P: Cardiac Output Flashcards
Where do sympathetic pre-ganglionic fibres originate?
T1-T5 in spinal cord
What nerve passes to entire thoracic and abdominal regions of the body including the heart?
Vagus nerve
What parts of the heart do post-ganglionic sympathetic nerves innervate?
- SA and AV nodes
- Contractile atrial and ventricular tissue
What parts of the heart do post-ganglionic parasympathetic (vagus) nerves innervate?
- SA and AV nodes
- Some innervation of contractile atrial and ventricular tissue
What’s the effect of ANS on cardiac APs? What do sympathetic and parasympathetic nerves release to do so?
- Regulates the heart rate by enhancing/inhibiting spontaneous generation of slow response APs of autorhythmic cells (heart generates its own APs, ANS modulates their rate and strength)
- Modulates fast response APs in contractile myocytes
- Sympathetic: noradrenaline (stimulatory)
- Parasympathetic (vagus): acetylcholine (inhibitory)
What does vagal nerve activity do to heart rate?
Reduces heart rate
Explain vagal escape
- Experimental electrical stimulation of vagus nerve: heartbeat stops for a few seconds
- If HR = 0 —> cardiac output = 0
- Reduction in CO triggers reflex stimulation of sympathetic nerves (baroreceptor reflex)
- Simultaneous sympathetic (+) and vagal (-) nerve activity —> HR of 20-40 bpm
Modulating ___ nerve activity exerts a more immediate control and is physiologically more important than ___ activity
- vagus nerve
- sympathetic
Explain sympathetic regulation of heart rate
Increase of HR:
- Noradrenaline released from sympathetic nerve endings binds Beta1 adrenergic receptors on pacemaker cells
- cAMP levels rise, PKA activity increases
- cAMP binds to Na+ channels and PKA phosphorylates Ca2+ channels
- Increased opening of HCN channels and increase of ions flow through them —> increases rate of autorhythmic cell depolarizations —> increases HR (threshold is achieved more rapidly)
Explain vagal regulation of heart rate
Reduction of HR:
- Release of ACh from vagus (parasympathetic) nerves causes opening of K+ channels: increased K+ efflux during phase 4 causes membrane potential to become more negative (hyperpolarization)
- Release of ACh from vagus nerve causes closing of HCN channels on pacemaker cells (by binding M2 muscarinic receptors —> inhibits cAMP production)
- These 2 factors reduce generation of slow response APs —> reduces HR (threshold is achieved slower)
SV is intrinsically (directly) proportional to ___ and ___
How?
What principle explains this?
- EDV and contractility
- Increase in EDV increases ventricular pressure (preload) —> stretches ventricular myocytes –> increases intrinsic contractility of myocytes –> increases SV
- Frank-Starling Law of the Heart
Definition of Frank-Starling mechanism
Ability of the heart to change its force of contraction and therefore stoke volume in response to changes in venous return
Changes in ___ produce significant changes in ejection fraction (EF)
Contractility/inotropy
What is ejection fraction (EF)? How to calculate it? Normal EF? Exercise EF? Severe heart failure EF?
- % of EDV ejected from heart
- EF = SV/EDV x 100
- Normally EF > 60%
- Exercise: EF > 90% (increased inotropy)
- Severe heart failure: EF < 20%
Effect of increased EDV on contractile force and how?
- Increased EDV increases sarcomere length to 2-2.4 µm
- Optimum overlap of thick/thin filaments: maximizes number of cross-bridges formed + increases affinity of troponin C for Ca2+
- Contractile force is increased
- When sacromeres stretched beyond optimum length (2.4 µm) –> contractility diminished (only happens in heart failure)
What is preload pressure in normal heart? At which pressure does contractility peak?
- 12 mmHg
- Peaks at 30 mmHg
Explain how Frank-Starling mechanism acts to restore normal cardiac output in bradycardia
- Bradycardia initially decreases cardiac output –> increases duration of diastole –> increased ventricular filling –> increased EDV or preload –> increased stretch + contractility –> increased SV
- Reduction in HR is compensated by increase in SV –> CO remains constant (CO = HR x SV)
Explain how Frank-Starling mechanism acts to restore normal cardiac output in afterload
Afterload: arterial pressure opposing opening of semilunar valves
- Increased BP (diastolic pressure) –> increased afterload
- Increased peripheral resistance –> increased afterload –> delays opening of valves and ventricular ejection –> ventricles contract for longer to open semilunar valves –> reduction in stroke volume + increase in ESV
Ventricles can adapt by increasing contractility:
- Decrease in SV = increased EDV in next cardiac cycle (constant venous return VR)
- ESV + VR = EDV in next cardiac cycle –> will cause subsequent contractions to be stronger –> increased contractility restores SV to normal
What is Frank-Starling Mechanism characterized by?
Increased EDV –> increased inotropy
Changes in cardiac contractility also occur ___ of preload —> unique to cardiac muscle, skeletal muscle can’t alter its ___ state
independently, intrinsic inotropic
Increase in frequency of contraction increases ___ of myocardial fibres
Contractility (frequency of contraction is determined by HR, increased HR increases contractility)
Explain Bowditch effect/Treppe phenomenon
Increased HR —> increased intracellular [Ca2+] —> increased contractility
- Ca2+ enters cell during each AP plateau phase —> increases # of AP/min –> rise in [Ca2+]
- Increased number of depolarizations also increases opening of Ca2+ channels
As HR increases, ___ progressively decreases. Why?
- SV decreases
- Increase in HR shortens diastolic time —> reduced time for ventricular filling —> reduced EDV (preload) —> reduced SV
(CO = HR x SV)
Explain relation between HR and cardiac output from 50-250 bpm
- 50-100 bpm: initial increases in HR elevate CO (effect of reduction in SV is less than effect of increase in HR)
- 100-200 bpm: CO is constant (effect of reduction in SV balances effect of increase in HR)
- > 200 bpm: CO decreases (ventricular filling time severely restricted)
What happens during excessively slow HR/profound bradycardia concerning CO and how to fix it?
- Slow sinus rhythm —> AV block
- EDV and SV increase can’t compensate for slow HR (overstretch of ventricular sarcomeres + pericardium limits ventricular filling)
- CO falls substantially
- Artificial pacemaker
Opening of L-type Ca2+ channels is regulated by the ___ to control the degree of Ca2+ influx and regulate ___ of the heart
ANS, contractile strength
Effects of increasing influx of Ca2+ on fast response:
- Prolongs length of plateau phase in AP
- Stronger contraction of sarcomeres in myocytes
Explain sympathetic regulation of contractility
- Sympathetic nerves release NA –> binds to B1 adrenergic receptors on myocytes –> cAMP levels increase –> activation of PKA –> phosphorylation of L-type Ca2+ channels –> increases opening time
- Contractile strength increases
- SV increases
Mechanism of stronger and more rapid ventricular contractions:
- Systole duration is shorter
- Relaxation happens earlier
- Diastole duration is longer
- Ventricular filling increases
Explain vagal regulation of contractility
Vagus nerves release ACh which promotes closure of L-type Ca2+ channels in 2 ways:
- ACh binding to M2 muscarinis receptors inhibits cAMP production —> down-regulation of cAMP 2nd messenger system —> phosphorylation + opening of Ca2+ channels is reduced
- ACh inhibits release of NA from neighbouring sympathetic nerves
- Contractile strength decreased —> SV decreased
Are vagus or sympathetic effects more important in regulating ventricular myocyte contractility?
Sympathetic
Describe positive and negative inotropic effect
- Positive: at the same EDV, sympathetic nerves increase contractility –> larger SV
- Negative: at the same EDV, vagus nerves reduce contractility –> smaller SV
What are factors increasing inotropy
- HR (Bowditch Effect)
- Parasympathetic (vagal) inhibition
- Sympathetic activation
- Afterload (Anrep Effect)
- Circulating catecholamines
Measurement of cardiac output (Q)
- q1 = rate of O2 delivery to lungs from RV
- q2 = O2 consumption by body
- q3 = rate of O2 transport to LA from lungs
- Q = CO
- q1 = Q[O2] pulm artery
- q2 = Q[O2] pulm vein
How is CO calculated nowadays?
Doppler echocardiography:
- Ultrasound utilizes Doppler effect to determine direction and velocity of blood flow
- SV and CO is calculated from velocity of blood and area of aorta
