tone and decreased parasympathetic tone
What occurs to beta receptors in heart failure?
Beta-adrenergic receptors are down-regulated decreasing the response to inotropic stimuli
What occurs to NE stores in heart failure?
It becomes depleted leading to the heart being functionally denervated and contractile dysfunction
What are V1, V2, V3 myosin isoforms respectively?
alpha/alpha (fast)
alpha/beta (intermediate)
beta/beta (slow)
What is the shift in myosin isoforms during pressure overload?
V1 shifts to V3
What does the heart prefer as an energy source?
Free fatty acids
During exercise what does the heart prefer as an energy source?
Lactate
In failing hearts substrate utilization changes from lipids to what?
Carbohydrates
