Determinants of Cardiac Output

This section covers determinants of cardiac output from the perspective of the heart. The relationship to and importance of venous return is covered elsewhere.

Define the components and determinants of cardiac output

Cardiac output a function of Heart Rate (HR) and Stroke Volume (SV):
$CO = HR \times SV$.

• Heart rate is fairly intuitive
• Stroke volume is defined as the difference between ESV and EDV, i.e. $SV = EDV - ESV$
  Stroke volume is a function of three factors:
  • Preload
  • Afterload
  • Contractility

• Preload and afterload have almost as many definitions as there are textbooks
• For the purpose of the exam, it's good to have both a laboratory and a clinical definition
• These definitions are those which have appeared in old examiner reports, or given to me by cardiac anaesthetists

Preload

Preload is defined as the myocardial sarcomere length just prior to contraction.

• As this is not measurable without removing the heart and cutting it into tiny pieces, clinically it is usually approximated by EDV or, less appropriately, by EDP
  • EDV is typically calculated on echocardiography
  • EDP is typically measured using a CVC or PAC
    • CVP ≈ RVEDP
    • PCWP ≈ LVEDP

Determinants of Preload

Preload is a function of:

• Venous Return
  • Intrathoracic Pressure
  • MSFP
    • Venous compliance
      A decrease in venous compliance will increase LVEDP.
    • Volume state
• Ventricular compliance
  Reduced in diastolic dysfunction.
• Pericardial compliance
• Valvular disease
  • AV valve disease will impair preload
  • Semilunar valve disease will increase preload
• Atrial kick
• Wall thickness
  Increased ventricular wall thickness decreases preload.
  • HOCM/Hypertrophy

Preload and the Respiratory Cycle

• Negative intrathoracic pressure causes RAP and PCWP to fall
• This increases RA filling, so and RVEDP and RVEDV increase relative to the pleural pressure (though absolute pressure is still low)
• LV effects are more variable
  Negative intrapleural pressures:
  • Increase LV transmural pressure
    This impairs ejection.
  • Cause bowing of the interventricular septum into the LV
    This reduces LVEDV.

Frank-Starling Mechanism

• The Frank-Starling Law of the Heart states that the strength of cardiac contraction is dependent on initial fibre length
• At a cellular level, additional stretch increases:
  • The number of myofilament crossbridges that can interact
  • Myofilament Ca²⁺ sensitivity

• This law is represented by the ventricular function curve
  Plot of preload against stroke volume (or cardiac output, assuming a constant heart rate).
  • Right shift of the curve demonstrates negative inotropy
  • Left shift of the curve demonstrates positive inotropy

The failing ventricle:

• In cardiac failure, the ventricle becomes overstretched
  This reduces the number of overlapping crossbridges, reducing contractility.
• This is limited in the acute setting by constriction of the pericardium, which prevents excessive ventricular dilation

Afterload

Afterload is the ventricular wall stress at the onset of systole. This is given by the Law of Laplace, $\theta \propto {P \times r \over T}$, where:

• $\theta$ is ventricular wall stress
• $r$ is ventricular chamber radius
  This is a proxy for ventricular size, or end-diastolic volume.
• $P$ is ventricular transmural pressure
• $T$ is ventricular wall thickness

End-Diastolic Volume

An increase in EDV increases ventricular radius and therefore wall tension.

Myocardial wall thickness

Increasing wall thickness (seen clinically as ventricular hypertrophy) decreases afterload by sharing wall tension (the product of pressure and radius) between a larger number of sarcomeres.

Ventricular transmural systolic pressure

Transmural pressure is the difference between intrathoracic pressure and the ventricular cavity pressure during ejection. Transmural pressure is dependent on:

• Intrathoracic Pressure
  Negative intrathoracic pressure will increase afterload, as the ventricle has to generate a greater change in pressure to achieve ejection.
  • PEEP reduces LV afterload
  • Negative-pressure ventilation with a high work of breathing increases afterload
    This is why APO deteriorates - increased work of breathing increases LV afterload and worsens LV failure, increased pulmonary oedema, causing increased work of breathing...
    
    
• Ventricular cavity pressure
  To facilitate ejection, the ventricle must overcome:
  • Outflow tract impedance
    • Valvular disease
      • e.g. aortic stenosis
    • HOCM
  • Systemic arterial impedance/Aortic input impedance
    Determined by resistance (SVR), reflected pressure waves, inertia, and compliance:
    • Determinants of resistance are stated in the Poiseuille Equation:
      $R = {8.\eta.l \over \pi.r^4}$, where:
      • η = Viscosity
        Affected by haematocrit (e.g. increased in polycythaemia)
      • l = Vessel length
        Essentially fixed.
      • r = Vessel radius
        • Greatest determinant
        • Function of degree of vasoconstriction of resistance vessels
    • Reflected pressure waves
      Reflection of pulse pressure waves from the distal circulation increases aortic pressure.
      • In normal circumstances this occurs during diastole (and so has less contribution to afterload)
      • Decreased compliance of the peripheral circulation increases the speed of propagation, so the pressure wave may return during systole and contribute to systolic blood pressure and afterload
    • Inertia
      • Given by the mass of blood in the column
      • Affected by heart rate
    • Arterial compliance
      Decreased arterial compliance increases afterload.
      • During ejection, the aorta and large arteries distend, reducing peak systolic pressure (impedance to further ejection)
        • Decreased arterial compliance increases the change in pressure for any given volume, increasing afterload during ejection
        • Decreased arterial compliance increases the speed of propagation of reflected pressures waves returning to the aortic root
          • Wave arrival in diastole augments coronary blood flow
          • Wave arrival during systole further increases afterload
      • In diastole the arteries recoil and blood pressure and flow are maintained - the Windkessel effect.

Contractility

Contractility describes the factors other than heart rate, preload, and afterload that are responsible for for changes in myocardial performance.

Determinants of Contractility

Contractility is primarily dependent on intracellular Ca²⁺. Determinants include:

• Drugs
• Disease
  • Ischaemia
    Reduced ATP production secondary to hypoxia, which impairs sarcoplasmic reticulum Ca²⁺ function. Further exacerbated by intracellular acidosis from anaerobic metabolism.
  • Heart Failure
    Impaired contractility reserve, i.e. minimal increase in contractility with sympathetic stimulation.
    • Reduced peak Ca²⁺ and sarcoplasmic reticulum uptake of Ca²⁺
• Autonomic Tone
• Bowditch Effect
  Contractility improves at faster heart rates. This is because the myocardium does not have time to remove calcium, so it accumulates intracellularly.
• Anrep Effect
  Contractility increases as afterload increases.

Measuring Contractility

• As with the other determinants of cardiac output, there has been some difficulty in developing measurable indices for contractility
• All measures of contractility are affected by preload or afterload to some extent

• dP/dt_max ($\Delta P \over \Delta T$)
  The rate of rise of LVP, assuming a constant preload and afterload
  • This index is preload dependent but afterload independent
  • Typically, the dP/dt_max in isovolumetric ventricular contraction is used
  • A greater rate of rise indicates a more forceful contraction
  • Measurement requires LV catheterisation

• End-Systolic Pressure-Volume Relationship
  • Uses the ventricular Pressure-Volume Relationship
  • Line plotted at the tangent to the curve from the end-systolic point (when isovolumetric ventricular relaxation begins)
    • The steeper the gradient the greater the contractility

• Ejection Fraction
  Most common method used clinically is ejection fraction:
  $EF \ (\%) = {SV \over EDV } \times 100 = {EDV - ESV \over EDV} \times 100$

Footnotes

• The use of wall stress for preload and afterload comes from the Cardiovascular Haemodynamics text, but is not used in the CICM texts

• This site has a nice overview of wall tension, and the relationship of pressure to radius

• This article discusses the wall stress definition for preload and afterload

• Changes with ventilation are described with pretty graphs here

References

1. Brandis K. The Physiology Viva: Questions & Answers. 2003.
2. Deranged Physiology - Haemodynamic changes during mechanical ventilation
3. Anwaruddin S, Martin JM, Stephens JC, Askari AT. Cardiovascular hemodynamics: an introductory guide, contemporary cardiology. New York: Springer; 2013. p. 29–51.
4. Norton JM. Toward Consistent Definitions for Preload and Afterload. Advances in Physiology Education Mar 2001, 25 (1) 53-61.
5. ANZCA July/September 2006