Micro-architecture of the heart and its application to preclinical research

Question 1

List the typical characteristics of a cardiac muscle cell.

Answer 1

Diameter 10-20um
Length 50-100um
Typically has single, central nucleus
Myocytes are typically branched

Question 2

List the typical characteristics of smooth muscle.

Answer 2

Myosin and actin fliaments (NOT organised into myofibrils, no sarcomeres)
Tropomyosin plays regulatory role
No troponin

Question 3

Describe the initiation of contraction in smooth muscle.

Answer 3

Telodendria (Pearl like structures with varicosites).

• They are wrapped around smooth muscle
• Contain neurotransmitter
• Inhibitory and excitatory
• Given neurotransmitter can produce different effects of different smooth muscle tissues

Question 4

What is the equation for ejection fraction?
What are the typical values?
Abnormal values and potential pathology?

Answer 4

SV/EDV (Expressed as percentage)
55-75%
>75% - Could indicate hypertrophic cardiomyopathy
<40% - Heart failure

Question 5

What happens when there is damage to cardiac muscle that may occur as a result of MI?
What implications may occur as a result of remodelling?

Answer 5

Insult = Decreased contractility, SV and CO.

Remodelling - Can decrease ventricular compliance - Reduced SV and CO. Heart failure can occur as a result.

Question 6

Why is assessment of left ejection fraction important?

How should experimental models be designed?

Answer 6

Independent risk factor for mortality for MI and HF patients.
Experimental models should measure contractility to understand myocyte damage and for research into new therapies and drugs.
Important to mimic in vivo cardiomyocyte contraction

Question 7

What is the role of the complex muscle fibre orientation of the heart?

Answer 7

Ensure efficient and directional movement of blood.

Question 8

What wave pattern does the muscle length follow?

Answer 8

Sinusoidal

Question 9

What happens when strain amplitude goes beyond 12%?

Answer 9

Power output reduces

Passive force also increases - Structural proteins resist over stretching of myofibrils

Question 10

Describe the length-force relationship.

Answer 10

With increasing starting muscle length there is increasing net power, until optimum, after which power decreases

Question 11

What is the optimum cycle frequency range?

Answer 11

3-4Hz which is around age predicted max (220-age)

Question 12

Why is it important to mimic your experimental group?

Answer 12

There are various clinical aspects of an aged heart which will be overlooked in young healthy models.

Question 13

What are the micro-architectural changes that occur to an aged heart?

Answer 13

Heart becomes fibrotic and hypertrophic.
Development of myofibroblasts
Perivascular fibrosis
Perimysial fibrosis
Endomysial fibrosis
Hypertrophic cardiomyocyte

Question 14

Compare aged versus young cardiac muscle

Answer 14

Aged muscle must elicit greater force for a lower ejection fraction.
Power output is significantly lower in aged muscle.
Young muscle may respond differently to treatments