Lecture 7: Cardiomyocyte Growth Remodelling

Question 1

What is eccentric cardiac growth?

Answer 1

The lumen/internal chamber of the heart increases - proportional to the centre of the lumen

Question 2

What is concentric cardiac growth?

Answer 2

Growth of muscle/thickening of wall, at expense of lumen size - cannot pump as much blood

Question 3

What is increase in heart size proportional to?

Answer 3

Body size

Question 4

How many people experience statistically significant hypertrophy?

Answer 4

10%

Question 5

What can hypertrophy be a response to?

Answer 5

Altered mechanical conditions, compensatory strategy to optimise thermodynamic state or to reduce wall stress

Question 6

What is physiologic hypertrophy?

Answer 6

Adaptation to CV training

Question 7

What kind of people does physiologic hypertrophy occur in?

Answer 7

Elite athletes

Question 8

What does physiologic hypertrophy involve?

Answer 8

Alteration in complex central and peripheral mechanisms

Question 9

How many athletes does cardiac remodelling occur in?

Answer 9

50%

Question 10

How many athletes does LV enlargement occur in?

Answer 10

15%

Question 11

What does endurance training lead to?

Answer 11

Increase LV EDV = Increase LV wall thickness

Question 12

What does strength training lead to?

Answer 12

Increase LV EDV

Question 13

What has the biggest influence on LV EDV?

Answer 13

Body size - 50%, followed by genetics -25%, sport - 14%

Question 14

What is altered in elite athletes by training?

Answer 14

Amount of perfusion volume

Question 15

What doesn’t influence LV EDV?

Answer 15

Not influenced by competitive performance achievement level

Question 16

What is pathologic hypertrophy?

Answer 16

Heart growth due to chronic events and acute events

Question 17

What are the chronic events that lead to pathologic hypertrophy?

Answer 17

Hypertension, renal disease, hormonal disturbance

Question 18

What are the acute chronic events that lead to pathologic hypertrophy?

Answer 18

Valve disease, infarction

Question 19

What happens with LV hypertrophy?

Answer 19

Systemic load effect

Question 20

What happens with LV and RV hypertrophy?

Answer 20

Trophic/hormonal effect

Question 21

What causes the heart to have a volume load and what growth does this lead to?

Answer 21

Obesity, eccentric

Question 22

What causes the heart to have a pressure load and what growth does this lead to?

Answer 22

Hypertension, concentric

Question 23

What myocyte growth does eccentric hypertrophy lead to?

Answer 23

Longer myocyte

Question 24

What myocyte growth does concentric hypertrophy lead to?

Answer 24

Fat myocyte

Question 25

What happens in sub cellular remodelling?

Answer 25

- 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

Question 26

What happens if there are fewer L-type calcium channels?

Answer 26

Calcium release is suppressed

Question 27

Does more t-type calcium channels make up for lost l-type channels?

Answer 27

Not necessarily - might not be positioned correctly

Question 28

What are the protein expression changes in hypertrophy (activation)?

Answer 28

Same calcium current, less l-type channels, more t-type channels, less SR calcium release channels

Question 29

What are the protein expression changes in hypertrophy (relaxation)?

Answer 29

Fewer SR calcium ATPase, increased Na/Ca exchanger

Question 30

What happens in relaxation in hypertrophied hearts?

Answer 30

SR calcium uptake delayed, longer calcium and myosin interaction, increased reliance of Na/Ca exchanger, prolonged relaxation

Question 31

What is the consequence of prolonged relaxation?

Answer 31

Next beat may come along before relaxation has finished, diastolic beat compromised

Question 32

What happens to SV in heart failure?

Answer 32

For same EDV, SV is reduced, sympathetic NS kicks in to compensate and curve is recovered - compensation cannot occur forever 0 decompensation phase

Question 33

What happens in the positive feedback system?

Answer 33

Ongoing exposure to growth promoting mediators, maintained growth signalling, increase heart muscle mass and wall thickness, arrhythmia vulnerability, ultimate functional decompensation, dilation and failure

Question 34

What are the three ways that myocytes can be lost?

Answer 34

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

Question 35

What doesn't occur as a result of physiologic hypertrophy?

Answer 35

Increased LV systolic function