Foundation course (Introductory) in Haemodynamics

Cardiovascular physiology refresher notes

Introduction
The cardiovascular (CV) system comprises the heart and the vasculature. Its aim is to drive and
control the circulation, keeping the blood rich in oxygen and nutrients to reach – as directly as
possible – the most cells in the body and bringing in return the oxygen-depleted blood and the
waste produced by cellular function. During this process, the CV system is also used as a
highway for the exchange of information between different paths of the body, e.g. by hormones,
cytokines and other signalling molecules. It is vital that all of these functions work smoothly, both
in health and in disease, and are able to adapt to the ever-changing environments of the body.
The cardiovascular system is composed of the heart, the arterial, vascular and capillary systems
and the blood with its constituents.

The right and left circulatory systems act in tandem to ensure:

 Distribution of oxygen and nutrients to all body tissues

 CO2 delivery to the lungs and waste products to their excretory organs
 Homeostasis (by hormone delivery) and distribution of electrolytes and water
 Thermoregulation.

Functionally, the circulation can be divided into two circuits:

 Right-sided, high-volume, low-pressure circulation

 From end-organ capillaries via venous drainage to the right side of the heart to the
pulmonary capillary beds
 Most patients have around 4 to 5 liters of blood, 80% of the total blood volume in the
body.
 This circuit comprises the venous system and the capillaries.
 Left-sided, low-volume, high-pressure circulation
 From the left side of the heart to the end-organ capillaries via the systemic circulation.
 This system comprises the arterial system.

The systemic circulation comprises of:

 Arterial system – acts to moderate blood pressure, ensure organ perfusion and convert
high pressure waveforms to constant end-organ flow. Contains approximately 20% of
circulating volume.
 Venous system – ensures venous return but also acts as a capacitance system for
circulating volume. Approximately 75% of circulating volume.

Capillary beds – allows microcirculatory exchange of O2/CO2, and nutrients and waste
products. Approximately 5% of circulating volume. The heart acts as the primary pump for both
right and left circulations with the same components to ensure efficient, unidirectional flow:

 The atria – allow storing of blood, and subsequent contraction, optimising ventricular

filling.
  The atrioventricular valves – prevent atrial regurgitation of blood during ventricular
contraction (tricuspid (TV) and mitral (MV) valves respectively).
 The ventricles – provide pressure to eject blood into the arterial system.
 The semilunar valves – prevent ventricular regurgitation (pulmonary (PV) and aortic (AV)
valves respectively); once closed, allows arterial elastic recoil to contribute to blood
pressure.

Conduction
 Figure 1: The conduction system of the heart. Activation of myocardial contraction is
initiated and co-ordinated by the heart’s conductive system. This results in a co-ordinated
ventricular contraction of the apices towards the heart’s base causing efficient ventricular
ejection.

Action potentials
Two forms of AP are generated within the heart:

 Slow AP (Figure 2) – results in spontaneous discharge from pacemaker cells

 Slow inward Na+ leak gradually increases membrane potential
 Voltage-gated Ca++ channels open, causing depolarisation
 K+ channels open (allowing potassium to leave the cell) to repolarise membrane

 Fast AP (Figure 3) – all other myocytes

 Membrane depolarisation causes opening of fast Na+ channels
 Partial repolarisation by closure of Na+ channels
 Opening of Ca++ channels causing plateau phase
 The duration of this plateau phase is proportional to tension developed in the myocyte
(Figure 4).
 Repolarisation by opening of K+ channels.

Figure 2: Changes in ion concentrations across cellular membranes, resulting in slow action
potentials
Figure 3: An example of an arterial waveform and its components

Figure 4: Prolongation of the plateau phase of fast APs result in a proportional increase in tension
generated by myocytess

Excitation-contraction coupling
Both myocyte contraction and relaxation are active, energydependent processes.

 Contraction:
 Plateau phase of membrane depolarisation crosses sarcolemma
 Intracellular Ca++ released from sarcolemma and sarcoplasmic reticulum initiates
contraction
 Ca++ binds with tropomyosin and troponin to expose actin binding sites
 Myosin heads cross link with actin, and hydrolyse ATP to allow formation of tension,
resulting in fibre shortening.
 Relaxation
 Voltage-gated Ca++ channels start actively pumping Ca2+ into the sarcoplasmic
reticulum, requiring ATP
 Voltage-gated Ca++ channels close, stopping influx of Ca++ into the cell
 With a reduction in intracellular Ca++, troponin/tropomyosin recover the actin binding
sites and cause the filament tension to reduce.
 Figure 5: Ca++: Ionised Calcium; SR: Sarcoplasmic reticulum; Na+: Sodium. Contraction
of cardiac Muscel is dependent on a process of ‘calcium-induced calcium release’.

An action potential initiated at the sino atrial node is propagated to cardiac myocytes via gap
junctions. This results in intracellular calcium entry via L-type calcium channels (Dihydropyridine
receptors). The resulting rise in intracellular calcium activates the ryanodine receptors that are
located on the sarcoplasmic reticulum, resulting in calcium release from the sarcoplasmic
reticulum (calcium-induced calcium release). 

This second process accounts for about 75% of the rise in intracellular calcium. Within the
sarcoplasmic reticulum is a calcium-binding protein, calsequestrin. This protein binds avidly to
ionised calcium and enables a large concentration of calcium ions to be stored within the
sarcoplasmic reticulum. 

Cytoplasmic calcium binds to troponin, displacing the troponin complex from the actin-binding
site. This allows the myosin head to bind to the actin filament. The myosin head pulls the actin
filament toward the center of the sarcomere, using energy from the hydrolysis of ATP. Relaxation
of the cardiac myocyte is an active process. The large amounts of intracellular calcium are taken
up by the sarcoplasmic reticulum.
This process is dependent on the sodium-calcium exchanger and calcium ATPase pump. The
gradient for the sodium-calcium exchanger is generated via the energy-dependent sodium-
potassium exchanger (inhibited by digoxin). Once intracellular calcium levels drop, the myosin-
actin bridge is lost and contraction ceases.

Figure 6: This image shows the position of actin (light blue) and myosin (red) filaments within a
sarcomere from the end of contraction at the top, to the end of relaxation at the bottom.

 Cardiac cycle

Atrial and ventricular events during the cardiac cycle are demonstrated in Figure 7, and consist
of:

Systole

 Early – isovolumetric contraction. Ventricular pressure increases with no change in

volume, MV closes. LA passively fills.
 Ejection – LV pressure exceeds aortic pressure. AV opens with blood excursion into
aorta.

Diastole 

 Beginning – isovolumetric relaxation (LV pressure decreases with no change in volume,

AV closes)
 Early – rapid ventricular filling
 AV closes, MV open, both LA and LV are relaxed
 80% ventricular filling from passive process
 Mid – LV pressure approaches LA pressure and passive filling slows
 Late – atrial contraction (responsible for 20% ventricular filling). As heart rate increases
there is a disproportionately greater decrease in the duration of diastole. At a heart rate
above 120/min, this may result in inadequate time for passive ventricular filling, and the
proportion contributed from coordinated atrial contraction significantly will increase, up to
30%.
Figure 7: Wiggers diagram, relating the electrical and mechanical changes taking place during
the cardiac cycle

Determinants of blood pressure cardiac output

Determinants of stroke volume: Preload,

afterload, contractility
Stroke volume is the marker of myocardial performance, and in itself is dependent on three main
factors:

 Preload
 Afterload
 Contractility

Preload
Preload can be defined as initial muscle fibre length at the end of diastole. As described by
Starling’s Law, with increasing muscle fibre length there is a proportional increase in the force of
subsequent contraction. As fibre length cannot be measured, the left ventricular end diastolic
volume (LVEDV) is used as the representative of the fibre length.

Figure 8 shows the relationship between pressure and volume in the left ventricle throughout the
cardiac cycle. During diastolic filling of the LV, the end diastolic volume (EDV) is used as the
marker of fibre length and therefore preload. By increasing our preload/EDV (from EDV to EDV2),
we can see the resultant increase in stroke volume.

Clinical Implications: By giving volume challenges, we aim to increase and optimise the LVEDV
and therefore increase the SV. Measurement of LVEDV, and assessment of preload and its
response will be covered in a later chapter (see chapter on assessment of fluid responsiveness).

Figure 8: Preload - The relationship of LV End-Diastolic Volume (EDV) and stroke volume

Afterload
Afterload is described as the cardiac work done to overcome the impedance to flow of ejected
blood, and is equated with the degree of LV wall tension.
This is derived from The Frank/Laplace’s law, which relates

Equation 1:
Where: P is the pressure across the LV, r is the LV radius and μ is the LV wall thickness.  
For example, if aortic pressure increases, this requires higher wall tension (i.e. myocardial work
or contraction) to generate sufficient LV pressure to eject the same SV.

Afterload is difficult to assess clinically, but LV end-systolic pressure (ESP) and therefore end-
systolic volume (ESV) can be used as a marker instead. Figure 9 shows the effect of an
increased afterload, for example, during a hypertensive crisis. During hypertension, ESP and
therefore ESV will be raised (from ESV to ESV2) due to incomplete emptying of the LV. As a
result, there will be a reduction in the subsequent SV (as demonstrated from SV1 to SV2).

Contractility is the intrinsic ability of the heart to contract independently of preload and afterload. It
is affected by factors such as:

 Sympathetic tone
 Circulating catecholamines
 Intracellular calcium concentrations.

Figure 9: Afterload -The effect of LV end-systolic pressure (ESP), thereby affecting end-systolic
volume (ESV), and stroke volume

Clinical implications:

 The interrelationship between preload, afterload and SV is complex, and changing one
will often cause changes that affect the others too.
 For example, contractility will increase to maintain SV in times of increased vasomotor
tone (i.e. afterload). This is true to a certain extent. After a certain point, further increases
in afterload will cause a decrease in SV and CO. A heart with poor contractility (i.e. in a
patient with heart failure) will compensate less than a heart with good contractility. The
 inotropic property of vasoactive drugs is required when one wants to improve the
contractility.

Relationship between blood pressure and cardiac output

Blood pressure is required to ensure end-organ flow for tissue perfusion, and its main
determinants are related as:

Equation 2:
Where MAP is Mean Arterial Pressure, CO is cardiac output, and SVR is systemic vascular
resistance. 
Clinical implications: MAP is not an indicator of CO and a normal MAP does not exclude shock.

Cardiac output is the product of the heart rate (HR) and the stroke volume (SV). Therefore, when
assessing a patient’s haemodynamics, the main determinants can be expressed as:

Equation 3:

SVR and arterial vasomotor tone is controlled by several factors:

 Sympathetic outflow
 Circulating catecholamines and hormones
 Local metabolic factors (O2, CO2, prostaglandins, etc.).

The heart rate is dependent on its intrinsic automaticity. However, this is influenced by:

 Vagal tone
 Sympathetic tone
 Endogenous hormones – e.g., thyroxin
 Temperature.

Venous return
Venous return is the quantity of blood that returns to the heart through the veins each minute.
The venous return and the cardiac output are equal to each other; this means that the heart
needs to pump all venous return.
According to Guyton it is not the heart that is the primary controller of cardiac output. It is the
demand of oxygen and flow in the tissues that determines how much flow is needed. In practice
the venous return (that equals cardiac output) is determined by the sum of all the local tissue
flows.

Guyton’s theory explains that the venous return is determined mainly by two factors: the pressure
gradient between the mean systemic filling pressure and the right atrial pressure, and the
vascular resistance.

Figure 10: Schematic representation of how unstressed volume, stressed volume, mean systemic
filling pressure and right atrial pressure interact in this model of the circulation. The heart works to
keep the right atrial pressure low, thus maintaining a gradient between the mean systemic filling
pressure and the right atrial pressure. Venous return depends on this gradient.

Figure 11: Venous return curves according to Guyton’s studies

Mathematically, this can be represented as follows:

VR= (Pms−RAP)/RVR

 Pms is the mean systemic filling pressure, which represents the degree of filling of the
systemic circulation
 RAP is the right atrial pressure (or CVP for simplicity)
 RVR is the resistance to venous return.

If the vessels are thought of as distensible tubes, then two volumes can be identified:

 The unstressed volume and the stressed volume

The volume to fill a distensible tube, such as a tyre or a blood vessel with no pressure rise, is
called the “unstressed” volume. Further volume additions to this volume cause an increase in
pressure rise (P) and an elastic distension of the wall of the tube, which depends on the
compliance (C) of the wall. This volume is the “stressed” volume” and is related to the pressure in
the next equation:

Pressure=stressed volume/compliance

As it is reflected in this equation, the mean systemic filling pressure (Pms) depends on the
stressed volume of the circulation.

The heart still plays an important role in this model of the circulation. A good performing heart is
able to maintain a low RAP and therefore maintain the necessary gradient to maintain the venous
return.

For this reason, the RAP (or CVP) can give us very valuable information about the circulatory
state of our patients. On the other hand, looking at absolute values of CVP may be of limited use
if we want to estimate the volume status of the patient because it gives us information about only
one side of the gradient of the venous return.

Frank-Starling law of the heart

The so-called Law of the heart states that as the heart muscle is stretched more, greater is the
force generated and the output from the ventricle. In practice, within some limits the heart needs
to pump all the venous return. We will see in the Assessment of fluid responsiveness chapter how
important this law is and how often we apply it in our clinical practice when we work on the
preload of patients.
Coronary perfusion

Figure 12: Coronary arterial blood supply (in this case the posterior descending artery is a branch
of the right coronary artery)

The heart is perfused by two coronary arteries (Figure 10), which arise behind the cusps of the
aortic valve: 

 Left coronary artery

 Originates as the left main stem, before dividing into the
 Left anterior descending (LAD), and diagonal branches – anterior LV wall
 Left circumflex, and marginal branch – lateral LV wall.
 Right coronary artery
 Supplies the right ventricle and usually
 Posterior descending artery (also known as posterior interventricular artery) – posterior
wall and septum, including AV node.

The posterior descending artery is a branch of the right coronary artery (known as right
dominance) in 70% but in 10% it is a branch of the circumflex artery (left dominance) and in 20%
it receives a supply from both right coronary and circumflex arteries (co-dominance).
Venous blood returns via the cardiac veins and into the coronary sinus before draining directly
into the right atrium. The myocardium has a high metabolic requirement, and extracts
approximately 60% of oxygen delivered; therefore, reductions in blood flow are poorly tolerated
and can result in ischaemia. Cardiac oxygenation is therefore flow dependent.

Figure 13: ECG positioning for the limb leads (left) and the anterior chest leads (right).
During rest, the myocardium extracts approximately 60-75% of the oxygen delivered by coronary
blood flow. Thus there is little reserve for increased extraction when myocardial oxygen demand
is increased. The myocardium has a limited anaerobic capacity, and the heart is dependent on a
continuous supply of oxygen from the coronary circulation.

In the isovolumetrically contracting ventricle, myocardial oxygen consumption correlates with

peak pressure. That is, myocyte contraction (which generates intraventricular pressure) is the
primary haemodynamic factor determining myocardial oxygen consumption.

Due to high myocardial demand and extraction, reductions in blood flow are poorly tolerated and
can result in ischaemia. Cardiac oxygenation is therefore flow dependent. Coronary perfusion
pressure (CPP) itself is determined by the difference between the arterial supply (i.e. aortic) and
the ventricular pressure. For the left ventricle, CPP throughout systole equates to 0, as LV
pressure equates to aortic pressure.

During diastole, however:

LV CPP=Aortic pressure− left ventricular diastolic pressure

Therefore optimal LV coronary perfusion occurs during diastole. Sympathetic β-adrenoceptor-

mediates coronary arteriolar vasodilation and contributes to an increase in coronary blood flow of
up to 25%. Adenosineand ATP dependent K+ channels are involved in pathophysiological
ischaemic or hypoxic coronary dilation and myocardial protection during ischaemia.

In contrast, the RV receives perfusion during systole (as aortic pressure is almost three times that
of pulmonary artery pressure), which continues during diastole (aortic diastolic pressure minus
RV diastolic pressure). Due to adequate perfusion throughout the cardiac cycle, RV perfusion is
dependent on MAP rather than diastolic pressure.
Difference between right and left sides of the heart
The right ventricle (RV) is a low-pressure chamber and the pulmonary circulation is a low-
resistance system. The RV chamber is ellipsoidal in cross section and seems to wrap around the
left ventricle during systole. The RV is thin walled, as it only needs to generate a fraction of the
pressures generated by the left ventricle to produce the same output. RV is preload sensitive and
has poor tolerance for acute increases in afterload. Acidosis, hypoxaemia and hypercapnia can
independently increase the resistance of the pulmonary circulation and therefore the RV
afterload.

The right ventricle (RV) and the pulmonary circulation need to provide sufficient blood flow for
efficient gas exchange to take place. The totality of cardiac output passes through the lungs and
is driven by the right ventricle. RV and pulmonary circulation are part of a low-pressure, high-
volume system that performs with variable changes in blood volume resulting from respiration,
the effect of gravity and increased respiratory demands during exercise and disease.

The pulmonary circulation is a low-pressure, low-resistance system that must be capable of

accommodating the entire right ventricular output. Pulmonary artery pressure is normally 25/10
mmHg and the low arterial pressure is key to keeping hydrostatic pressure low, thereby
minimising the fluid transudates that may interfere with gas exchange. 

During times of high RV output, due to pulmonary arterial capacitance, the rise in blood volume
results in recruitment of smaller arterial vessels increasing the relative number of lung units
perfused adequately for efficient gas exchange. 

Blood distribution in the lung is relative to the dependent position of the patient, and the relative
proportion of drain directly from the LV) into the left circulation. Ventilation to perfusion (or V/Q
ratio) is described by three physiological zones ( West’s zones). Although the entire lung is
adequately perfused, optimal perfusion occurs at the lung bases relative to its perfusion. 

Although there is both sympathetic and parasympathetic innervation of the pulmonary circulation,
the main determinant in optimising ventilation and perfusion is hypoxic pulmonary
vasoconstriction (HPV). Within areas of low oxygen tensions (i.e. poor ventilation), hypoxia
causes a localised vasoconstriction and diverts blood to areas of better ventilation. This improves
gas exchange and reduces the degree of venous shunting. 

A small degree of venous admixture or shunting takes place in the form of venous return from the
bronchial circulation and the Thebesian veins (which drain directly from the LV) into the left
circulation. 

RV and pulmonary circulation properties:

 Preload sensitivity, e.g right ventricular infarction 

 Poor tolerance to acute afterload increases (e.g. massive pulmonary embolism) 
 Acidosis, hypoxaemia and hypercapnia increase pulmonary vascular resistance and RV
afterload. 
 Pulmonary circulation is sensitive to chemical stimuli (vasodilation with nitric oxide).
Using the pulmonary artery catheter to monitor
pulmonary circulation

Insertion Technique

Figure 14: Pulmonary artery catheter (yellow) within a sheath (white)

Before obtaining central access successfully with the PAC sheath, as with a central line, the
sheath must be prepared by flushing all lumens, attaching a sterile outer sheath and connecting a
zeroed transducer to the distal port. The flotation of the catheter is guided by the change in
pressure waves as it passes through the right heart. Therefore, knowledge of the physiology of
the right-sided circulation is essential.

The prepared catheter is advanced into the SVC via its sheath, and the balloon is inflated and
locked when you have established that the tip is not within the right atrium. The catheter is then
slowly advanced, allowing flow to carry the catheter through the right heart.
 Figure 15: The changes in measured pressure at the catheter tip during passage into the
pulmonary artery and during pulmonary artery occlusion (or “wedging”) An example of an arterial
waveform and its components

Figure 15 shows the change in the pressure waveform as the transduce tip of the catheter is
successfully placed:

 Central venous pressure trace (as it passes through the SVC and right atrium)
 Right ventricular trace as it traverses the tricuspid valve
 Pulmonary artery trace as the balloon proceeds through the pulmonary valve
 Pulmonary artery occlusion waveform (i.e. left atrial pressure trace).

During insertion, careful attention should be made to the graduations of length on the catheter.
Often, placement is not successful on first pass and frequently the first sign is that a significant
length has been inserted without the confirmatory waveform change expected. This can be
associated with a risk of knotting of the catheter.

If position is uncertain, then the balloon must be deflated and then withdrawn. It is paramount that
the catheter is NEVER withdrawn whilst the balloon is inflated, as this can cause valvular
damage.

Once a PA trace has been obtained, the catheter should slowly be advanced until the balloon
gently rests against the walls of an artery, at which point the waveform will convert to that of the
PA occlusion waveform (i.e. a CVP waveform representing the left atrial trace).

At this point, the balloon is deflated and reinflated to confirm the change between PA and LA
traces. Next, the length of catheter at the sheath should be noted; this will be helpful should the
catheter become displaced or require readjusting in the future.

Once the PAC has been correctly placed and wedged, this essentially results in a continuous
column of fluid from the distal transduced catheter port to the pulmonary vein (and therefore left
atrium) without influence from the pulmonary artery, which resembles the left atrial pressure
trace. This of course will vary with respiration; therefore, an average pressure is taken from the
transducer over a number of cardiac cycles to obtain a Pulmonary Artery Occlusion Pressure
(PAOP).

PAOP pressure measurement
The idea behind using an inflated balloon to measure the PAOP is that the inflated balloon
occludes the pulmonary artery flow (back of the balloon) so that a column of fluid is generated
and this transmits the pressure from the left atrium to the tip of the catheter.

In order for the PAOP to be an accurate measure of left atrial pressure, there are several
assumptions, the most important being:

 The catheter lies in a Zone 3 area according to the West classification, where:
 The pulmonary artery pressure is greater than the pulmonary venous pressure, and this is
greater than the alveolar pressure
 There is no mitral valve stenosis
 There is no transmitted pressure from the ventilation.

In practice, ventilation always affects readings of PAOP. To minimize this effect, PAOP is best
measured at the end of expiration.

Different scenarios are possible:

 Patient is spontaneously breathing without any assistance.
 In these patients, end of expiration usually corresponds to the highest point in the
pressure trace.
 Patient is completely ventilated.
 In these patients, the end of expiration corresponds to the lowest point in the pressure
trace.
 Patient is undergoing assisted mechanical ventilation during spontaneous breathing. In
this situation, it is important to recognise that the ventilator is triggered by an inspiration
(negative pressure) and then the assisted breath delivers a positive pressure. One needs
to identify the end of expiration correctly. In some patients, this may be very difficult.
Heart-lung interactions
The heart, lungs and large blood vessels share the same contained space within the thoracic
cavity. Each respiratory cycle (spontaneous or mechanical) and the associated changes in
intrathoracic pressure interact with the heart, lungs, great veins and aorta, causing changes in
cardiac output.

The pressure exerted by the blood within the cardiac chambers is the intramural pressure. The
external wall of the atria, ventricles and great vessels are subjected to intrathoracic pressure or
extramural pressure changes. The transmural pressure results from the difference between the
intrachamber and the extramural pleural pressure. It is important to highlight that our invasive
pressure devices record only the intramural or intravascular pressure.

Spontaneous Respiration:
Inspiration:

 Drop in intrathoracic pressure causes rise in transmural pressure of cardiac chambers

 Increase in diastolic filling (preload) of right ventricle (RV)
 Increase in afterload of left ventricle (LV)
 Net effect is a small drop in systolic blood pressure

Expiration:

 LV afterload returns to baseline

 Increased inspiratory venous return reaches LV (increase in preload)
 Net effect is a small rise in systolic BP
 During normal inspiration, the negative intrathoracic pressure causes an increase in the
diastolic filling of the right ventricle (RV). The increased volume of the RV causes the
interventricular septum to protrude toward the left, impede left ventricular (LV) filling and
decrease stroke volume. The process is reversed during expiration. The interventricular
septum protrudes now towards the right-increasing LV volume and stroke volume.

The effect of interventricular interdependence is of small physiological significance in health.

However, conditions such as pericardial effusion, high heart volumes and overinflated lungs can
produce significant effects in the cardiac output.

Mechanical Ventilation
Positive pressure ventilation results in:

 Rise in pleural pressure (note that this is more closely related to alveolar pressure and
lung volume than airway pressure)
 Rise in intra-abdominal pressure
 Increased lung volumes

These result in changes in preload, afterload, pulmonary vascular resistance, myocardial oxygen
consumption and total body oxygen consumption.
In any individual patient, the overall effects will depend on the patient's underlying
pathophysiology.

Effect on right ventricular preload

Venous return is determined by the pressure gradient between mean systemic venous pressure
and right atrial pressure. Positive pressure ventilation increases intrathoracic pressure and hence
increases right atrial pressure (Figure 14). This results in a decrease in venous return. However,
the effect is minimised by two concomitant effects:

 Compensatory increase in sympathetic tone (may by impaired by anaesthesia or

sedation)
 Increase in intra-abdominal pressure (Figure 16) resulting in a rise in mean systemic
venous pressure. As more than half of the venous blood volume is in the abdomen, this is
a very significant mechanism

Figure 16: he effect of positive pressure ventilation on right atrial and mean systemic venous
pressure in a normovolaemic patient
 

 In a patient with an open abdomen this second mechanism does not apply and the
sympathetic response is blunted. As a result, there is a significant fall in venous return.

In a volume-depleted patient:

 Collapse of intra-abdominal veins and superior vena cava occurs as a result of positive
pressure intrathoracic pressure
 Collapse of intra-abdominal veins appears to occur behind the liver as a result of positive
pleural pressure transmitted through the diaphragm and liver
 As a result, venous return falls despite the increased mean systemic venous pressure
(Figure 17).
Figure 17: Effect of positive pressure ventilation in hypovolaemic patient with collapse of intra-
abdominal veins and SVC

Effect on pulmonary vascular resistance

 Overinflation of the lung results in an increase in pulmonary vascular resistance due to
compression and stretching of pulmonary vessels. This may cause or exacerbate right
heart failure, resulting in RV distension
 Conversely, re-inflating atelectatic lung may reduce pulmonary vascular resistance
 Pulmonary blood vessels in atelectatic lung constrict as a result of local hypoxia
(pulmonary hypoxic vasoconstriction)
 Re-inflation of the lung reverses local hypoxia and therefore results in vasodilatation of
previously constricted vessels
 Marked pulmonary hypertension (e.g. following massive pulmonary embolus) may result
in severe right atrial hypertension, a right-to-left shunt through a patent foramen ovale and
hence arterial desaturation.

Effect on left ventricular preload

 Fall in RV stroke volume will result in fall in LV preload
 In addition, RV size will have a direct impact on LV preload as the heart is confined within
the pericardium
 Thus an increase in RV size may result in a decrease in LV preload (Figure 18-19) and
vice versa
Figure 18: Transverse section through thorax, viewed from below

Figure 19: Effect of RV dilatation

 

 As a result the effect of ventilation on LV preload will depend on both the pre-existing
cardiovascular status and the effect of ventilation on pulmonary vascular resistance. For
example, in in a patient with pulmonary hypertension, a reduction in venous return as a
result of positive pressure ventilation will reduce the size of a dilated RV and hence
increase LV compliance and LV preload
 At high lung volumes, lungs compress the heart which reduces LV end-diastolic volume.

Effect on left ventricular afterload

Under normal circumstances, maximal LV wall tension (T), or afterload, occurs at the end of
isometric contraction (before ejection) and is determined by: 

 Where: Ptm= transmural pressure, R=radius and H=wall thickness

 Transmural pressure=intraventricular pressure-pleural pressure

 Pleural pressure is increased by positive pressure
 Therefore, transmural pressure and afterload must be decreased by positive pressure
ventilation
 With LV dilation, maximal wall tension occurs during ejection, making the heart more
sensitive to changes in aortic pressure. Intrathoracic pressure affects both LV and aortic
transmural pressure. However, arterial pressure is kept constant by baroreceptor
feedback and as a result, the gradient across the aortic valve is increased and ejection is
facilitated. Again, maximal LV wall tension (afterload) is reduced.
Effect on myocardial oxygen consumption
 Myocardial oxygen consumption was previously thought to be determined by stroke work.
However, it is now known that it is determined by the sum of stroke work and elastance-
defined potential work. The latter is the potential energy in the ventricle at end-systole.
Figure 20 below illustrates this relationship. Myocardial oxygen consumption is
proportional to the shaded area. As mechanical ventilation generally decreases preload
and afterload, it shifts the pressure-volume loop to the left and down, decreasing
elastance-defined potential work and thus myocardial oxygen consumption.

Figure 20: Volume-pressure loop of left ventricle (LV) illustrating potential energy of the LV at end
systole
 

 In patients with coronary artery disease, reducing myocardial oxygen consumption may
improve the balance between oxygen demand and supply, resulting in an improvement in
LV function. Thus in these patients mechanical ventilation may increase LV contractility.
 In patients with respiratory failure, work of breathing is increased. Metabolic demand of
breathing may reach 25% of total oxygen consumption. If this work of breathing is
reduced, more oxygen will be available for other organs.
 Improvement in mixed venous saturation as a result in decrease in oxygen consumption
will result in an increased PaO2 if there is any significant degree of shunting
 In patients with severe cardiovascular disease, the terminal event is often respiratory
muscle failure. This can be precipitated by inappropriate positioning, e.g. putting the
patient head-down for insertion of a central line.

Overall effect on cardiac output

 Overall effect depends on whether cardiovascular system is more preload dependent or
afterload dependent
  Patients who have a normal cardiovascular system are usually preload dependent. In
these patients or in patients who are hypovolaemic, positive pressure ventilation will result
in a fall in cardiac output
 Patients with RV failure and hyperinflation may similarly suffer a fall in cardiac output
during mechanical ventilation
 Patients with congestive heart failure are usually afterload dependent and in these
patients, mechanical ventilation is associated with improved cardiovascular function.

Weaning
 It is important to note that all the cardiovascular effects of mechanical ventilation are
reversed when the patient is weaned from the ventilator
 Thus cardiac failure may be precipitated by weaning. This is the cause of weaning failure
in a significant proportion of patients

Starling equation and the pathophysiology of acute

pulmonary oedema
Pulmonary fluid homeostasis is an equilibrium between forces that drive fluid into the
alveolar spaces and the mechanisms responsible for its clearance. Fluid flux across the
pulmonary capillary is governed by Starling’s forces (Figure 21).

Figure 21: Starling forces across the capillary wall

Hydrostatic pressure in the microvessels (Pmv) tends to push fluid out of the vessels. This is
opposed by the perimicrovascular pressure (Ppmv). At the same time, microvascular oncotic
pressure (πmv) tends to pull fluid into the vessels, opposed by perimicrovascular oncotic
pressure (πpmv). The effect of the balance of these forces is affected by the permeability of the
microvessel wall, with the whole relationship being described by the Starling equation.

Equation 5:

The permeability of pulmonary capillaries to albumin is higher than systemic capillaries. As a

result, the gradient in oncotic pressure is lower and fluid shifts in and out of the capillaries are
largely dependent on hydrostatic pressures. Also, capillary permeability and changes in albumin
concentrations have little effect.

Under normal circumstances, there is a net flow of fluid from the capillaries into the lung
interstitium, but this does not normally result in pulmonary oedema because there are a number
of mechanisms which prevent this occurring. 

 Leakage of fluid into interstititum reduces interstitial oncotic pressure due to dilution;
reduces further leakage of fluid 
 Interstitial oncotic pressure is further reduced by removal of proteins by lymphatics
(Figure 22).

Figure 22: Removal of proteins by lymphatics in the alveolar interstitium

 

 Lymphatic system has large reserve flow capacity

 Interstitial space can increase its volume by as much as 40% (Figure 23) 
 Junctions between alveolar epithelial cells are tight junctions. As a result, fluid does not
pass into the alveolar space until the interstitial hydrostatic pressure is high.
 Figure 23: Interstitial space volume expansion
 

 Active transport mechanisms in alveolar epithelial cells remove fluid from the alveolar
space. These mechanisms involve active transport of sodium across type I and II
epithelial cells. The sodium enters the cell from the alveolar space via sodium channels
and then is pumped out of the cell into the interstitial space by a sodium potassium
ATPase. Water follows passively via specialised hydropores. This clearance is enhanced
by beta agonists, such as salmeterol and dobutamine
 Net result is that alveolar fluid does not accumulate, under normal circumstances, until
the left atrial pressure exceeds approximately 20 cm H2O. However, if the capillary
permeability is increased, e.g. due to acute lung injury, fluid accumulates at lower

pressures (Figure 24).

 Figure 24: Alveolar fluid accumulation in relation to left atrial pressure under normal
conditions and with increased capillary permeability
 
The capillary endothelium and the alveolar epithelium may occur in association with
hypoxia or high capillary pressures. As a result, alveolar fluid may continue to accumulate
even if the capillary pressure is restored to normal. However, this effect is probably
transient as 70% of disruptions have closed within minutes of restoring capillary pressure
to normal (Figure 25).

Figure 25: Capillary fractures in the alveolar epithelium and capillary endothelium

Conditions associated with capillary fracture include: 

 High altitude 
 Neurogenic conditions 
 Scuba diving 
 Mitral stenosis 
 Prolonged strenuous exercise 
 Flash pulmonary oedema 

Accumulation of alveolar fluid results in shunting. This is a result of collapse due to washing out of
surfactant and the filling of alveoli with fluid.
Pulmonary oedema due to acute heart failure
May be due to: 

 Systolic dysfunction 
 Diastolic dysfunction 
 Valvular heart disease 
 Left-to-right shunt 
 Combination of above.

Systolic dysfunction
 Decreased left ventricular contractility results in a rise of left ventricular end diastolic
pressure 
 This results in pulmonary oedema and hypoxaemia, which triggers inflammatory and
neurohumoral activation, leading to a further reduction in left ventricular contractility 
 Rise in LVEDP also results in a decrease in coronary perfusion pressure, resulting in an
increased likelihood of coronary ischaemia, which is exacerbated by hypoxaemia and
which reduces left ventricular contractility 
 At the same time, a reduction in left ventricular contractility decreases cardiac output,
resulting in a compensatory tachycardia which exacerbates coronary ischaemia 
  Reduction in cardiac output may also cause end organ dysfunction, which leads to salt
and water retention and further pulmonary oedema, as well as inflammatory and
neurohumoral activation and reduced LV contractility.

Diastolic dysfunction
Diastole involves active and passive mechanisms. The active component is most easily
understood from examining the events involved in excitation contraction coupling. 

Active, energy-requiring components of diastole are: 

 Release of calcium from troponin C

 Detachment of actin-myosin cross bridges 
 Active transport of Ca into SR
 Active transport of Ca out of cell
 Return of sarcomere to resting length.

The passive component of diastole results from deformation of cytoskeletal proteins, such at titin,
during contraction. These act like springs, exerting a recoiling force during diastole. 

Other important factors affecting relaxation are sensitivity to calcium and the amount of collagen
deposition in the extracellular matrix and the characteristics of that collagen. Collagen deposition
is enhanced and hence diastolic function is impaired by pressure overload hypertropy, aging,
heart failure and myocardial infarction. 

Extrinsic factors that affect LV diastolic function are RV function, due to ventricular coupling,
pericardial disease and the presence or absence of atrial contraction. 

In patients with diastolic dysfunction, acute pulmonary oedema is often accompanied or

precipitated by hypertension. 

Stress, such as acute volume loading, exercise or venoconstriction, acutely increases systemic
venous return and results in an increased RV stroke volume (Figure 26).
 Figure 26: Illustrates the effects of increased venous return in to the right ventricle

In the presence of diastolic dysfunction, the LV cannot accommodate this increased blood flow
without a rise in LAP. This results in a rise in pulmonary blood volume and when pulmonary
capillary pressure rises far enough, in acute pulmonary oedema (Figure 27).

Figure 27: Pulmonary congestion resulting from impaired left ventricle (LV) filling

Increasing pulmonary congestion promotes neurohumoral activation with elevated circulating

catecholamines and angiotensin II. This results in increased vascular tone, systolic hypertension
and a further increase in venous return.
 Figure 28: Neurohumoral activation resulting from pulmonary congestion

Coronary perfusion pressure (LV) = Diastolic arterial pressure – LVEDP

Therefore elevated diastolic pressure results in decreased coronary perfusion pressure, which
results in ischaemia further impairing relaxation, because ischaemia impairs the active
component of diastole. This results in a further increased in LVEDP and a downward spiral. 

Other important causes of diastolic dysfunction include hypertension, which results in left
ventricular hypertrophy and cardiomyopathy. 

Reversible factors include ischaemia, hypoxaemia, sympathetic over activity, activation of the
renin-angiotension system and new onset atrial fibrillation, which is often the precipitant.

Valvular heart disease
Acute heart failure may be due to acute mitral or aortic valve dysfunction, or due to
decompensated chronic valve disease. Pulmonary oedema is often very severe in patients with
acute valve dysfunction, as there is insufficient time for compensatory changes to occur. These
include heart chamber dilatation as well as pulmonary changes: 

 Alveolar fibrosis 
 Thickening of alveolar epithelial basement membrane 
 Intimal fibrosis and medial hypertrophy of arterioles 
 Abnormally thick-walled pulmonary veins 
 Lymphatic dilatation and muscularisation. 

As with diastolic dysfunction, acute pulmonary oedema due to decompensated chronic valvular
disease is often precipitated by an arrhythmia, such as atrial fibrillation.

The heart is not alone

Apart from then major interactions between the lung and the heart, addressed elsewhere in this
text, the heart interacts directly and indirectly with many other organs and systems. Of special
clinical significance are the interactions with the liver and the interactions with the kidney.

Heart-liver interactions
Being a highly metabolic organ, the liver function is affected in all patients with heart failure, either
as a result of an increased pre-load and/or as a decrease in cardiac output. 

In clinical practice, two major clinical scenarios are seen, sometimes in combination: 

 Congestion with elevated alkaline phosphatase (AP), gglutamyltransferase ( GGT), and

direct and indirect serum bilirubin, usually called nutmeg liver; this situation, when
chronic, can cause hepatic cirrhosis of the liver with fibrosis and an impaired liver
function. Clinically, the patients could be asymptomatic or complain of jaundice,
discomfort or pain in the right upper quadrant due to liver capsule distention and ascites.
As cirrhosis progresses, other symptoms can became apparent, due to decreased
 synthesis of clothing factors and albumin. At the extreme, fulminant liver failure has been
described as a consequence of acute cardiac failure. 
 Centrilobular hepatocellular damage and necrosis with elevated aminotransferases due to
low cardiac output, usually called “hepatic ischaemic hepatitis" or “hepatic ischaemic
injury”. A less severe clinical picture, characterised by chronic elevated
aminotransferases, can be sometimes seen in chronic liver failure and is associated with
poor outcome.  

There are still no specific treatments for these situations.

Heart-kidney interactions
These broad spectrum of interactions have been classified as “disorders of the heart and kidneys,
whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of
the other” and is classified in 5 types: 

 Acute cardio-renal syndrome (Type 1), or the acute worsening of heart function leading to
kidney injury and/or dysfunction 
 Chronic cardio-renal syndrome (Type 2), in which chronic abnormalities in heart function
lead to kidney injury or dysfunction 
 Acute reno-cardiac syndrome (Type 3), or the acute worsening of kidney function leading
to heart injury and/or dysfunction 
 Chronic reno-cardiac syndrome (Type 4), characterised by chronic kidney disease (CKD)
leading to heart injury, disease, and/or dysfunction 
 Secondary cardio-renal syndromes (Type 5), in which systemic conditions lead to
simultaneous injury and/or dysfunction of heart and kidney. In these cases, that includes
most of the patients with severe sepsis, the bidirectionality of signaling conducts to a
vicious cycle in which the acute kidney injury and the poor cardiac function have a
synergic effect in the deterioration of each other and in the deterioration of the function of
other organs and tissues. Many of the physiopathological aspects, markers or therapeutic
actions are still unknown but therapy is based mainly in the support and /or substitution of
the kidney and hearth function. 

Please be aware that with time, patients may move from one type to another of cardio-renal
syndromes.

Conclusion

Key points:
 Two forms of action potentials are generated within the heart; slow AP and fast AP
 Both myocyte contraction and relaxation are active, energy-dependent processes.
Ischaemia therefore impairs both systolic and diastolic function of the ventricles
 MAP is not an indicator of CO and a normal MAP does not exclude shock
 In practice, the main determinant of cardiac output is the venous return
 When faced with a patient in circulatory failure due to a low cardiac output, it is important
to recognise if the cause the low cardiac output has originated from a pump problem or
from a decreased venous return (preload)
 A rise in CVP could be the result of either an increased venous return after volume
expansion or the inability of the heart to cope with the venous return
 As described by Starling’s law, with increasing muscle fibre length there is a proportional
increase in the force of subsequent contraction
 Afterload is described as the cardiac work done to overcome the impedance to flow of
ejected blood, and is equated with the degree of LV wall tension
 Contractility is the intrinsic ability of the heart to contract independently of preload and
afterload
 The interrelationship between preload, afterload and SV is complex, and changing one
will often cause changes that affect the others too
 LV coronary perfusion occurs during diastole
 The pulmonary circulation is a low-pressure, lowresistance system that must be capable
of accommodating the entire right ventricular output
 Flotation of the PA catheter is guided by the change in pressure waves as it passes
through the right heart, and therefore knowledge of the physiology of the right-sided
circulation is essential
 The heart, lungs and large blood vessels share the same contained space within the
thoracic cavity. Interactions that can potentially affect the cardiac output occur in each
respiratory cycle (spontaneous or mechanical) and the associated changes in
intrathoracic pressure interact with the heart, lungs, great veins and aorta, causing
changes in cardiac output
 Pulmonary fluid homeostasis is governed by Starling’s forces
 Pulmonary oedema due to acute heart failure can be due to either systolic dysfunction,
diastolic dysfunction, valvular heart disease, left to right shunt or a combination of these
factors.