cardiac contractility: interdependence on preload and afterload

Question 1

Describe the structure of cardiac myocytes

Answer 1

• cardiac muscle cells can be uni-nucleated or can have more than 1 nucleus
• they are straited and contain sarcomeres, like skeletal muscle
• they contain intercalated disks which are gap junctions to allow the myocytes to electrically communicate together and act like a single unit

Question 2

Describe how contraction takes place in cardiac muscle

Answer 2

• an increase in intracellular calcium (which may be caused by neural or hormonal stimuli) and some of the Ca2+ binds to troponin and this causes a change in the configuration that shifts the tropomyosin and exposes the myosin binding site for actin
• the myosin head can now bind to actin - forming a cross bridge

Question 3

Explain what determines the contractile force and why

Answer 3

• the number of cross bridges activated
• unlike skeletal muscle where troponin can become saturated with Ca2+, the ca2+ concentration in cardiac muscle is only sufficient enough to activate a fraction of the potential cross bridges which produces a submaximal contraction
• therefore,** anything that increases the amount of intracellular Ca2+** eg adrenaline will activate more cross bridges and increase the cardiac contractility

Question 4

where are ryanodine receptors located … and what is their role in cardiac contraction?

Answer 4

• ryanodine receptors are located in the sarcoplasmic reticulum
• their role is to release Ca2+ from the sarcoplasmic reticulum during excitation- contraction coupling in cardiac muscle cells

Question 5

Describe the excitation - contraction coupling mechanism in cardiac muscle

Answer 5

• Na+ entry causes depolarisation
• this depolarisation causes L type Ca2+ channels to open in the T tubules
• this causes ca2+ induced ca2+ release from the SR by activating the ryanodine receptors in the SR
• Ca2+ then flows from the SR into the cytosol
• Ca2+ then binds to troponin etc

Question 6

what is an inotropic effect?

Answer 6

• An ionotropic effect is the **effect of a transmitter substance or hormone **that activates or deactivates ionotropic receptors
• can either be a positive or negative effect
• positive eg - adrenaline or noradrenaline

Question 7

what is an example of a hormone that causes increased contractility of the heart?

Answer 7

noradrenaline
* causes a positive ionotropic effect
* it causes an increase in contractility as it reaches threshold faster and causes a higher intracellular [Ca2+] and therefire causes an increase in heart rate aswell

Question 8

what 2 effects does an increase in contractility caused by a postive ionotropic agent have on the heart?

Answer 8

• **increases the SV **(wider loop) - more stroke work
• ** increases systolic pressure** (taller loop)

Question 9

what 2 intrinsic factors regulate the stroke volume (and hence cardiac output)?

Answer 9

• pre load and afterload
• the greater the preload, the more forceful the contraction and the greater the stroke volume
• if the preload increases, the afterload will also increase
• the increase in stroke volume also causes an increase in HR

Question 10

what are the 4 factors that determine cardiac output?

Answer 10

• cardiac factors : heart rate & cardiac contractility
• coupling factors: preload and afterload

Question 11

Describe the signalling mechanism of NA or Adr on cardiac myocytes?

Answer 11

• NA or Adr binds to B adrenoceptors on the cardiac muscle
• this activates adenylate cyclase which increases levels of cAMP
• the cAMP activates protein kinase A
• protein kinase A phophorylates the L type Ca2+ channels, the Ca2+ATPase (phospholamban), the troponin, protein on thick filaments and the ryanodine receptor
• these effects increase the cytosolic Ca2+ and therefore increase the contractility of the heart

Question 12

what is cardiac failure?

Answer 12

• heart failure occurs when the heart is unable to pump sufficient blood around the body at normal filling pressures to meet the metabolic demands of the body

Question 13

what kind of reasons cause cardiac failure? compare intra-cardiac vs extra-cardiac..

Answer 13

1. Intra-cardiac
   * impairment of cardiac contractility
   * the heart may not fill effectively
   * may not be able to pump efficiently #
2. **Extra-cardiac **
   * preload or afterload may become excessive - ie the ventricles become too stretched

Question 14

what is the loss of healthy cardiac muscle mass called? how can this occur?

Answer 14

myocardial infarction
* it can occur if the myocardium experiences hypoxia or ichaemia because of the loss of normal blood supply (and oxygen) for example, **following a coronary thrombosis **(blood clot inside blood vessel)

Question 15

what are 2 examples of clinical conditions in which** impairment of the filling of the heart** is seen?

Answer 15

• **atrial fibrillation **
• the ventricles will not be completely filled at the onset of atrial systole (contraction) and therefore cardiac output will fall as not as much blood is being pumped out
• also in mitral valve stenosis (narrowing of the valve) will cause abnormal filling of the heart