Regulation of the Cardiac Output I and II

Question 1

Preload and Afterload

• Preload
• Afterload
• Factors contributing to afterload
• Effect of increasing afterload on preload

Answer 1

• Preload
  
  • Pressure stretching the ventricle after passive filling & atrial contraction
  • Major factor that augments cardiac output via the Frank-Starling mechanism
  • Heart can contract more with greater ability to stretch/contract
  • Increased by the same factors that increase venous return
• Afterload
  
  • Mean tension produced by a chamber of the heart in order to eject blood
  • Force that must be overcome to eject blood from the ventricle
  • Total peripheral resistance (TPR): main determinant of afterload
  • Hypertension –> increased pressure –> more afterload –> heart has to work harder
• Factors contributing to afterload
  
  • Aortic pressure: an increase in peripheral resistance increases afterload
    
    • Aortic valve closes earlier during the cardiac cycle, cardiac output is reduced, & end systolic volume increases
  • Aortic valve stenosis increases ventricular stiffness
• Effect of increasing afterload on preload
  
  • Increasing afterload increases preload
  • Increased end systolic volume is added to normal venous return
  • Increase in preload activates the Frank-Starling mechanism to compensate for the reduction in stroke volume caused by the increase in afterload

Question 2

Treatment following a heart attack where the left ventricle is damaged

Answer 2

• Vasodilator drugs
  
  • Augment stroke volume by decreasing afterload
  • Reduce ventricular preload
• When arterial pressure is reduced, ventricle can eject blood more rapidly
  
  • Increases troke volume
  • Decreases end-systolic volume
  • Ventricle won’t fill to same end-diastolic volume before the afterload reduction
  • Higher stroke volumes can be sustained by weaker ventricular contractions
  • Diminishes risk of congestive heart failure

Question 3

Intrinsic and extrinsic factors that influence cardiac output

Answer 3

• Intrinsic factors
  
  • Heart rate
  • Contractility (end systolic pressure-volume relationship)
• Extrinsic factors
  
  • Preload (end diastolic volume)
    
    • If preload increases, CO increases w/o any changes in HR & contractility
  • Afterload (end systolic pressure / mean arterial pressure)
    
    • If afterload increases, CO decreases unless HR & contractility also increase

Question 4

Influence of heart and vasculature on cardiac output

• Vascular function curve (venous return curve)
• Cardiac function curve
• Assumptions
• Equations
• Significance

Answer 4

• Vascular function curve (venous return curve)
  
  • Considers how changes in vasculature (flow, cardiac output) affects systemic venous pressure (pressure in the circulation, atrial pressure)
• Cardiac function curve
  
  • Considers how changes in systemic venous pressure affects cardiac output
• Assumptions
  
  • Cardiac output = venous return
  • Central venous pressure = right atrial pressure
• Equations
  
  • Pa = systemic arterial pressure
  • Pv = systemic venous pressure
  • R = 20 mmHg / L/min
  • Q = CO = 5 L/min
  • R = ΔP / Q = (Pa - Pv) / Q
  • Pa = 100 mmHg + Pv
• Significance
  
  • Systemic arterial pressure is 100 mmHg greater than Pv

Question 5

Systemic filling pressure (Psf)

• Definition
• Value
• Compliance & pressure

Answer 5

• Systemic filling pressure (Psf)
  
  • Effective pressure head in the systemic circulation pushing the blood back into the heart
  • Equal pressure in the veins & arteries when the heart is stopped
• Pv = 2 mmHg, Pa = 102 mmHg –> Psf = 7 mmHg
  
  • Psf is closer to venous pressure than arterial pressure b/c venous compliance is ~19x higher than arterial compliance
• Compliance & pressure
  
  • C = ΔV/ΔP
  • ΔVa = ΔVv when the heart is stopped
  • CaΔPa = CvΔPv
  • Cv = 19Ca
  • ΔPa = 19ΔPv
  • The change in arterial pressure is 19x larger than the change in venous pressure when the heart is stopped

Question 6

Vascular function curve (venous return curve)

• Equations
• Cardiac factors
• Vascular factors

Answer 6

• Equations
  
  • Pv = Psf - (R*Ca / Ca+Cv)*Q
  • Pa = Psf + (R*Cv / Ca+Cv)*Q
• Cardiac factors
  
  • Venous pressure (Pv) = right atrial pressure
  • Flow through the vascular system (Q) = venous return = cardiac output
• Vascular factors
  
  • Peripheral resistance (R)
  • Arterial & venous compliance (Ca & Cv)
  • Systemic filling pressure (Psf)

Question 7

Relationship b/n right atrial pressure & venous return (cardiac output)

Answer 7

• Relates venous return (cardiac output) to right atrial pressure
• When right atrial pressure = Psf, venous return (or cardiac output) is 0 since there’s no pressure difference to drive blood flow
• As right atrial (venous) pressure increases, venous return (cardiac output) decreases
• As right atrial (venous) pressure decreases, flow through the CV system (venous return or cardiac output) increases
• Little additional venous return b/n right atrial pressure of 0 & -8 mmHg
  
  • Negative right atrial pressure tends to suck together the walls of the large veins near the heart, limiting further increase in blood flow

Question 8

Resistance to vascular return (RVR) & its relation to the vascular function curve

Answer 8

• Resistance to movement of blood through the vasculature
  
  • Total peripheral resistance + consideration of compliance & vasculature
  • RVR = (R*Ca / Ca+Cv) = (Psf - Pv) / Q = 1mmHg / L/min
• Slope of vascular function curve = 1 / RVR
  
  • As RVR increases, slope decreases
  • Higher RVR
    
    • A given change in right atrial/venous pressure causes smaller changes in cardiac output/venous return
    • Max cardiac output / venous return is lower

Question 9

Circulatory blood volume

• Unstressed volume
• Stressed volume
• Circulatory blood volume vs. Psf

Answer 9

• Unstressed volume = 4L
  
  • At a circulatory blood volume of 4L, Psf = 0
  • Volume is insufficient to contribute to pressure b/c there’s insufficient stretch of the vessel walls
• Stressed volume > 4L
  
  • Any additional volume inside the CV system above the unstresed volume
• Small change in circulatory blood volume –> huge change in Psf
  
  • –> vascular function curve shifts up & to the right
  • –> at a particular right atrial pressure, cardiac output & venous return are much larger
  • When circulatory blood volume increases, it’s easier for the heart to fill w/ blood, & cardiac output increases

Question 10

Cardiac function curve

• Definition
• Right atrial pressure vs. cardiac output
• Heart rate vs. cardiac output
• Hypereffective vs. hypoeffective ventricle

Answer 10

• Cardiac function curve
  
  • Effects of right atrial pressure on cardiac output
  • Effects of changing preload on cardiac output & blood pressure
• Right atrial pressure vs. cardiac output
  
  • Low right atrial pressure –> cardiac output = 0
    
    • Too little blood in cardiac chambers to generate pressure during systole
  • Right atrial pressure > 4 mmHg –> cardiac output = max
    
    • Ventricle fills maximally & can’t accommodate more blood
• Heart rate vs. cardiac output
  
  • Modest increases in HR facilitate cardiac output despite shorter ventricular filling time due to the Bowditch effect
  • Large increases in HR shorten filling time so much that cardiac output plummets
• Hypereffective vs. hypoeffective ventricle
  
  • Hypereffective ventricle: when SNS activity is high or ventricle is hypertrophied, muscle mass has increased, & afterload increases
  • Hypoeffective ventricle: when SNS activity is low or ventricle is damaged, afterload decreases

Question 11

Equilibrium Point

• Definition
• Normal
• Increased blood volume
• SNS stimulation
• Exercise

Answer 11

• ​Equilibrium point: where vascular function & cardiac function curves intersect
  
  • Indicates cardiac output, venous return, & right atrial pressure at this physiological condition
• Normal
  
  • Right atrial pressure = 0 mmHg
  • Cardiac output & venous return = 5 L/min
• Increased blood volume
  
  • Psf increases
  • Shifts vascular function curve up
  • Doesn’t affect cardiac function curve
• SNS stimulation
  
  • Cardiac function shifts up & to the left
  • Vascular function curve shifts up & to the right
  • Due to…
    
    • Increased cardiac contractility
    • Increased heart rate
    • Decreased venous compliance
    • Increased total peripheral resistance
  • Increased afterload opposes this shift so cardiac output only rises a little
• Exercise
  
  • Afterload decreases as arterioles dilate
  • Skeletal muscle pumping –> increase venous return –> increase cardiac output

Question 12

Pressure volume relationship: external work, diastolic & systolic pressure curves

Answer 12

• External work (EW): funcitonal pressure-volume curve
• Diastolic pressure curve: end diastolic pressure-volume relationship (EDPVR)
  
  • Below 150ml: diastolic pressure doesn’t increase greatly w/ increased volume in noncontracting ventricles
  • Above 150ml: diastolic pressure increases rapidly b/c the ventricle is fully filled & the heart tissue can’t stretch anymore
• Systolic pressure curve: end systolic pressure-volume relationship (ESPVR)
  
  • Represents the max pressure at a particular ventricular volume
  • During ventricular contraction, systolic pressure increases & reaches a maximum at a ventricular volume of 150-170ml
  • As volume increases further, systolic pressure decreases b/c the actin & myosin of cardiac muscle are pulled apart to suboptimal lengths

Question 13

Pressure-volume loops

• Aortic valve closure
• Slope of ESPVR
• Effect of increasing cardiac output on MAP & afterload

Answer 13

• Aortic valve closure: upper left corner of pressure-volume curve
  
  • Pressure at this poitn is nearly MAP
  • ESPVR shows mean arterial pressure generated at different ventricular volumes
• Slope of ESPVR: dependent on ventricular contractility
  
  • Under sympathetic stimulation, slope steepens so that at a particular ventricular volume, pressure is greater
• Increasing cardiac output increases MAP & afterload
  
  • Increasing contractility facilitates & opposes increasing cardiac output
  • Increases in cardiac output are thus relatively modest

Question 14

Stroke volume vs. afterload and preload

• Effects of increased afterload on stroke volume
• Effects of increased preload on stroke volume
• Factors that contribute to an increase in preload
  
  • Venous compliance (venoconstriction)
  • Resistance to venous return (RVR)
  • Blood volume
  • Intrathoracic pressure
  • Heart rate
  • Ventricular stiffness
  • Posture
  • Skeletal muscle pumping

Answer 14

• Effects of increased afterload on stroke volume
  
  • Alpha-receptor agonist increases afterload
  • Ventricular pressure must increase for aortic valve to open
  • Valve closes earlier
  • Stroke volume is reduced
  • Effects are ameliorated when contractility increases w/ afterload
• Effects of increased preload on stroke volume
  
  • More filling of ventricle during diastole
  • Stroke volume increases w/ additional filling due to the Frank-Starling effect
• Factors that contribute to an increase in preload
  
  • Decreased venous compliance (venoconstriction)
  • Decreased resistance to venous return (RVR)
  • Increased blood volume
  • Negative intrathoracic pressure
  • Decreased heart rate (more time for ventricle to fill)
  • Decreased ventricular stiffness
  • Supine posture
  • Increased skeletal muscle pumping

Question 15

Effects of cardiomyopathy and myocardial infarction on the pressure-volume relationship

Answer 15

• Cardiomyopathy
  
  • Causes scarring & stiffening of the left ventricle
  • EDPVR curve shifts up
  • Pressure inside ventricle increases quickly as fluid enters the chamber
  • Filling is limited before intraventricular pressure matches atrial pressure
  • EDV decreases –> SV decreases
• Myocardial infarction
  
  • Causes scarring of the ventricular wall
  • Loss of contractility
  • SV decreases