Cardiac Output, Index, and Volumes

Cardiac Output

• Cardiac output is the product of stroke volume and heart rate
• With an average stroke volume of 70 ml and a heart rate of 72 beats per minute, cardiac output is 5040 ml/min
• The blood flow delivered by the left ventricle of the heart into the systemic circulation
• An average person will have a cardiac output of 5 liters/min
• The cardiac output equals the blood flow delivered by the right ventricle into the pulmonary circulation
• During physical activity cardiac output can increase up to 5x higher
• In trained persons cardiac output can increase up to 7x higher

Cardiac Index

• Resting cardiac output correlates with body size, mainly body surface
• Cardiac index normalizes cardiac output based on body surface area (BSA)
• Cardiac index is calculated as cardiac output divided by BSA
• Ideal range for cardiac index: 2.5 – 3.5 L/min/m² for healthy adult men

Cardiac Volumes

• Endsystolic volume
• End-diastolic

Systolic and Diastolic Volumes

• The heart undergoes atrial systole, isovolumetric contraction, ejection, isovolumetric relaxation, rapid filling and slow filling

End-Diastolic Volume (EDV)

• EDV is the volume of blood in the right and/or left ventricle at the end of the filling in diastole
• Greater EDV causes greater distension of the ventricle
• EDV determines PRELOAD, which is the lengths of the sarcomeres in cardiac muscle before contraction (systole)
• Typical EDV value is around 120 ml
• Normal EDV range: 65–240 ml

Determinants of EDV

• Venous return is the volume returning from veins into the atrium.
• Venous compliance increased capacitance of veins, thereby decreasing venous return and EDV
• Extracellular fluid (ECF) volume, also known as blood volume, increases EDV
• The filling time of atria

Stroke Volume

• Stroke volume (SV) is the volume of blood pumped from one ventricle of the heart with each beat
• Stroke volume calculated using measurements of ventricle volumes on an echocardiogram by subtracting ESV from EDV
• Stroke volume refers to each of the heart's two ventricles, but it usually refers to the left ventricle
• The stroke volumes for each ventricle are generally equal
• Stroke volume is an important determinant of cardiac output
• Stroke volume itself correlates with cardiac function
• Typical stroke volume value: 70 ml
• Normal stroke volume range: 55 -100 ml

Determinants of Stroke Volume

• Heart size (larger in males than females)
• Preload (end-diastolic volume), and a reduced heart rate prolongs ventricular filling
• Afterload, which is the aortic pressure during systole
• Duration of contraction (calcium, potassium channels affect this duration)
• Contractility is the ability of the heart to eject a stroke volume at a given afterload and preload, which is influened by cardiac glycosides, catecholamines, prostaglandins, phosphodiesterase inhibitors

End-Systolic Volume

• (ESV) is the volume of blood in the right and/or left ventricle at the end of ejection (systole)
• End-systolic volume is affected by afterload and the contractility of the heart
• Typical ESV value: 50 ml
• Normal ESV range: 16 - 140 ml

Ejection Fraction

• Ejection fraction is the fraction of the end-diastolic volume ejected in each stroke volume
• Ejection fraction is stroke volume divided by end-diastolic volume
• A normal ejection fraction amount is ~ 58% - 60% under physiological conditions
• Ejection fraction is related to contractility

Determination of Cardiac Output

• The Fick principle factors in Fick's law of diffusion
• With The Fick method, variables to be measured consist of
• Oxygen consumption in ml/min (VO2)
• Oxygen concentration of blood taken from the pulmonary artery (deoxygenated blood; Cv)
• Oxygen concentration of blood in a peripheral artery (oxygenated blood; Ca)

Determination of Cardiac Output (cont.)

• VO2 = oxygen consumption (ml/min)
• CO = cardiac output (l/min)
• Ca = oxygen concentration of arterial blood (ml/l)
• Cv = oxygen concentration of mixed venous blood (ml/l).
• VO2 = CO × (Ca - Cv)
• CO = VO2/(Ca - Cv)

Indicator Dilution Method

• The output of the heart is equal to the amount of indicator injected divided by its average concentration in the arterial blood after a single circulation through the heart.

Pulmonary Artery Thermodilution (Trans-Right-Heart Thermodilution)

• Modification of the indicator dilution method
• The indicator diluted is cooled or heated fluid
• Pulmonary artery catheter (Swan-Ganz)
• Cold fluid injected into the RA and the temperature is measured at known distance away (6–10 cm) with temperature sensor set apart at a known distance
• Cardiac output is calculated from a measured time/temperature curve
• High CO registers temperature change rapidly – the degree of change in temperature is directly proportional to the cardiac output.

Regulation of the Cardiac Output

• Heart rate is regulated via regulation of the cardiac chronotropy
• Stroke volume is controlled via regulation of the cardiac contractility or inotropy

Regulation of Heart Rate

• Chronotropic effects produce changes in heart rate
• Positive chronotropic effects increase in rate of spontaneous diastolic depolarization (SDD)
• Increased heart rate reduces duration of cardiac cycle and Diastole reduced relatively more than systole
• Critical value of HR = 180/min
• Negative chronotropic effects Decrease in rate of SDD or shift in Maximum Diastolic Potential (MDP)

Regulation of Heart Rate cont.

• Positive chronotropic effects speeds up spontaneous diastolic depolarization (SDD)
• Sympathetic stimulation releases noradrenaline, causing Beta 1 (β1) receptors
• Adrenaline from adrenal medulla causes Beta 1 (β1) receptors
• Phosphodiesterase inhibitors (methylxanthines like caffeine) decreases cAMP degradation, which increases heart rate
• Increased body temperature

Regulation of Heart Rate cont. 2

• Negative chronotropic effects lowers spontaneous diastolic depolarization (SDD) or shift in Maximum Diastolic Potential (MDP)
• Parasympathetic stimulation uses muscarinic (M) receptors coupled to Gi protein
• Decreased body temperature

Autonomic Regulation of the Heart

• Heart rate, Conduction velocity (AV node), Contractility are increased by Sympathetic regulation by with Beta 1 receptors
• Heart rate, Conduction velocity (AV node), Contractility are decreased by Parasympathetic regulation with Muscarinic receptors

Regulation of Stroke Volume

• Preload, via the Frank-Starling law
• Afterload
• Heart rate
• Autonomic innervation
• Drugs and hormones
• Energy

Regulation of Stroke Volume: Preload

• Preload equates to end-diastolic volume, the contractile force developed by a muscle fiber is related to its initial length.
• Work of Otto Frank extended by Ernest Starling and their Frank-Starling relationship states that increased venous return leads to distension of the ventricle (increased EDV) followed by an increased contraction
• Mechanism matches cardiac output to venous return.

Contributors To Frank-Starling Law

• Theodor Schwann explained length-tension relationship in skeletal muscle, recognition of the role of resting length in subsequent contraction
• Carl Ludwig said in "... a strong heart that is filled with blood empties itself more or less completely, in other words, [filling of the heart with blood] changes the extent of contractile power."
• Julius Cohnheim described the interplay between cardiac filling and ejection

Contributors To Frank-Starling Law cont.

• The general consensus is that the ventricle, in the normal condition, expels at each contraction the whole, or very nearly the whole, of its contents
• quantity of blood thrown out at each systole will depend on the degree of distension assumed by the relaxed ventricle
• Otto Frank showed dependence of peak isovolumic pressure on ventricular volume
• Ernest Henry Starling explained why cardiac output remains constant over a fairly broad range of arterial pressures, heart rates, and temperatures

The Frank-Starling Law

• The Frank-Starling law is thus the same as the law of muscular tissue generally, that the energy of contraction, however measured, is a function of the length of the muscle fiber
• Dario Maestrini demonstrated the relationship between the volume of blood contained in the heart cavities and the contractile energy of the heart
• The Frank-Starling (Maestrini) Law states that the lengthening of the heart fibers is the cause of the dilation of the heart, corresponds to a greater contractile energy
• The Frank-Starling law also has to do with:
• Saromere length
• Calcium sensitivity
• Role of titin and its position in the thick myofilament

Tension-Length Curves

• Cardiac muscle has high resistance to stretch when compared with skeletal muscle
• When cardiac or skeletal muscle stretches, there is an increase in resting tension (RT = passive tension)
• After muscle stimulation, it generates maximum contraction, generating more tension (total tension-TT)
• The bell-shaped dependence of active tension on muscle length is consistent with the sliding filament theory of cardiac and skeletal muscle
• Cardiac muscle is, difficult to stretch beyond its optimal sarcomere length

Regulation of Stroke Volume: Afterload

• Afterload is the force required to begin ventricular ejection in the left ventricle
• Opposition of ejection includes aortic pressure, the flow resistance by the aortic valve orifice, distensibility of the vascular system, and peripheral vascular resistance
• Afterload is equal to the arterial pressure in a simplified model
• A sudden increase in blood pressure causes decreased stroke volume and increased end systolic volume (ESV), assuming venous return remains the same
• Increased end diastolic volume (EDO) results in stronger contraction via the Frank-Starling law
• Untreated hypertension causes chronic increased afterload, leading to LV hypertrophy and cardiac failure

Regulation of Stroke Volume: Heart Rate

• Increased heart rate is caused by accumulation of intracellular calcium that normally leaves the cell via Na/Ca exchanger during diastole

Regulation of Stroke Volume: Autonomic Innervation

• Sympathetic Stimulation causes
• Activation Noradrenaline causes activation of Beta 1 adrenergic receptor
• Adenylate cyclase activation
• cAMP activates cAMP-dependent protein kinase (PKA)
• ICaL phosphorylation
• Increased sensitivity to Ca
• Increased phospholamban phosphorylation, leading to increased SERCA activity
• Sarcolemmal Na-K-ATPase stimulation, which causes effective restoration of intracellular ionic composition
• Stimulation of enzymes of energy metabolism

Regulation of Stroke Volume: Autonomic Innervation cont.

• The effect of parasympathetic system on inotropy is mainly indirect through changes in heart rate (reduction in heart rate increases diastolic calcium loss)
• Direct effect of the parasympathetic system is negative inotropic on atrial myocardium by increasing the permeability for potassium ions

Regulation of Stroke Volume: Autonomic Innervation cont. 2

• Parasympathetic stimulation causes a negative inotropic effect in the atria only
• Muscarinic (M) receptor activation causes decreased ICaL phosphorylation leading to slower Spontaneous Diastolic Depolarization (SDD) and action potential depolarization.
• Activated (Ach) current stimulation leads to hyperpolarization of Action Potential (AP), decreased SDD, and cell inhibition

Regulation of Stroke Volume: Drugs and Hormones

• Cardiac glycosides like digitalis
• Catecholamines
• Phosphodiesterase inhibitors
• Glucagon
• Hormones of thyroid gland
• PGE2
• Beta-blockers
• ICaL inhibitors
• Acetylcholine

Regulation of Stroke Volume: Energy Supply

• Lack of energy (hypoxia) causes
• Slowing down of contraction and relaxation, causing calcium handling problems
• Slower detachment of myosin head, causing increased diastolic tension
• Decreased contraction force
• Insufficient phosphorylation of L-type calcium channels, leading to risk of arrhythmia
• Opening of metabotropic potassium channels leading to risk of arrhythmia

Pressure-Volume Loops

• The relationship between pressure and volume in the ventricle

Pressure-Volume Loops cont.

• Increased preload (increased venous return) causes increased end diastolic volume (EDV) and increased stroke volume
• Increased afterload (hypertension) causes decreased stroke volume and increased end systolic volume (ESV)
• Increased contractility (sympathetic stimulation) causes increased stroke volume and decreased ESV