L25: Control Of The Heart

Question 1

Cardiac output

Answer 1

HR x Stroke volume

SV - depends on venous return

Question 2

Control of force of contraction

Answer 2

1. Heterometric: Changing length of ventricular muscle —> Keep same rate of force development for longer (intrinsic)
2. Homeometric: Increase rate of force development for same duration —> ↑ contractility (intrinsic: Treppe effect / extrinsic: ANS)

Question 3

Contractility

Answer 3

Rate of force development

depends on:
Intracellular calcium
—> excitation-contraction coupling
—> formation of cross bridges between actin and myosin

Question 4

Cardiac contractile cycle

Answer 4

*Excitation-contraction coupling:
—> Action potential arrival
—> Na influx, depolarisation
—> voltage-sensitive protein at T-tubule changes shape
—> Ca-induced Ca release: Depolarisation by Na causes Ca go into sarcoplasm (L type Ca channel / Dihydropyridine receptor)
—> trigger Ca release from SR (via Ryanodine receptor)
—> Binding of Ca to Troponin
—> Rotate and swings Tropomyosin away
—> Expose myosin binding site to actin (higher Ca conc —> more site exposed)
—> begin contractile cycle

Relaxation
—> Ca uptake to SR
—> Ca reabsorption into SR via SERCA (Sarco-endoplasmic reticulum Ca-ATPase)
—> Ca pumped from SR to extracellular space in diastole (via Na/Ca exchanger, Ca-ATPase)

Question 5

Sympathetic nerves on control of force of contraction

Answer 5

Extrinsic:
NE bind to β1 receptor
—> adenyl cyclase activation
—> ATP —> cAMP (2nd messenger)
—> activate Protein Kinase A
—> phosphorylation of Ca channel
—> ↑ time in open state
—> ↑ permeability to Ca
—> ↑ Ca entry
1. ↑ intracellular Ca —> ↑ rate of force development
2. ↑ rate of Ca reabsorption into SR (via SERCA) —> faster relaxation —> more forceful contraction in shorter time + ↑ Ca storage

Intrinsic:
Rate-induced regulation / Treppe effect
↑ HR
—> shorten diastole
—> less Ca pumped into extracellular space
—> ↑ Ca storage in SR
—> ↑ force

Question 6

Vagus nerve on control of force of contraction

Answer 6

Only innervate atria and nodal tissues
—> CANNOT influence force
—> only change HR
—> indirectly: rate-induced regulation of force (Treppe effect)

Question 7

Effect of venous return on force of contraction

Answer 7

Heterometric autoregulation / Frank-Starling’s law of the heart

1. ↑ venous return (preload) —> ↑ filling of ventricle —> ↑ force of contraction
2. ↑ arterial pressure (afterload) —> ↓ P gradient (ventricular - artery) —> ↓ stroke volume —> ↑ end-systolic volume —> ↑ end diastolic volume —> ↑ force of contraction

Importance: adjust force to match degree of filling —> prevent overstretching of heart

Natural position of cardiac muscle: shorter-than-optimal length
—> ↑ stretch of heart
—> ↑ cross bridge formation
—> ↑ force

Decrease in sarcomere length:
1. Thin filament overlap (initial drop in force)
2. Thick filament distorted and push against Z line (greater drop in force)
—> reduce cross bridge formation

Increase in sarcomere length (too long): e.g. Congestive heart failure
- reduces overlap between actin and myosin (drop in force)
—> reduce cross bridge formation

Question 8

Cardiac function curve

Answer 8

Force of contraction against ventricular muscle length
—> CO/SV against RAP

Heterometric change: cardiac function curve does not change (↑ filling —> ↑ force —> shift along curve)

Homeometric change: cardiac function curve shifts upward (↑ intracellular Ca —> ↑ rate of force development / contractility)

Question 9

Congestive heart failure and cardiac function curve

Answer 9

↓ contractility of heart (due to ischaemia / scarring)
—> cardiac function curve shift downwards
—> in order to maintain same CO
—> compensatory behaviour
—> shift along new curve (move to higher RAP) —> compensated
—> if further ↓ contractility
—> over the top of cardiac function curve
—> decompensatory behaviour
—> cannot keep up with same CO —> decompensated