Cardiac output: it

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Cardiac output its REGULATION AND CONTROL OF
CARDIAC FUNCTION

• Dr Priyanka

University College of Medical Science s GTB
Hospital, Delhi
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INDEX

• Definition of cardiac output
• Determinants of stroke volume
• Preload Venous return , EDV
• Contractility EF
• Afterload PVR SVR
• Determinants of Heart Rate
• sympathetic innervation
• parasympathetic innervation
• Control of cardiac function
• Neural control
• Hormonal control
• Cardiac Reflexes

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Cardiac output

• Amount of blood pumped by each ventricle per
  minute into circulation
• 5-6 l/min
• 10-20 less for females
• Principle of continuity
• Law of conservation of mass--volume of blood
  ejected by left heart volume of blood received
  by right heart

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Clinical significance

• If RV output increases LV output by
• 0.1 ml/ minute/beat
• Then RV output will increase LV output by
• 7 ml/minute
• In 3 hrs, RV output increases LV output by
• 7360 1260 ml
• This example demonstrates that even small
  imbalances in stroke volumes of the two hearts
  could lead to accumulation of blood in one
  portion of CVS
• LV output is exactly equal to the RV output

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• Cardiac index
• Measure used to compare cardiac output of
  different sized individuals
• CI CO/BSA
• 2.5 3.5 l/min/m2
• Stroke volume
• Amount of blood pumped by each ventricle per beat
  
• 70 - 90 ml

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Control of cardiac output (CO HR SV)

• Control of heart rate (extrinsic)
• Control of stroke volume(intrinsic)

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Control of stroke volume

• Heterometric regulation
• factors affecting venous return (preload)
• Homometric regulation
• factors affecting cardiac contractility
• Factors affecting afterload

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Preload

• Ventricular wall stress at end-diastole
• Force imposed on a resting muscle i.e. prior to
  the onset of muscle contraction which stretches
  the muscle to a new length
• Determined by
• ventricular EDV
• EDP
• Wall thickness

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Preload and afterload
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Factors affecting preload

• Total blood volume
• Venous return
• Intra thoracic pressure ( thoracic pump)
• Cardiac pump
• Pumping action of skeletal muscles
• Ventricular filling(compliance)
• Body position
• Intra pericardial pressure

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Total blood volume (Clinical implication)

• Perioperative ventricular hypervolemia (? TBV)
• Regurgitant valvular heart lesions
• Ischemic heart disease
• Viral and idiopathic cardiomyopathy
• End stage stenotic valvular lesions

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• Causes of perioperative ventricular hypovolemia
  (? TBV)
• Diminished intravascular volume
• Excessive surgical bleeding
• Extravasation
• Excessive diuresis
• Reduced fluid intake
• Reduced venous return
• Increased capacitance (anaesthetics,
  vasodilators, sympatholytics)
• increased resistance to venous inflow(PEEP,
  acute pulmonary HTN, PE, atrial masses,
  tamponade)

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Venous return

• Quantity of blood flowing from the veins into the
  right atrium each minute
• CO is controlled by venous return heart is not
  the primary controller of CO
• Peripheral factors are more important in
  controlling cardiac output
• Cardiac output regulation is the sum total of all
  local blood flow regulations
• In built mechanism of heart

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HETEROMETRIC REGULATION Factors affecting
preload and systolic performance

• Frank starling law
• (Described by Otto Frank and Ernest Starling )
• ? length ? force of cardiac contraction
• Effect depends on venous return is independent
  of cardiac innervation
• In myocardium, actin and myosin filaments are
  brought to a more optimal degree of
  interdigitation
• In normal heart, diastolic volume is the
  principal force that governs the strength of
  ventricular contraction

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Frank-Starling Law (heterometric regulation)
Force of contraction of myocardium
Initial length of myocardial fibers
Extent of preload (venous return)

• Increased by
• Increase in total blood volume
• Increase venous tone
• Increase pumping of skeletal muscle (e.g.
  exercise)
• Atrial contraction
• Decrease in intrathoracic pressure during
  inspiration

• Decreased by
• Decrease in total blood volume
• Increase in intra-pericardial pressure
• Increase in intrathoracic pressure during
  inspiration
• Body position sitting or standing

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Pressure volume curve showing the influence of
diastolic volume on the strength of ventricular
contraction

• 
  
• systolic pressure
• (total tension)
  strength of ventricular
• 
  contraction
• pressure
• diastolic pressure (passive
  tension)
• 
  volume
• FRANK STARLING LAW OF HEART

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Significance

• LVF causes accumulation of blood in LV
• ?
• ? Blood supply to vital organs
• ?
• accumulation of blood in LV
• ?
• operation of Frank Starling mechanism
• ?
• greater LV output

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• Ventricular function curves describing the
  relationship between preload and the systolic
  performance of heart

Failing heart
Stroke volume
End-diastolic volume
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Factors affecting preload

• Total blood volume
• Venous return
• Intra thoracic pressure (thoracic pump)
• Cardiac pump
• Pumping action of skeletal muscles
• Ventricular filling(compliance)
• Body position
• Intra pericardial pressure

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Factors affecting preload

• Intrathoracic pressure
• Thoracic pump
• Inspiration -2 mmHg
• ?
• -5 mmHg
• Diaphragm descends down ? ? VR

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Factors affecting preload

• Cardiac pump (flow of blood in veins is towards
  heart)

Vis-a-tergo Force from behind which drives blood
forwards ( m. imp) imparted by-- Contraction of
heart Elastic recoil of arterial wall Pressure of
blood in veins is more than RA pressure
Vis-a-fronte Force acting from front 2 components
Ventricular systolic suction
Ventricular diastolic suction
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Factors affecting preload

• Role of skeletal muscle contraction
• Rhythmic contraction of skeletal muscles
• ?
• venous segments are squeezed
• ?
• rise of pressure forces blood towards
  heart
• ?
• venous valves prevent backflow

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ROLE OF SKELETAL MUSCLES
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Factors affecting preloadVentricular compliance

• Stretch imposed on cardiac muscle determined not
  only by the volume of blood in the ventricles,
  but also by the tendency of the ventricular wall
  to distend or stretch in response to ventricular
  filling
• Compliance ?EDV /?EDP

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Diastolic pressure volume curve in the normal and
non compliant ventricle

• Compliance ? EDV /?EDP
• Normal
  ventricle
• 
  decreased
• 
  compliance
• End Diastolic
• Volume Stiff ventricle
• End Diastolic Pressure

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HOMOMETRIC REGULATIONCardiac contractility

• Intrinsic property of the cardiac cell that
  defines the amount of work heart can perform at
  a given load
• Determined primarily by the availability of Ca 2
• Attributed to interactions between contractile
  proteins arranged in parallel rows in the
  sarcomere

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CARDIAC CONTRACTILITY

• Indices of contractility are classified according
  to the phase of cardiac cycle
• Isovolumic contraction phase dP/dt
• dP/dt 8 contractility 8 initial length of the
  cardiac muscle
• Ejection phase indices
• EFSV/EDV
• EF is imp in predicting the prognosis of CAD
• Load independent indices
• Time varying elastance the ratio of
  ventricular pressure over volume, which varies
  throughout the cardiac cycle
• Slope of ESPVR line 8 contractility

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• ESPVR is obtained by connecting all end-systolic
  points during a rapid decrease in preload

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• Slope of ESPVR line determines cardiac
  contractility

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FACTORS AFFECTING MYOCARDIAL CONTRACTILITY

• Effect of changes in myocardial contractility on
  the Frank-Starling curve

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Afterload

• Load which acts on muscle after it begins to
  contract
• Opposes muscle contraction
• Systolic ventricular wall stress
• Laplace law
• s P . r/2h
• s Peak systolic transmural wall tension of
  the ventricle
• P transmural pressure across the ventricle at
  the end of sysole
• r chamber radius at the end of diastole
• h thickness

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Preload and afterload
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Factors affecting afterload

• Wall stress
• Impedance
• Compliance
• Effective arterial resistance
• Systolic intraventricular pressure
• Systemic vascular resistance
• Pulmonary vascular resistance

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Factors that contribute to ventricular Afterload

• transmural wall tension (Afterload)
• systolic pressure chamber radius
• PLEURAL PRESSURE END DIASTOLIC VOLUME
• Outflow impedance
• VASCULAR RESISTANCE
• VASCULAR COMPLIANCE

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IMPEDANCE

• Principal determinant of ventricular afterload
  that opposes phasic changes in pressure and flow
• Most prominent in large arteries close to heart
• Opposing the pulsatile output of ventricles
• Influenced by
• Compliance- force which opposes the rate of
  change in flow (pulsatile flow)
• Resistance- force which opposes the steady
  flow (non pulsatile flow)

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Vascular Resistance

• Resistance to flow in a hydraulic circuit
• It is expressed by the relationship between
  pressure gradient across the circuit (? P) and
  the rate of flow(Q)
• ? P8 Q (Ohms law )
• ? P QR, where
• ? P Pressure, QFlow, RResistance
• Applying Ohms law to CVS
• SVR MAP RAP/ CO
• PVR PAP LAP / CO
• Clinical implication Shift from a low CO/ high
  SVR to a more favourable high CO / low SVR
  condition by using vasodilators (heart failure)

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Pleural pressure

• Afterload (transmural) is affected by pleural
  pressure which acts on the outer surface of heart
• -ve pleural pressure ve pleural pressure
• ? ?
• Opposes ventricular emptying
  facilitates ventricular emptying
• ? ?
• ? systolic blood pressure ? systolic blood
  pressure

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• Respiratory variations in BP during positive
  pressure ventilation

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SUMMARISEFactors affecting cardiac stroke output
Definition Clinical parameters
Preload Load imposed on resting muscle that stretches the muscle to a new length End diastolic pressure
Contractility The velocity of muscle contraction when muscle load is fixed Cardiac stroke volume when preload and afterload are constant
Afterload The total load that must be moved by a muscle when it contracts PVR SVR
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Interactions between the components that regulate
cardiac output and arterial pressure
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Control of heart rate

• Role of cardiac innervation
• Role of medullary cardiovascular centres

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Cardiac innervation

• Sympathetic

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• Parasympathetic

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Medullary regulation

• Medullary cardiovascular centre also known as
  vasomotor centre
• Cardiac vagal centre

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Organisation of vasomotor centre

• Vasoconstrictor area area C1
• located in RVLM
• Contain glutaminergic neurons which excite
  spinal sympathetic neurons
• inherent tonic activity
• ? sympathetic activity pressor effect
  on CVS
• Vasodilator area area A1
• located in CVLM
• Inhibit the vasoconstrictor activity of area
  c1

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• Sensory area- area A2 ( nucleus tractus
  solitarius )
• Receives sensory signals from IX X nerves
• provides reflex for controlling activity of
  both vasodilator and vasoconstrictor areas

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VAGUS

• Dorsal motor nucleus of vagus
• Nucleus tractus solitarius
• receives afferents from baroreceptors
• fibres project to NA DMNV
• Nucleus Ambiguus (CARDIAC VAGAL CENTRE)
• Sends vagal impulses to heart
• Neurons are not tonically active

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Factors affecting VMC CVC

• Baroreceptors
• arterial baroreceptors carotid sinus and
  arch of aorta
• cardiac baroreceptors
• Chemoreceptors carotid and aortic bodies
• Cortico hypothalamic descending pathways

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Feedback control of blood pressure
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Pathway relating interaction of cardiac and
respiratory reflexes
I neurons

-

Chemoreceptors


Nucleus tractus solitarius
Nucleus ambiguus
Baroreceptor
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Cortico hypothalamic Descending Pathways
CEREBRAL CORTEX
Corticohypothalamic descending pathways
HYPOTHALAMUS
()
()
PRESSOR AREA
DEPRESSOR AREA
Baroreceptors ? (-) Chemoreceptors ? ()
(-)
Medulla
() ? Baroreceptors (-) ? Chemoreceptors
CVC
(-)
()
SYMPATHETIC PRE GANGLIONIC NEURONS
Spinal cord
(-)
Heart
()
Blood vessels
()
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Control of cardiac function

• Neural regulation
• Hormones affecting cardiac function
• Cardiac reflexes

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ADRENORECEPTOR SIGNALLING CASCADE

• ADRENORECEPTORS

a 1 ADRENORECEPTOR
a 2 ADREORECEPTOR
ß ADRENORECEPTOR
ß2
a 2A,2B,2D
ß1,3
a 1A, 1B
a 1D
Gi
Gs/i
Gs
G q / 11
Gi
AC
AC
cAMP, AC
PLC ß
PLC ß
?cAMP / PKA
cAMP / PKA / MAPK
IP3, DAG, MAPK
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• MUSCARINIC RECEPTORS
• M1,3,5 receptors Gq11 protein
  PLC,DAG.IP
• M2receptors Gi protein cAMP

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Cardiac hormones

• Polypeptides secreted by normal cardiac tissue
  into the circulation in the normal heart
• Hormones secreted by cardiomyocytes
• Natriuretic peptides
• Aldostrone
• Adrenomedullin

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Angiotensin II

• Key modulator of cardiac growth and function
• Acts on AT I AT II receptors
• AT I receptors - ve inotropic ve
  chronotropic effect
• Mediates cell growth and proliferation
• Involved in cardiac hypertrophy
• AT II receptors - Counteregulatory apoptotic
• Fetal heart

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Natriuretic peptides

• ANP BNP
• Secreted by cardiomyocytes of the atria and
  ventricles of heart respectively Response to
  pressure or volume overload
• Stimulated by increased stretch and
  sympathetic stimulation
• Acts on NRP 1,2,3 receptors
• Stimulates guanylyl cyclase and ? cGMP
• Clinical significance
• Used in the diagnosis and in predicing the
  prognosis in patients of heart failure
• NEP inhibitors, nesiritide used in CHF

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Adrenomedullin

• ve chronotropic effect
• ? NO production
• Potent vasodilator
• Acts on CRLR receptors
• Local regulator of inflammation
• ?sed in
• septic shock
• pregnancy
• haemorrhagic shock
• high altitude

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Aldosterone

• ?s the reabsorption of Na and water and ?s
  secretion of K
• Secretion is stimulated by ? in Angiotensin,
  ACTH, K
• ? Expression or activity of cardiac NaKATPase,
  NaK cotransporter , Cl- HCO3- and NaH
  antiporter
• Clinical significance
• Modifies cardiac structure
• Induce fibrosis in both ventricles
• Impairment of cardiac contractile function

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SEX STEROID HORMONES

• ESTROGEN
• PROGESTERONE
• TESTOSTERONE
• Account for gender differences in cardiac
  physiology
• ESTRADIOL
• Interacts with its receptors to effect post
  synaptic target cell responses---- influences
  sympathoadrenergic system
• BP by NOS
• Action on Ca channels

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Cardiac Reflexes

• Bainbridge reflex
• Stimulation of stretch receptprs in RA wall
  cavo-atrial junction ? in right sided filling
  pressure

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Bezold-Jarisch reflex / coronary chemoreflex,
pulmonary reflex Inj of vertradine, serotonin,
nicotine into coronary artery, pulmonary artery
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Cushing Reflex ? ICP ? cerebral ischemia /
hypoxia hypercapnia of RVLM
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Oculocardiac reflex Stretch Reflex ? in EOM
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SUMMARY ----REGULATION OF CARDIAC OUTPUT

• Neural Regulation
• ( VMC, CVC )

PRELOAD
CARDIAC OUTPUT
Cardiac Hormones
STROKE VOLUME
CONTRACTILITY

HEART RATE
Cardiac Reflexes
Chemoreceptors
AFTERLOAD
Baroreceptors
SYMPATHETIC AND PARASYMPATHETIC SYSTEM
Corticohypothalamic Descending Pathways
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REFERENCES

• Kaplan JA. Kaplans cardiac anesthesia. 5th ed.
  Cardiac physiology. p. 71-90.
• Mohrman DE, Heller LJ. Lange cardiovascular
  physiology. 2006. The heart pump.
• Guyton and Hall. Textbook of Medical Physiology.
  11th edition. Heart muscle the Heart as a pump
  and function of the Heart valves.
• Ganong WF. 22nd edition. The heart as a pump.
• Miller RD. Millers Anesthesia. 7th edition.
  Cardiac physiology.

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