Lecture 7: Cardiomyocyte Growth Remodelling Flashcards
What is eccentric cardiac growth?
The lumen/internal chamber of the heart increases - proportional to the centre of the lumen
What is concentric cardiac growth?
Growth of muscle/thickening of wall, at expense of lumen size - cannot pump as much blood
What is increase in heart size proportional to?
Body size
How many people experience statistically significant hypertrophy?
10%
What can hypertrophy be a response to?
Altered mechanical conditions, compensatory strategy to optimise thermodynamic state or to reduce wall stress
What is physiologic hypertrophy?
Adaptation to CV training
What kind of people does physiologic hypertrophy occur in?
Elite athletes
What does physiologic hypertrophy involve?
Alteration in complex central and peripheral mechanisms
How many athletes does cardiac remodelling occur in?
50%
How many athletes does LV enlargement occur in?
15%
What does endurance training lead to?
Increase LV EDV = Increase LV wall thickness
What does strength training lead to?
Increase LV EDV
What has the biggest influence on LV EDV?
Body size - 50%, followed by genetics -25%, sport - 14%
What is altered in elite athletes by training?
Amount of perfusion volume
What doesn’t influence LV EDV?
Not influenced by competitive performance achievement level
What is pathologic hypertrophy?
Heart growth due to chronic events and acute events
What are the chronic events that lead to pathologic hypertrophy?
Hypertension, renal disease, hormonal disturbance
What are the acute chronic events that lead to pathologic hypertrophy?
Valve disease, infarction
What happens with LV hypertrophy?
Systemic load effect
What happens with LV and RV hypertrophy?
Trophic/hormonal effect
What causes the heart to have a volume load and what growth does this lead to?
Obesity, eccentric
What causes the heart to have a pressure load and what growth does this lead to?
Hypertension, concentric
What myocyte growth does eccentric hypertrophy lead to?
Longer myocyte
What myocyte growth does concentric hypertrophy lead to?
Fat myocyte
What happens in sub cellular remodelling?
- Myosin heavy chain – alpha (fast) to beta (slow)
- Major changes in calcium transport
- Reduced maximum velocity of shortening to economize on energy
- Reactivation of fetal and embryonic expression patterns
- Ultimately short term adaptations and don’t work forever
- No real change in calcium current due to channels balancing each other out
What happens if there are fewer L-type calcium channels?
Calcium release is suppressed
Does more t-type calcium channels make up for lost l-type channels?
Not necessarily - might not be positioned correctly
What are the protein expression changes in hypertrophy (activation)?
Same calcium current, less l-type channels, more t-type channels, less SR calcium release channels
What are the protein expression changes in hypertrophy (relaxation)?
Fewer SR calcium ATPase, increased Na/Ca exchanger
What happens in relaxation in hypertrophied hearts?
SR calcium uptake delayed, longer calcium and myosin interaction, increased reliance of Na/Ca exchanger, prolonged relaxation
What is the consequence of prolonged relaxation?
Next beat may come along before relaxation has finished, diastolic beat compromised
What happens to SV in heart failure?
For same EDV, SV is reduced, sympathetic NS kicks in to compensate and curve is recovered - compensation cannot occur forever 0 decompensation phase
What happens in the positive feedback system?
Ongoing exposure to growth promoting mediators, maintained growth signalling, increase heart muscle mass and wall thickness, arrhythmia vulnerability, ultimate functional decompensation, dilation and failure
What are the three ways that myocytes can be lost?
Myocyte lysis through NECROSIS: cell swelling, membrane rupture, oxygen deficiency
Myocyte suicide through APOPTOSIS: programmed cell death, mitochondrially mediated – related to critical energy deficit state
Myocyte self-eating through AUTOPHAGY: metabolic stress induced internal breakdown – goes beyond recycling and breaks itself down
What doesn’t occur as a result of physiologic hypertrophy?
Increased LV systolic function
