Control of cardiac output Flashcards
What are the basic elements of cardiac control?
Primary aim is to deliver oxygen (DO2) to the tissues at an adequate perfusion pressure (PP).
The amount of oxygenated bloods circulated depends on the arterial O2 content (CaO2) and the CO.
CO=HR x SV
PP= CO x PVR (peripheral vascular resistance)
Stroke volume determined by: preload, contractility and afterload.
Where is the end diastolic point on the pressure-Volume loop?
PV loop describes the mechanical performance of the heart.
EDP- the cycle starts at the EDP when the ventricle has received the blood volume from the atrium.
The Vent volume is high and the pressure is low.
Where is the isovolumetric contraction part of the pressure-volume loop?
Pressure within the ventricle rises without any change in volume.
Begins with closure of the AV valve (mitral valve in the case of the LV) and ends with the opening of the semilunar valve (aortic for LV).
This means that during this phase both valves remain closed.
What/ where is the ejection phase of the pressure-volume loop?
During this phase the ventricle pumps blood into the major blood vessel. Passes the top of the loop from right to left.
Begins with the opening of the semilunar valve and ends with its closure at the end systolic point.
What happens during isovolumetric relaxation on the pressure volume loop?
Represented by the vertical descending segment of the loop.
There is a fall in intraventricular pressure without a change in volume.
Ends with the opening of the atrioventricular valve.
Where is systole on the pressure-volume loop?
Consists of isovolumetric contraction and the ejection phase.
Where is diastole on the pressure-volume loop?
The diastole consists of isovolumetric relaxation and ventricular filling. Ventricular filling is further consists of three phases:
Rapid ventricular filling
Slow ventricular filling (diastasis), and
Atrial contraction
How does the pressure-volume loop derive parameters reflecting ventricular function?
- Stroke volume = End diastolic volume - end systolic volume
- Stroke work = area in the loop (volume x pressure)
- End diastolic volume = Total volume ventricle fills to before systole (before isovolumetric contraction starts)
- End systolic volume = total volume in ventricle once ejection phase ends.
What is the end diastolic pressure-volume relationship (EDPVR)?
The end diastolic pressure-volume relationship (EDPVR) records the volume and pressure at the end of diastole.
If PV loops are plotted at different volumes for a given ventricle, different EDPs are obtained (Fig 1a). These points form a PV relationship for the ventricle at end diastole when plotted. This is called the end diastolic PV relationship.
The gradient of EDPVR (Fig 1b) represent the elastance of a ventricle during filling. For a compliant ventricle the EDPVR gradient is approximately linear over the normal range of ventricular filling volumes. The steeper gradient is representative of poorly compliant ventricles during ventricle filling.
Can you think of any pathological conditions where EDPVR curve shifts up and to the left?
Pathological conditions which cause ventricular diastolic dysfunction such as ischaemia and ventricular hypertrophy shift the EDPVR curve up and to the left.
What is the end systolic pressure-volume relationship (ESPVR)?
The end systolic pressure-volume relationship (ESPVR) (Fig 1a) is obtained in a similar fashion to EDPVR (Fig 1b).
Here ESP, instead of EDP, points from different PV loops form the PV relationship for the ventricle at the end of systole. The gradient of the ESPVR curve represents the elastance of the ventricle at the end of systole. A change in gradient represents poor or better contractile function of the ventricle.
Can you think of any pathological conditions where the ESPVR curve shifts upwards and to the left?
Sympathetic stimulation and use of positive inotropic drugs shifts the ESPVR curve upwards and to the left.
Can you think of any pathological conditions where the ESPVR curve shifts downwards and to the right?
Negative inotropic drugs (β blockers) and inhalational anaesthetic agents shift the ESPVR curve downwards and to the right.
How does the Frank-Starling curve explain the intrinsic ability of the heart to change its contractility according to the continuously changing venous return?
In an isolated muscle fibre, tension developed on contraction is dependent on the initial length of the fibre. As the initial fibre length increases from fibre length at resting value, the tension developed during contraction increases and reaches a maximum. After this point tension declines despite any further increase in fibre length. This applies to both skeletal and cardiac muscles, although cardiac muscle is more sensitive to such stretch.
The Frank-Starling Law states that:
The contractile force of a cardiac muscle fibre is proportional to the initial fibre length
What is the Frank-Starling curve also known as?
The ventricular function curve
What are common examples on the x axis of the FS curve/VF curve?
In reality they all are same as they all use an index of resting fibre length. Examples on the x axis include:
Central venous pressure (CVP)
Right ventricular end diastolic pressure (RVEDP)
Left ventricular end diastolic pressure (LVEDP)
Right ventricular end diastolic volume (RVEDV)
Left ventricular end diastolic volume (LVEDV)
What are common examples on the y axis of the FS curve/VF curve?
Similarly, on the y axis an index of contractility is used. Examples include:
Stroke volume (SV)
Stroke work (SW)
Right ventricular end systolic pressure (RVESP)
Left ventricular end systolic pressure (LVESP)
What is the effect of a fluid challenge on the Frank-Starling curve?
For an empty cardiovascular system (CVS) the heart contractility is represented on the left ascending side of the ventricular function curve. The fluid challenge not only provides the volume available to improve the stroke volume but also increases the contractility by increasing the end diastolic volume, or resting muscle fibre length.
How does cardiac failure alter the ventricular function?
With cardiac failure the heart is pathologically dilated or the muscle fibres are overstretched, and ventricular function shifts to the right descending portion of the Frank-Starling curve.
Intravenous fluid therapy in such patients worsens the contractility and so SV decreases. This, along with the added intravenous fluid, causes the congestion in pulmonary and systemic circulation, depending on which ventricle fails.
What is the effect of ventricular contractility on the Frank-Starling curve?
For a given CVP (initial fibre length) the increase or decrease in contractility subsequently increases or decreases the stroke volume (tension developed) provided afterload also remains unchanged.
Fig 1 represents the Frank-Starling curves of a normal heart in different circumstances. The middle curve shows normal contractility, while top and bottom curves show increased and decreased contractility respectively. CVP is the same at point a, b and c, but stroke volume varies due to different contractile states.
What is Laplace’s law and how does it apply to the human heart?
In a living human it is not practically possible to measure the resting fibre length and tension developed in the ventricular wall.
CVP, EDV and EDP are all related to resting fibre length so they are used as an indirect index of resting fibre length on the x-axis of the ventricular function curve. A well-filled ventricle has increased resting fibre length as represented by higher CVP, EDV and EDP.
Similarly, it is not practically possible to measure the tension developed in cardiac fibre during the ventricular contraction. Based on Laplace’s law an indirect index of tension has been suggested.
Laplace’s law formula:
Laplace’s law relates tension, i.e. wall stress, to internal pressure in an elastic sphere by the following formula.
P= 2Th/r
P= Internal pressure
T= Tension (wall stress)
h= wall thickness
r= radius of sphere
Intraventricular pressure (P) ∝ tension (T)
So intraventricular pressure (RVESP, LVESP) can be used as an indirect index of tension on the y-axis of ventricular function curve.
How does Laplace’s law apply to different ventricular states?
Remember that P=2Th/r
(h= wall thickness, r = radius of ventricle sphere)
If P is constant then T is proportional to r/h
This means that for the same value of P, i.e intraventricular pressure, ventricular wall tension in a hypertrophic ventricle is smaller as compared to ventricular wall tension in a dilated ventricle (Fig 1).
Or in other words, a hypertrophic ventricle needs to generate less tension as compared to a dilated ventricle to create the same pressure.
Increased wall tension means higher oxygen consumption by the ventricles
What 3 things determine stroke volume?
- preload
- contractility
- afterload
What determine preload?
Blood volume
Intrathoracic pressure
Body posture
What determine contractility?
Sympathetic stimulation
Catecholamine
Inotropes
What determines afterload?
SVR
Intrapericardial pressure
Inotropes
Explain preload:
In its pure form preload is the initial length of muscle fibre, i.e. presystolic fibre length. It is impractical to measure such length in the real clinical situation. As the presystolic fibre length is directly related to EDV it would be good if we can use it as an index of preload but this is again practically difficult.
EDV is related to EDP by EDPVR. As the relationship between the two is not absolutely linear, EDP is a reasonable, but not perfect, index of preload under normal conditions.
In practice EDP is estimated on the left side of heart by measuring pulmonary capillary wedge pressure (PCWP) or pulmonary artery diastolic pressure (PADP). On the right side of the heart it is reflected by CVP.
The normal ventricle changes its performance in response to changes in preload according to the Frank-Starling law. An increase in intravascular volume, e.g from fluid therapy, causes a rise in EDV and so an increase in presystolic fibre length. This leads to an increase in SV.
What are the limitations in using indirect indices when describing/calculating preload?
The relationship between parameters like CVP, PCWP, EDP, EDV and preload gets distorted with abnormal ventricle compliance, valvular pathology, pulmonary hypertension, positive intrathoracic pressure, etc.
In such situations we have to be careful while using these indices as a measure of preload.
What is afterload?
Afterload is a measure of how forcefully the ventricle contracts during systole to eject blood. Normal ventricle contractility increases with afterload, through the Anrep effect.
SVR and MAP are common indices to measure afterload.
The tension developed in muscle fibres during ventricle contraction is impractical to measure in real clinical scenarios. Intraventricular pressure (P) is related to wall stress (T, i.e. tension per unit area) through Laplace’s law: P=2Th/r
End-systolic intraventricular pressure is the practical concept which is used to estimate afterload, i.e. wall stress, and indices such as systemic vascular resistance (SVR) and mean arterial pressure (MAP) relate well to intraventricular pressure in the normal heart.
SVR is calculated as:
(MAP-CVP)x80/CO dyn.s/cm5
Arerial pressure and ventricular pressure during systole follow each other and are indirect indices of ventricular wall tension.
Which drug is commonly used in septic patients to correct excessive vasodilatation, i.e. decreased afterload?
Noradrenaline.
In septic patients excessive systemic vasodilatation (decreased SVR) lowers the blood pressure despite normal or even high CO. The lower blood pressure means lower perfusion pressure and inadequate supply of oxygen and nutrients to the peripheral tissue.
When used in appropriate doses noradrenaline raises the SVR and hence the BP.
What is contractility?
Contractility describes the power of the ventricle for a given preload and afterload.
Contractility is increased by:
Sympathetic stimulation and parasympathetic blockade
Inotropes
Increased levels of Ca2+
Contractility is decreased by:
Sympathetic blockade and parasympathetic stimulation
Decreased Ca2+ levels
What is the Anrep effect?
An increase in afterload should normally lead to a reduction in SV as the ventricle has to pump the blood against higher resistance, but in reality an increase in afterload usually causes a rise in SV initially due to increase in contractility.
In summary, contractility can change in isolation as with sympathetic or parasympathetic stimulation, or as a result of changes in preload and afterload.
How is HR controlled?
Normally the HR is controlled by spontaneous, i.e. autonomic control, depolarization of SA node cells in the right atrium, which itself is under control of medullary nuclei and higher centres in the hypothalamus and cortex.
The normal heart is innervated by noradrenergic sympathetic and cholinergic parasympathetic fibres.
At rest both sympathetic and parasympathetic fibres discharge, but there is dominance of parasympathetic, i.e. vagal, tone which maintains the heart rate of 60-90 bpm in most adults. It means that complete denervation of the heart produces a heart rate of more than 100 bmp due to abolishment of dominant parasympathetic tone.
Described the parasympathetic nerve supply to the heart:
Originates in the dorsal motor nucleus of vagus and the nucleus ambiguus in the medulla (Fig 2). These fibres reach the heart via right and left vagus. Parasympathetic stimulation decreases the slope of phase 4 of SA node action potential and also increases the hyperpolarization which results in a slowing of the heart rate.
Described the sympathetic nerve supply to the heart:
Originates in the thoracic (T1-T5) sympathetic chain (Fig 3). These fibres pass through the stellate ganglion and supply not only the SA and AV nodes but also innervate the ventricular muscle mass. Sympathetic stimulation increases the slope of phase 4 of action potential which increases the heart rate.
Can you think how atropine changes the heart rate?
Atropine is a parasympatholytic anticholinergic drug which inhibits the effect of parasympathetic tone on the heart, while the sympathetic effect remains intact. In other words, it is chemical denervation of the parasympathetic nerve supply only.
A completely denervated heart beats at a rate of more than 100 bpm. A parasympathetic block with atropine would produce a much higher rate in an otherwise normal heart due to unopposed sympathetic activity.
Heart rate is increased by (sympathomimetic effect):
Fever
Exercise
Inspiration
Adrenaline, dobutamine, adrenaline
Thyroid hormone
Decreased BP due to decreased baroreceptors activity.
Fear, anger, excitement
Heart rate is decreased by (sympatholytic or parasympathomimetic effect):
Vagal stimulation (vasovagal arrest, vasovagal syncope)
Expiration
B blockers, neostogmine
Hypothyroidism
Increased BP due to increased baroreceptors activity.
What happens to the stroke volume with a very persistently high HR?
From it is evident that an increase in HR leads to an increase in CO, but this holds true only to a certain extent. As the heart rate becomes very high, i.e. usually more than 150 bpm, SV falls due to decrease in end diastolic volume as a result of shorter diastolic filling time.
At very high HR there is reduction in both systolic time and diastolic time. However, the latter is affected more and so limits the filling time and SV for ventricles.
The Treppe Effect:
The Treppe effect, also known as the Bowditch effect, is an increase in inotropy, i.e. contractility, that occurs in response to an increase in HR. This usually occurs from an HR of 40-140 bpm. The reduced diastolic time in response to an increase in HR leads to more available intracellular calcium for excitation-contraction coupling.
Overview of cardiovascular coupling:
LV performance is affected by the opposing arterial load, and the arterial properties themselves are influenced by left ventricle performance. Interaction between the LV and the arterial system is known as ventriculo-arterial coupling. This interaction can be illustrated by plotting the ventricular elastance (Ees) and arterial elastance (Ea) on the same diagram.
To understand this it is important to consider the opposing ventricular and arterial elastance individually:
Ees is determined from the slope of the ESPV relationship curve (Fig 1)
Ea is a measure of arterial afterload that is imposed on LV. It is expressed by the arterial end-systolic pressure (Pa) - stroke volume (SV) relationship (Fig 2)
Because the ventricle and arterial pressure system oppose each other when their elastance curves are displayed on the same diagram (Fig 3), equilibrium lies at ESP, at which point the ventricle pressure is equal to the arterial pressure. In this diagram Ea is the negative slope of the line joining the EDV and ESP points.
Changes in arterial pressure on cardiovascular coupling:
Changes in the arterial pressure results in a shift of the position of ESP. When preload (EDP) is kept constant, then displacement of ESP tells us the degree to which ventricular contractility or arterial elastance is responsible.
Maximum work occurs when Ees = Ea, though this is not an efficient state. Maximum mechanical efficiency or optimal ventriculoarterial coupling occurs when:
Ees = 2 x Ea
Mismatch or uncoupling of these opposing forces may lead to ventricular dysfunction, as with, for example, vasodilatation due to sepsis.
