Lecture 7: Regulation of cardiac function

Question 1

What are the determinants of stroke volume and thus cardiac output?

Answer 1

Preload
Afterload (Time for ejection)
Inotropic state

and thus Heart rate as it influences inotropic state and preload. (filling time and time for Ca reuptake)

Question 2

What is lusitropy?

Answer 2

Relaxation of the myocardium (Ca removal)

Question 3

What is dromotropy?

Answer 3

Conduction velocity of AV node

Question 4

What are some key channels to be aware of in the myocyte?

Answer 4

L type Ca channel
RyR (JSR)
SERCA
NCX
Ca ATPase on cell membrane not SERCA.
Na/K ATPase

Question 5

What is inotropic state?

Answer 5

Magnitude and rate of CA release from SR.
- Amount of Ca in SR (balance amongst fluxes)
- Inc. HR = Increased Ca and inotropy.
- Affinity of troponin C for Ca
-> Sarcomere length-dependent Ca sensitivity of troponin C (Frank starling mechanism)

Question 6

What influences inotropic state?

Answer 6

• HR
• Length-tension relationship i.e frank starlings law
• SNS

Question 7

How does the SNS enhance inotropic state?

Describe the signalling pathway and effects

Answer 7

Gs stimulates adenylate cyclase
- increased cAMP
- Increased cAMP dependent protein kinase A (PKA)
= Phosphorylation of
-> L type Ca channels
-> Phospholambam
-> RyR
-> Troponin 1
-> Other proteins
= Inc. L-type Ca channel opening, stimulation of SR and cell membrane Ca pumps, Faster Ca kinetics, Faster X bridge cycling.

More vigorous and rapid contraction (and relaxation)

Question 8

What are the effects of parasymp on heart?

Answer 8

Muscunaric receptor
- Inhibits PKA formation
- Enhances Kir activity

Question 9

Describe the force sarcomere length tension relationship in myocardiocytes

Answer 9

• No descending limb of relationship because high passive stiffness
• Steeper ascending limb because actin/myosin overlap
• Length dependent sensitivity of troponin C to Ca

Question 10

Whats the deformation that occurs during the cardiac cycle?

Answer 10

Circumferential shortening
Longitudinal shortening
Torsion
Transmural shear
Radial wall thickening

Fibers arranged orthoganally.

Question 11

What happens to myocyte shortening in heart failure?

Answer 11

Over time fractional shortening is reduced

Question 12

Where are the ANS nerves found in the heart?

Answer 12

Vagus:PSNS: SA and AV node.

Cardiac SN: SA, AV and ventricular myocardium

Heterogenous distribution of PNS and SNS throughout the heart

Question 13

How does SNS impact the heart? (Rate and Rhythm)

Answer 13

• Increased HR (~3s to take effect)
• Duration of cardiac AP reduced.
• Acceleration of impulse propagation through AV node
• May facilitate pacemaker activity of cells in the AV node

Question 14

How does PSNS impact the heart?

Answer 14

• Reduced HR (Rapid)
• AP duration in atrial myocardium is reduced
• Deceleration of impulse propagation through the AV node
• Vagus nerve decreases inotropic state of atria (BUT less so on ventricles because of sparse innervation)

Question 15

What determines oxygen supply to the heart?

Answer 15

• Perfusion pressure (aortic pressure and extravascular compression)
• Impedance (local auto-regulation)
  = Coronary supply

To increase O2 supply must:
- Increased O2 conc.
- Increase blood flow.

Question 16

What determines the oxygen demand of the heart?

Answer 16

• Basal metabolism
• Wall force development (Pressure*Time, Geometry (LaPlace)
• Inotropic state
• Heart rate

(Afterload)

Question 17

Insert slide 28

Answer 17

plaease

Question 18

What is coronary blood flow determined by?

Answer 18

Q = P / R

insert slide32

Question 19

What determines local autoregulation of coronary vessels?

Answer 19

Active myocytes producing:
- Adenosine
- K, Pi, H, CO2
= Changes in osmolarity

Question 20

Whats of note when it comes to the diastolic pressure time index vs tension time index?

Answer 20

In the healthy heart the coronary perfusion pressure * diastolic time > Systolic pressure * systolic time

i.e Supply>Demand

slide 34

Question 21

What is happening to the myocyte in a hypoxic state?

Answer 21

Reduced ATP
= Reduced Na/K ATPase
= Hyperkalemia (inc. IKo)
= Reduced RMP
= Reduced AP upstroke speed and magnitude
= Shorted AP
= Reduced myosin head detatch
= Reduced NCX, SERCA
= Increased cytoplasmic Ca = impaired relaxation and filling = electrical instability
= reduced pH (acidosis), H competes with Ca on trop C
= Dec inotropic state and dec CO
= Reduced gap junction coupling etc (slows conduction)

etc
etc