Regulation of Cardiac Output

Question 1

CO=

Answer 1

HRxSV

Question 2

Factors affecting heart rate

Answer 2

atrial reflex
autonomic innervation
hormones

Question 3

factors affecting stroke volume

Answer 3

Preload factors: venous return, filling time
Contractility factors: autonomic innervation, hormones
Afterload factors: vasodilation & vasoconstriction

Question 4

chronotropy

Answer 4

changes in heart rate

Question 5

impacts on sinoatrial node depolarization rate

Answer 5

Parasympathetic (vagal) input: acetylcholine -> cholinergic (M2 muscarinic receptors), negative chronotropy, decreases heart rate.

sympathetic input: norepinephrine–> adrenergic (beta adrenoceptors) - positive chronotropy, increases heartrate

Question 6

Norepinephrine effects (beta 1 agonists)

Answer 6

Increases HR
↑ If
Increases slow depolarization rate (↑ steepness of phase 4)

↑ ICa (in all myocardial cells)
Increases slow depolarization rate (↑ steepness of phase 4)
Threshold more negative (reached sooner)

↓ IK
Increases steepness of phase 4 slow depolarization

Result: Shorter time for depolarization to threshold; ↑ HR

Question 7

Parasympathetic N.S. effects

Answer 7

Decreases HR
Acetylcholine effects (M2 agonists):

↓ If
Decreases slow depolarization rate (↓ steepness of phase 4)

↓ ICa:
Decreases slow depolarization rate (↓ steepness of phase 4)
Threshold more positive (takes longer to reach)

↑ IK
More negative maximum diastolic potential (KAch channel)

Result: Longer time for depolarization to threshold; ↓HR

Question 8

Examples of Factors Which Can Influence the Firing Rate of the SA Node (Positive and Negative Chronotropic Factors)

Answer 8

Increasing heart rate: sympathetic stimulation (Muscarinic receptor antagonist, beta adrenoceptor agonist, circulating catecholamines)

Decreasing heart rate: parasympathetic stimulation (muscarinic receptor agonist, beta 1 blocker, Calcium channel blocker)

Question 9

Dromotropy definition

Answer 9

changes in conduction velocity

Question 10

Dromotropy affectors

Answer 10

Sympathetic norepinephrine effects (β1 agonists):
↑ rate of depolarization (AP slope)  ↑ conduction velocity

Parasympathetic acetylcholine effects (M2 agonists):
↓ rate of depolarization (AP slope )  ↓ conduction velocity

Question 11

Examples of factors which can influence conduction velocity

Answer 11

Increasing conduction velocity: sympathetic stimulation (m2 muscarinic receptor antagonist, beta1-adrenoceptor agonist, circulating catecholamines)

Decreasing conduction velocity: parasympathetic stimulation (M2 muscarinic receptor agonist, beta-1 blocker, Na and Ca channel blockers, ischemia/ hypoxia

Question 12

Stroke volume definition

Answer 12

SV = volume of blood ejected in 1 heartbeat (ml/beat)

SV = EDV - ESV

Question 13

general affects on stroke volume

Answer 13

In general:
↑ SV when:
↑ Preload = ↑ End-diastolic volume (EDV)
↑ Contractility/Inotropy

↓ SV when:
↑ Afterload

Question 14

6 Factors Which Can Promote ↑ EDV

Answer 14

. ↑ Central Venous Pressure (CVP) 
decreased heart rate
increased ventricular compliance
increased atrial contractility
increased afterload
pathological conditions (systolic failure, valve defects)

Question 15

Central venous pressure promotes increased EDV via

Answer 15

[Mean venous pressure/filling pressure/thoracic vena cava pressure]
a. ↓ venous compliance, ↑ resistance
Sympathetic venoconstriction

b. ↑ thoracic blood volume by:
↑ total blood volume 
↑ venous return through:
↑ respiratory activity
↑ skeletal muscle pump activity
↑ CO
Result:
↑ CVP --> ↑ VR --> ↑ atrial filling pressure                                ↑ ventricular filling pressure --> ↑ EDV

Question 16

promoting increased EDV via decreased heart rate

Answer 16

↑ filling time –> ↑ EDV

Relatively longer time in diastole vs. systole

Question 17

promoting increased EDV by increasing ventricular compliance

Answer 17

↑ chamber filling volume (EDV) at a given filling pressure

↑ ventricular relaxation rate (see section on lusitropy)

Question 18

promoting increased EDV via increased atrial contractility

Answer 18

Sympathetic stimulation

Increased ventricular filling (EDV) from atria

Question 19

promoting increased EDV via increased afterload

Answer 19

Increased afterload
Ex: Increased aortic pressure
Increased ESV, decreased SV
2° increase in preload for next cycle                            
Not a “good” way to increase EDV

Question 20

pathological conditions that lead to increased EDV

Answer 20

Systolic failure
Valve defects: aortic stenosis, aortic regurgitation
Pulmonary valve stenosis & regurgitation (RV preload)
Not a “good” way to increase EDV

Question 21

effects of increased afterload

Answer 21

↑ Afterload –> ↑ ESV –> ↓ SV

Question 22

definition of afterload

Answer 22

force opposing ventricular ejection (Systolic pressure)

Pressure which contracting fibers must oppose for ejection
Direct measure: maximum systolic ventricular pressure
Indirect estimates:
LV: aortic pressure (mean systemic arterial pressure)
RV: pulmonary a. pressure (mean pulmonary arterial pressure)

↑ afterload –> greater proportion of systole spent in isovolumetric contraction phase

- -> ↓ SV and ejection fraction

- -> ↑ ESV --> ↓ SV

Question 23

Examples of conditions which may increase afterload on the left ventricle/right ventricle:

Answer 23

Systemic hypertension/pulmonary hypertension

Stenotic aortic valve/stenotic pulmonary valve

Question 24

another word for contractility

Answer 24

inotropy

Question 25

Contractility/ inotropy in cardiac muscle

Answer 25

Not possible to increase force production via motor-unit recruitment or twitch summation Contractility Force generation that is independent of preload (EDV, sarcomere length) ↑ contractility = ↑ systolic function ↓ ESV ↑ SV and ejection fraction Positive inotropic factors: ↑ contractility by ↑ [Ca2+]i Negative inotropic factors: ↓ contractility by ↓ [Ca2+]i

Question 26

ESPVR (what does the acronym stand for)

Answer 26

end systolic pressure volume relationship

Question 27

how changes in contractility affect ESPVR

Answer 27

↑ contractility --> ↑ slope of ESPVR --> ↑ SV (independent of EDV) ↓ contractility --> ↓ slope of ESPVR --> ↓ SV (independent of EDV)

Question 28

How the sympathetic NS impacts contractility

Answer 28

Activation of β1-adrenergic receptors on atrial and ventricular contractile myocytes: ↑ Ca2+ availability --> ↑ contractile force --> ↑ CO How: 1.↑ Ca2+ influx via L-type DHDP channels: ↑ [Ca2+]i and ↑ Ca2+-dependent Ca2+ release from the SR 2. ↑ sensitivity of RYR to [Ca2+]i 3. ↑ SERCA activity (remove phospholamban inhibition), ↑ Ca2+ stores